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| Mendeliome v2.246 | TMEM63B | Zornitza Stark Phenotypes for gene: TMEM63B were changed from Developmental and epileptic encephalopathy 118, MIM#621250; Hereditary pulmonary alveolar proteinosis, MONDO:0012580, TMEM63B-related to Developmental and epileptic encephalopathy 118, MIM#621250; Lung-brain developmental disorder, MIM# 621645 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.245 | TMEM63B | Zornitza Stark edited their review of gene: TMEM63B: Changed phenotypes: Lung-brain developmental disorder, MIM# 621645 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.115 | TMEM63B | Zornitza Stark Phenotypes for gene: TMEM63B were changed from Developmental and epileptic encephalopathy 118, MIM#621250 to Developmental and epileptic encephalopathy 118, MIM#621250; Hereditary pulmonary alveolar proteinosis, MONDO:0012580, TMEM63B-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.114 | TMEM63B | Zornitza Stark Publications for gene: TMEM63B were set to 37421948 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.113 | TMEM63B | Zornitza Stark Mode of inheritance for gene: TMEM63B was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.112 | TMEM63B | Zornitza Stark reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Hereditary pulmonary alveolar proteinosis, MONDO:0012580, TMEM63B-related; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.106 | TMEM63B |
Eleanor Williams changed review comment from: Heterozygous variants in TMEM63B are associated with Developmental and epileptic encephalopathy 118 (OMIM:621250, accessed 25th Jun 2026) with a gain-of-function mechanism proposed. Variants reported are either missense or an in-frame deletion. The main phenotypic features are severe early-onset developmental and epileptic encephalopathy, intellectual disability, and severe motor and cortical visual impairment associated with progressive neurodegenerative brain changes (PMID: 37421948, doi:10.1016/j.bdcasr.2024.100043). Hearing loss is reported in mouse TMEM63B knockouts PMID: 32375046). PMID: 42259295 Chan et al 2026 report five individuals from four unrelated families with childhood interstitial lung disease and biallelic predicted loss-of-function variants in TMEM63B. Other phenotypic characteristics include moderate/severe developmental delay (5/5), white matter changes, (1/5), mild global atrophy on brain imaging (1/5) and severe short stature (2/5). None of the individuals had epilepsy or hearing loss. Individuals were from Saudi Arabian, Malay, European and Native American ethnicities. 5 different variants were reported including nonsense, frameshift and splice donor variants. In family A a heterozygous ABCA3 missense variant of unknown significance was also inherited from the mother. Biallelic variants in ABCA3 are associated with Surfactant metabolism dysfunction, pulmonary, 3, OMIM:610921. The authors report that while there are 53 TMEM63B pLoF variants in gnomAD v.4.1.0 database none are in the homozygous state. Histopathological examination of lung tissue also showed a pattern consistent with surfactant dysfunction. The authors conclude that biallelic loss of function variants result in a distinct pulmonary-predominant phenotype characterized by hypoxemia, early-onset respiratory failure, histological features of surfactant dysfunction, and chest imaging consistent with chILD.; to: Heterozygous variants in TMEM63B are associated with Developmental and epileptic encephalopathy 118 (OMIM:621250, accessed 25th Jun 2026) with a gain-of-function mechanism proposed. PMID: 42259295 Chan et al 2026 report five individuals from four unrelated families with childhood interstitial lung disease and biallelic predicted loss-of-function variants in TMEM63B. Other phenotypic characteristics include moderate/severe developmental delay (5/5), white matter changes, (1/5), mild global atrophy on brain imaging (1/5) and severe short stature (2/5). None of the individuals had epilepsy or hearing loss. Individuals were from Saudi Arabian, Malay, European and Native American ethnicities. 5 different variants were reported including nonsense, frameshift and splice donor variants. In family A a heterozygous ABCA3 missense variant of unknown significance was also inherited from the mother. Biallelic variants in ABCA3 are associated with Surfactant metabolism dysfunction, pulmonary, 3, OMIM:610921. The authors report that while there are 53 TMEM63B pLoF variants in gnomAD v.4.1.0 database none are in the homozygous state. Histopathological examination of lung tissue also showed a pattern consistent with surfactant dysfunction. The authors conclude that biallelic loss of function variants result in a distinct pulmonary-predominant phenotype characterized by hypoxemia, early-onset respiratory failure, histological features of surfactant dysfunction, and chest imaging consistent with chILD. |
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| Mendeliome v2.106 | TMEM63B | Eleanor Williams reviewed gene: TMEM63B: Rating: GREEN; Mode of pathogenicity: None; Publications: 37421948, 42259295, doi:10.1016/j.bdcasr.2024.100043; Phenotypes: Developmental and epileptic encephalopathy 118, MIM:621250, autosomal-recessive TMEM63B-related syndromic surfactant dysfunction disorder; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v2.0 | TMEM63B | Gene migrated from ENSG00000137216 to ENSG00000137216 (gene set migration) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.2692 | TMEM63B | Zornitza Stark Phenotypes for gene: TMEM63B were changed from developmental and epileptic encephalopathy, MONDO:0100062, TMEM63B-related to Developmental and epileptic encephalopathy 118, MIM#621250 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1048 | TMEM63B | Zornitza Stark Marked gene: TMEM63B as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1048 | TMEM63B | Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1048 | TMEM63B | Zornitza Stark Phenotypes for gene: TMEM63B were changed from developmental and epileptic encephalopathy, MONDO:0100062 to developmental and epileptic encephalopathy, MONDO:0100062, TMEM63B-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1047 | TMEM63B | Zornitza Stark Classified gene: TMEM63B as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1047 | TMEM63B | Zornitza Stark Gene: tmem63b has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mendeliome v1.1045 | TMEM63B |
Achchuthan Shanmugasundram changed review comment from: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature; to: There is sufficient evidence for this gene to be included with green rating in 'Intellectual disability syndromic and non-syndromic' and 'Genetic epilepsy' panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature |
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| Mendeliome v1.1045 | TMEM63B |
Achchuthan Shanmugasundram gene: TMEM63B was added gene: TMEM63B was added to Mendeliome. Sources: Literature Mode of inheritance for gene: TMEM63B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TMEM63B were set to 37421948 Phenotypes for gene: TMEM63B were set to developmental and epileptic encephalopathy, MONDO:0100062 Review for gene: TMEM63B was set to GREEN Added comment: There is sufficient evidence for this gene to be included with green rating in intellectual disability and epilepsy panels. 17 unrelated individuals with severe early-onset developmental and epileptic encephalopathy (DEE), intellectual disability, and severe motor and cortical visual impairment were identified with ten distinct heterozygous variants inTMEM63B. The variants occurred de novo in 16/17 individuals for whom parental DNA was available and either missense or in-frame. All individuals had global developmental delay, with moderate-to-profound intellectual disability and severe motor impairment. All individuals had early-onset drug-resistant epilepsy, whose onset ranged from birth to 3 years but occurred within the first year in 14/17 (82%) and in the first month of life in 6/17 (35%). Sources: Literature |
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