DNAJA2

Chr 16

DnaJ heat shock protein family (Hsp40) member A2

Also known as: CPR3, DJ3, DJA2, DNAJ, DNJ3, HIRIP4, PRO3015, RDJ2

NCBI Gene: 10294ENSG00000069345UniProt: O60884

The protein encoded by this gene belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain. The product of this gene works as a cochaperone of Hsp70s in protein folding and mitochondrial protein import in vitro. [provided by RefSeq, Jul 2008]

69
ClinVar variants
14
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— DNAJA2
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
14 Pathogenic / Likely Pathogenic· 33 VUS of 69 total submissions
Some data sources returned errors (1)

clinvar: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.21LOEUF
pLI 0.998
Z-score 4.20
OE 0.04 (0.01–0.21)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.48Z-score
OE missense 0.55 (0.47–0.63)
131 obs / 238.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.55 (0.47–0.63)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 1 / 22.5Missense obs/exp: 131 / 238.8Syn Z: 0.03

ClinVar Variant Classifications

69 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
VUS33
14
Pathogenic
33
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
0
0
0
VUS
0
25
8
0
33
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total02522047

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJA2 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hsp70 and DNAJA2 limit CFTR levels through degradation.
Kim Chiaw P et al.·PLoS One
2019
DnaJs are enriched in tau regulators.
Esquivel AR et al.·Int J Biol Macromol
2023
Polymorphism in Genes Encoding HSP40 Family Proteins is Associated with Ischemic Stroke Risk and Brain Infarct Size: A Pilot Study.
Kobzeva KA et al.·J Integr Neurosci
2024
Genetic variants in HSP40 co-chaperones modulate ischemic heart disease risk.
Polshvedkina O et al.·Mol Biol Rep
2025
Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system.
Velasco-Carneros L et al.·Protein Sci
2024
A novel fatty acid metabolism-related signature identifies MUC4 as a novel therapy target for esophageal squamous cell carcinoma.
Li S et al.·Sci Rep
2024
Genes Encoding Heat Shock Proteins Are Associated with Risk and Clinical Course of Severe COVID-19: A Pilot Study.
Karpenko AR et al.·Int J Mol Sci
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools