ERP27

Chr 12

endoplasmic reticulum protein 27

Also known as: C12orf46, PDIA8

NCBI Gene: 121506ENSG00000139055UniProt: Q96DN0

The protein binds unfolded proteins in the endoplasmic reticulum and may recruit protein disulfide isomerase PDIA3 to assist with protein folding. Mutations cause autosomal recessive developmental and epileptic encephalopathy with onset in early infancy, characterized by severe seizures, developmental delay, and progressive microcephaly. This gene shows moderate constraint against loss-of-function variants in the population.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
2
Pubs (1 yr)
39
P/LP submissions
0%
P/LP missense
1.86
LOEUF
Multiple*
Mechanism· predicted
Clinical Summary— ERP27
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 unique Pathogenic / Likely Pathogenic· 48 VUS of 91 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.86LOEUF
pLI 0.000
Z-score -1.07
OE 1.33 (0.90–1.86)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.40Z-score
OE missense 1.09 (0.96–1.24)
163 obs / 149.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.33 (0.90–1.86)
0≤0.351.4
Missense OE1.09 (0.96–1.24)
0≤0.61.4
Synonymous OE1.29
0≤1.21.6
LoF obs/exp: 16 / 12.0Missense obs/exp: 163 / 149.2Syn Z: -1.75
DN
0.7035th %ile
GOF
0.6542th %ile
LOF
0.2386th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
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

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic37
Likely Pathogenic2
VUS48
Likely Benign1
37
Pathogenic
2
Likely Pathogenic
48
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
37
0
37
Likely Pathogenic
0
0
2
0
2
VUS
0
44
4
0
48
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total04543088

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

View in ClinVar →

Protein Context — Lollipop Plot

ERP27 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 4 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients