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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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DNAJB5
DnaJ heat shock protein family (Hsp40) member B5
Chromosome 9 · 9p13.3
NCBI Gene: 25822Ensembl: ENSG00000137094.16HGNC: HGNC:14887UniProt: A0A7I2RN43
32PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
response to unfolded proteincytosolprotein-folding chaperone bindingprotein bindingperipheral neuropathySkeletal myopathyattention deficit hyperactivity disorderattention deficit-hyperactivity disorder 8
✦AI Summary

DNAJB5 (DnaJ heat shock protein family member B5) is a molecular chaperone protein that functions in protein folding and the cellular response to proteotoxic stress. As a member of the Hsp40 family, DNAJB5 facilitates protein folding and prevents aggregation of misfolded proteins 1. In the context of neurodegenerative disease, DNAJB5 plays a protective role against TDP-43 pathology associated with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). DNAJB5 is upregulated early in disease progression and co-localizes with TDP-43 pathology in diseased human motor cortex; overexpression decreases TDP-43 aggregation in cell and neuron cultures, while DNAJB5 knockout exacerbates motor impairments in mouse models 1. DNAJB5 expression is regulated by microRNA-21 (miR-21), which targets DNAJB5 to mediate drug resistance in cholangiocarcinoma; restoration of DNAJB5 levels re-sensitizes resistant cells to HSP90 inhibitors 2. Additionally, DNAJB5 expression is altered in several disease contexts including inflammatory bowel disease (downregulated in ulcerative colitis) 3, epilepsy (upregulated as part of a neuroprotective response) 4, and serves as a biomarker for particulate matter air pollution exposure 5. These findings suggest DNAJB5 as a potential therapeutic target in neurodegenerative and malignant diseases.

Sources cited
1
DNAJB5 functions in protein folding, is upregulated in TDP-43 models of ALS/FTLD, decreases TDP-43 aggregation, and protects against motor impairments
PMID: 38374041
2
miR-21 targets DNAJB5 to mediate HSP90 inhibitor resistance in cholangiocarcinoma; DNAJB5 restoration re-sensitizes cells
PMID: 29113809
3
DNAJB5 is downregulated in ulcerative colitis intestinal biopsy samples
PMID: 18340362
4
DNAJB5 is upregulated in epileptic mouse hippocampus as part of a proposed neuroprotective response
PMID: 33153970
5
DNAJB5 expression is associated with particulate matter air pollution exposure in men and functions as an exposure biomarker
PMID: 27740511
6
DNAJB5 is dysregulated in human hippocampal dentate gyrus in association with memory-related genetic variants
PMID: 28380666
Disease Associationsⓘ20
peripheral neuropathyOpen Targets
0.27Weak
Skeletal myopathyOpen Targets
0.27Weak
attention deficit hyperactivity disorderOpen Targets
0.09Suggestive
attention deficit-hyperactivity disorder 8Open Targets
0.07Suggestive
hereditary attention deficit-hyperactivity disorderOpen Targets
0.07Suggestive
intellectual disability, autosomal recessive 59Open Targets
0.07Suggestive
movement disorderOpen Targets
0.07Suggestive
schizophrenia 15Open Targets
0.07Suggestive
Phelan-McDermid syndromeOpen Targets
0.05Suggestive
autismOpen Targets
0.05Suggestive
Tourette syndromeOpen Targets
0.05Suggestive
X-linked non-syndromic intellectual disabilityOpen Targets
0.04Suggestive
intellectual disability, autosomal dominant 50Open Targets
0.04Suggestive
Potocki-Lupski syndromeOpen Targets
0.04Suggestive
FRAXE intellectual disabilityOpen Targets
0.04Suggestive
X-linked dominant intellectual disability - epilepsy syndromeOpen Targets
0.03Suggestive
intellectual developmental disorder, X-linked, syndromic, Pilorge typeOpen Targets
0.03Suggestive
Smith-Magenis syndromeOpen Targets
0.03Suggestive
intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse faciesOpen Targets
0.03Suggestive
amyotrophic lateral sclerosisOpen Targets
0.02Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DNAJC4Shared pathway100%HSPA4LShared pathway100%HSPA9Protein interaction95%HSPA5Protein interaction95%P2RX6Protein interaction88%HSPA4Protein interaction81%
Tissue Expression6 tissues
Heart
100%
Brain
27%
Lung
15%
Ovary
7%
Liver
6%
Bone Marrow
3%
Gene Interaction Network
Click a node to explore
DNAJB5DNAJC4HSPA4LHSPA9HSPA5P2RX6HSPA4
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O75953
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.60LoF Tolerant
pLIⓘ
0.65Intermediate
Observed/Expected LoF0.37 [0.24–0.60]
RankingsWhere DNAJB5 stands among ~20K protein-coding genes
  • #11,500of 20,598
    Most Researched32
  • #4,182of 17,882
    Most Constrained (LOEUF)0.60 · top quartile
Genes detectedDNAJB5
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis · 2022
1.00
2
A transient protein folding response targets aggregation in the early phase of TDP-43-mediated neurodegeneration.
PMID: 38374041
Nat Commun · 2024
0.90
3
Dysplastic oral leukoplakia is molecularly distinct from leukoplakia without dysplasia.
PMID: 31295760
Oral Dis · 2019
0.80
4
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
PMID: 29113809
Gastroenterology · 2018
0.70
5
Critical role of zebrafish dnajb5 in myocardial proliferation and regeneration.
PMID: 33191150
J Genet Genomics · 2020
0.60