ENOX2

protein-coding

ecto-NOX disulfide-thiol exchanger 2, the group of RNA binding motif containing

Gene summary

This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

Previous symbols:

COVA1

MANE transcript

NM_006375.4

Inheritance

—

ClinVar variants

U:168B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.56

Max pathogenic AF

—

Genomic locus

chrX:130,622,325-130,903,234

External References & Databases

Ensembl (ENSG00000165675)

Transcript & Mutation Effects

hg38 • Region Span ~280.9 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 ENOX2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006375.4. 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			16 clinvar	1 clinvar	1 clinvar	18
missense			105 clinvar			105
nonsense			12 clinvar			12
start loss			1 clinvar			1
frameshift						0
splice donor/acceptor (+/-2bp)			34 clinvar			34
Total	0	0	168	1	1	170

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 99 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006375.4	RefSeq	NP_006366.2	12	MANE Select
ENST00000394363.6	Ensembl	ENSP00000377890.1	12	MANE Select
NM_001281736.2	RefSeq	NP_001268665.1	12	Standard
NM_001382516.1	RefSeq	NP_001369445.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ultradian rhythm
regulation of growth
oxidation-reduction process

Molecular Function

nucleic acid binding
protein disulfide oxidoreductase activity

Cellular Component

extracellular space
cytosol
external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000338144
Coding exons: 13
Length: 279859
Individuals with no LoFs: 125712
Homozygous LoFs: 17
Heterozygous LoFs: 17
Defined: 125746
p: 0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.828	207	243	0.851	0.0000193	4056
Missense (PolyPhen)		79	106.03	0.7451		1599
Synonymous	-0.441	86	81.0	1.06	0.00000629	1099
Loss of Function	1.96	13	23.2	0.561	0.00000174	395

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000063	0.000046	rare
European (Non-Finnish)	0.000050	0.000035	rare
South Asian	0.0013	0.00082	notable
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide- thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock. {ECO:0000269|PubMed:12356293, ECO:0000269|PubMed:9932650}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.143
RVIS EVS: -0.43
RVIS percentile EVS: 25.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.698

Gene Damage Prediction

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