DNAJC5

Chr 20AD

DnaJ heat shock protein family (Hsp40) member C5

Also known as: CLN4, CLN4B, CSP, DNAJC5A, NCL, mir-941-2, mir-941-3, mir-941-4

NCBI Gene: 80331ENSG00000101152UniProt: Q9H3Z4

This gene is a member of the J protein family. J proteins function in many cellular processes by regulating the ATPase activity of 70 kDa heat shock proteins. The encoded protein plays a role in membrane trafficking and protein folding, and has been shown to have anti-neurodegenerative properties. The encoded protein is known to play a role in cystic fibrosis and Huntington's disease. A pseudogene of this gene is located on the short arm of chromosome 8. [provided by RefSeq, Nov 2010]

Primary Disease Associations & Inheritance

Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominantMIM #162350
AD
468
ClinVar variants
42
Pathogenic / LP
0.81
pLI score
1
Active trials
Clinical Summary— DNAJC5
🧬
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.
📋
ClinVar Variants
42 Pathogenic / Likely Pathogenic· 195 VUS of 468 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.48LOEUF
pLI 0.812
Z-score 2.62
OE 0.10 (0.04–0.48)
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.
1.79Z-score
OE missense 0.54 (0.44–0.67)
66 obs / 121.6 exp
Tolerant

Mild missense constraint

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.0.10 (0.04–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.54 (0.44–0.67)
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.1.19
0≤1.21.6
LoF obs/exp: 1 / 9.9Missense obs/exp: 66 / 121.6Syn Z: -1.12

ClinVar Variant Classifications

468 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic8
VUS195
Likely Benign161
Benign54
Conflicting16
34
Pathogenic
8
Likely Pathogenic
195
VUS
161
Likely Benign
54
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
32
0
34
Likely Pathogenic
0
0
8
0
8
VUS
3
88
103
1
195
Likely Benign
0
2
75
84
161
Benign
0
0
52
2
54
Conflicting
—16
Total39227087468

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Ceroid lipofuscinosis, neuronal, 4 (Kufs type), autosomal dominant

MIM #162350

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — DNAJC5
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
DNAJC5 facilitates the proliferation and migration of lung adenocarcinoma cells by augmenting EGFR trafficking.
Chen C et al.·Commun Biol
2025
CHIP protects lysosomes from CLN4 mutant-induced membrane damage.
Lee J et al.·Nat Cell Biol
2025
Extracellular chaperone networks and the export of J-domain proteins.
Braun JEA·J Biol Chem
2023Review
Human pathology in NCL.
Anderson GW et al.·Biochim Biophys Acta
2013Review
Autosomal dominant neuronal ceroid lipofuscinosis: Clinical features and molecular basis.
Naseri N et al.·Clin Genet
2021Review
The bacterial toxin ExoU requires a host trafficking chaperone for transportation and to induce necrosis.
Deruelle V et al.·Nat Commun
2021
Recurrent mutations in DNAJC5 cause autosomal dominant Kufs disease.
Cadieux-Dion M et al.·Clin Genet
2013
Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.
Jarrett P et al.·Can J Neurol Sci
2018
Molecular subtype identification of cerebral ischemic stroke based on ferroptosis-related genes.
Wang Y et al.·Sci Rep
2024
Autosomal-dominant adult neuronal ceroid lipofuscinosis caused by duplication in DNAJC5 initially missed by Sanger and whole-exome sequencing.
Jedličková I et al.·Eur J Hum Genet
2020
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
Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING
NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08
Natural History

External Resources

Links to major genomics databases and tools