ATP6V1G1
protein-codingATPase H+ transporting V1 subunit G1, 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, three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. The protein encoded by this gene is one of three V1 domain G subunit proteins. Pseudogenes of this gene have been characterized. [provided by RefSeq, Jul 2008]
- ATP6J
- ATP6G1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ATP6V1G1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004888.4. 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 | 0 | |||||
| missense | 18 | 18 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 18 | 0 | 0 | 18 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004879.1 | 3 | MANE Select | |
| Ensembl | ENSP00000363162.3 | 3 | MANE Select | |
| Ensembl | ENSP00000503684.1 | 1 | Standard | |
| Ensembl | ENSP00000503566.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- Synaptic vesicle cycle - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
- Oxidative phosphorylation - Homo sapiens (human)
Biological Process
- cellular iron ion homeostasis
- insulin receptor signaling pathway
- regulation of macroautophagy
- transferrin transport
- ion transmembrane transport
Molecular Function
- protein binding
- proton-exporting ATPase activity, phosphorylative mechanism
- ATPase binding
Cellular Component
- lysosomal membrane
- cytosol
- plasma membrane
- vacuolar proton-transporting V-type ATPase complex
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000374050
- Coding exons
- 3
- Length
- 10628
- Individuals with no LoFs
- 115232
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 1
- Defined
- 115233
- p
- 0.00000434
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.620 | 43 | 56.1 | 0.767 | 0.00000276 | 751 |
| Missense (PolyPhen) | 6 | 9.9372 | 0.60379 | 172 | ||
| Synonymous | 0.631 | 17 | 20.6 | 0.823 | 9.03e-7 | 202 |
| Loss of Function | 1.23 | 2 | 4.97 | 0.403 | 2.10e-7 | 70 |
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 | 0.000062 | 0.000062 | rare |
| 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: Catalytic subunit of the peripheral V1 complex of vacuolar ATPase (V-ATPase). V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). {ECO:0000269|PubMed:28296633}.;
Recessive Scores
- pRec
- 0.125
Intolerance Scores
- LoFtool
- 0.430
- RVIS EVS
- 0.41
- RVIS percentile EVS
- 76.67
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.965
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |