ATP7A
ATPase copper transporting alpha, the group of ATPase copper transporting
Basic information
Region (hg38): X:77910690-78050395
Previous symbols: [ "MNK" ]
Links
Phenotypes
GenCC
Source:
- occipital horn syndrome (Strong), mode of inheritance: XL
- Menkes disease (Definitive), mode of inheritance: XL
- X-linked distal spinal muscular atrophy type 3 (Moderate), mode of inheritance: XL
- Menkes disease (Supportive), mode of inheritance: XL
- Hirschsprung disease (Supportive), mode of inheritance: AD
- occipital horn syndrome (Supportive), mode of inheritance: XL
- X-linked distal spinal muscular atrophy type 3 (Supportive), mode of inheritance: XL
- X-linked distal spinal muscular atrophy type 3 (Definitive), mode of inheritance: XL
- Menkes disease (Definitive), mode of inheritance: XL
- X-linked distal spinal muscular atrophy type 3 (Strong), mode of inheritance: XL
- Menkes disease (Strong), mode of inheritance: XL
- Menkes disease (Definitive), mode of inheritance: XL
- X-linked distal spinal muscular atrophy type 3 (Moderate), mode of inheritance: XL
- occipital horn syndrome (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Menkes disease | XL | Biochemical; Renal | With early diagnosis, daily copper injections may be beneficial (SQ injections before 10 days of life have been reported as resulting in improvement of neurologic outcome); Individuals may be prone to urinary tract infections, and measures such as antibiotic prophylaxis may be beneficial | Biochemical; Cardiovascular; Dermatologic; Gastrointestinal; Genitourinary; Musculoskeletal; Neurologic; Renal | 14472668; 5045346; 1218238; 953234; 6104292; 6140952; 4075564; 2839049; 2512453; 8490646; 8490647; 8490659; 8099605; 7842019; 8149649; 7887410; 8923001; 8528242; 9111998; 9138147; 9511979; 9894833; 14635105; 14985388; 15981243; 16630173; 17108763; 18256395; 19153371; 20652413; 20301586; 20170900; 22992316; 22711717; 22695177; 21221114 |
ClinVar
This is a list of variants' phenotypes submitted to
- Menkes_kinky-hair_syndrome (1888 variants)
- Cutis_laxa,_X-linked (1595 variants)
- X-linked_distal_spinal_muscular_atrophy_type_3 (1585 variants)
- not_provided (355 variants)
- Inborn_genetic_diseases (183 variants)
- not_specified (96 variants)
- ATP7A-related_disorder (47 variants)
- Ehlers-Danlos_syndrome (26 variants)
- Intellectual_disability (4 variants)
- See_cases (3 variants)
- History_of_neurodevelopmental_disorder (2 variants)
- Charcot-Marie-Tooth_disease (2 variants)
- ATP7A-realted_disorder (1 variants)
- Charcot-Marie-Tooth_disease_type_2 (1 variants)
- Menkes_disease,_copper-replacement_responsive (1 variants)
- Neuronopathy,_distal_hereditary_motor,_autosomal_dominant_1 (1 variants)
- Menkes_disease,_mild (1 variants)
- Au-Kline_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP7A gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000052.7. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 15 | 425 | 27 | 467 | ||
| missense | 20 | 39 | 607 | 298 | 36 | 1000 |
| nonsense | 46 | 20 | 22 | 88 | ||
| start loss | 1 | 1 | ||||
| frameshift | 46 | 57 | 54 | 157 | ||
| splice donor/acceptor (+/-2bp) | 19 | 13 | 24 | 57 | ||
| Total | 131 | 129 | 723 | 724 | 63 |
Highest pathogenic variant AF is 9.12674e-7
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ATP7A | protein_coding | protein_coding | ENST00000341514 | 22 | 139699 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000167 | 125722 | 3 | 5 | 125730 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.53 | 448 | 549 | 0.816 | 0.0000395 | 9789 |
| Missense in Polyphen | 143 | 234.17 | 0.61068 | 4197 | ||
| Synonymous | 2.00 | 161 | 197 | 0.819 | 0.0000144 | 3053 |
| Loss of Function | 5.47 | 4 | 42.4 | 0.0942 | 0.00000324 | 761 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000219 | 0.000219 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000374 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.;
- Disease
- DISEASE: Menkes disease (MNKD) [MIM:309400]: An X-linked recessive disorder of copper metabolism characterized by generalized copper deficiency. MNKD results in progressive neurodegeneration and connective-tissue disturbances: focal cerebral and cerebellar degeneration, early growth retardation, peculiar hair, hypopigmentation, cutis laxa, vascular complications and death in early childhood. The clinical features result from the dysfunction of several copper-dependent enzymes. A mild form of the disease has been described, in which cerebellar ataxia and moderate developmental delay predominate. {ECO:0000269|PubMed:10079817, ECO:0000269|PubMed:10319589, ECO:0000269|PubMed:10401004, ECO:0000269|PubMed:11241493, ECO:0000269|PubMed:11350187, ECO:0000269|PubMed:15981243, ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:22992316, ECO:0000269|PubMed:7977350, ECO:0000269|PubMed:8981948}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Occipital horn syndrome (OHS) [MIM:304150]: An X-linked recessive disorder of copper metabolism. Common features are unusual facial appearance, skeletal abnormalities, chronic diarrhea and genitourinary defects. The skeletal abnormalities include occipital horns, short, broad clavicles, deformed radii, ulnae and humeri, narrowing of the rib cage, undercalcified long bones with thin cortical walls and coxa valga. {ECO:0000269|PubMed:11431706, ECO:0000269|PubMed:17108763, ECO:0000269|PubMed:21667063, ECO:0000269|PubMed:9246006}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Distal spinal muscular atrophy, X-linked, 3 (DSMAX3) [MIM:300489]: A neuromuscular disorder. Distal spinal muscular atrophy, also known as distal hereditary motor neuronopathy, represents a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. {ECO:0000269|PubMed:20170900}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Mineral absorption - Homo sapiens (human);Platinum Pathway, Pharmacokinetics/Pharmacodynamics;Copper homeostasis;Ion influx/efflux at host-pathogen interface;Ion channel transport;Antimicrobial peptides;Innate Immune System;Immune System;Transport of small molecules;Ion transport by P-type ATPases
(Consensus)
Intolerance Scores
- loftool
- 0.0197
- rvis_EVS
- 0.41
- rvis_percentile_EVS
- 76.49
Haploinsufficiency Scores
- pHI
- 0.217
- hipred
- Y
- hipred_score
- 0.629
- ghis
- 0.535
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.491
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Atp7a
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; embryo phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); limbs/digits/tail phenotype; pigmentation phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); respiratory system phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);
Zebrafish Information Network
- Gene name
- atp7a
- Affected structure
- melanocyte
- Phenotype tag
- abnormal
- Phenotype quality
- intensity
Gene ontology
- Biological process
- blood vessel development;in utero embryonic development;liver development;blood vessel remodeling;regulation of oxidative phosphorylation;tryptophan metabolic process;catecholamine metabolic process;copper ion transport;cellular copper ion homeostasis;mitochondrion organization;lactation;locomotory behavior;response to iron(III) ion;response to manganese ion;response to zinc ion;detoxification of copper ion;regulation of gene expression;positive regulation of lamellipodium assembly;copper ion import;peptidyl-lysine modification;removal of superoxide radicals;cerebellar Purkinje cell differentiation;pyramidal neuron development;central nervous system neuron development;extracellular matrix organization;collagen fibril organization;hair follicle morphogenesis;negative regulation of iron ion transmembrane transport;cellular response to platelet-derived growth factor stimulus;T-helper cell differentiation;epinephrine metabolic process;norepinephrine metabolic process;dopamine metabolic process;serotonin metabolic process;positive regulation of catalytic activity;negative regulation of catalytic activity;pigmentation;skin development;positive regulation of cell size;elastic fiber assembly;lung alveolus development;neuron projection morphogenesis;positive regulation of epithelial cell proliferation;cartilage development;positive regulation of oxidoreductase activity;elastin biosynthetic process;copper ion export;cellular response to amino acid stimulus;cellular response to antibiotic;cellular response to cadmium ion;cellular response to cobalt ion;cellular response to copper ion;cellular response to iron ion;cellular response to lead ion;cellular response to hypoxia;ATP hydrolysis coupled cation transmembrane transport;positive regulation of response to wounding;positive regulation of vascular associated smooth muscle cell migration;regulation of cytochrome-c oxidase activity
- Cellular component
- nucleus;late endosome;endoplasmic reticulum;Golgi apparatus;trans-Golgi network;cytosol;plasma membrane;microvillus;membrane;integral component of membrane;basolateral plasma membrane;apical plasma membrane;trans-Golgi network transport vesicle;secretory granule;phagocytic vesicle membrane;cell leading edge;brush border membrane;neuron projection;neuronal cell body;perikaryon;membrane raft;perinuclear region of cytoplasm
- Molecular function
- copper-exporting ATPase activity;copper ion transmembrane transporter activity;copper ion binding;protein binding;ATP binding;superoxide dismutase copper chaperone activity;copper-dependent protein binding;copper-transporting ATPase activity;Rac GTPase binding;chaperone binding;cuprous ion binding