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{
"count": 220833,
"next": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1239",
"previous": "https://panelapp-aus.org/api/v1/activities/?format=api&page=1237",
"results": [
{
"created": "2021-08-14T15:13:40.761558+10:00",
"panel_name": "Growth failure in early childhood",
"panel_id": 3631,
"panel_version": "0.85",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8013627, 7849697; Phenotypes: Isolated growth hormone deficiency, type III, with agammaglobulinaemia, MIM# 307200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:12:16.631869+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.89",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BTK as ready",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:12:16.620832+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.89",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: btk has been classified as Green List (High Evidence).",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:12:12.233113+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.89",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BTK were changed from to Agammaglobulinaemia, X-linked 1, MIM# 300755; Isolated growth hormone deficiency, type III, with agammaglobulinaemia, MIM# 307200",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:10:53.205365+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.88",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: BTK were set to ",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:10:20.933974+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.87",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: BTK was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T15:09:54.405311+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.86",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BTK: Rating: GREEN; Mode of pathogenicity: None; Publications: 8013627, 7849697; Phenotypes: Agammaglobulinaemia, X-linked 1, MIM# 300755, Isolated growth hormone deficiency, type III, with agammaglobulinaemia, MIM# 307200; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females",
"entity_name": "BTK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:59:42.411229+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8821",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: MOCOS as ready",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:59:42.400550+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8821",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: mocos has been classified as Green List (High Evidence).",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:59:34.133703+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8821",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: MOCOS were changed from to Xanthinuria type II, MIM#603592",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:59:14.091570+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8820",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: MOCOS were set to ",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:58:44.512442+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8819",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: MOCOS was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:58:22.826235+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8818",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: MOCOS: Rating: GREEN; Mode of pathogenicity: None; Publications: 11302742, 17368066, 14624414, 25967871, 34356852, 32073534, 30758870, 27919260; Phenotypes: Xanthinuria type II, MIM#603592; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "MOCOS",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:49:00.166547+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8818",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: HNMT as ready",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:49:00.157654+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8818",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: hnmt has been classified as Green List (High Evidence).",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:48:52.356805+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8818",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: HNMT were changed from to Mental retardation, autosomal recessive 51, MIM#616739",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:48:34.441577+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8817",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: HNMT were set to ",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:48:11.856284+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8816",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: HNMT was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:47:56.222209+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8815",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: HNMT: Rating: GREEN; Mode of pathogenicity: None; Publications: 26206890, 30744146, 33310825, 33739554; Phenotypes: Mental retardation, autosomal recessive 51, MIM#616739; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:47:25.941942+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4053",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: HNMT were set to 26206890; 30744146",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:46:53.382770+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4052",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: HNMT: Added comment: Verhoeven et al. 2020 (PMID: 33310825) report an adult male patient with severe intellectual disability and autism, born to second cousins, with a homozygous nonsense variant (c.88C>T; p.Gln30*). Treatment with antihistaminergic medication and a histamine-restricted diet resulted in significant general improvement, supporting an etiological role for HNMT deficiency. Taskiran et al. 2021 (PMID: 33739554) report an adult male patient with severe intellectual disability, pervasive developmental disorder and ADHD, born to consanguineous parents, with a homozygous nonsense variant (c.100G>T; p.Glu34*).; Changed publications: 26206890, 30744146, 33310825, 33739554",
"entity_name": "HNMT",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:43:37.644485+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.86",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BLNK as ready",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:43:37.634046+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.86",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: blnk has been classified as Green List (High Evidence).",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:43:18.820106+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8815",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: BLNK as ready",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:43:18.809718+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8815",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: blnk has been classified as Green List (High Evidence).",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:43:09.751158+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8815",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BLNK were changed from to Agammaglobulinaemia 4, MIM# 613502",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:42:46.205968+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8814",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: BLNK were set to ",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:42:26.880939+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8813",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: BLNK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:42:20.645333+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.86",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: BLNK were changed from to Agammaglobulinaemia 4, MIM# 613502",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:42:07.488693+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8812",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BLNK: Rating: GREEN; Mode of pathogenicity: None; Publications: 10583958, 32194234, 25893637; Phenotypes: Agammaglobulinaemia 4, MIM# 613502; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:41:54.524853+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.85",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: BLNK were set to ",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:41:22.739808+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.84",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: BLNK was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:40:49.859423+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: BLNK: Changed phenotypes: Agammaglobulinaemia 4, MIM# 613502",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:40:42.359633+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: BLNK: Changed rating: GREEN",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:40:35.667129+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: BLNK: Rating: ; Mode of pathogenicity: None; Publications: 10583958, 32194234, 25893637; Phenotypes: Agammaglobulinemia 4, MIM# 613502; Mode of inheritance: None",
"entity_name": "BLNK",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:03:39.490588+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8812",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: AICDA as ready",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:03:39.481375+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8812",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: aicda has been classified as Green List (High Evidence).",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:03:32.314350+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8812",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: AICDA were changed from to Immunodeficiency with hyper-IgM, type 2, MIM# 605258",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:03:13.833081+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8811",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: AICDA were set to ",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:02:58.058735+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8810",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: AICDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:02:34.702390+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8809",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11007475; Phenotypes: Immunodeficiency with hyper-IgM, type 2, MIM# 605258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:01:36.789842+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: AICDA as ready",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:01:36.780616+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: aicda has been classified as Green List (High Evidence).",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:01:33.019546+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.83",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: AICDA were changed from to Immunodeficiency with hyper-IgM, type 2, MIM# 605258",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:00:58.349806+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.82",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: AICDA were set to ",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:00:30.820061+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.81",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: AICDA was changed from Unknown to BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T12:00:04.437105+10:00",
"panel_name": "Predominantly Antibody Deficiency",
"panel_id": 222,
"panel_version": "0.80",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: AICDA: Rating: GREEN; Mode of pathogenicity: None; Publications: 11007475; Phenotypes: Immunodeficiency with hyper-IgM, type 2, MIM# 605258; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "AICDA",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:52:50.391384+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.202",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SLC51B as ready",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:52:50.381094+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.202",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: slc51b has been classified as Red List (Low Evidence).",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:52:43.649622+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.202",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: SLC51B was added\ngene: SLC51B was added to Cholestasis. Sources: Literature\nMode of inheritance for gene: SLC51B was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: SLC51B were set to 28898457\nPhenotypes for gene: SLC51B were set to Bile acid malabsorption, primary, 2, MIM# 619481; Congenital diarrhoea; Cholestasis\nReview for gene: SLC51B was set to RED\nAdded comment: Two siblings reported with homozygous LOF variant in this gene and congenital diarrhoea/cholestasis. \nSources: Literature",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:51:15.284261+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8809",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: SLC51B were changed from Congenital diarrhoea; Cholestasis to Bile acid malabsorption, primary, 2, MIM# 619481; Congenital diarrhoea; Cholestasis",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:50:55.638119+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8808",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLC51B: Changed phenotypes: Bile acid malabsorption, primary, 2, MIM# 619481, Congenital diarrhoea, Cholestasis",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:50:37.432875+10:00",
"panel_name": "Congenital Diarrhoea",
"panel_id": 89,
"panel_version": "1.6",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: SLC51B were changed from Congenital diarrhoea; Cholestasis to Bile acid malabsorption, primary, 2, MIM# 619481; Congenital diarrhoea; Cholestasis",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T11:50:02.347328+10:00",
"panel_name": "Congenital Diarrhoea",
"panel_id": 89,
"panel_version": "1.5",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "edited their review of gene: SLC51B: Changed phenotypes: Bile acid malabsorption, primary, 2, MIM# 619481, Congenital diarrhoea, Cholestasis",
"entity_name": "SLC51B",
"entity_type": "gene"
},
{
"created": "2021-08-14T09:02:07.893013+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.40",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: VPS50 as ready",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T09:02:07.879188+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.40",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T09:02:02.222936+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.40",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T09:02:02.210683+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.40",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T09:01:31.492867+10:00",
"panel_name": "Microcephaly",
"panel_id": 138,
"panel_version": "1.39",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Microcephaly. Sources: Literature\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to 34037727\nPhenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.\r\n\r\nCommon features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. \r\n\r\nBoth individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).\r\n\r\nVPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.\r\n\r\nAs discussed by Schneeberger et al (refs provided in text):\r\n- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.\r\n- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.\r\n\r\nStudies performed by Schneeberger et al included:\r\n- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).\r\n- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.\r\n- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.\r\n- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.\r\n\r\nAs the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\".\r\n\r\nThere is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. \nSources: Literature",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:59:58.750200+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.201",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: VPS50 as ready",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:59:58.740382+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.201",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:59:54.790807+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.201",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:59:54.780501+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.201",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:59:29.836481+10:00",
"panel_name": "Cholestasis",
"panel_id": 78,
"panel_version": "0.200",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Cholestasis. Sources: Literature\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to 34037727\nPhenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.\r\n\r\nCommon features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. \r\n\r\nBoth individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).\r\n\r\nVPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.\r\n\r\nAs discussed by Schneeberger et al (refs provided in text):\r\n- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.\r\n- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.\r\n\r\nStudies performed by Schneeberger et al included:\r\n- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).\r\n- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.\r\n- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.\r\n- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.\r\n\r\nAs the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\".\r\n\r\nThere is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. \nSources: Literature",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:58:01.362651+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8808",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: VPS50 as ready",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:58:01.352582+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8808",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:57:51.660678+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8808",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:57:51.647567+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8808",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:57:34.432100+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8807",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Mendeliome. Sources: Literature\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to 34037727\nPhenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.\r\n\r\nCommon features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. \r\n\r\nBoth individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).\r\n\r\nVPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.\r\n\r\nAs discussed by Schneeberger et al (refs provided in text):\r\n- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.\r\n- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.\r\n\r\nStudies performed by Schneeberger et al included:\r\n- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).\r\n- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.\r\n- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.\r\n- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.\r\n\r\nAs the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\".\r\n\r\nThere is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes. \nSources: Literature",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:55:48.650640+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1169",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: VPS50 as ready",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:55:48.640635+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1169",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:55:25.583158+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1169",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:55:25.574393+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1169",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:54:27.167154+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4052",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: VPS50 as ready",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:54:27.158215+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4052",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:54:18.156561+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4052",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: VPS50 as Amber List (moderate evidence)",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-14T08:54:18.143971+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4052",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: vps50 has been classified as Amber List (Moderate Evidence).",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-13T23:35:30.220026+10:00",
"panel_name": "Genetic Epilepsy",
"panel_id": 202,
"panel_version": "0.1168",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Genetic Epilepsy. Sources: Literature\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to 34037727\nPhenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum\nPenetrance for gene: VPS50 were set to Complete\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.\r\n\r\nCommon features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. \r\n\r\nBoth individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).\r\n\r\nVPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.\r\n\r\nAs discussed by Schneeberger et al (refs provided in text):\r\n- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.\r\n- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.\r\n\r\nStudies performed by Schneeberger et al included:\r\n- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).\r\n- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.\r\n- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.\r\n- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.\r\n\r\nAs the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\".\r\n\r\nThere is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.\r\n\r\nConsider inclusion in other relevant gene panels (e.g. for neonatal cholestasis, epilepsy, microcephaly, growth failure in early infancy, corpus callosum anomalies, etc) with amber rating pending further reports. \nSources: Literature",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-13T23:35:27.127812+10:00",
"panel_name": "Intellectual disability syndromic and non-syndromic",
"panel_id": 250,
"panel_version": "0.4051",
"user_name": "Konstantinos Varvagiannis",
"item_type": "entity",
"text": "gene: VPS50 was added\ngene: VPS50 was added to Intellectual disability syndromic and non-syndromic. Sources: Literature\nMode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal\nPublications for gene: VPS50 were set to 34037727\nPhenotypes for gene: VPS50 were set to Neonatal cholestatic liver disease; Failure to thrive; Profound global developmental delay; Postnatal microcephaly; Seizures; Abnormality of the corpus callosum\nPenetrance for gene: VPS50 were set to Complete\nReview for gene: VPS50 was set to AMBER\nAdded comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants.\r\n\r\nCommon features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. \r\n\r\nBoth individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)).\r\n\r\nVPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor.\r\n\r\nAs discussed by Schneeberger et al (refs provided in text):\r\n- VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development.\r\n- Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality.\r\n\r\nStudies performed by Schneeberger et al included:\r\n- Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del).\r\n- Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels.\r\n- Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts.\r\n- Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function.\r\n\r\nAs the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term \"GARP and/or EARP deficiency disorders\".\r\n\r\nThere is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.\r\n\r\nConsider inclusion in other relevant gene panels (e.g. for neonatal cholestasis, epilepsy, microcephaly, growth failure in early infancy, corpus callosum anomalies, etc) with amber rating pending further reports. \nSources: Literature",
"entity_name": "VPS50",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:27:11.293134+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "1.0",
"user_name": "Zornitza Stark",
"item_type": "panel",
"text": "promoted panel to version 1.0",
"entity_name": null,
"entity_type": null
},
{
"created": "2021-08-13T16:26:52.914144+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: SMARCD2 as ready",
"entity_name": "SMARCD2",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:26:52.903481+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: smarcd2 has been classified as Red List (Low Evidence).",
"entity_name": "SMARCD2",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:26:23.565382+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.72",
"user_name": "Zornitza Stark",
"item_type": "panel",
"text": "Panel types changed to Victorian Clinical Genetics Services; Rare Disease",
"entity_name": null,
"entity_type": null
},
{
"created": "2021-08-13T16:20:27.549801+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.71",
"user_name": "Zornitza Stark",
"item_type": "panel",
"text": "removed gene:TUFT1 from the panel",
"entity_name": null,
"entity_type": null
},
{
"created": "2021-08-13T16:18:55.451935+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.70",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: TP63 as ready",
"entity_name": "TP63",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:18:55.440865+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.70",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: tp63 has been classified as Red List (Low Evidence).",
"entity_name": "TP63",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:18:52.353349+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.70",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TP63 were changed from Split hand-split foot-ectodermal dysplasia and amelogenesis imperfecta to Split-hand/foot malformation 4, MIM# 605289",
"entity_name": "TP63",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:18:43.438043+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.69",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: TP63 were set to ",
"entity_name": "TP63",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:18:31.396405+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TP63: Rating: RED; Mode of pathogenicity: None; Publications: 22065540; Phenotypes: Split-hand/foot malformation 4, MIM# 605289; Mode of inheritance: None",
"entity_name": "TP63",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:16:34.131838+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: TMEM165 as ready",
"entity_name": "TMEM165",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:16:34.122541+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: tmem165 has been classified as Red List (Low Evidence).",
"entity_name": "TMEM165",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:16:23.609305+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.68",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Phenotypes for gene: TMEM165 were changed from amelogenesis imperfecta to Congenital disorder of glycosylation, type IIk, MIM# 614727; amelogenesis imperfecta",
"entity_name": "TMEM165",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:16:07.617927+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: TMEM165: Rating: RED; Mode of pathogenicity: None; Publications: 22683087; Phenotypes: Congenital disorder of glycosylation, type IIk, MIM# 614727; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "TMEM165",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:14:48.263229+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "reviewed gene: SMARCD2: Rating: RED; Mode of pathogenicity: None; Publications: 28369036; Phenotypes: Specific granule deficiency 2, MIM# 617475; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal",
"entity_name": "SMARCD2",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:12:38.702410+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Marked gene: KCNJ1 as ready",
"entity_name": "KCNJ1",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:12:38.689396+10:00",
"panel_name": "Amelogenesis imperfecta",
"panel_id": 3564,
"panel_version": "0.67",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: kcnj1 has been classified as Red List (Low Evidence).",
"entity_name": "KCNJ1",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:11:33.277493+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8806",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Publications for gene: SP6 were set to 32167558; 18156176; 18297738; 22676574",
"entity_name": "SP6",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:11:11.486971+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8805",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Mode of inheritance for gene: SP6 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted",
"entity_name": "SP6",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:10:50.476458+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8804",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Classified gene: SP6 as Green List (high evidence)",
"entity_name": "SP6",
"entity_type": "gene"
},
{
"created": "2021-08-13T16:10:50.466648+10:00",
"panel_name": "Mendeliome",
"panel_id": 137,
"panel_version": "0.8804",
"user_name": "Zornitza Stark",
"item_type": "entity",
"text": "Gene: sp6 has been classified as Green List (High Evidence).",
"entity_name": "SP6",
"entity_type": "gene"
}
]
}