DNAJA1

Chr 9

DnaJ heat shock protein family (Hsp40) member A1

Also known as: DJ-2, DjA1, HDJ2, HSDJ, HSJ-2, HSJ2, HSPF4, NEDD7

NCBI Gene: 3301ENSG00000086061UniProt: P31689

This gene encodes a member of the DnaJ family of proteins, which act as heat shock protein 70 cochaperones. Heat shock proteins facilitate protein folding, trafficking, prevention of aggregation, and proteolytic degradation. Members of this family are characterized by a highly conserved N-terminal J domain, a glycine/phenylalanine-rich region, four CxxCxGxG zinc finger repeats, and a C-terminal substrate-binding domain. The J domain mediates the interaction with heat shock protein 70 to recruit substrates and regulate ATP hydrolysis activity. In humans, this gene has been implicated in positive regulation of virus replication through co-option by the influenza A virus. Several pseudogenes of this gene are found on other chromosomes. [provided by RefSeq, Sep 2015]

0
ClinVar variants
0
Pathogenic / LP
0.09
pLI score
0
Active trials
Clinical Summary— DNAJA1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.
Some data sources returned errors (1)

clinvarCount: 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
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.
0.54LOEUF
pLI 0.091
Z-score 3.14
OE 0.27 (0.15–0.54)
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.
2.23Z-score
OE missense 0.58 (0.50–0.67)
127 obs / 220.2 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.0.27 (0.15–0.54)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.58 (0.50–0.67)
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: 6 / 21.8Missense obs/exp: 127 / 220.2Syn Z: 0.03

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

DNAJA1 · 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
The stability and function of human cochaperone Hsp40/DNAJA1 are affected by zinc removal and partially restored by copper.
de Jesus JR et al.·Biochimie
2023
Identification and validation of a novel defined stress granule-related gene signature for predicting the prognosis of ovarian cancer via bioinformatics analysis.
Chen X et al.·Medicine (Baltimore)
2024
DNAJA1 Dysregulates Metabolism Promoting an Antiapoptotic Phenotype in Pancreatic Ductal Adenocarcinoma.
Roth HE et al.·J Proteome Res
2021
High expression of DNAJA1 (HDJ2) predicts unfavorable survival outcomes in breast cancer.
Ileri FC et al.·Biomark Med
2021
The interplay between mutant p53 and the mevalonate pathway.
Parrales A et al.·Cell Death Differ
2018Review
Truncating biallelic variant in DNAJA1, encoding the co-chaperone Hsp40, is associated with intellectual disability and seizures.
Alsahli S et al.·Neurogenetics
2019Case report
Hsp70 and DNAJA2 limit CFTR levels through degradation.
Kim Chiaw P et al.·PLoS One
2019
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
DnaJA1 antagonizes constitutive Hsp70-mediated stabilization of tau.
Abisambra JF et al.·J Mol Biol
2012
Dealing with difficult clients via personalized chaperone inhibitors.
Truman AW·J Biol Chem
2021
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.

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External Resources

Links to major genomics databases and tools