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

    Gene ID: 50617, updated on 28-Oct-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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    See ATP6V0A4 in Genome Data Viewer
    Location:
    7q34
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (138706294..138798196, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (140018750..140111076, complement)
    RS_2024_09 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 ZC3HAV1 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 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 compound heterozygous ATP6V0A4 mutations in an infant with distal renal tubular acidosis. Saito T, et al. Eur J Pediatr, 2010 Oct. PMID 20221774
    3. H(+)V-ATPase-dependent luminal acidification in the kidney collecting duct and the epididymis/vas deferens: vesicle recycling and transcytotic pathways. Brown D, et al. J Exp Biol, 2000 Jan. PMID 10600682
    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. The renal v-ATPase a4 subunit is expressed in specific subtypes of human gliomas. Gleize V, et al. Glia, 2012 May. PMID 22460948

    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_2024_08

    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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