ERO1B

Chr 1

endoplasmic reticulum oxidoreductase 1 beta

Also known as: ERO1LB, Ero1beta

NCBI Gene: 56605 ENSG00000086619 UniProt: Q86YB8 OMIM: 615437

This gene encodes an oxidoreductase that catalyzes disulfide bond formation in the endoplasmic reticulum by reoxidizing protein disulfide isomerase (PDI) and other disulfide isomerase family members, enabling proper protein folding. ERO1B is not constrained against loss-of-function mutations and currently has no established disease associations in humans. The protein may contribute to glucose homeostasis through its role in proinsulin folding in pancreatic cells.

OMIM ResearchSummary from RefSeq, UniProt

Enables protein-disulfide reductase activity and thiol oxidase activity. Involved in protein folding in endoplasmic reticulum. Predicted to be located in endoplasmic reticulum. Predicted to be active in endoplasmic reticulum lumen and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.85

Clinical Summary— ERO1B

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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

62 VUS of 100 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?

0.85LOEUF

pLI 0.000

Z-score 2.22

OE 0.58 (0.40–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.91Z-score

OE missense 0.83 (0.74–0.94)

198 obs / 237.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.58 (0.40–0.85)

0≤0.351.4

Missense OE?0.83 (0.74–0.94)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 19 / 32.7Missense obs/exp: 198 / 237.5Syn Z: -0.36

This gene — mechanism propensity

0.6841th %ile

GOF

0.4776th %ile

LOF

0.3258th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS62

Likely Benign2

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	62	62
Likely Benign	2	2
Benign	1	1
Total	65	65

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

View in ClinVar →

50 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap ERO1B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →