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ATP7A |
- 3
Haplo
Score - 0
Triplo
Score
Gene Facts External Data Attribution
- HGNC Symbol
- ATP7A (HGNC:869) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
- HGNC Name
- ATPase copper transporting alpha
- Gene type
- protein-coding gene
- Locus type
- gene with protein product
- Previous symbols
- MNK
- Alias symbols
- No aliases found
- %HI
- 30.07(Read more about the DECIPHER Haploinsufficiency Index)
- pLI
- 1(Read more about gnomAD pLI score)
- LOEUF
- 0.22(Read more about gnomAD LOEUF score)
- Cytoband
- Xq21.1
- Genomic Coordinates
-
GRCh37/hg19: chrX:77166190-77305892 NCBI Ensembl UCSC GRCh38/hg38: chrX:77910693-78050395 NCBI Ensembl UCSC - MANE Select Transcript
- NM_000052.7 ENST00000341514.11 (Read more about MANE Select)
- Function
- ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to ... (Source: Uniprot)
Dosage Sensitivity Summary (Gene)
Haploinsufficiency (HI) Score Details
- Menkes disease Monarch
-
PUBMED:
14635105
Tumer et al., 2013 performed review of 274 previously published and 18 novel variants in ATP7A associated with Menkes disease or occipital horn syndrome. All variants except 89 missense variants and a single dinucleotide inversion were predicted to result in nonfunctional truncated protein or nonsense mediated decay, suggesting loss of function mechanism for these diseases. Seven chromosome abnormalities were reported, including a male with an insertional event, inherited from a mother with preferential inactivation of the affected chromosome. The remaining females with chromosome abnormalities included a female patient with mosaic Turner syndrome, and five females with X;autosome translocations in which the derivative X chromosome was preferentially active, leading to a Menkes disease phenotype.
-
PUBMED:
32994893
Mhaske 2020 compiled reported variants in ATP7A into a comprehensive database that included 602 variants. The authors concluded that nonsense, frameshift-insertion, and deletions which are truncating and cause protein disruption typically lead to severe phenotypes.
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
Triplosensitivity (TS) Score Details
The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.
