ATP6V1C2

protein-coding

ATPase H+ transporting V1 subunit C2, the group of V-type ATPase subunits

Gene summary

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle 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,three B, and two G subunits, as well as a C, D, E, F, and H subunit. The V1 domain contains the ATP catalytic site. This gene encodes alternate transcriptional splice variants, encoding different V1 domain C subunit isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001039362.2

Inheritance

ClinVar variants

P:1U:71B:3

Top phenotype

Distal renal tubular acidosis

gnomAD constraint

pLI —, LoF o/e 0.62

Max pathogenic AF

—

Genomic locus

chr2:10,721,100-10,785,110

External References & Databases

Ensembl (ENSG00000143882)

Transcript & Mutation Effects

hg38 • Region Span ~64.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

distal renal tubular acidosisLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0015827

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP6V1C2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 7

Distal renal tubular acidosisTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001039362.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar		1 clinvar	2
missense		1 clinvar	66 clinvar	2 clinvar		69
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	1	71	2	1	75

Highest pathogenic variant AF is 0.0004838562

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 31 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001039362.2	RefSeq	NP_001034451.1	13	MANE Select
ENST00000272238.9	Ensembl	ENSP00000272238.4	13	MANE Select
NM_001410707.1	RefSeq	NP_001397636.1	14	Standard
NM_144583.4	RefSeq	NP_653184.2	12	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

mTOR signaling pathway - Homo sapiens (human)
Synaptic vesicle cycle - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Epithelial cell signaling in Helicobacter pylori infection - Homo sapiens (human)
Oxidative phosphorylation - Homo sapiens (human)

Biological Process

insulin receptor signaling pathway
ATP hydrolysis coupled proton transport
regulation of macroautophagy
positive regulation of Wnt signaling pathway
transferrin transport

Molecular Function

proton-exporting ATPase activity, phosphorylative mechanism
proton-transporting ATPase activity, rotational mechanism
protein dimerization activity

Cellular Component

vacuolar proton-transporting V-type ATPase, V1 domain
lysosomal membrane
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000272238
Coding exons: 13
Length: 63462
Individuals with no LoFs: 125682
Homozygous LoFs: 0
Heterozygous LoFs: 66
Defined: 125748
p: 0.000262

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.827	205	241	0.850	0.0000131	2793
Missense (PolyPhen)		50	69.48	0.71963		832
Synonymous	0.167	97	99.1	0.979	0.00000616	816
Loss of Function	1.80	16	25.9	0.618	0.00000140	296

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00046	0.00046	rare
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00017	0.00016	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Subunit of the peripheral V1 complex of vacuolar ATPase. Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells.;

Recessive Scores

pRec: 0.118

Intolerance Scores

LoFtool: 0.921
RVIS EVS: -0.02
RVIS percentile EVS: 52.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.289

Gene Damage Prediction

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