ATP7B

ATPase copper transporting beta, the group of ATPase copper transporting

Basic information

Region (hg38): 13:51930436-52012125

Previous symbols: [ "WND" ]

Links

ENSG00000123191 ∙ NCBI:540 ∙ OMIM:606882 ∙ HGNC:870 ∙ Uniprot:P35670 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Wilson disease (Definitive), mode of inheritance: AR
• Wilson disease (Strong), mode of inheritance: AR
• Wilson disease (Strong), mode of inheritance: AR
• Wilson disease (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the ATP7B gene.

• Wilson_disease (3222 variants)
• not_provided (569 variants)
• not_specified (267 variants)
• Inborn_genetic_diseases (237 variants)
• ATP7B-related_disorder (82 variants)
• Epileptic_encephalopathy (2 variants)
• See_cases (2 variants)
• Hand_tremor (1 variants)
• Developmental_and_epileptic_encephalopathy_93 (1 variants)
• Breast-ovarian_cancer,_familial,_susceptibility_to,_5 (1 variants)
• Hearing_loss,_autosomal_recessive_109 (1 variants)
• Kayser-Fleischer_ring (1 variants)
• Abnormality_of_metabolism/homeostasis (1 variants)
• Anhaptoglobinemia (1 variants)
• Spastic_ataxia (1 variants)
• Intellectual_disability,_Wolff_type (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. These statistics are base on transcript: NM_000000053.4. 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	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1	5	34	825	20	885
missense	45	286	1105	45	9	1490
nonsense	66	62	3			131
start loss		1				1
frameshift	179	189	6		1	375
splice donor/acceptor (+/-2bp)	24	75	3			102
Total	315	618	1151	870	30

Highest pathogenic variant AF is 0.0012898254

GnomAD

Source: gnomAD

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
		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: dbNSFP

• 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

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

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