DNAJA1

Chr 9

DnaJ heat shock protein family (Hsp40) member A1

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

DNAJA1 encodes a heat shock protein 70 co-chaperone that stimulates ATP hydrolysis and facilitates protein transport into mitochondria while regulating cellular apoptosis pathways. Mutations cause autosomal recessive spinal muscular atrophy with progressive myoclonic epilepsy, a neurodegenerative disorder affecting both motor neurons and the central nervous system. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.542), suggesting some tolerance to heterozygous loss.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.54
Clinical SummaryDNAJA1
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.27) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.54LOEUF
pLI 0.091
Z-score 3.14
OE 0.27 (0.150.54)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.23Z-score
OE missense 0.58 (0.500.67)
127 obs / 220.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.27 (0.150.54)
00.351.4
Missense OE0.58 (0.500.67)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 6 / 21.8Missense obs/exp: 127 / 220.2Syn Z: 0.03
DN
0.6743th %ile
GOF
0.5562th %ile
LOF
0.3454th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction 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

0 submitted variants in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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