DNAJB5

Chr 9

DnaJ heat shock protein family (Hsp40) member B5

Also known as: Hsc40

The protein is a DNAJ heat shock protein 40 family co-chaperone that contains an N-terminal DNAJ domain and C-terminal substrate binding domain, and functions as part of a multi-protein complex that negatively regulates cardiac hypertrophy. 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 shows moderate constraint against loss-of-function variants (LOEUF 0.587), consistent with its role in this recessive condition.

OMIMResearchSummary from RefSeq
DNmechanismLOEUF 0.59
Clinical SummaryDNAJB5
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.59LOEUF
pLI 0.206
Z-score 2.72
OE 0.26 (0.130.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.15Z-score
OE missense 0.44 (0.380.52)
113 obs / 254.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.26 (0.130.59)
00.351.4
Missense OE0.44 (0.380.52)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 4 / 15.6Missense obs/exp: 113 / 254.3Syn Z: 1.32
DN
0.76top 25%
GOF
0.5562th %ile
LOF
0.3551th %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

DNAJB5 · 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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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found