ENTREP3

Chr 1

endosomal transmembrane epsin interactor 3

Also known as: C1orf2, COTE1, FAM189B

NCBI Gene: 10712 ENSG00000160767 UniProt: P81408 OMIM: 619447

This gene is located near the gene for the lysosomal enzyme glucosylceramidase; a deficiency in this enzyme is associated with Gaucher disease. The encoded protein has been identified as a potential binding partner of a WW domain-containing protein which is involved in apoptosis and tumor suppression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

OMIM Research

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.75

Clinical Summary— ENTREP3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

108 VUS of 123 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.75LOEUF

pLI 0.000

Z-score 2.56

OE 0.47 (0.31–0.75)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.68Z-score

OE missense 0.90 (0.82–0.99)

339 obs / 376.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.31–0.75)

0≤0.351.4

Missense OE?0.90 (0.82–0.99)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 13 / 27.5Missense obs/exp: 339 / 376.3Syn Z: 0.66

This gene — mechanism propensity

0.6163th %ile

GOF

0.72top 25%

LOF

0.58top 25%

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

123 submitted variants in ClinVar

ClinVar

Classification Summary

VUS108

108

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	108	108
Likely Benign	0	0
Benign	0	0
Total	108	108

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 20) ClinVar copy-number / structural variants overlap ENTREP3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →