DNAJB2

Summary

DNAJB2 (DnaJ heat shock protein family (Hsp40) member B2, HGNC:5228) is a protein-coding gene on chromosome 2q35, encoding DnaJ homolog subfamily B member 2 (P25686). Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family.

This gene is almost exclusively expressed in the brain, mainly in the neuronal layers. It encodes a protein that shows sequence similarity to bacterial DnaJ protein and the yeast homologs. In bacteria, this protein is implicated in protein folding and protein complex dissociation. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.

Source: NCBI Gene 3300 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuronopathy, distal hereditary motor, autosomal recessive 5 (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 345 total — 10 pathogenic, 15 likely-pathogenic (top 9% of genes corpus-wide)
• GTEx eGene: eQTL in 11 tissues, sQTL in 21 (q < 0.05)
• Phenotypes (HPO): 12
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.84 (unconstrained)
• MANE Select transcript: NM_006736

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5228
Approved symbol	DNAJB2
Name	DnaJ heat shock protein family (Hsp40) member B2
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	HSPF3, CMT2T
Ensembl gene	ENSG00000135924
Ensembl biotype	protein_coding
OMIM	604139
Entrez	3300

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 11 protein_coding, 10 retained_intron, 3 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000336576

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 8, TSL 3: 8, TSL 5: 1

ENST00000336576, ENST00000392086, ENST00000392087, ENST00000421532, ENST00000425450, ENST00000439026, ENST00000442681, ENST00000463463, ENST00000470530, ENST00000472019, ENST00000473750, ENST00000476254, ENST00000477917, ENST00000480537, ENST00000481815, ENST00000482988, ENST00000485220, ENST00000487855, ENST00000683651, ENST00000684599, ENST00000933785, ENST00000975365, ENST00000975366, ENST00000975367, ENST00000975368, ENST00001144635

RefSeq mRNA: 2 — MANE Select: NM_006736 NM_001039550, NM_006736

CCDS: CCDS2439, CCDS46519

Canonical transcript exons

ENST00000336576 — 9 exons

Exon	Start	End
ENSE00001422614	219284632	219286895
ENSE00001589801	219279366	219279518
ENSE00003463024	219279798	219279898
ENSE00003467684	219283133	219283235
ENSE00003632977	219280578	219280687
ENSE00003658169	219283419	219283489
ENSE00003660776	219281939	219282061
ENSE00003673301	219281718	219281771
ENSE00003787797	219282837	219282929

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 99.14.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 56.7074 / max 1040.5450, expressed in 1804 samples.

Highest expression (Bgee): C1 segment of cervical spinal cord, hemisphere of cerebellum, cerebellar hemisphere, spinal cord, frontal lobe.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DNAJB2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 21 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 32 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	3.9e-31	-0.89	2:219279688:G:C
Brain Spinal cord cervical c-1	sqtl	6.4e-11	-1.10	2:219279688:G:C
Testis	sqtl	1.3e-09	+0.76	2:219273686:A:G
Muscle Skeletal	sqtl	4.1e-07	-0.35	2:219281474:G:T
Skin Sun Exposed Lower leg	sqtl	6.0e-06	-0.38	2:219279688:G:C
Brain Amygdala	sqtl	1.6e-04	+0.86	2:219279688:G:C
Brain Substantia nigra	sqtl	2.6e-04	+0.94	2:219276074:G:A
Brain Cortex	sqtl	2.8e-04	-0.63	2:219279688:G:C
Esophagus Mucosa	eqtl	3.0e-04	-0.42	2:219279325:C:A
Brain Nucleus accumbens basal ganglia	sqtl	8.1e-04	+0.63	2:219273686:A:G
Skin Not Sun Exposed Suprapubic	sqtl	8.2e-04	+0.41	2:219279688:G:C
Artery Tibial	sqtl	4.9e-03	+0.36	2:219281474:G:T
Adipose Subcutaneous	eqtl	6.7e-03	-0.42	2:219011359:T:C
Artery Tibial	eqtl	9.6e-03	-0.30	2:219024193:T:A
Adipose Visceral Omentum	sqtl	1.3e-02	+0.39	2:219279688:G:C
Brain Hippocampus	sqtl	1.3e-02	-0.59	2:219279688:G:C
Breast Mammary Tissue	sqtl	1.4e-02	-0.72	2:219283125:G:A
Brain Putamen basal ganglia	sqtl	1.5e-02	-1.84	2:219286259:G:C
Thyroid	sqtl	1.6e-02	-0.79	2:220019927:G:A
Colon Sigmoid	eqtl	1.7e-02	-0.27	2:219915140:A:G

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
25440	44.2886	1782
25441	8.2124	1713
25442	2.5451	1048
25439	0.8574	388
25443	0.4888	20
25444	0.1718	77
25438	0.1036	30
25445	0.0398	25

Top tissues by expression

showing 100 of 292 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
C1 segment of cervical spinal cord	UBERON:0006469	99.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.80	gold quality
cerebellar hemisphere	UBERON:0002245	98.66	gold quality
spinal cord	UBERON:0002240	98.62	gold quality
right frontal lobe	UBERON:0002810	98.62	gold quality
cerebellar cortex	UBERON:0002129	98.59	gold quality
adenohypophysis	UBERON:0002196	98.09	gold quality
amygdala	UBERON:0001876	98.07	gold quality
cingulate cortex	UBERON:0003027	97.97	gold quality
anterior cingulate cortex	UBERON:0009835	97.96	gold quality
prefrontal cortex	UBERON:0000451	97.95	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.95	gold quality
tibial nerve	UBERON:0001323	97.62	gold quality
pituitary gland	UBERON:0000007	97.61	gold quality
cerebellum	UBERON:0002037	97.60	gold quality
skin of leg	UBERON:0001511	97.52	gold quality
nucleus accumbens	UBERON:0001882	97.49	gold quality
right adrenal gland	UBERON:0001233	97.48	gold quality
left adrenal gland cortex	UBERON:0035825	97.47	gold quality
left adrenal gland	UBERON:0001234	97.42	gold quality
left testis	UBERON:0004533	97.41	gold quality
right adrenal gland cortex	UBERON:0035827	97.41	gold quality
apex of heart	UBERON:0002098	97.30	gold quality
corpus callosum	UBERON:0002336	97.28	gold quality
hypothalamus	UBERON:0001898	97.25	gold quality
skin of abdomen	UBERON:0001416	97.23	gold quality
putamen	UBERON:0001874	97.16	gold quality
right testis	UBERON:0004534	97.14	gold quality
gastrocnemius	UBERON:0001388	97.09	gold quality
right lobe of thyroid gland	UBERON:0001119	97.08	gold quality
inferior vagus X ganglion	UBERON:0005363	96.99	gold quality
adrenal cortex	UBERON:0001235	96.93	gold quality
left lobe of thyroid gland	UBERON:0001120	96.82	gold quality
body of pancreas	UBERON:0001150	96.82	gold quality
caudate nucleus	UBERON:0001873	96.82	gold quality
neocortex	UBERON:0001950	96.72	gold quality
muscle of leg	UBERON:0001383	96.64	gold quality
cortical plate	UBERON:0005343	96.63	gold quality
frontal cortex	UBERON:0001870	96.62	gold quality
middle frontal gyrus	UBERON:0002702	96.55	gold quality
adrenal gland	UBERON:0002369	96.46	gold quality
central nervous system	UBERON:0001017	96.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.39	gold quality
brain	UBERON:0000955	96.34	gold quality
mucosa of stomach	UBERON:0001199	96.31	gold quality
forebrain	UBERON:0001890	96.31	gold quality
substantia nigra	UBERON:0002038	96.29	gold quality
right uterine tube	UBERON:0001302	96.26	gold quality
midbrain	UBERON:0001891	96.18	gold quality
telencephalon	UBERON:0001893	96.18	gold quality
Ammon’s horn	UBERON:0001954	96.18	gold quality
thyroid gland	UBERON:0002046	96.14	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.09	gold quality
minor salivary gland	UBERON:0001830	95.94	gold quality
left ovary	UBERON:0002119	95.93	gold quality
islet of Langerhans	UBERON:0000006	95.89	gold quality
testis	UBERON:0000473	95.87	gold quality
endocervix	UBERON:0000458	95.85	gold quality
cerebral cortex	UBERON:0000956	95.85	gold quality
metanephros cortex	UBERON:0010533	95.85	gold quality
ventricular zone	UBERON:0003053	95.76	gold quality
ectocervix	UBERON:0012249	95.76	gold quality
body of stomach	UBERON:0001161	95.60	gold quality
right ovary	UBERON:0002118	95.56	gold quality
medulla oblongata	UBERON:0001896	95.46	gold quality
lower esophagus mucosa	UBERON:0035834	95.44	gold quality
body of uterus	UBERON:0009853	95.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.33	gold quality
temporal lobe	UBERON:0001871	95.27	gold quality
gall bladder	UBERON:0002110	95.27	gold quality
medial globus pallidus	UBERON:0002477	95.22	gold quality
pancreas	UBERON:0001264	95.17	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.16	gold quality
saliva-secreting gland	UBERON:0001044	95.12	gold quality
right atrium auricular region	UBERON:0006631	95.10	gold quality
mucosa of transverse colon	UBERON:0004991	95.09	gold quality
zone of skin	UBERON:0000014	95.07	gold quality
ventral tegmental area	UBERON:0002691	95.06	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.94	gold quality
ganglionic eminence	UBERON:0004023	94.91	gold quality
right lung	UBERON:0002167	94.90	gold quality
superior vestibular nucleus	UBERON:0007227	94.88	gold quality
primary visual cortex	UBERON:0002436	94.87	gold quality
right lobe of liver	UBERON:0001114	94.82	gold quality
cranial nerve II	UBERON:0000941	94.80	gold quality
lower esophagus	UBERON:0013473	94.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.67	gold quality
mouth mucosa	UBERON:0003729	94.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.63	gold quality
globus pallidus	UBERON:0001875	94.57	gold quality
heart left ventricle	UBERON:0002084	94.57	gold quality
ascending aorta	UBERON:0001496	94.43	gold quality
left uterine tube	UBERON:0001303	94.39	gold quality
occipital lobe	UBERON:0002021	94.39	gold quality
popliteal artery	UBERON:0002250	94.39	gold quality
thoracic aorta	UBERON:0001515	94.38	gold quality
tibial artery	UBERON:0007610	94.38	gold quality
vagina	UBERON:0000996	94.34	gold quality
aorta	UBERON:0000947	94.30	gold quality
subthalamic nucleus	UBERON:0001906	94.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.84

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Corpus callosum	tissue	278.1
Locus coeruleus	tissue	162.9
Spinal cord	tissue	158.2
Medulla oblongata	tissue	155.9
Substantia nigra	tissue	154.1
Midbrain	tissue	152.0
Pons	tissue	140.8
Nucleus accumbens	tissue	137.4
Thalamus	tissue	136.1
Putamen	tissue	135.2
Hippocampus	tissue	133.6	medium
Superior colliculi	tissue	132.9
Postcentral gyrus	tissue	128.0
Ventral forebrain	tissue	127.0
Hypothalamus	tissue	125.9
Periaqueductal gray	tissue	124.8
Hippocampal formation	tissue	108.2
Skeletal muscle	tissue	106.2	medium
Pituitary gland	tissue	105.6
Septum	tissue	105.4
Choroid plexus	tissue	102.0
Basal ganglia	tissue	90.9	medium
Cerebral cortex	tissue	82.6	medium
Somatosensory cortex	tissue	82.6
Retrosplenial cortex	tissue	80.8
Amygdala	tissue	78.8
Motor cortex	tissue	76.6
Occipital cortex	tissue	76.3
Insular cortex	tissue	74.2
Caudate putamen	tissue	72.4
Cerebellum	tissue	71.8	medium
Prefrontal cortex	tissue	71.3
Retrosplenial and cingulate cortex	tissue	70.9
Pancreas	tissue	64.8	medium
Entorhinal cortex	tissue	63.8
Frontal cortex	tissue	62.8
Olfactory bulb	tissue	62.3
Temporal cortex	tissue	62.2
Skin 1	tissue	60.2	medium
Retina	tissue	59.9
Salivary gland	tissue	59.0	medium
Vagina	tissue	56.5	medium
Tongue	tissue	53.3
Adrenal gland	tissue	51.9	medium
Parathyroid gland	tissue	51.5	low
Heart muscle	tissue	44.2	not detected
Epididymis	tissue	43.6	medium
Thyroid gland	tissue	41.7	medium
Testis	tissue	38.5	medium
Fallopian tube	tissue	38.2	medium
Prostate	tissue	37.7	medium
Ovary	tissue	35.8	medium
Kidney	tissue	34.7	medium
Seminal vesicle	tissue	33.8	medium
Stomach 1	tissue	33.0	low
Adipose tissue	tissue	32.4	medium
Lung	tissue	30.1	medium
Thymus	tissue	26.8
Cervix	tissue	26.3	medium
Breast	tissue	25.7	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Parieto-temporal junction (white matter) (367.9), Temporal white matter (323.5), Corpus callosum, genu (white matter) (302.4), Corpus callosum, splenium (white matter) (292.8), White matter (278.1).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DNAJB2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 39 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-2115-3P	99.31	69.68	2026
HSA-MIR-3978	99.24	68.39	2201
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-3670	97.88	64.39	763

Functional genomics

gnomAD constraint: pLI 0.000221, LOEUF 0.836, missense Z 1.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000336576 — one region, missense o/e 0.85.

Literature-anchored findings (GeneRIF, showing 13)

• data provide evidence that cytoplasmic chaperones HSJ1a and HSJ1b when targeted to the endoplasmic reticulum can influence the folding and processing of rhodopsin (PMID:12754272)
• HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome. (PMID:15936278)
• Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase (PMID:16604191)
• Damaging exercise induced the expression of capZalpha, MCIP1, CARP1, DNAJB2, c-myc, and junD, each of which are likely involved in skeletal muscle growth, remodeling, and stress management. (PMID:18321953)
• Data show that DNAJB2 is expressed in skeletal muscle at the neuromuscular junction of normal fibers, in the cytoplasm and membrane of regenerating fibers, and in protein aggregates and vacuoles in protein aggregate myopathies. (PMID:20395441)
• a mutation causing a loss-of-function of HSJ1 is linked to a pure lower motor neuron disease, strongly suggesting that HSJ1 also plays an important and specific role in motor neurons. (PMID:22522442)
• HSJ1a acts on mutant SOD1 through a combination of chaperone, co-chaperone and pro-ubiquitylation activity. (PMID:24023695)
• The results of this study confirm that HSJ1 mutations are a rare but detectable cause of autosomal recessive dHMN and CMT2. (PMID:25274842)
• Study describes the identi fi cation of the fi rst deletion reported at the DNAJB2 locus, further expanding its phenotypic and genotypic spectrums as well as its disease-associated mechanisms with spinal muscular atrophy and parkinsonism. (PMID:27449489)
• Our results disclose a novel interplay between ubiquitin- and phosphorylation-dependent signalling, and represent the first report of a regulatory mechanism for UIM-dependent function. They also suggest that CK2 inhibitors could release the full neuroprotective potential of HSJ1, and deserve future interest as therapeutic strategies for neurodegenerative disease. (PMID:28031292)
• DNAJB2 expression in healthy human palatal mucosa is strongly negatively correlated with serum cotinine levels (PMID:31682009)
• DNAJB2-related Charcot-Marie-Tooth disease type 2: Pathomechanism insights and phenotypic spectrum widening. (PMID:35286755)
• The heat shock protein DNAJB2 as a novel biomarker for essential thrombocythemia diagnosis associated with immune infiltration. (PMID:36746103)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dnajb2	ENSMUSG00000026203
rattus_norvegicus	Dnajb2	ENSRNOG00000019506
drosophila_melanogaster	CG2887	FBGN0030207
drosophila_melanogaster	CG5001	FBGN0031322
drosophila_melanogaster	CG3061	FBGN0038195
drosophila_melanogaster	CG30156	FBGN0050156
drosophila_melanogaster	DnaJ-1	FBGN0263106
caenorhabditis_elegans		WBGENE00001019
caenorhabditis_elegans		WBGENE00001044

Paralogs (11): DNAJB11 (ENSG00000090520), DNAJB6 (ENSG00000105993), DNAJB9 (ENSG00000128590), DNAJB1 (ENSG00000132002), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB4 (ENSG00000162616), DNAJB14 (ENSG00000164031), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1928739) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased anxiety-related response	1
abnormal vocalization	1
abnormal coat/hair pigmentation	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R8H0	99.7%	Diamond
Bos taurus	Q2NL21	96.8%	Diamond
Macaca fascicularis	Q4R7Y5	96.1%	Diamond
Oryza sativa Japonica Group	A0A0P0VG31	94.7%	Diamond
Xenopus laevis	Q5FWN8	87.2%	Diamond
Xenopus tropicalis	Q6P642	87.2%	Diamond
Gallus gallus	Q5F3Z5	85.7%	Diamond
Macaca fuscata fuscata	Q862Z4	85.5%	Diamond
Saccharomyces cerevisiae S288C	P53863	66.7%	Diamond
Nakaseomyces glabratus CBS 138	Q6FP17	60.6%	Diamond
Schizosaccharomyces pombe 972h-	O59731	54.5%	Diamond
Arabidopsis thaliana	Q39079	53.2%	Diamond
Plasmodium falciparum 3D7	Q8IM77	38.2%	Diamond
Gammapolyomavirus avis	P13895	89.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
RESP18	protein-coding	389075
MIR153-1	ncRNA	406944
PTPRN	protein-coding	5798
ANKZF1	protein-coding	55139
TUBA4A	protein-coding	7277
ATG9A	protein-coding	79065
GLB1L	protein-coding	79411
TUBA4B	protein-coding	80086
STK16	protein-coding	8576

Protein

Protein identifiers

DnaJ homolog subfamily B member 2 — P25686 (reviewed: P25686)

Alternative names: Heat shock 40 kDa protein 3, Heat shock protein J1

All UniProt accessions (6): C9J1G2, C9JRD2, C9JX00, C9JXB9, E7ETU0, P25686

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a co-chaperone, regulating the substrate binding and activating the ATPase activity of chaperones of the HSP70/heat shock protein 70 family. In parallel, also contributes to the ubiquitin-dependent proteasomal degradation of misfolded proteins. Thereby, may regulate the aggregation and promote the functional recovery of misfolded proteins like HTT, MC4R, PRKN, RHO and SOD1 and be crucial for many biological processes. Isoform 1 which is localized to the endoplasmic reticulum membranes may specifically function in ER-associated protein degradation of misfolded proteins.

Subunit / interactions. Interacts with HSP70 (HSPA1A or HSPA1B). Interacts with HSPA8/Hsc70. Interacts with PSMA3 and most probably with the whole proteasomal complex.

Subcellular location. Cytoplasm. Nucleus Endoplasmic reticulum membrane.

Tissue specificity. More abundantly expressed in neocortex, cerebellum, spinal cord and retina where it is expressed by neuronal cells (at protein level). Detected at much lower level in non-neuronal tissues including kidney, lung, heart, skeletal muscle, spleen and testis (at protein level). Isoform 1 is more abundant in neocortex and cerebellum compared to isoform 2 (at protein level).

Post-translational modifications. Ubiquitinated by STUB1; does not lead to proteasomal degradation.

Disease relevance. Neuronopathy, distal hereditary motor, autosomal recessive 5 (HMNR5) [MIM:614881] A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular disorders caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. The overall clinical picture consists of a classical distal muscular atrophy syndrome in the legs without clinical sensory loss. The disease starts with weakness and wasting of distal muscles of the anterior tibial and peroneal compartments of the legs. Later on, weakness and atrophy may expand to the proximal muscles of the lower limbs and/or to the distal upper limbs. HMNR5 is characterized by young adult onset of slowly progressive distal muscle weakness and atrophy resulting in gait impairment and loss of reflexes. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The J domain is sufficient to interact with HSP70 (HSPA1A or HSPA1B) and activate its ATPase activity. The J domain is also required for the HSP70-mediated and ubiquitin-dependent proteasomal degradation of proteins like ATXN3. The J domain is required to reduce PRKN cytoplasmic aggregation. The UIM domains mediate interaction with ubiquitinated chaperone clients and with the proteasome. The UIM domains may have an opposite activity to the J domain, binding ubiquitinated proteins and protecting them from HSP70-mediated proteasomal degradation. The UIM domains are not required to reduce PRKN cytoplasmic aggregation.

Isoforms (2)

UniProt ID	Names	Canonical?
P25686-3	1, HSJ1b	yes
P25686-2	2, HSJ1a, DNAJB2a

RefSeq proteins (2): NP_001034639, NP_006727* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR003903	UIM_dom	Conserved_site
IPR018253	DnaJ_domain_CS	Conserved_site
IPR036869	J_dom_sf	Homologous_superfamily
IPR043183	DNJB2/6-like	Family

Pfam: PF00226

UniProt features (35 total): mutagenesis site 8, helix 4, compositionally biased region 3, modified residue 3, domain 3, splice variant 2, sequence variant 2, region of interest 2, initiator methionine 1, chain 1, lipid moiety-binding region 1, propeptide 1, sequence conflict 1, strand 1, turn 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
2LGW	Solution Structure of the J Domain of HSJ1a	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25686-F1	68.73	0.25

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear membrane

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4)

Type	Positions
N-acetylalanine	2
Phosphoserine	311
Cysteine methyl ester	321
S-geranylgeranyl cysteine	321

Mutagenesis-validated functional residues (8)

Position	Phenotype
31–33	loss of interaction with hsp70 and loss of the ability to promote atxn3 proteasomal degradation.
31	probable loss of interaction with hsp70 and loss of the ability to reduce prkn aggregation.
219	loss of interaction with polyubiquitin chains, loss of interaction with psma3, and loss of the ability to protect atxn3 from proteasomal …
222	loss of interaction with polyubiquitin chains, loss of interaction with psma3, and loss of the ability to protect atxn3 from proteasomal …
262	loss of interaction with polyubiquitin chains, loss of interaction with psma3, and loss of the ability to protect atxn3 from proteasomal …
265	loss of interaction with polyubiquitin chains, loss of interaction with psma3, and loss of the ability to protect atxn3 from proteasomal …
321	loss of localization to the endoplasmic reticulum and relocalization to cytoplasm and nucleus.
324	no effect on localization to the endoplasmic reticulum membrane.

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 335 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_BINDING, PAX4_01, ENK_UV_RESPONSE_KERATINOCYTE_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (17): protein folding (GO:0006457), response to unfolded protein (GO:0006986), negative regulation of cell population proliferation (GO:0008285), negative regulation of cell growth (GO:0030308), regulation of protein ubiquitination (GO:0031396), positive regulation of protein ubiquitination (GO:0031398), negative regulation of protein binding (GO:0032091), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of ATP-dependent activity (GO:0032781), regulation of protein localization (GO:0032880), ERAD pathway (GO:0036503), protein refolding (GO:0042026), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), neuron cellular homeostasis (GO:0070050), negative regulation of inclusion body assembly (GO:0090084), negative regulation of protein deubiquitination (GO:0090086), regulation of protein folding (GO:1903332)

GO Molecular Function (11): ATPase activator activity (GO:0001671), Hsp70 protein binding (GO:0030544), polyubiquitin modification-dependent protein binding (GO:0031593), ubiquitin protein ligase binding (GO:0031625), ubiquitin binding (GO:0043130), protein-folding chaperone binding (GO:0051087), proteasome binding (GO:0070628), protein serine/threonine kinase binding (GO:0120283), ubiquitin-modified protein reader activity (GO:0140036), protein transporter activity (GO:0140318), protein binding (GO:0005515)

GO Cellular Component (9): proteasome complex (GO:0000502), nucleus (GO:0005634), cytoplasm (GO:0005737), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), inclusion body (GO:0016234), nuclear membrane (GO:0031965), perinuclear region of cytoplasm (GO:0048471), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554)

GO top-level categories

showing 60 of 62 GO namespaces:

Category	Terms
cellular anatomical structure	3
negative regulation of cellular process	2
protein ubiquitination	2
protein binding	2
ATP-dependent activity	2
proteasomal protein catabolic process	2
protein folding	2
intracellular anatomical structure	2
organelle membrane	2
cytoplasm	2
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
cell population proliferation	1
regulation of cell population proliferation	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
regulation of protein modification by small protein conjugation or removal	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of protein binding	1
negative regulation of binding	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
regulation of ATP-dependent activity	1
positive regulation of molecular function	1
intracellular protein localization	1
regulation of localization	1
response to endoplasmic reticulum stress	1
response to chemical	1
ubiquitin-dependent protein catabolic process	1
cellular homeostasis	1
negative regulation of cellular component organization	1
inclusion body assembly	1
regulation of inclusion body assembly	1
protein deubiquitination	1
regulation of protein deubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
regulation of cellular process	1
molecular function activator activity	1
heat shock protein binding	1
protein-folding chaperone binding	1
modification-dependent protein binding	1
ubiquitin-like protein ligase binding	1
ubiquitin-like protein binding	1
protein-containing complex binding	1
protein kinase binding	1
ubiquitin-like protein reader activity	1
transporter activity	1
binding	1
intracellular protein-containing complex	1
endopeptidase complex	1
intracellular membrane-bounded organelle	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
nucleus	1
nuclear envelope	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 32 of 38 annotations. The rest are phylogenetic / computational / electronic (IEA).

32 experimentally-supported GO terms:

GO term	NS	Evidence
ERAD pathway	BP	direct assay
negative regulation of cell growth	BP	genetic interaction
negative regulation of cell population proliferation	BP	genetic interaction
negative regulation of inclusion body assembly	BP	direct assay
negative regulation of protein binding	BP	direct assay
negative regulation of protein deubiquitination	BP	direct assay
positive regulation of ATP-dependent activity	BP	direct assay
positive regulation of proteasomal ubiquitin-dependent protein catabolic process	BP	direct assay
positive regulation of protein ubiquitination	BP	direct assay
proteasome-mediated ubiquitin-dependent protein catabolic process	BP	mutant phenotype
protein folding	BP	mutant phenotype
protein refolding	BP	direct assay
regulation of protein folding	BP	direct assay
regulation of protein localization	BP	mutant phenotype
regulation of protein ubiquitination	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
endoplasmic reticulum membrane	CC	direct assay
inclusion body	CC	direct assay
nuclear membrane	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
proteasome complex	CC	direct assay
ATPase activator activity	MF	direct assay
Hsp70 protein binding	MF	direct assay
polyubiquitin modification-dependent protein binding	MF	direct assay
proteasome binding	MF	direct assay
protein serine/threonine kinase binding	MF	physical interaction
protein-folding chaperone binding	MF	physical interaction
ubiquitin binding	MF	direct assay
ubiquitin protein ligase binding	MF	physical interaction
ubiquitin-modified protein reader activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,674 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB2	HSPB8	Q9UJY1	703
DNAJB2	DNAJC6	O75061	668
DNAJB2	DNAJC13	O75165	666
DNAJB2	HSPA1A	P08107	614
DNAJB2	GRPEL1	Q9HAV7	608
DNAJB2	DNAJC28	Q9NX36	602
DNAJB2	SACS	Q9NZJ4	552
DNAJB2	DNAJC19	Q96DA6	515
DNAJB2	HSPB3	Q12988	505
DNAJB2	DNAJC12	Q9UKB3	498
DNAJB2	IGHMBP2	P38935	497
DNAJB2	DNAJB12	Q9NXW2	474
DNAJB2	HSPA4	P34932	473
DNAJB2	HSPA8	P11142	472
DNAJB2	BAG2	O95816	465

IntAct

Human interaction partners of DNAJB2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
MLF1	physical association	0.560	1
UBQLN1	physical association	0.460	2
RPS27A	direct interaction	0.440	1
MLF2	physical association	0.400	1
PSMD2	physical association	0.400	1
ECE1	physical association	0.370	1
SMAD4	physical association	0.370	1
UBB	association	0.350	2
DNAJB6	association	0.350	1
NSMCE4A	association	0.350	1
UBA1	ubiquitination reaction	0.000	1
VPS26C	physical association	0.000	1

BioGRID (178 interactions; top human partners by supporting records): HSPA4 (Co-localization; 4 records), UBC (Reconstituted Complex; 4 records), BIRC2 (Affinity Capture-MS; 3 records), CTSA (Affinity Capture-MS; 3 records), CYHR1 (Affinity Capture-MS; 3 records), DNAJB6 (Affinity Capture-MS; 3 records), DNAJB8 (Affinity Capture-MS; 3 records), FAM83H (Affinity Capture-MS; 3 records), GLB1 (Affinity Capture-MS; 3 records), HSPA8 (Affinity Capture-MS; 3 records), LACC1 (Affinity Capture-MS; 3 records), NSMCE4A (Affinity Capture-MS; 3 records), RFWD3 (Affinity Capture-MS; 3 records), RHO (Co-localization; 3 records), RNF19B (Affinity Capture-MS; 3 records)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
DNAJB2-HSPA8-PSMA3 complex	3	DNAJB2, HSPA8, PSMA3

Disease & clinical

Genetic variants

Variant evidence for DNAJB2: 345 ClinVar records (25 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

345 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	15
Uncertain significance	134
Likely benign	154
Benign	18

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 25 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
217886	NM_006736.6(DNAJB2):c.352+1G>A	Pathogenic	criteria provided, multiple submitters, no conflicts	11
1441902	NM_006736.6(DNAJB2):c.119_120del (p.Glu40fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1709938	NM_006736.6(DNAJB2):c.65+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
183041	NM_006736.6(DNAJB2):c.229+1G>A	Pathogenic	criteria provided, single submitter	4
209147	NM_006736.6(DNAJB2):c.343G>T (p.Glu115Ter)	Pathogenic	criteria provided, single submitter	1
246691	NM_006736.6(DNAJB2):c.620-1G>A	Pathogenic	criteria provided, single submitter	1
864789	NM_006736.6(DNAJB2):c.394C>T (p.Arg132Ter)	Pathogenic	criteria provided, single submitter	1
1452257	NM_006736.6(DNAJB2):c.204T>G (p.Tyr68Ter)	Pathogenic	criteria provided, single submitter	1
1789094	NM_006736.6(DNAJB2):c.229+2T>A	Pathogenic	criteria provided, single submitter	1
1895597	NM_006736.6(DNAJB2):c.118G>T (p.Glu40Ter)	Pathogenic	criteria provided, single submitter	1
183042	NM_006736.6(DNAJB2):c.14A>G (p.Tyr5Cys)	Likely pathogenic	criteria provided, single submitter	4
243085	NM_006736.6(DNAJB2):c.310del (p.Arg104fs)	Likely pathogenic	criteria provided, single submitter	1
623377	NM_006736.6(DNAJB2):c.446-2A>G	Likely pathogenic	criteria provided, single submitter	1
873313	NM_006736.6(DNAJB2):c.757G>A (p.Glu253Lys)	Likely pathogenic	criteria provided, single submitter	1
1464699	NM_006736.6(DNAJB2):c.446-1G>A	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore DNAJB2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 860):

Position(s)	Effect	Δscore	Sites
2:219279899–219279900	donor_loss	1.0000	4
2:219281772–219281773	donor_loss	1.0000	5
2:219281928	acceptor_gain	1.0000
2:219281937–219281938	acceptor_loss	1.0000	5
2:219282062–219282063	donor_loss	1.0000	4
2:219283124	acceptor_gain	1.0000
2:219279796–219279797	acceptor_loss	0.9900	6
2:219279899–219279900	donor_loss	0.9900	2
2:219280576–219280577	acceptor_loss	0.9900	5
2:219280667	donor_gain	0.9900

AlphaMissense

675 missense substitutions predicted likely pathogenic (of 2,095 scored), across 159 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H31	8	0.998	1.000
D33	8	0.996	0.998
F46	8	0.995	1.000
F103	8	0.992	0.999
F107	8	0.989	0.999
N35	8	0.961	0.997
F96	8	0.960	0.998
F113	8	0.960	0.991
D66	8	0.942	0.992
D58	8	0.914	0.981
F106	8	0.911	0.996
F117	8	0.872	0.950
W30	7	0.995	1.000
F94	7	0.974	0.997
E54	7	0.963	0.991
D111	7	0.888	0.938
D210	7	0.869	0.920
F92	7	0.826	0.963
E43	7	0.823	0.930
E193	7	0.821	0.939

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	2.35e-05
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000425
Pancreatic Adenocarcinoma (validation)	unfavorable	0.000571

Disease associations

OMIM: gene MIM:604139 | disease phenotypes: MIM:614881, MIM:605726, MIM:118220, MIM:302800, MIM:302900

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
neuronopathy, distal hereditary motor, autosomal recessive 5	Definitive	Autosomal recessive	4
Charcot-Marie-Tooth disease axonal type 2T	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
neuronopathy, distal hereditary motor, autosomal recessive 5	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (4 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

4 panels:

Panel	Rating
Adult-onset neurological disorders	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Neurodegenerative disorders, adult onset	green

Mondo (5): neuronopathy, distal hereditary motor, autosomal recessive 5 (MONDO:0013947), autosomal recessive distal spinal muscular atrophy 2 (MONDO:0011585), Charcot-Marie-Tooth disease (MONDO:0015626), Charcot-Marie-Tooth disease X-linked dominant 1 (MONDO:0010549), (MONDO:0014866)

Orphanet (5): Young adult-onset distal hereditary motor neuropathy (Orphanet:314485), DNAJB2-related Charcot-Marie-Tooth disease type 2 (Orphanet:443950), Distal hereditary motor neuropathy, Jerash type (Orphanet:139552), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), X-linked Charcot-Marie-Tooth disease type 1 (Orphanet:101075)

HPO phenotypes

12 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001618	Dysphonia
HP:0001761	Pes cavus
HP:0002460	Distal muscle weakness
HP:0002936	Distal sensory impairment
HP:0003677	Slowly progressive
HP:0007269	Spinal muscular atrophy
HP:0008944	Distal lower limb amyotrophy
HP:0009027	Foot dorsiflexor weakness
HP:0011462	Young adult onset

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C564446	Charcot-Marie-Tooth Peroneal Muscular Atrophy and Friedreich Ataxia, Combined *(supp.)*
C535715	Spinal muscular atrophy, Jerash type *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

63 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects cotreatment, decreases expression, increases expression, affects expression	4
Cyclosporine	increases expression, decreases expression	4
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Aflatoxin B1	affects expression, decreases methylation, increases expression	3
Cadmium Chloride	decreases expression, increases expression	3
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
Cadmium	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
beta-N-methylamino-L-alanine	increases expression	1
chloroacetaldehyde	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1
trichostatin A	increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
dinophysistoxin 1	increases expression	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
darinaparsin	increases expression	1
eprenetapopt	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
PCI 5002	increases expression, affects cotreatment	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

59 trials:

NCT	Phase	Status	Title
NCT04762758	Phase 3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00271635	Phase 2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	Phase 2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	Phase 2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	Phase 2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	Phase 2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	Phase 2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	Phase 2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	Phase 2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	Phase 2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT01289704	Phase 2/3	UNKNOWN	Treadmill, Stretching and Proprioceptive Exercise (TreSPE) Rehabilitation Program for Charcot-Marie-Tooth Neuropathy Type 1A (CMT1A)
NCT00541164	Phase 1/2	COMPLETED	Effects of Coenzyme Q10 on Charcot-Marie-Tooth Disease
NCT05361031	Phase 1/2	COMPLETED	The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
NCT07223632	Phase 1/2	ACTIVE_NOT_RECRUITING	Treatment of Charcot-Marie-Tooth Disease, Axonal, Type 2S (CMT2S) in an Individual Patient
NCT00149045	Not specified	COMPLETED	Follow up and Observation of Charcot Marie Tooth Disease in Families
NCT01193075	Not specified	RECRUITING	Natural History Evaluation of Charcot Marie Tooth Disease (CMT) Types CMT1B, CMT2A, CMT4A, CMT4C, and Others
NCT01203085	Not specified	COMPLETED	Development of Charcot Marie Tooth Disease (CMT) Pediatric Scale for Children With CMT
NCT01455623	Not specified	COMPLETED	Development and Validation of a Disability Severity Index for CMT
NCT01918826	Not specified	COMPLETED	Evaluation of the Analgesic Efficiency of the Transcutaneous Neurostimulation in the Charcot Syndrome Marie Tooth on the Pains of Lower Limbs
NCT02001038	Not specified	COMPLETED	Survey of Current Management of Orthopaedic Complications in CMT Patients
NCT02011204	Not specified	COMPLETED	Study of Electrical Impedance Myography (EIM) in ALS
NCT02194010	Not specified	COMPLETED	Disability Severity Scale (DSI) and Hereditary Motor and Sensory Neuropathy Overall Disability Scale (HMSN-R-ODS)
NCT02429947	Not specified	COMPLETED	An Analysis of the Symptomatic Domains Most Relevant to Charcot Marie Tooth Neuropathy (CMT) Patients
NCT02532244	Not specified	COMPLETED	Genetics of Pediatric-Onset Motor Neuron and Neuromuscular Diseases
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02788734	Not specified	COMPLETED	Patient Reported Outcomes Measures (PROM) in Carpal Tunnel Therapies in Patients With Inherited Neuropathies
NCT02979145	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Infant Scale (INC-6611)
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03460951	Not specified	COMPLETED	Diffusion Tensor Imaging in Chronic Inflammatory Demyelinating Polyneuropathy (PIDC)
NCT03715283	Not specified	COMPLETED	Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care
NCT03782883	Not specified	COMPLETED	The Impact of Charcot-Marie-Tooth Disease in the Real World
NCT03810508	Not specified	TERMINATED	A Natural History Study of Charcot-Marie-Tooth 4J (CMT4J)
NCT03966287	Not specified	COMPLETED	Analysis of Pain and Quality of Life in Patients With Charcot-Marie-Tooth Neuropathy (CMT)
NCT04010188	Not specified	RECRUITING	A Registered Cohort Study on Charcot-Marie-Tooth Disease
NCT04283175	Not specified	COMPLETED	Validation Study of Posturology Platforms for Evaluating Postural Control of Hemiparetic and Neuro-muscular Patients
NCT04461613	Not specified	UNKNOWN	Physical Activity in Persons With Charcot-Marie-Tooth: Developing a Measurement Instrument
NCT04786522	Not specified	COMPLETED	Irisin Levels in Patients With Charcot-Marie-Tooth (CMT) Disease
NCT04967716	Not specified	UNKNOWN	Genetics of Charcot-Marie-Tooth Dystrophy and Related Diseases
NCT04980807	Not specified	COMPLETED	Observational Study of Neuromuscular Function in CMT Type 1&2 and Healthy Controls
NCT05011006	Not specified	TERMINATED	NT-3 Levels and Function in Individuals With CMT
NCT05827419	Not specified	TERMINATED	Hearing and Balance Disorders in Peripheral Neuropathy
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
NCT06203093	Not specified	UNKNOWN	Charcot-Marie-Tooth Disease (CMT) Biological Sample Collection for IPSC Generation and Biobanking
NCT06666816	Not specified	RECRUITING	Observational Study to Observe Variations of Gait Parameters in Patients With Neuromuscular Diseases
NCT06708468	Not specified	RECRUITING	Personalized Training for People With Rare Neuromuscular Disorders
NCT06794489	Not specified	RECRUITING	Longitudinal Biomarkers With Selected Outcome Measures In CMT
NCT06808581	Not specified	COMPLETED	EVALUATION OF SERUM INFLAMMATORY CYTOKINE CONCENTRATION IN HEREDITARY SENSITIVOMOTOR NEUROPATHIES
NCT06881979	Not specified	RECRUITING	High-Tech Rehabilitation Pathway for Chronic Adult Neuromuscular Diseases - Fit4MedRob-Chronic MND Project
NCT06945835	Not specified	COMPLETED	High Intensity Exercise and Improving Physical Activity Among People With Neurologic Dysfunction
NCT07038239	Not specified	RECRUITING	Genotype/Phenotype Correlation of MORC2 Mutations
NCT07072676	Not specified	ENROLLING_BY_INVITATION	The Use of Assistive Gait Devices Can Reduce the Risk of Falls in Patients With Neuromuscular Diseases Following a Training Period.
NCT07136844	Not specified	RECRUITING	Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
NCT07152197	Not specified	RECRUITING	Effects of Resistance Exercises in Hereditary Sensory-Motor Neuropathy (Charcot-Marie-Tooth Disease)
NCT07188415	Not specified	RECRUITING	CMT Gait, Mobility, Balance - AOFAS Grant
NCT07432035	Not specified	NOT_YET_RECRUITING	Walking Function Outcomes Following Surgical Correction With Rehabilitation Versus Physical Therapy Alone in Charcot-Marie-Tooth Disease: A Bidirectional Cohort Study
NCT07476365	Not specified	RECRUITING	A Multi-omic Approach to the Identification of Novel Biomarkers in Early Charcot-Marie-Tooth 1A Disease (CMT1A)
NCT07478172	Not specified	RECRUITING	Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
NCT07570446	Not specified	RECRUITING	AUTONOMOUS DISORDERS IN CMT
NCT07570459	Not specified	RECRUITING	TREMOR IN CHARCOT-MARIE-TOOTH