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ATP6V0A4 ATPase H+ transporting V0 subunit a4 [ Homo sapiens (human) ]

Gene ID: 50617, updated on 5-Mar-2024

Summary

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Official Symbol
ATP6V0A4provided by HGNC
Official Full Name
ATPase H+ transporting V0 subunit a4provided by HGNC
Primary source
HGNC:HGNC:866
See related
Ensembl:ENSG00000105929 MIM:605239; AllianceGenome:HGNC:866
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
A4; STV1; VPH1; VPP2; DRTA3; RTA1C; RTADR; ATP6N2; RDRTA2; ATP6N1B
Summary
This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent 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 is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]
Expression
Biased expression in kidney (RPKM 28.8), salivary gland (RPKM 15.2) and 1 other tissue See more
Orthologs
mouse all
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Genomic context

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Location:
7q34
Exon count:
23
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (138706294..138798196, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (140018750..140111076, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (138391039..138482941, complement)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene SVOP like Neighboring gene ribosomal protein L17 pseudogene 27 Neighboring gene ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 pseudogene 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr7:138429227-138429398 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138434906-138435708 Neighboring gene MPRA-validated peak6777 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138458197-138458700 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138458701-138459203 Neighboring gene Sharpr-MPRA regulatory region 1249 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr7:138506625-138507179 Neighboring gene transmembrane protein 213 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138515129-138515628 Neighboring gene Sharpr-MPRA regulatory region 5807 Neighboring gene KIAA1549 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26744 Neighboring gene RNA, U6 small nuclear 1272, pseudogene Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138601214-138601736 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138601737-138602257 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138609273-138609791 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138627684-138628464 Neighboring gene NANOG hESC enhancer GRCh37_chr7:138629820-138630361 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138658812-138659312 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:138659313-138659813 Neighboring gene Sharpr-MPRA regulatory region 8027 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:138665054-138665940 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18689 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18690 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26745 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr7:138720195-138721114 Neighboring gene zinc finger CCCH-type containing, antiviral 1 like

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. A novel splice-site mutation in ATP6V0A4 gene in two brothers with distal renal tubular acidosis from a consanguineous Tunisian family. Nagara M, et al. J Genet, 2014 Dec. PMID 25572248
  2. Novel ATP6V0A4 mutation described in a Tunisian patient with distal renal tubular acidosis. El Hayek D, et al. Clin Nephrol, 2014 Feb. PMID 22854161
  3. The renal v-ATPase a4 subunit is expressed in specific subtypes of human gliomas. Gleize V, et al. Glia, 2012 May. PMID 22460948
  4. Novel mutations in ATP6V0A4 are associated with atypical progressive sensorineural hearing loss in a Chinese patient with distal renal tubular acidosis. Li X, et al. Int J Pediatr Otorhinolaryngol, 2012 Jan. PMID 22093743
  5. Novel compound heterozygous ATP6V0A4 mutations in an infant with distal renal tubular acidosis. Saito T, et al. Eur J Pediatr, 2010 Oct. PMID 20221774

See all (62) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay.
    Title: Identification of seven exonic variants in the SLC4A1, ATP6V1B1, and ATP6V0A4 genes that alter RNA splicing by minigene assay.
  2. a novel heterozygous intronic mutation (c.639 + 1G>A) in the ATP6V0A4 gene was identified along with a heterozygous nonsense variant (c.580C>T, p.Arg194*).
    Title: Five Novel Mutations in Chinese Children with Primary Distal Renal Tubular Acidosis.
  3. The p. P137S and p. R302W mutations in ATP6V1B1 and p. S473F and p. R807X in ATP6V0A4, were novel disease-causing mutations of distal renal tubular acidosis.
    Title: Clinical and genetic analysis of distal renal tubular acidosis in three Chinese children.
  4. Distal renal acidosis patient carries two novel mutations, one in each of the genes ATP6V0A4 and ATP6V1B1.
    Title: Distal renal tubular acidosis in a Libyan patient: Evidence for digenic inheritance.
  5. The aim of this work was to analyze the prevalence of genetic defects in SLC4A1, ATP6V0A4, and ATP6V1B1 genes and to assess the clinical phenotype of distal renal tubular acidosis patients that are eventually typical of the different genetic forms of the disease.
    Title: The genetic and clinical spectrum of a large cohort of patients with distal renal tubular acidosis.
  6. ITM2A expression is positively regulated by PKA-CREB signaling and ITM2A expression interferes with autophagic flux by interacting with vacuolar ATPase.
    Title: The integral membrane protein ITM2A, a transcriptional target of PKA-CREB, regulates autophagic flux via interaction with the vacuolar ATPase.
  7. e have described patients with severe distal renal tubular acidosis and a novel splicing mutation in the ATP6V0A4 gene in a family originating from the Siliana region in northwestern Tunisia
    Title: A novel splice-site mutation in ATP6V0A4 gene in two brothers with distal renal tubular acidosis from a consanguineous Tunisian family.
  8. Functional analysis of selected regulated proteins revealed that knockdown of HNRPD, PHB2 and UB2V2 can increase HCMV replication, while knockdown of A4 and KSRP resulted in decreased HCMV replication.
    Title: Subcellular quantitative proteomic analysis reveals host proteins involved in human cytomegalovirus infection.
  9. For the remaining patients, two mutations in the ATP6V0A4 gene, one of them being novel, were found in three Tunisian cases.
    Title: Molecular investigation of distal renal tubular acidosis in Tunisia, evidence for founder mutations.
  10. Two from different families carrying ATP6V0A4 mutations manifested early onset moderate mixed HL and moderate SNHL
    Title: Mutation analysis and audiologic assessment in six Chinese children with primary distal renal tubular acidosis.
Submit: New GeneRIF Correction See all GeneRIFs (21)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study identifies genetic variants influencing F-cell levels in sickle-cell patients.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC130016, MGC130017

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATPase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ATPase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables proton-transporting ATPase activity, rotational mechanism IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in intracellular pH reduction NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in ossification IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proton transmembrane transport IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in proton transmembrane transport NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in regulation of pH IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in renal tubular secretion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in sensory perception of sound IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in synaptic vesicle lumen acidification IEA
Inferred from Electronic Annotation
more info
  
involved_in vacuolar acidification IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in apical part of cell IDA
Inferred from Direct Assay
more info
 PubMed 
located_in apical plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in basolateral plasma membrane IEA
Inferred from Electronic Annotation
more info
  
located_in brush border membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endosome ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in endosome membrane TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in lysosomal membrane HDA PubMed 
located_in phagocytic vesicle membrane TAS
Traceable Author Statement
more info
  
is_active_in plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in plasma membrane NAS
Non-traceable Author Statement
more info
 PubMed 
part_of proton-transporting V-type ATPase complex NAS
Non-traceable Author Statement
more info
 PubMed 
located_in synaptic vesicle membrane IEA
Inferred from Electronic Annotation
more info
  
part_of vacuolar proton-transporting V-type ATPase complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of vacuolar proton-transporting V-type ATPase complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of vacuolar proton-transporting V-type ATPase, V0 domain IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
V-type proton ATPase 116 kDa subunit a 4
Names
ATPase, H+ transporting, lysosomal (vacuolar proton pump) non-catalytic accessory protein 1B
ATPase, H+ transporting, lysosomal (vacuolar proton pump) non-catalytic accessory protein 2 (38kD)
ATPase, H+ transporting, lysosomal V0 subunit a4
H(+)-transporting two-sector ATPase, noncatalytic accessory protein 1B
V-ATPase 116 kDa
V-ATPase 116 kDa isoform a 4
V-ATPase subunit a4
V-type proton ATPase 116 kDa subunit a
vacuolar proton pump 116 kDa accessory subunit
vacuolar proton pump, subunit 2
NP_065683.2
NP_570855.2
NP_570856.2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008145.1 RefSeqGene

    Range
    5001..96903
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_1175

mRNA and Protein(s)

  1. NM_020632.3 → NP_065683.2  V-type proton ATPase 116 kDa subunit a 4

    See identical proteins and their annotated locations for NP_065683.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) is the longest transcript. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AF245517, BC109304, BC109305, DB230144
    Consensus CDS
    CCDS5849.1
    UniProtKB/Swiss-Prot
    A4D1R4, A8KA80, Q32M47, Q9HBG4
    Related
    ENSP00000308122.2, ENST00000310018.7
    Conserved Domains (1) summary
    pfam01496
    Location:27 → 830
    V_ATPase_I; V-type ATPase 116kDa subunit family

  2. NM_130840.3 → NP_570855.2  V-type proton ATPase 116 kDa subunit a 4

    See identical proteins and their annotated locations for NP_570855.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AF245517, BC109304, BC109305, DB230144
    Consensus CDS
    CCDS5849.1
    UniProtKB/Swiss-Prot
    A4D1R4, A8KA80, Q32M47, Q9HBG4
    Related
    ENSP00000253856.6, ENST00000353492.4
    Conserved Domains (1) summary
    pfam01496
    Location:27 → 830
    V_ATPase_I; V-type ATPase 116kDa subunit family

  3. NM_130841.3 → NP_570856.2  V-type proton ATPase 116 kDa subunit a 4

    See identical proteins and their annotated locations for NP_570856.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, and 3 encode the same protein.
    Source sequence(s)
    AF245517, BC109304, BC109305, DA857655
    Consensus CDS
    CCDS5849.1
    UniProtKB/Swiss-Prot
    A4D1R4, A8KA80, Q32M47, Q9HBG4
    Related
    ENSP00000376774.1, ENST00000393054.5
    Conserved Domains (1) summary
    pfam01496
    Location:27 → 830
    V_ATPase_I; V-type ATPase 116kDa subunit family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

    Range
    138706294..138798196 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060931.1 Alternate T2T-CHM13v2.0

    Range
    140018750..140111076 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9HBG4.2 GenPept UniProtKB/Swiss-Prot:Q9HBG4

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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