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Cholestasis v4.17 ATP6AP2 Ida Ertmanska edited their review of gene: ATP6AP2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cholestasis v4.17 ATP6AP2 Ida Ertmanska Mode of inheritance for gene: ATP6AP2 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cholestasis v4.16 ATP6AP2 Eleanor Williams Publications for gene: ATP6AP2 were set to 29127204; 41131679
Cholestasis v4.15 ATP6AP2 Ida Ertmanska edited their review of gene: ATP6AP2: Changed mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cholestasis v4.15 ATP6AP2 Ida Ertmanska edited their review of gene: ATP6AP2: Changed publications to: 29127204, 38075676, 41131679
Cholestasis v4.15 ATP6AP2 Ida Ertmanska Mode of inheritance for gene: ATP6AP2 was changed from X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cholestasis v4.14 ATP6AP2 Ida Ertmanska Mode of pathogenicity for gene: ATP6AP2 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Cholestasis v4.13 ATP6AP2 Ida Ertmanska Classified gene: ATP6AP2 as Amber List (moderate evidence)
Cholestasis v4.13 ATP6AP2 Ida Ertmanska Added comment: Comment on list classification: There are 3 unrelated families reported in literature where individuals harboured hemizygous ATP6AP2 missense variants, and presented with a congenital disorder of glycosylation (primarily manifesting by liver disease and immunodeficiency). Liver features reported: early-onset cirrhosis and steatosis, neonatal liver failure, hepatosplenomegaly, liver transplant before 1 year of age. Patients with hemizygous splicing variants present with a different phenotype (DEE-type neurological presentation), with no liver involvement. Hence, this gene should be promoted to Green on Cholestasis, based on cases with missense variants.
Cholestasis v4.13 ATP6AP2 Ida Ertmanska Gene: atp6ap2 has been classified as Amber List (Moderate Evidence).
Cholestasis v4.12 ATP6AP2 Ida Ertmanska changed review comment from: PMID: 41131679 Raynor et al., 2026
Authors identified three males and one female from three families with ATP6AP2 splicing variants and ID/DD, epilepsy, axial hypotonia, axonal neuropathy and microcephaly; the heterozygous female has a milder phenotype. RNA-Seq in patient-derived fibroblasts validated defective splicing, correlated with lowered ATP6AP2 protein levels in fibroblasts alongside glycosylation abnormalities.

PMID: 29127204 Rujano et al., 2017
Report of 3 individuals from 2 families with two hemizygous missense mutations in ATP6AP2. Seq method: WES.
P1 - Portuguese male, hemizygous for the ATP6AP2:c.293T>C (p.L98S) variant. Liver biopsy at 16 mo of age showing cirrhosis and steatosis; recurrent infections noted.
P2, P3 - 2 males from a German family, hemizygous for a ATP6AP2:c.212G>A (p.R71H) variant. P2: recurrent pulmonary and upper respiratory tract infections throughout infancy and childhood; ultrasounds showed hepatosplenomegaly. P3: developed liver failure at 5 months of age, liver biopsy revealed lipid accumulation and enlarged vacuolar structures within hepatocytes; suffered from recurrent infections.
Functional: Authors also show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects.
Sources: Literature; to: PMID: 41131679 Raynor et al., 2026
Authors identified three males and one female from three families with ATP6AP2 splicing variants (confirmed splicing effects by RNA-seq) and ID/DD, severe epilepsy (3 male patients), axial hypotonia, axonal neuropathy and microcephaly; the heterozygous female has a milder phenotype (at 14yrs she had mild ID, autism, and progressive microcephaly). RNA-Seq in patient-derived fibroblasts validated defective splicing, correlated with lowered ATP6AP2 protein levels in fibroblasts alongside glycosylation abnormalities. No liver involvement in these 4 patients.

PMID: 38075676 Fang et al., 2023
11mo Chinese male patient with a novel hemizygous ATP6AP2 variant c.185G>A (p.Gly62Glu) and a congenital disorder of glycosylation. He presented with recurrent jaundice, cutis laxa, cirrhosis, growth retardation, coagulopathy, anemia, and cardiomegaly, and underwent liver transplantation.
Functional: metabolomics analysis revealed that the exogenously introduced Gly62Glu mutant resulted in the downregulation of numerous metabolites involved in lipid metabolism pathway.

PMID: 29127204 Rujano et al., 2017
Report of 3 individuals from 2 families with two hemizygous missense mutations in ATP6AP2. Seq method: WES.
P1 - Portuguese male, hemizygous for the ATP6AP2:c.293T>C (p.L98S) variant. Liver biopsy at 16 mo of age showing cirrhosis and steatosis; recurrent infections noted.
P2, P3 - 2 males from a German family, hemizygous for a ATP6AP2:c.212G>A (p.R71H) variant. P2: recurrent pulmonary and upper respiratory tract infections throughout infancy and childhood; ultrasounds showed hepatosplenomegaly. P3: developed liver failure at 5 months of age, liver biopsy revealed lipid accumulation and enlarged vacuolar structures within hepatocytes; suffered from recurrent infections.
Functional: Authors also show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects.

ATP6AP2 is associated with X-linked Congenital disorder of glycosylation, type IIr, OMIM:301045, Intellectual developmental disorder, X-linked syndromic, Hedera type, OMIM:300423, and ?Parkinsonism with spasticity, X-linked, OMIM:300911 (OMIM accessed 8th July 2026).
Sources: Literature
Cholestasis v4.12 ATP6AP2 Ida Ertmanska gene: ATP6AP2 was added
gene: ATP6AP2 was added to Cholestasis. Sources: Literature
Q3_26_promote_green tags were added to gene: ATP6AP2.
Mode of inheritance for gene: ATP6AP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ATP6AP2 were set to 29127204; 41131679
Phenotypes for gene: ATP6AP2 were set to Congenital disorder of glycosylation, type IIr, OMIM:301045; congenital disorder of glycosylation, type IIr, MONDO:0026765; congenital disorder of glycosylation, type IIr, X-linked recessive
Review for gene: ATP6AP2 was set to GREEN
Added comment: PMID: 41131679 Raynor et al., 2026
Authors identified three males and one female from three families with ATP6AP2 splicing variants and ID/DD, epilepsy, axial hypotonia, axonal neuropathy and microcephaly; the heterozygous female has a milder phenotype. RNA-Seq in patient-derived fibroblasts validated defective splicing, correlated with lowered ATP6AP2 protein levels in fibroblasts alongside glycosylation abnormalities.

PMID: 29127204 Rujano et al., 2017
Report of 3 individuals from 2 families with two hemizygous missense mutations in ATP6AP2. Seq method: WES.
P1 - Portuguese male, hemizygous for the ATP6AP2:c.293T>C (p.L98S) variant. Liver biopsy at 16 mo of age showing cirrhosis and steatosis; recurrent infections noted.
P2, P3 - 2 males from a German family, hemizygous for a ATP6AP2:c.212G>A (p.R71H) variant. P2: recurrent pulmonary and upper respiratory tract infections throughout infancy and childhood; ultrasounds showed hepatosplenomegaly. P3: developed liver failure at 5 months of age, liver biopsy revealed lipid accumulation and enlarged vacuolar structures within hepatocytes; suffered from recurrent infections.
Functional: Authors also show that ATP6AP2 deficiency in the mouse liver caused hypoglycosylation of serum proteins and autophagy defects.
Sources: Literature