DNAJA3

Chr 16

DnaJ heat shock protein family (Hsp40) member A3

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

This gene encodes a mitochondrial-localized DNAJ/Hsp40 co-chaperone protein that stimulates Hsp70 ATPase activity and modulates apoptotic signaling pathways, including cytochrome C release and caspase 3 activation. Mutations cause autosomal recessive spinal muscular atrophy with congenital bone fractures, a severe early-onset neuromuscular disorder affecting motor neurons and bone development. The gene is highly constrained against loss-of-function variation (LOEUF 0.59), reflecting its essential cellular functions.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.59
Clinical SummaryDNAJA3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.33) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.010
Z-score 3.09
OE 0.33 (0.190.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.39Z-score
OE missense 1.06 (0.971.17)
307 obs / 288.5 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.33 (0.190.59)
00.351.4
Missense OE1.06 (0.971.17)
00.61.4
Synonymous OE1.04
01.21.6
LoF obs/exp: 8 / 24.5Missense obs/exp: 307 / 288.5Syn Z: -0.38
DN
0.76top 25%
GOF
0.6345th %ile
LOF
0.3258th %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

DNAJA3 · 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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