ATP7B
ATPase copper transporting beta, the group of ATPase copper transporting
Basic information
Region (hg38): 13:51930435-52012125
Previous symbols: [ "WND" ]
Links
Phenotypes
GenCC
Source:
- Wilson disease (Strong), mode of inheritance: AR
- Wilson disease (Strong), mode of inheritance: AR
- Wilson disease (Supportive), mode of inheritance: AR
- Wilson disease (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Wilson disease | AR | Biochemical; Gastrointestinal | Dietary measures (eg, avoidance of copper-containing foods), as well as medications (eg, penicillamine, zinc, vitamin B6, tetrathiomolybdate), and possible liver transplant, can be beneficial | Biochemical; Gastrointestinal; Neurologic; Ophthalmologic | 463930; 3900322; 3561699; 3328213; 8298639; 8298641; 8201263; 7884606; 8610495; 9794697; 10435491; 10435489; 10673307; 12376745; 12633149; 12756138; 16283883; 16216950; 20301685; 16606763; 21901655; 22327203; 21832955; 22083169 |
ClinVar
This is a list of variants' phenotypes submitted to
- Wilson disease (2151 variants)
- not provided (459 variants)
- not specified (200 variants)
- Inborn genetic diseases (164 variants)
- ATP7B-related condition (16 variants)
- Epileptic encephalopathy (2 variants)
- See cases (2 variants)
- Congenital disorder of glycosylation (2 variants)
- Intellectual disability, Wolff type (1 variants)
- Abnormality of metabolism/homeostasis (1 variants)
- - (1 variants)
- Spastic ataxia (1 variants)
- Anhaptoglobinemia (1 variants)
- Hand tremor;Kayser-Fleischer ring (1 variants)
- ALG11-congenital disorder of glycosylation (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP7B gene is commonly pathogenic or not.
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.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 11 | 557 | 577 | |||
| missense | 33 | 159 | 519 | 19 | 11 | 741 |
| nonsense | 47 | 52 | 100 | |||
| start loss | 0 | |||||
| frameshift | 131 | 124 | 259 | |||
| inframe indel | 17 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 28 | 47 | 76 | |||
| splice region ? | 3 | 10 | 32 | 67 | 3 | 115 |
| non coding ? | 65 | 154 | 42 | 266 | ||
| Total | 240 | 391 | 618 | 730 | 62 |
Highest pathogenic variant AF is 0.000932
Variants in ATP7B
This is a list of pathogenic ClinVar variants found in the ATP7B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 13-51932855-C-T | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51932951-G-A | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51932973-TG-T | Wilson disease | Uncertain significance (Jun 14, 2016) | ||
| 13-51932974-G-C | Wilson disease | Benign (Jul 14, 2021) | ||
| 13-51932983-G-C | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933000-A-G | Wilson disease | Uncertain significance (Jan 12, 2018) | ||
| 13-51933010-G-A | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933012-G-A | Wilson disease | Likely benign (Jan 13, 2018) | ||
| 13-51933039-C-A | Wilson disease | Benign (Jan 13, 2018) | ||
| 13-51933048-T-C | Wilson disease | Benign (Jan 12, 2018) | ||
| 13-51933097-T-C | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933138-C-T | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933164-A-G | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933198-A-T | Wilson disease | Uncertain significance (Jan 12, 2018) | ||
| 13-51933257-T-A | Wilson disease | Uncertain significance (Jan 12, 2018) | ||
| 13-51933263-A-G | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933265-T-C | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933333-A-G | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933347-T-G | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933371-C-T | Wilson disease | Conflicting classifications of pathogenicity (Jul 01, 2023) | ||
| 13-51933470-C-T | Wilson disease | Uncertain significance (Jan 12, 2018) | ||
| 13-51933491-T-C | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933516-A-C | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933550-C-T | Wilson disease | Uncertain significance (Jan 13, 2018) | ||
| 13-51933574-G-A | Wilson disease | Benign (Jan 13, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ATP7B | protein_coding | protein_coding | ENST00000242839 | 21 | 78822 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 4.80e-30 | 0.000252 | 124554 | 0 | 294 | 124848 | 0.00118 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.881 | 885 | 814 | 1.09 | 0.0000471 | 9571 |
| Missense in Polyphen | 359 | 355.11 | 1.0109 | 4109 | ||
| Synonymous | -1.02 | 357 | 333 | 1.07 | 0.0000222 | 3041 |
| Loss of Function | 0.448 | 47 | 50.4 | 0.932 | 0.00000231 | 651 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00100 | 0.00100 |
| Ashkenazi Jewish | 0.000596 | 0.000596 |
| East Asian | 0.00122 | 0.00122 |
| Finnish | 0.000743 | 0.000742 |
| European (Non-Finnish) | 0.00149 | 0.00148 |
| Middle Eastern | 0.00122 | 0.00122 |
| South Asian | 0.00160 | 0.00160 |
| Other | 0.00116 | 0.00115 |
dbNSFP
Source:
- Function
- FUNCTION: Copper ion transmembrane transporter involved in the export of copper out of the cells. It is involved in copper homeostasis in the liver, where it ensures the efflux of copper from hepatocytes into the bile in response to copper overload. {ECO:0000269|PubMed:18203200, ECO:0000269|PubMed:22240481, ECO:0000269|PubMed:24706876, ECO:0000269|PubMed:26004889}.;
- Disease
- DISEASE: Wilson disease (WD) [MIM:277900]: An autosomal recessive disorder of copper metabolism in which copper cannot be incorporated into ceruloplasmin in liver, and cannot be excreted from the liver into the bile. Copper accumulates in the liver and subsequently in the brain and kidney. The disease is characterized by neurologic manifestations and signs of cirrhosis. {ECO:0000269|PubMed:10051024, ECO:0000269|PubMed:10194254, ECO:0000269|PubMed:10447265, ECO:0000269|PubMed:10453196, ECO:0000269|PubMed:10502776, ECO:0000269|PubMed:10502777, ECO:0000269|PubMed:10544227, ECO:0000269|PubMed:10721669, ECO:0000269|PubMed:10790207, ECO:0000269|PubMed:10942420, ECO:0000269|PubMed:11043508, ECO:0000269|PubMed:11093740, ECO:0000269|PubMed:11180609, ECO:0000269|PubMed:11216666, ECO:0000269|PubMed:11231950, ECO:0000269|PubMed:11243728, ECO:0000269|PubMed:11405812, ECO:0000269|PubMed:11690702, ECO:0000269|PubMed:11954751, ECO:0000269|PubMed:12325021, ECO:0000269|PubMed:12376745, ECO:0000269|PubMed:12544487, ECO:0000269|PubMed:14639035, ECO:0000269|PubMed:14966923, ECO:0000269|PubMed:14986826, ECO:0000269|PubMed:15024742, ECO:0000269|PubMed:15557537, ECO:0000269|PubMed:15811015, ECO:0000269|PubMed:15845031, ECO:0000269|PubMed:15952988, ECO:0000269|PubMed:15967699, ECO:0000269|PubMed:16088907, ECO:0000269|PubMed:16207219, ECO:0000269|PubMed:16283883, ECO:0000269|PubMed:16649058, ECO:0000269|PubMed:17718866, ECO:0000269|PubMed:17823867, ECO:0000269|PubMed:17919502, ECO:0000269|PubMed:17949296, ECO:0000269|PubMed:18203200, ECO:0000269|PubMed:18373411, ECO:0000269|PubMed:19033537, ECO:0000269|PubMed:20333758, ECO:0000269|PubMed:21398519, ECO:0000269|PubMed:21454443, ECO:0000269|PubMed:21645214, ECO:0000269|PubMed:21682854, ECO:0000269|PubMed:22075048, ECO:0000269|PubMed:22240481, ECO:0000269|PubMed:22484412, ECO:0000269|PubMed:22763723, ECO:0000269|PubMed:23159873, ECO:0000269|PubMed:23235335, ECO:0000269|PubMed:23275100, ECO:0000269|PubMed:23333878, ECO:0000269|PubMed:23518715, ECO:0000269|PubMed:23962630, ECO:0000269|PubMed:24476933, ECO:0000269|PubMed:24555712, ECO:0000269|PubMed:24706876, ECO:0000269|PubMed:25704634, ECO:0000269|PubMed:25982861, ECO:0000269|PubMed:26004889, ECO:0000269|PubMed:28856630, ECO:0000269|PubMed:7626145, ECO:0000269|PubMed:8298641, ECO:0000269|PubMed:8533760, ECO:0000269|PubMed:8782057, ECO:0000269|PubMed:8931691, ECO:0000269|PubMed:8938442, ECO:0000269|PubMed:8980283, ECO:0000269|PubMed:9222767, ECO:0000269|PubMed:9311736, ECO:0000269|PubMed:9452121, ECO:0000269|PubMed:9482578, ECO:0000269|PubMed:9554743, ECO:0000269|PubMed:9671269, ECO:0000269|PubMed:9772425, ECO:0000269|PubMed:9829905, ECO:0000269|PubMed:9837819, ECO:0000269|PubMed:9887381}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Platinum Pathway, Pharmacokinetics/Pharmacodynamics;Copper homeostasis;Ion channel transport;Transport of small molecules;Ion transport by P-type ATPases
(Consensus)
Recessive Scores
- pRec
- 0.636
Intolerance Scores
- loftool
- 0.0340
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.38
Haploinsufficiency Scores
- pHI
- 0.308
- hipred
- N
- hipred_score
- 0.197
- ghis
- 0.506
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.805
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Atp7b
- Phenotype
- endocrine/exocrine gland phenotype; growth/size/body region 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); muscle phenotype; immune system phenotype; homeostasis/metabolism phenotype; cellular phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); pigmentation phenotype; hematopoietic system 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); 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);
Gene ontology
- Biological process
- copper ion transport;cellular copper ion homeostasis;cellular zinc ion homeostasis;lactation;copper ion import;protein maturation by copper ion transfer;ion transmembrane transport;response to copper ion;sequestering of calcium ion;copper ion export;ATP hydrolysis coupled cation transmembrane transport
- Cellular component
- Golgi membrane;mitochondrion;late endosome;Golgi apparatus;trans-Golgi network;integral component of plasma membrane;membrane;basolateral plasma membrane;cytoplasmic vesicle;trans-Golgi network membrane;perinuclear region of cytoplasm
- Molecular function
- copper-exporting ATPase activity;copper ion transmembrane transporter activity;copper ion binding;protein binding;ATP binding;copper-transporting ATPase activity