ERP44

Chr 9ADAR

endoplasmic reticulum protein 44

Also known as: PDIA10, TXNDC4

This protein functions as a pH-regulated chaperone in the endoplasmic reticulum, mediating thiol-dependent retention of proteins in the early secretory pathway and inhibiting calcium channel activity. Mutations cause Gillespie syndrome, spinocerebellar ataxias (types 15 and 29), and congenital nonprogressive spinocerebellar ataxia with both autosomal dominant and autosomal recessive inheritance patterns. The gene is highly constrained against loss-of-function variants (pLI = 0.99), indicating that such variants are likely to be pathogenic.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
AD/ARLOEUF 0.273 OMIM phenotypes
Clinical SummaryERP44
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 44 VUS of 91 total submissions
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GeneReview available — ERP44
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.27LOEUF
pLI 0.991
Z-score 4.05
OE 0.09 (0.040.27)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.29Z-score
OE missense 0.56 (0.480.65)
120 obs / 214.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.040.27)
00.351.4
Missense OE0.56 (0.480.65)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 2 / 23.0Missense obs/exp: 120 / 214.1Syn Z: -0.11

ClinVar Variant Classifications

91 submitted variants in ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic4
VUS44
Likely Benign1
31
Pathogenic
4
Likely Pathogenic
44
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
4
0
4
VUS
0
38
6
0
44
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total03941080

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

View in ClinVar →

Protein Context — Lollipop Plot

ERP44 · 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

No active trials found for this gene.

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Clinical Literature
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