ATP6V1D
protein-codingATPase H+ transporting V1 subunit D, 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. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This gene encodes the V1 domain D subunit protein. [provided by RefSeq, Jul 2008]
- ATP6M
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~65.9 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 ATP6V1D variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015994.4. 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) | 4 | 4 | ||||
| Total | 0 | 0 | 22 | 0 | 0 | 22 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057078.1 | 9 | MANE Select | |
| Ensembl | ENSP00000216442.7 | 9 | MANE Select | |
| Ensembl | ENSP00000450834.1 | 3 | Standard | |
| Ensembl | ENSP00000452492.1 | 2 | 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
- insulin receptor signaling pathway
- regulation of macroautophagy
- transferrin transport
- ion transmembrane transport
- neutrophil degranulation
Molecular Function
- protein binding
- proton-transporting ATPase activity, rotational mechanism
Cellular Component
- lysosomal membrane
- centrosome
- cytosol
- plasma membrane
- cilium
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216442
- Coding exons
- 9
- Length
- 65895
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.13 | 97 | 134 | 0.725 | 0.00000694 | 1599 |
| Missense (PolyPhen) | 24 | 42.585 | 0.56358 | 550 | ||
| Synonymous | 0.478 | 42 | 46.1 | 0.910 | 0.00000232 | 469 |
| Loss of Function | 1.91 | 10 | 19.0 | 0.527 | 0.00000116 | 200 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.000092 | 0.000092 | rare |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Subunit of the peripheral V1 complex of vacuolar ATPase. 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). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. {ECO:0000250, ECO:0000269|PubMed:21844891}.;
Recessive Scores
- pRec
- 0.163
Intolerance Scores
- LoFtool
- 0.467
- RVIS EVS
- -0.03
- RVIS percentile EVS
- 51.4
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- N
- Indispensability score
- 0.341
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |