ATP6V1H
protein-codingATPase H+ transporting V1 subunit H, the group of V-type ATPase subunits|Armadillo like helical domain containing
Gene summary
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular organelles. V-ATPase-dependent organelle acidification is necessary for multiple processes including protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. The encoded protein is the regulatory H subunit of the V1 domain of V-ATPase, which is required for catalysis of ATP but not the assembly of V-ATPase. Decreased expression of this gene may play a role in the development of type 2 diabetes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, May 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~128.0 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 ATP6V1H variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015941.4. 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 | 1 | 1 | ||||
| missense | 63 | 63 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 70 | 1 | 0 | 71 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057025.2 | 13 | MANE Select | |
| Ensembl | ENSP00000352522.2 | 13 | MANE Select | |
| RefSeq | NP_998784.1 | 12 | Standard | |
| RefSeq | NP_998785.1 | 13 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| atp6v1h | Danio rerio | Structure: melanocyte Quality: translucent abnormal |
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)
- Lysosome - Homo sapiens (human)
- Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
Biological Process
- endocytosis
- vacuolar acidification
- insulin receptor signaling pathway
- ATP hydrolysis coupled proton transport
- regulation of macroautophagy
Molecular Function
- protein binding
- ATPase activity
- enzyme regulator activity
- proton-transporting ATPase activity, rotational mechanism
Cellular Component
- vacuolar proton-transporting V-type ATPase, V1 domain
- lysosomal membrane
- cytosol
- plasma membrane
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000359530
- Coding exons
- 13
- Length
- 128002
- Individuals with no LoFs
- 125728
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125748
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.28 | 212 | 272 | 0.781 | 0.0000151 | 3204 |
| Missense (PolyPhen) | 70 | 111.58 | 0.62738 | 1365 | ||
| Synonymous | 0.860 | 83 | 93.6 | 0.887 | 0.00000524 | 856 |
| Loss of Function | 3.14 | 12 | 30.8 | 0.389 | 0.00000159 | 356 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000060 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Subunit of the peripheral V1 complex of vacuolar ATPase. Subunit H activates the ATPase activity of the enzyme and couples ATPase activity to proton flow. Vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells, thus providing most of the energy required for transport processes in the vacuolar system (By similarity). Involved in the endocytosis mediated by clathrin-coated pits, required for the formation of endosomes. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.182
Intolerance Scores
- LoFtool
- 0.0719
- RVIS EVS
- -0.73
- RVIS percentile EVS
- 14.02
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- E
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.926
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |