DNAJA3

Chr 16

DnaJ heat shock protein family (Hsp40) member A3

Also known as: HCA57, TID1, Tid1-L, Tid1-S, hTID-1

NCBI Gene: 9093ENSG00000103423UniProt: Q96EY1

This gene encodes a member of the DNAJ/Hsp40 protein family. DNAJ/Hsp40 proteins stimulate the ATPase activity of Hsp70 chaperones and play critical roles in protein folding, degradation, and multimeric complex assembly. The encoded protein is localized to mitochondria and mediates several cellular processes including proliferation, survival and apoptotic signal transduction. The encoded protein also plays a critical role in tumor suppression through interactions with oncogenic proteins including ErbB2 and the p53 tumor suppressor protein. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2011]

146
ClinVar variants
31
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— DNAJA3
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 109 VUS of 146 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.59LOEUF
pLI 0.010
Z-score 3.09
OE 0.33 (0.19–0.59)
Moderately constrained

More LoF-intolerant than ~75% 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.
-0.39Z-score
OE missense 1.06 (0.97–1.17)
307 obs / 288.5 exp
Tolerant

Tolerant to missense variation

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.0.33 (0.19–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.97–1.17)
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.1.04
0≤1.21.6
LoF obs/exp: 8 / 24.5Missense obs/exp: 307 / 288.5Syn Z: -0.38

ClinVar Variant Classifications

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
VUS109
Likely Benign6
31
Pathogenic
109
VUS
6
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
0
0
0
VUS
0
98
11
0
109
Likely Benign
0
6
0
0
6
Benign
0
0
0
0
0
Total0104420146

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

View in ClinVar →

Protein Context — Lollipop Plot

DNAJA3 · 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
A genetic basis of mitochondrial DNAJA3 in nonalcoholic steatohepatitis-related hepatocellular carcinoma.
Chang CW et al.·Hepatology
2025
Mitochondrial "dysmorphology" in variant classification.
Shamseldin HE et al.·Hum Genet
2022
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
Discovery of a new mitophagy-related gene signature for predicting the outlook and immunotherapy in triple-negative breast cancer.
Liu G et al.·Sci Rep
2025
Characterization of DNA hydroxymethylation profile in cervical cancer.
Wang J et al.·Artif Cells Nanomed Biotechnol
2019
Analysis of the TID-I and TID-L Splice Variants' Expression Profile under In Vitro Differentiation of Human Mesenchymal Bone Marrow Cells into Osteoblasts.
Krakowian D et al.·Cells
2024
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