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

Summary

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

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_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Associated conditions

Description	Tests
Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss MedGen: C5399980 OMIM: 602722 GeneReviews: Hereditary Distal Renal Tubular Acidosis	Compare labs

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D7S1636 (e-PCR)
- UniSTS:43291

GDB:1317754 (e-PCR)
- UniSTS:68647

D7S3183 (e-PCR)
- UniSTS:225940

RH92345 (e-PCR)
- UniSTS:86178

D7S3193 (e-PCR)
- UniSTS:225974

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 more info	PubMed
located_in lysosomal membrane	HDA more info	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

EC 7.1.2.2

NP_570855.2

EC 7.1.2.2

NP_570856.2

EC 7.1.2.2

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

NG_008145.1 RefSeqGene

Range

5001..96903

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1175

mRNA and Protein(s)

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
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
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