DNAJC5

Chr 20AD

DnaJ heat shock protein family (Hsp40) member C5

The encoded protein regulates 70 kDa heat shock protein ATPase activity and functions in membrane trafficking and protein folding. Mutations cause autosomal dominant neuronal ceroid lipofuscinosis type 4 (Kufs disease), an adult-onset neurodegenerative disorder characterized by progressive dementia and movement abnormalities. The pathogenic mechanism involves gain-of-function mutations that disrupt normal cellular protein homeostasis.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
GOFmechanismADLOEUF 0.481 OMIM phenotype
Clinical SummaryDNAJC5
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Gene-Disease Validity (ClinGen)
adult neuronal ceroid lipofuscinosis · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.81) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.812
Z-score 2.62
OE 0.10 (0.040.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.79Z-score
OE missense 0.54 (0.440.67)
66 obs / 121.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.10 (0.040.48)
00.351.4
Missense OE0.54 (0.440.67)
00.61.4
Synonymous OE1.19
01.21.6
LoF obs/exp: 1 / 9.9Missense obs/exp: 66 / 121.6Syn Z: -1.12
DN
0.5772th %ile
GOF
0.77top 25%
LOF
0.4430th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction 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

DNAJC5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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