DNAJC10

Chr 2

DnaJ heat shock protein family (Hsp40) member C10

Also known as: ERdj5, JPDI, MTHr, PDIA19

This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2012]

OMIMResearchGenerating clinical summary…
MultiplemechanismLOEUF 0.63
Clinical SummaryDNAJC10
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
101 VUS of 150 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint?
0.63LOEUF
pLI 0.000
Z-score 3.65
OE 0.44 (0.320.63)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-0.11Z-score
OE missense 1.02 (0.941.10)
406 obs / 399.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.44 (0.320.63)
00.351.4
Missense OE?1.02 (0.941.10)
00.61.4
Synonymous OE?1.06
01.21.6
LoF obs/exp: 22 / 49.8Missense obs/exp: 406 / 399.9Syn Z: -0.58

This gene — mechanism propensity

DN
0.7132th %ile
GOF
0.6638th %ile
LOF
0.2385th %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

150 submitted variants in ClinVar

Classification Summary

VUS101
Likely Benign1
101
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
0
0
0
Likely Pathogenic
0
0
0
0
0
VUS
0
101
0
0
101
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total010200102

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

View in ClinVar →

24 pathogenic / likely-pathogenic (of 26) ClinVar copy-number / structural variants overlap DNAJC10 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →

Protein Context — Lollipop Plot

DNAJC10 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →