DNAJC3

Chr 13AR

DnaJ heat shock protein family (Hsp40) member C3

Also known as: ACPHD, ERdj6, HP58, P58, P58IPK, PRKRI, p58(IPK)

NCBI Gene: 5611ENSG00000102580UniProt: Q13217OMIM: 601184

The protein regulates the unfolded protein response during endoplasmic reticulum stress and acts as a co-chaperone that stimulates HSPA8/HSC70 ATPase activity. Biallelic mutations cause autosomal recessive ataxia with combined cerebellar and peripheral involvement, hearing loss, and diabetes mellitus. The gene is not highly constrained against loss-of-function variation.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismARLOEUF 0.521 OMIM phenotype
Clinical Summary— DNAJC3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.30) despite low pLI — interpret in context.
📋
ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 62 VUS of 179 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.52LOEUF
pLI 0.017
Z-score 3.60
OE 0.30 (0.18–0.52)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.71Z-score
OE missense 0.70 (0.62–0.79)
186 obs / 264.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.30 (0.18–0.52)
0≤0.351.4
Missense OE0.70 (0.62–0.79)
0≤0.61.4
Synonymous OE0.89
0≤1.21.6
LoF obs/exp: 9 / 30.5Missense obs/exp: 186 / 264.4Syn Z: 0.84
DN
0.7131th %ile
GOF
0.6638th %ile
LOF
0.2680th %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

179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic85
Likely Pathogenic4
VUS62
Likely Benign17
Benign2
Conflicting3
85
Pathogenic
4
Likely Pathogenic
62
VUS
17
Likely Benign
2
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
1
80
0
85
Likely Pathogenic
4
0
0
0
4
VUS
1
52
9
0
62
Likely Benign
0
3
3
11
17
Benign
0
0
1
1
2
Conflicting
—3
Total9569312173

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJC3 · 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 5 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