ATP6V1E2

protein-coding

ATPase H+ transporting V1 subunit E2, the group of V-type ATPase subunits

Gene summary

Predicted to enable proton-transporting ATPase activity, rotational mechanism. Predicted to be involved in regulation of macroautophagy. Predicted to act upstream of or within proton transmembrane transport. Predicted to be located in cytosol. Predicted to be part of proton-transporting two-sector ATPase complex, catalytic domain. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ATP6EL2
ATP6V1EL2

MANE transcript

NM_001318063.2

Inheritance

—

ClinVar variants

U:26B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr2:46,490,750-46,542,577

External References & Databases

Ensembl (ENSG00000250565)

Transcript & Mutation Effects

hg38 • Region Span ~51.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ATP6V1E2 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 27

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001318063.2. 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						0
missense			26 clinvar	1 clinvar		27
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	26	1	0	27

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001318063.2	RefSeq	NP_001304992.1	1	MANE Select
ENST00000522587.6	Ensembl	ENSP00000428141.1	1	MANE Select
NM_001371281.1	RefSeq	NP_001358210.1	1	Standard
NM_001371282.1	RefSeq	NP_001358211.1	1	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
transferrin transport
ion transmembrane transport

Molecular Function

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

Cellular Component

acrosomal vesicle
cytosol
proton-transporting two-sector ATPase complex, catalytic domain

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306448
Coding exons: 1
Length: 51808
Individuals with no LoFs: 125705
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125743
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.550	143	126	1.14	0.00000657	1484
Missense (PolyPhen)		30	29.261	1.0253		406
Synonymous	0.122	48	49.1	0.978	0.00000254	441
Loss of Function	1.12	5	8.54	0.586	6.32e-7	83

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00038	0.00038	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0.00020	0.00020	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Subunit of the peripheral V1 complex of vacuolar ATPase essential for assembly or catalytic function. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. This isoform is essential for energy coupling involved in acidification of acrosome (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.121

Intolerance Scores

LoFtool: 0.380
RVIS EVS: 0.08
RVIS percentile EVS: 60.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0529

Gene Damage Prediction

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