ATP6V0A4

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

Basic information

Region (hg38): 7:138706294-138799560

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 (260 variants)
Renal_tubular_acidosis,_distal,_3,_with_or_without_sensorineural_hearing_loss (205 variants)
Inborn_genetic_diseases (93 variants)
Autosomal_recessive_distal_renal_tubular_acidosis (87 variants)
not_specified (16 variants)
ATP6V0A4-related_disorder (16 variants)
Distal_renal_tubular_acidosis (3 variants)
Renal_tubular_acidosis_with_progressive_nerve_deafness (1 variants)
Renal_tubulopathies (1 variants)
Distal_Renal_Tubular_Acidosis,_Recessive (1 variants)
Sensorineural_hearing_loss_disorder (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. These statistics are base on transcript: NM_000020632.3. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		6 clinvar	55 clinvar	6 clinvar	68
missense	1 clinvar	12 clinvar	206 clinvar	9 clinvar	2 clinvar	230
nonsense	7 clinvar	12 clinvar	1 clinvar			20
start loss						0
frameshift	14 clinvar	11 clinvar				25
splice donor/acceptor (+/-2bp)	6 clinvar	19 clinvar				25
Total	29	54	213	64	8

Highest pathogenic variant AF is 0.000305047

Loading clinvar variants...

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