ENOX1

protein-coding

ecto-NOX disulfide-thiol exchanger 1, the group of RNA binding motif containing

Gene summary

The protein encoded by this gene is involved in plasma membrane electron transport pathways. The encoded protein has both a hydroquinone (NADH) oxidase activity and a protein disulfide-thiol interchange activity. The two activities cycle with a periodicity of 24 minutes, with one activity being at its peak when the other is at its lowest. [provided by RefSeq, Dec 2016]

MANE transcript

NM_001347969.2

Inheritance

—

ClinVar variants

U:84B:2

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.43

Max pathogenic AF

—

Genomic locus

chr13:43,213,130-43,786,972

External References & Databases

Ensembl (ENSG00000120658)

Transcript & Mutation Effects

hg38 • Region Span ~573.8 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 ENOX1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 78

not providedTotal: 4

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001347969.2. 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
missense			82 clinvar	1 clinvar		83
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	84	2	0	86

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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_001347969.2	RefSeq	NP_001334898.1	14	MANE Select
ENST00000690772.1	Ensembl	ENSP00000509229.1	14	MANE Select
NM_001127615.3	RefSeq	NP_001121087.1	14	Standard
NM_001242863.3	RefSeq	NP_001229792.1	14	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
enox1	Danio rerio	Structure: trunk Quality: decreased occurrence abnormal

Gene / Model

Organism

Observed Phenotype

enox1

Danio rerio

Structure: trunk

Quality: decreased occurrence

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ultradian rhythm
oxidation-reduction process

Molecular Function

nucleic acid binding
protein binding
oxidoreductase activity

Cellular Component

extracellular space
plasma membrane
external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000261488
Coding exons: 14
Length: 573391
Individuals with no LoFs: 125720
Homozygous LoFs: 0
Heterozygous LoFs: 28
Defined: 125748
p: 0.000111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.03	270	382	0.708	0.0000222	4264
Missense (PolyPhen)		69	116.5	0.59227		1255
Synonymous	0.201	134	137	0.978	0.00000806	1183
Loss of Function	3.25	16	37.4	0.428	0.00000202	407

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.00014	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: 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 24 minutes and play a role in control of the ultradian cellular biological clock. {ECO:0000269|PubMed:11360993, ECO:0000269|PubMed:12565167, ECO:0000269|PubMed:17027975, ECO:0000269|PubMed:19055324}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.660
RVIS EVS: -0.44
RVIS percentile EVS: 24.46

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.972

Gene Damage Prediction

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