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Mendeliome v1.4492 SREBF2 Zornitza Stark Phenotypes for gene: SREBF2 were changed from Neurocutaneous syndrome, MONDO:0042983, SREBF2-related to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related; Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related
Mendeliome v1.4491 SREBF2 Zornitza Stark Publications for gene: SREBF2 were set to 38847193
Mendeliome v1.4490 SREBF2 Zornitza Stark Mode of inheritance for gene: SREBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4489 SREBF2 Zornitza Stark edited their review of gene: SREBF2: Added comment: PMID 39814172: reports three homozygous missense variants (p.L604W, p.T984A, p.S517F) in three unrelated families (two consanguineous families). Detailed clinical descriptions are provided for two families: Family 1 (two affected siblings, onset 39 y and 25 y, progressive spastic gait, pyramidal signs, no cognitive or peripheral neuropathy) and Family 2 (single female, onset 24 y, spastic gait, internal foot deformity, normal cognition). All carriers are asymptomatic. Functional assays in patient‑derived fibroblasts show increased mature SREBP2, cholesterol accumulation, and autophagosome/lysosome enlargement. Overexpression of the nuclear SREBP2 in Drosophila recapitulates locomotor deficits. The authors conclude that biallelic SREBF2 missense variants cause an autosomal recessive hereditary spastic paraplegia through gain‑of‑function overactivation of SREBP2.; Changed publications: 38847193, 39814172; Changed phenotypes: Neurocutaneous syndrome, MONDO:0042983, SREBF2-related, Hereditary spastic paraplegia, MONDO:0019064, SREBF2-related; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mendeliome v1.4309 EBF2 Zornitza Stark Mode of inheritance for gene: EBF2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4308 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mendeliome v1.4308 EBF2 Zornitza Stark Classified gene: EBF2 as Amber List (moderate evidence)
Mendeliome v1.4308 EBF2 Zornitza Stark Gene: ebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark edited their review of gene: EBF2: Changed rating: AMBER
Mendeliome v1.4307 EBF2 Zornitza Stark Marked gene: EBF2 as ready
Mendeliome v1.4307 EBF2 Zornitza Stark Gene: ebf2 has been classified as Red List (Low Evidence).
Mendeliome v1.4307 EBF2 Zornitza Stark gene: EBF2 was added
gene: EBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: EBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: EBF2 were set to 41615236; 38978649; 29704291
Phenotypes for gene: EBF2 were set to Lipodystrophy, MONDO:0006573, EBF2-related
Review for gene: EBF2 was set to RED
Added comment: PMIDs 38978649 and 41615236 each describe a single patient with a heterozygous nonsense p.Glu165Ter variant and childhood‑onset partial lipodystrophy, providing extensive functional validation. Heterozygous knock‑in mice (Ebf2^E165X/+) recapitulate restricted adipogenesis, extracellular matrix fibrosis, reduced leptin and adiponectin, metabolic impairment on high‑fat diet and mitochondrial gene down‑regulation, supporting pathogenicity. Dominant negative mechanism suggested.

Also note PMID 29704291 reports six affected individuals from one family with a heterozygous missense p.Ala72Val variant and isolated imperforate anus. No functional data provided.
Sources: Literature
Mendeliome v1.1873 SREBF2 Zornitza Stark Marked gene: SREBF2 as ready
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1873 SREBF2 Zornitza Stark Classified gene: SREBF2 as Amber List (moderate evidence)
Mendeliome v1.1873 SREBF2 Zornitza Stark Gene: srebf2 has been classified as Amber List (Moderate Evidence).
Mendeliome v1.1872 SREBF2 Zornitza Stark gene: SREBF2 was added
gene: SREBF2 was added to Mendeliome. Sources: Literature
Mode of inheritance for gene: SREBF2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SREBF2 were set to 38847193
Phenotypes for gene: SREBF2 were set to Neurocutaneous syndrome, MONDO:0042983, SREBF2-related
Review for gene: SREBF2 was set to AMBER
Added comment: Two individuals with de novo missense variants, presenting with neurological, cutaneous and skeletal features; supportive functional data.
Sources: Literature