ATP6V0C
protein-codingATPase H+ transporting V0 subunit c, the group of V-type ATPase subunits
Gene summary
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c", and d. This gene encodes the V0 subunit c. Alternative splicing results in transcript variants. Pseudogenes have been identified on chromosomes 6 and 17. [provided by RefSeq, Nov 2010]
- ATPL
- ATP6C
- ATP6L
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~6.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0958196
Submitter: PanelApp Australia
Inheritance Pattern: AD
Disease ID:MONDO:0958196
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0100062
Submitter: Ambry Genetics
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular; Craniofacial; Dental; Neurologic
Intervention: Cardiovascular
Rationale: Individuals have been described as being affected by congenital cardiovascular anomalies, and awareness may enable early identification and management
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ATP6V0C variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001694.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 5 | ||||
| missense | 6 | 9 | 29 | 44 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 2 | 3 | 2 | 7 | ||
| splice donor/acceptor (+/-2bp) | 1 | 3 | 4 | |||
| Total | 9 | 13 | 35 | 5 | 0 | 62 |
Highest pathogenic variant AF is 7.113448e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001685.1 | 3 | MANE Select | |
| Ensembl | ENSP00000329757.4 | 3 | MANE Select | |
| RefSeq | NP_001185498.1 | 3 | Standard | |
| Ensembl | ENSP00000454868.1 | 2 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| atp6v0cb | Danio rerio | Structure: voltage-gated calcium channel activity Quality: disrupted abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Synaptic vesicle cycle - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Lysosome - Homo sapiens (human)
- Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
- Oxidative phosphorylation - Homo sapiens (human)
Biological Process
- insulin receptor signaling pathway
- ATP hydrolysis coupled proton transport
- viral process
- regulation of macroautophagy
- positive regulation of Wnt signaling pathway
Molecular Function
- protein binding
- ubiquitin protein ligase binding
- proton-transporting ATP synthase activity, rotational mechanism
- proton-transporting ATPase activity, rotational mechanism
Cellular Component
- lysosomal membrane
- plasma membrane
- focal adhesion
- endosome membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000330398
- Coding exons
- 3
- Length
- 6349
- Individuals with no LoFs
- 0
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 0
- Defined
- 0
- p
- 0.00
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.99 | 21 | 109 | 0.194 | 0.00000712 | 987 |
| Missense (PolyPhen) | 4 | 44.649 | 0.089588 | 387 | ||
| Synonymous | -0.991 | 62 | 52.8 | 1.17 | 0.00000424 | 346 |
| Loss of Function | 1.96 | 0 | 4.48 | 0.00 | 2.77e-7 | 46 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Proton-conducting pore forming subunit of the membrane integral V0 complex of vacuolar ATPase. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.;
Recessive Scores
- pRec
- 0.161
Intolerance Scores
- LoFtool
- 0.0894
- RVIS EVS
- -0.14
- RVIS percentile EVS
- 42.88
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.925