ATP6V0A4

ATPase H+ transporting V0 subunit a4, the group of V-type ATPase subunits

Basic information

Region (hg38): 7:138706293-138799560

Previous symbols: [ "ATP6N1B", "ATP6N2", "RTA1C" ]

Links

ENSG00000105929 ∙ NCBI:50617 ∙ OMIM:605239 ∙ HGNC:866 ∙ Uniprot:Q9HBG4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• renal tubular acidosis, distal, 3, with or without sensorineural hearing loss (Strong), mode of inheritance: AR
• renal tubular acidosis, distal, 3, with or without sensorineural hearing loss (Strong), mode of inheritance: AR
• autosomal recessive distal renal tubular acidosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss	AR	Renal	The condition can involve electrolyte abnormalities, and medical management of these (eg, with alkali replacement) can reverse most biochemical abnormalities, and may be effective, especially in severe cases, to prevent eventual renal insufficiency	Audiologic/Otolaryngologic; Renal	10973252; 12414817

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ATP6V0A4 gene.

• not provided (293 variants)
• Autosomal recessive distal renal tubular acidosis (106 variants)
• Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss (55 variants)
• Inborn genetic diseases (35 variants)
• not specified (20 variants)
• ATP6V0A4-related condition (4 variants)
• Distal renal tubular acidosis (1 variants)
• Sensorineural hearing loss disorder (1 variants)
• Bailey-Bloch congenital myopathy (1 variants)
• Distal Renal Tubular Acidosis, Recessive (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ATP6V0A4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	32	8	43
missense	1	4	97	6	4	112
nonsense	6	4				10
start loss						0
frameshift	7	2	1			10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	5	6				11
splice region	1		8	12	5	26
non coding			17	35	93	145
Total	19	16	120	73	105

Highest pathogenic variant AF is 0.000125

Variants in ATP6V0A4

This is a list of pathogenic ClinVar variants found in the ATP6V0A4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-138706385-C-T		Autosomal recessive distal renal tubular acidosis	Benign (Nov 10, 2018)
7-138706444-C-A		Autosomal recessive distal renal tubular acidosis	Uncertain significance (Jan 12, 2018)
7-138706462-G-A		Autosomal recessive distal renal tubular acidosis	Benign (Nov 10, 2018)
7-138706513-G-T		Autosomal recessive distal renal tubular acidosis	Benign (Jun 07, 2020)
7-138706551-G-A		Autosomal recessive distal renal tubular acidosis	Benign (Jan 13, 2018)
7-138706600-A-T		Autosomal recessive distal renal tubular acidosis	Uncertain significance (Jan 12, 2018)
7-138706626-A-G		not specified	Uncertain significance (Dec 06, 2021)
7-138706632-C-T		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
7-138706633-G-A			Likely benign (Jun 14, 2023)
7-138706666-T-C		Autosomal recessive distal renal tubular acidosis • Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss	Benign/Likely benign (Dec 07, 2023)
7-138706676-T-C		Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss • Inborn genetic diseases	Uncertain significance (Mar 20, 2023)
7-138706689-C-T		Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss	Uncertain significance (Dec 03, 2023)
7-138706696-G-T		Autosomal recessive distal renal tubular acidosis	Likely pathogenic (May 28, 2019)
7-138706701-T-C		Distal renal tubular acidosis	Pathogenic (Oct 22, 2019)
7-138706717-C-T			Uncertain significance (Oct 06, 2023)
7-138706736-C-T		Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss	Uncertain significance (-)
7-138706737-G-A			Likely benign (May 25, 2022)
7-138706809-G-A			Benign (Nov 10, 2018)
7-138706851-A-G			Benign (Nov 10, 2018)
7-138706876-G-A			Likely benign (Oct 13, 2020)
7-138706889-AT-A			Benign (Nov 26, 2019)
7-138706889-A-AT			Benign (Aug 20, 2019)
7-138709609-G-C		Autosomal recessive distal renal tubular acidosis	Uncertain significance (Jan 13, 2018)
7-138709621-T-G			Uncertain significance (Oct 24, 2022)
7-138709625-A-G		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ATP6V0A4	protein_coding	protein_coding	ENST00000310018	20	93266

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.15e-20	0.163	125624	0	124	125748	0.000493

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.855	408	460	0.888	0.0000272	5582
Missense in Polyphen		190	219.99	0.86366		2716
Synonymous	0.0807	176	177	0.992	0.0000116	1572
Loss of Function	1.53	37	48.5	0.763	0.00000292	503

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00141	0.00141
Ashkenazi Jewish	0.00129	0.00129
East Asian	0.000489	0.000435
Finnish	0.000146	0.000139
European (Non-Finnish)	0.000370	0.000369
Middle Eastern	0.000489	0.000435
South Asian	0.000524	0.000523
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Part of the proton channel of the V-ATPase that is involved in normal vectorial acid transport into the urine by the kidney. {ECO:0000250}.
• Pathway: Synaptic vesicle cycle - Homo sapiens (human);Phagosome - Homo sapiens (human);Lysosome - Homo sapiens (human);Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human);Oxidative phosphorylation - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Collecting duct acid secretion - Homo sapiens (human);Vibrio cholerae infection - Homo sapiens (human);Rheumatoid arthritis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Signal Transduction;Transferrin endocytosis and recycling;Ion channel transport;Insulin receptor recycling;Signaling by Insulin receptor;ROS, RNS production in phagocytes;Purine metabolism;Innate Immune System;Immune System;Transport of small molecules;Iron uptake and transport;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.223

Intolerance Scores

• loftool: 0.0336
• rvis_EVS: -0.17
• rvis_percentile_EVS: 40.68

Haploinsufficiency Scores

• pHI: 0.232
• hipred: Y
• hipred_score: 0.702
• ghis: 0.445

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.624

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Atp6v0a4
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); taste/olfaction phenotype; hearing/vestibular/ear phenotype; skeleton phenotype; renal/urinary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: ossification;regulation of pH;vacuolar acidification;excretion;sensory perception of sound;insulin receptor signaling pathway;ATP hydrolysis coupled proton transport;transferrin transport;ion transmembrane transport;proton transmembrane transport
• Cellular component: vacuolar proton-transporting V-type ATPase, V0 domain;lysosomal membrane;endosome;plasma membrane;endosome membrane;integral component of membrane;apical plasma membrane;vacuolar proton-transporting V-type ATPase complex;phagocytic vesicle membrane;brush border membrane;apical part of cell;extracellular exosome
• Molecular function: protein binding;proton-transporting ATPase activity, rotational mechanism;ATPase binding