DNAJB6

Summary

DNAJB6 (DnaJ heat shock protein family (Hsp40) member B6, HGNC:14888) is a protein-coding gene on chromosome 7q36.3, encoding DnaJ homolog subfamily B member 6 (O75190). Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. It is a selective cancer dependency (DepMap: 29.2% of cell lines).

This gene encodes a member of the DNAJ protein family. DNAJ family members are characterized by a highly conserved amino acid stretch called the ‘J-domain’ and function as one of the two major classes of molecular chaperones involved in a wide range of cellular events, such as protein folding and oligomeric protein complex assembly. This family member may also play a role in polyglutamine aggregation in specific neurons. Alternative splicing of this gene results in multiple transcript variants; however, not all variants have been fully described.

Source: NCBI Gene 10049 — RefSeq curated summary.

At a glance

• Gene–disease (curated): muscular dystrophy, limb-girdle, autosomal dominant (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 551 total — 17 pathogenic, 3 likely-pathogenic (top 6% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 21 tissues, sQTL in 32 (q < 0.05)
• Phenotypes (HPO): 29
• Cancer dependency (DepMap): dependent in 29.2% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.92 (unconstrained)
• MANE Select transcript: NM_058246
• Interaction hub: 1,985 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14888
Approved symbol	DNAJB6
Name	DnaJ heat shock protein family (Hsp40) member B6
Location	7q36.3
Locus type	gene with protein product
Status	Approved
Aliases	MRJ
Ensembl gene	ENSG00000105993
Ensembl biotype	protein_coding
OMIM	611332
Entrez	10049

Gene structure

Transcript identifiers

Ensembl transcripts: 94 — 73 protein_coding, 15 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined, 3 retained_intron

MANE Select: ENST00000262177

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 2, TSL 3: 5, TSL 4: 3, TSL 5: 4

ENST00000262177, ENST00000412557, ENST00000417758, ENST00000429029, ENST00000437030, ENST00000439402, ENST00000441291, ENST00000441561, ENST00000443280, ENST00000453383, ENST00000459889, ENST00000465908, ENST00000468928, ENST00000486083, ENST00000486247, ENST00000487480, ENST00000488001, ENST00000634080, ENST00000867734, ENST00000867735, ENST00000867736, ENST00000867737, ENST00000867738, ENST00000867739, ENST00000867740, ENST00000867741, ENST00000867742, ENST00000911732, ENST00000911733, ENST00000911734, ENST00000911735, ENST00000911736, ENST00000911737, ENST00000911738, ENST00000911739, ENST00000956617, ENST00000956618, ENST00000956619, ENST00000956620, ENST00000956621, ENST00000956622, ENST00000956623, ENST00000956624, ENST00000956625, ENST00000956626, ENST00000956627, ENST00000956628, ENST00000956629, ENST00000956630, ENST00000956631, ENST00000956632, ENST00000994951, ENST00000994952, ENST00000994953, ENST00000994955, ENST00001034422, ENST00001034423, ENST00001034424, ENST00001034428, ENST00001034431, ENST00001034433, ENST00001034435, ENST00001034436, ENST00001034437, ENST00001034438, ENST00001034439, ENST00001064631, ENST00001064632, ENST00001064634, ENST00001064635, ENST00001095169, ENST00001095170, ENST00001095171, ENST00001095172, ENST00001095173, ENST00001095174, ENST00001095175, ENST00001095176, ENST00001095177, ENST00001095178, ENST00001095179, ENST00001095180, ENST00001111446, ENST00001122505, ENST00001122506, ENST00001122507, ENST00001122508, ENST00001122509, ENST00001129210, ENST00001129211, ENST00001129212, ENST00001129213, ENST00001129214, ENST00001137741

RefSeq mRNA: 3 — MANE Select: NM_058246 NM_001363676, NM_005494, NM_058246

CCDS: CCDS47755, CCDS5946, CCDS87571

Canonical transcript exons

ENST00000262177 — 10 exons

Exon	Start	End
ENSE00001705365	157337004	157337144
ENSE00001931810	157416016	157417439
ENSE00003486218	157382246	157382377
ENSE00003519262	157384867	157385008
ENSE00003572534	157409795	157410001
ENSE00003592526	157367373	157367483
ENSE00003595878	157358547	157358637
ENSE00003612095	157385541	157385611
ENSE00003648894	157363161	157363270
ENSE00003681432	157366502	157366561

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.19.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.1451 / max 516.7301, expressed in 1815 samples.

Highest expression (Bgee): cortical plate, primordial germ cell in gonad, ganglionic eminence, gastrocnemius, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DNAJB6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 21 tissues and its splicing (sQTL) in 32 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 53 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	3.0e-55	+0.84	7:157369409:A:G
Nerve Tibial	sqtl	9.0e-40	+0.64	7:157369409:A:G
Adipose Subcutaneous	sqtl	1.9e-34	+0.60	7:157369409:A:G
Artery Tibial	sqtl	4.3e-33	+0.54	7:157369409:A:G
Testis	sqtl	1.7e-32	+0.74	7:157369409:A:G
Esophagus Muscularis	sqtl	6.2e-31	+0.58	7:157369409:A:G
Artery Aorta	sqtl	2.6e-30	+0.62	7:157369409:A:G
Skin Not Sun Exposed Suprapubic	sqtl	6.4e-25	+0.44	7:157369409:A:G
Colon Transverse	sqtl	5.5e-24	+0.66	7:157369409:A:G
Esophagus Gastroesophageal Junction	sqtl	2.6e-23	+0.63	7:157369409:A:G
Lung	sqtl	2.9e-23	+0.48	7:157369409:A:G
Breast Mammary Tissue	sqtl	4.5e-23	+0.56	7:157369409:A:G
Skin Sun Exposed Lower leg	sqtl	8.2e-23	+0.42	7:157369409:A:G
Esophagus Mucosa	sqtl	2.5e-22	+0.51	7:157369409:A:G
Thyroid	sqtl	2.6e-22	+0.49	7:157369409:A:G
Pituitary	sqtl	3.7e-22	+0.83	7:157369409:A:G
Colon Sigmoid	sqtl	6.5e-20	+0.56	7:157369409:A:G
Whole Blood	eqtl	9.6e-20	+0.18	7:157352780:T:C
Adipose Visceral Omentum	sqtl	7.2e-15	+0.46	7:157369409:A:G
Prostate	sqtl	1.5e-14	+0.73	7:157369409:A:G

FANTOM5 promoters

6 alternative TSS:

Promoter ID	TPM avg	Samples expressed
82289	27.4140	1814
82290	4.3417	1307
82291	0.8188	382
82293	0.3234	125
82288	0.2389	85
82294	0.0083	3

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.19	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.99	gold quality
ganglionic eminence	UBERON:0004023	98.68	gold quality
gastrocnemius	UBERON:0001388	98.59	gold quality
muscle of leg	UBERON:0001383	98.51	gold quality
skin of abdomen	UBERON:0001416	98.48	gold quality
skin of leg	UBERON:0001511	98.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	98.16	gold quality
popliteal artery	UBERON:0002250	98.11	gold quality
tibial artery	UBERON:0007610	98.11	gold quality
ventricular zone	UBERON:0003053	98.09	gold quality
right testis	UBERON:0004534	98.05	gold quality
muscle organ	UBERON:0001630	98.00	gold quality
skeletal muscle organ	UBERON:0014892	98.00	gold quality
monocyte	CL:0000576	97.96	gold quality
left testis	UBERON:0004533	97.96	gold quality
aorta	UBERON:0000947	97.94	gold quality
ascending aorta	UBERON:0001496	97.94	gold quality
thoracic aorta	UBERON:0001515	97.94	gold quality
right coronary artery	UBERON:0001625	97.87	gold quality
artery	UBERON:0001637	97.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.78	gold quality
mononuclear cell	CL:0000842	97.77	gold quality
descending thoracic aorta	UBERON:0002345	97.76	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.72	gold quality
lower esophagus	UBERON:0013473	97.71	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.71	gold quality
leukocyte	CL:0000738	97.69	gold quality
left coronary artery	UBERON:0001626	97.69	gold quality
lower esophagus mucosa	UBERON:0035834	97.63	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.62	gold quality
cerebellar hemisphere	UBERON:0002245	97.61	gold quality
esophagus	UBERON:0001043	97.58	gold quality
body of uterus	UBERON:0009853	97.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.57	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.56	gold quality
esophagus mucosa	UBERON:0002469	97.54	gold quality
right atrium auricular region	UBERON:0006631	97.50	gold quality
ectocervix	UBERON:0012249	97.50	gold quality
adrenal tissue	UBERON:0018303	97.48	gold quality
right lung	UBERON:0002167	97.44	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.44	gold quality
cerebellar cortex	UBERON:0002129	97.43	gold quality
left ovary	UBERON:0002119	97.39	gold quality
minor salivary gland	UBERON:0001830	97.34	gold quality
right frontal lobe	UBERON:0002810	97.33	gold quality
heart left ventricle	UBERON:0002084	97.18	gold quality
endocervix	UBERON:0000458	97.17	gold quality
mucosa of stomach	UBERON:0001199	97.12	gold quality
left uterine tube	UBERON:0001303	97.10	gold quality
vagina	UBERON:0000996	97.08	gold quality
cardiac atrium	UBERON:0002081	97.06	gold quality
tibial nerve	UBERON:0001323	97.04	gold quality
colonic epithelium	UBERON:0000397	97.03	gold quality
right ovary	UBERON:0002118	97.01	gold quality
omental fat pad	UBERON:0010414	97.01	gold quality
testis	UBERON:0000473	96.98	gold quality
adenohypophysis	UBERON:0002196	96.96	gold quality
skeletal muscle tissue	UBERON:0001134	96.95	gold quality
peritoneum	UBERON:0002358	96.94	gold quality
cardiac ventricle	UBERON:0002082	96.92	gold quality
apex of heart	UBERON:0002098	96.78	gold quality
gall bladder	UBERON:0002110	96.78	gold quality
vastus lateralis	UBERON:0001379	96.76	gold quality
heart	UBERON:0000948	96.75	gold quality
stromal cell of endometrium	CL:0002255	96.72	gold quality
biceps brachii	UBERON:0001507	96.61	gold quality
zone of skin	UBERON:0000014	96.56	gold quality
quadriceps femoris	UBERON:0001377	96.52	gold quality
coronary artery	UBERON:0001621	96.50	gold quality
calcaneal tendon	UBERON:0003701	96.50	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.30	gold quality
upper lobe of left lung	UBERON:0008952	96.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.19	gold quality
muscle tissue	UBERON:0002385	96.17	gold quality
right uterine tube	UBERON:0001302	96.13	gold quality
transverse colon	UBERON:0001157	96.04	gold quality
mouth mucosa	UBERON:0003729	96.01	gold quality
left adrenal gland	UBERON:0001234	95.98	gold quality
metanephros cortex	UBERON:0010533	95.97	gold quality
rectum	UBERON:0001052	95.91	gold quality
granulocyte	CL:0000094	95.86	gold quality
left lobe of thyroid gland	UBERON:0001120	95.84	gold quality
left adrenal gland cortex	UBERON:0035825	95.82	gold quality
right adrenal gland	UBERON:0001233	95.77	gold quality
right adrenal gland cortex	UBERON:0035827	95.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.64	gold quality
prefrontal cortex	UBERON:0000451	95.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.48	gold quality
islet of Langerhans	UBERON:0000006	95.47	gold quality
tibialis anterior	UBERON:0001385	95.44	gold quality
deltoid	UBERON:0001476	95.39	gold quality
right lobe of thyroid gland	UBERON:0001119	95.38	gold quality
body of stomach	UBERON:0001161	95.36	gold quality
upper lobe of lung	UBERON:0008948	95.19	gold quality
ovary	UBERON:0000992	95.18	gold quality
sigmoid colon	UBERON:0001159	95.08	gold quality
cingulate cortex	UBERON:0003027	95.04	gold quality
sural nerve	UBERON:0015488	94.96	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	1724.64
E-GEOD-124263	yes	1369.64
E-CURD-112	no	3.19
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	307.4	high
Frontal cortex	tissue	197.0
Bone marrow	tissue	172.8	medium
Tongue	tissue	165.6
Caudate putamen	tissue	141.8
Cerebellum	tissue	138.3	medium
Cerebral cortex	tissue	120.6	medium
Occipital cortex	tissue	120.6
Motor cortex	tissue	119.4
Choroid plexus	tissue	119.3
Somatosensory cortex	tissue	117.9
Prefrontal cortex	tissue	114.1
Pons	tissue	111.1
Testis	tissue	110.5	high
Locus coeruleus	tissue	110.1
Heart muscle	tissue	108.5	high
Hippocampal formation	tissue	106.5
Retrosplenial and cingulate cortex	tissue	104.7
Epididymis	tissue	103.3	medium
Entorhinal cortex	tissue	103.1
Thalamus	tissue	101.9
Putamen	tissue	100.1
Midbrain	tissue	98.5
Retrosplenial cortex	tissue	98.5
Superior colliculi	tissue	98.2
Postcentral gyrus	tissue	96.5
Temporal cortex	tissue	95.0
Nucleus accumbens	tissue	92.9
Hippocampus	tissue	92.6	medium
Ventral forebrain	tissue	91.6
Hypothalamus	tissue	91.1
Septum	tissue	91.1
Esophagus	tissue	91.0	medium
Substantia nigra	tissue	90.7
Basal ganglia	tissue	90.5	medium
Insular cortex	tissue	90.4
Vagina	tissue	88.7	medium
Urinary bladder	tissue	86.6	medium
Olfactory bulb	tissue	86.0
Medulla oblongata	tissue	85.6
Periaqueductal gray	tissue	82.4
Breast	tissue	81.4	low
Corpus callosum	tissue	81.4
Spinal cord	tissue	81.1
Retina	tissue	80.9
Amygdala	tissue	80.8
Skin 1	tissue	75.6	medium
Thymus	tissue	75.6
Adipose tissue	tissue	69.5	not detected
Placenta	tissue	69.3	medium
Smooth muscle	tissue	68.4	medium
Kidney	tissue	66.7	medium
Seminal vesicle	tissue	66.4	low
Tonsil	tissue	63.7	medium
Endometrium 1	tissue	63.2	medium
Adrenal gland	tissue	62.4	medium
Pituitary gland	tissue	61.5
Ovary	tissue	61.4	medium
Fallopian tube	tissue	56.0	medium
Salivary gland	tissue	55.9	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Corpus callosum, genu (white matter) (142.9), Area parastriata, superior (131.1), Parieto-temporal junction (white matter) (130.2), Blood vessel (126.2), Cerebellar white matter (124.2).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFATC3

miRNA regulators (miRDB)

Targeting DNAJB6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 38 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-4725-5P	98.67	65.42	628
HSA-MIR-504-5P	98.67	65.40	631
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6776-5P	98.54	67.43	1304
HSA-MIR-5691	98.23	67.02	1335
HSA-MIR-6805-3P	98.23	67.02	1334

Functional genomics

gnomAD constraint: pLI 0.000771, LOEUF 0.92, missense Z 0.09 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000262177 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:157,358,573–157,367,390	78 / 102.1	0.76	no
7:157,367,391–157,367,453	5 / 26.7	0.19	yes (p 2.7e-05)
7:157,367,454–157,416,095	264 / 288.0	0.92	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map
DepMap (CRISPR cell-line fitness): dependent in 29.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OE33 (-1.241), HNT-34 (-1.168), VCaP (-1.135), KP-N-SI9s (-1.097), KYAE-1 (-1.093), KYSE-220 (-1.093), UPCI-SCC-116 (-1.08), TALL-1 (-1.063), EPLC-272H (-1.058), KMS-11 (-1.057), Sa3 (-1.052), CCLF_PEDS_0019_T (-1.018), CME-1 (-1.015), LB771-HNC (-1.012), HPAF-II (-1.006).

Literature-anchored findings (GeneRIF, showing 40)

• MRJ has a relevant functional role in neurons. (PMID:11896048)
• Role of Hsp40 co-chaperone Hdj-1 in CFTR turnover with HSP70 (PMID:12069690)
• NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj (PMID:16260608)
• msj-1 gene might be conserved among vertebrates and might exert fundamental functions in reproduction. (PMID:18184612)
• Large isoform of MRJ(L), DNAJB6, is a nuclear protein that is lost in breast cancer, that regulates several key players in tumor formation and metastasis, and that is functionally able to retard tumor growth. (PMID:18328103)
• DnaJB6 is necessary for translocation of Slfn1 into the nucleus, where Slfn1 down-regulates cyclin D1, induces cell-cycle arrest and programmes a quiescent state of T-cells (PMID:18373498)
• we report the up-regulation of Mrj protein in M-phase of HeLa cells implicating its role in mitosis related activities. (PMID:19002655)
• DNAJB6b and DNAJB8 are superior suppressors of aggregation and toxicity of disease-associated polyglutamine proteins. (PMID:20159555)
• the interaction between urokinase receptor and heat shock protein MRJ enhances cell adhesion (PMID:20372789)
• DNAJB6 induces degradation of beta-catenin and causes partial reversal of mesenchymal phenotype (PMID:20522561)
• Mutations within the Pro96Arg domain of DNAJB6 are a novel cause of dominantly-inherited myopathy. (PMID:22334415)
• studied 9 Limb-girdle muscular dystrophy type 1D affected families from Finland, the United States and Italy and identified 4 dominant missense mutations leading to p.Phe93Leu or p.Phe89Ile changes in the co-chaperone DNAJB6 (PMID:22366786)
• A novel regulatory mechanism for DNAJB6-mediated DKK1 transcriptional up-regulation might influence epithelial-mesenchymal transition. (PMID:22455953)
• MRJ (short form) shows nuclear localization signal independent nuclear localization in response to heat shock and hypoxia. (PMID:22504047)
• miR-632 is a potentially important epigenetic regulator of DNAJB6, which contributes to the downregulation of DNAJB6 and plays a supportive role in malignant progression (PMID:22710984)
• the relative expression levels of DNAJB6 isoforms may play a key role in regulating the cellular localization of UL70, leading to modulation of HCMV DNA synthesis and lytic infection. (PMID:23133382)
• we detected cytoplasmic accumulations associated with chaperone-assisted selective autophagy together with intranuclear accumulations of DNAJB6 and HSPB8. This is the first report of Asian patients with limb-girdle muscular dystrophy type 1D (PMID:23394708)
• The mechanism of DNAJB6 and DNAJB8 is suppression of polyQ protein aggregation by directly binding the polyQ tract. (PMID:23612975)
• have previously reported clinical, genetic and molecular pathomechanistic findings in DNAJB6 mutated LGMD1D (PMID:23865856)
• DNAJB6 is a peptide-binding chaperone that can interact with polyQ peptides that are incompletely degraded by and released from the proteasome. (PMID:23904097)
• We identified DNAJ/HSP40B6 as a potential negative regulator of HIV-1 replication in our genetic screens. (PMID:24047968)
• A 56-year-old woman, like 3 other family members, becomes symptomatic in childhood with slowly progressive limb-girdle muscle weakness, normal serum creatine kinase (CK) values, and myopathic electromyographic findings. (PMID:24170373)
• using exome sequencing, study identified a mutation in DNAJB6 in a family with limb-girdle muscular dystrophy type 1D; work further confirms the causative role of DNAJB6 mutations in limb-girdle muscular dystrophy type 1D (PMID:24594375)
• DNAJB6 G/F domain mutants disrupt the processing of nuclear TDP-43 stress granules in mammalian cells. (PMID:24920671)
• There was a positive correlation between DNAJB6 and IQGAP1 expression. (PMID:25044025)
• Findings suggest a novel function of HSP70/MRJ/uPAR complex in cell adhesion, invasion and migration, and may provide more understanding in the mechanisms of uPAR-mediated cancer metastasis. (PMID:25175595)
• DNAJB6 interacts with growing amyloid-beta 42 (Abeta42) aggregates, which leads to sub-stoichiometric inhibition of amyloid formation (PMID:25217638)
• Geneticanalysis indicated a heterozygous missense mutation of c.279C>G (PMID:25306414)
• This study showed that Complete loss of the DNAJB6 G/F domain and novel missense mutations cause distal-onset DNAJB6 myopathy. (PMID:26205529)
• DNAJB6a reduces AKT signaling, and DNAJB6 expression in cancer cells reduces their proliferation and growth of xenograft esophageal squamous cell tumors in mice. (PMID:26302489)
• DNAJB6 mutations p.F91I and p.F91L show a significant reduction of the anti-aggregation function compared to the wild-type and p.F93L mutation (PMID:26338452)
• LGMD1D mutations in DNAJB6 disrupt its sarcoplasmic function suggesting a role for DNAJB6b in Z-disc organization and stress granule kinetics. (PMID:26362252)
• Functional study using zebrafish embryos demonstrated that p.Phe91Leu elicits more severe muscle defects than the reported p.Phe93Leu and p.Pro96Arg mutations (PMID:26371419)
• DnaJB6-protected yeast cells from polyglutamine toxicity and cured yeast of both [URE3] prions and weak variants of [PSI(+)] prions but not strong [PSI(+)] prions (PMID:26702057)
• The results indicate both genetic and physical interactions between disease-linked RNA-binding proteinss and DNAJB6/mrj, suggesting etiologic overlap between the pathogenesis of adult-onset inherited myopathies initiated by mutations in hnRNPA2B1 and DNAJB6. (PMID:26744327)
• mRNA levels of HSP family members (HSP70B’, HSP72, HSP40/DNAJ, and HSP20/CRYAB) are upregulated by the intracellular MMP3 overload. (PMID:27206651)
• DNAJB6 is a central and versatile player in the protein aggregation and degradation system.DNAJB6 protein keeps Parkin C289G mutant protein in a soluble, degradation-competent form. (PMID:27713507)
• This study expands the molecular spectrum of DNAJB6 mutations and also emphasizes the pathogenic role of DNAJB6 dysfunction in distal-onset myopathy. (PMID:28233300)
• the cytoprotective effects of DNAJB6(S) may be mediated, at least in part, by the mitochondrial pathway of apoptosis. (PMID:28280525)
• Expression of the heat shock protein DNAJB6/MRJ was elevated in neutrophils and lymphocytes of patients with atopic dermatitis compared with healthy donors. The highest level of the DNAJB6/MRJ protein was found to be in neutrophils at acute phase of severe atopic dermatitis and gradually decline as continue to the disease. (PMID:29244458)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
mus_musculus	Dnajb6	ENSMUSG00000029131
rattus_norvegicus	Dnajb6	ENSRNOG00000010353
rattus_norvegicus	Dnajb6-ps10	ENSRNOG00000017884
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), DNAJB9 (ENSG00000128590), DNAJB1 (ENSG00000132002), DNAJB2 (ENSG00000135924), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB4 (ENSG00000162616), DNAJB14 (ENSG00000164031), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1344381) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased embryo size	1
embryonic growth arrest	1
abnormal extraembryonic tissue morphology	1
absent placental labyrinth	1
failure of chorioallantoic fusion	1
embryonic lethality during organogenesis, complete penetrance	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	Q29455	98.5%	Diamond
Macaca fascicularis	Q4R7Y5	96.1%	Diamond
Xenopus tropicalis	Q5HZT9	94.8%	Diamond
Oryza sativa Japonica Group	A0A0P0VG31	94.7%	Diamond
Sus scrofa	F1RTY8	94.0%	Diamond
Ailuropoda melanoleuca	D2H417	92.5%	Diamond
Xenopus laevis	Q5FWN8	87.2%	Diamond
Tetronarce californica	P56101	86.2%	Diamond
Gallus gallus	Q5F3Z5	85.7%	Diamond
Macaca fuscata fuscata	Q862Z4	85.5%	Diamond
Vibrio cholerae O1 biovar El Tor str. N16961	Q9KUR8	79.4%	Diamond
Arabidopsis thaliana	Q9LYW9	69.3%	Diamond
Saccharomyces cerevisiae S288C	P53863	66.7%	Diamond
Danio rerio	Q6PGY5	63.5%	Diamond
Schizosaccharomyces pombe 972h-	Q10209	62.7%	Diamond
Nakaseomyces glabratus CBS 138	Q6FP17	60.6%	Diamond
Dictyostelium discoideum	Q54M21	57.7%	Diamond
Shewanella oneidensis MR-1	Q8EB99	56.3%	Diamond
Plasmodium falciparum 3D7	Q8IM77	38.2%	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
UBE3C	protein-coding	9690
MIR153-2	ncRNA	406945
PTPRN2	protein-coding	5799

Protein

Protein identifiers

DnaJ homolog subfamily B member 6 — O75190 (reviewed: O75190)

Alternative names: HHDJ1, Heat shock protein J2, MRJ, MSJ-1

All UniProt accessions (10): A0A0J9YX62, C9J2C4, C9J2P2, C9JB42, C9JDR7, C9JDX6, C9JN01, E9PH18, F8WCZ4, O75190

UniProt curated annotations — full annotation on UniProt →

Function. Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Also reduces cellular toxicity and caspase-3 activity. Isoform B but not isoform A inhibits huntingtin aggregation.

Subunit / interactions. Homooligomer. Interacts with BAG3, HSPB8 and STUB1. Interacts with ALKBH1. Interacts with HSP70, KRT18 and PTTG. Interacts with histone deacetylases HDAC4, HDAC6, and SIRT2, HDAC activity is required for antiaggregation.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus. Myofibril. Sarcomere. Z line.

Tissue specificity. Widely expressed. Highest levels in testis and brain, and lower levels in heart, spleen, intestine, ovary, placenta, lung, kidney, pancreas, thymus, prostate, skeletal muscle, liver and leukocytes. In testis, expressed in germ cells in the earlier stages of differentiation pathway as well as in spermatids. In brain, expressed at a higher level in hippocampus and thalamus and a lower level in amygdala, substantia nigra, corpus callosum and caudate nucleus.

Disease relevance. Muscular dystrophy, limb-girdle, autosomal dominant 1 (LGMDD1) [MIM:603511] An autosomal dominant myopathy characterized by adult onset of proximal muscle weakness, beginning in the hip girdle region and later progressing to the shoulder girdle region. The disease is caused by variants affecting the gene represented in this entry. There is evidence that LGMDD1 is caused by dysfunction of isoform B.

Domain organisation. The antiaggregation activity of isoform B resides in the serine-rich region and the C-terminus.

Isoforms (4)

UniProt ID	Names	Canonical?
O75190-1	A	yes
O75190-2	B
O75190-3	C, a
O75190-4	D

RefSeq proteins (3): NP_001350605, NP_005485, NP_490647* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00226

UniProt features (33 total): helix 7, strand 5, splice variant 4, sequence variant 4, turn 3, region of interest 3, sequence conflict 2, modified residue 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
6U3R	Solution NMR structure of the DNAJB6b deltaST variant (Aligned on the J domain)	SOLUTION NMR
6U3S	Solution NMR structure of the DNAJB6b deltaST variant (Aligned on the CTD domain)	SOLUTION NMR
7JSQ	Refined structure of the C-terminal domain of DNAJB6b	SOLUTION NMR
7QBY	Refined structure of the T193A mutant in the C-terminal domain of DNAJB6b	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75190-F1	64.04	0.10

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): nucleoplasm; cytosol

Antibody reliability (HPA): IH supported · IF supported

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 (2)

Type	Positions
Omega-n-methylarginine	135
Phosphoserine	277

Function

Pathways and Gene Ontology

Reactome pathways

4 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-3371568	Attenuation phase	curated
R-HSA-3371511	HSF1 activation	curated
R-HSA-3371571	HSF1-dependent transactivation	curated
R-HSA-3371453	Regulation of HSF1-mediated heat shock response	curated
R-HSA-3371556	Cellular response to heat stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—

MSigDB gene sets: 357 (showing top): GGGACCA_MIR133A_MIR133B, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_INTERMEDIATE_FILAMENT_ORGANIZATION, TGCACTT_MIR519C_MIR519B_MIR519A, ENK_UV_RESPONSE_KERATINOCYTE_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_DN, CACCAGC_MIR138, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_HEAT, ATGTTAA_MIR302C, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_CELL_DIFFERENTIATION_INVOLVED_IN_EMBRYONIC_PLACENTA_DEVELOPMENT

GO Biological Process (6): protein folding (GO:0006457), regulation of protein localization (GO:0032880), intermediate filament organization (GO:0045109), nervous system process (GO:0050877), negative regulation of inclusion body assembly (GO:0090084), regulation of cellular response to heat (GO:1900034)

GO Molecular Function (8): ATPase activator activity (GO:0001671), DNA binding (GO:0003677), Hsp70 protein binding (GO:0030544), heat shock protein binding (GO:0031072), identical protein binding (GO:0042802), protein folding chaperone (GO:0044183), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), Z disc (GO:0030018), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Cellular response to heat stress	3
Cellular responses to stimuli	1
Cellular responses to stress	1
HSF1-dependent transactivation	1

GO top-level categories

27 GO namespaces:

Category	Terms
cellular anatomical structure	6
protein binding	3
cytoplasm	2
cellular process	1
protein maturation	1
intracellular protein localization	1
regulation of localization	1
intermediate filament cytoskeleton organization	1
supramolecular fiber organization	1
system process	1
negative regulation of cellular component organization	1
inclusion body assembly	1
regulation of inclusion body assembly	1
cellular response to heat	1
regulation of cellular response to stress	1
ATP-dependent activity	1
molecular function activator activity	1
nucleic acid binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
molecular_function	1
protein folding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
I band	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 15 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

15 experimentally-supported GO terms:

GO term	NS	Evidence
intermediate filament organization	BP	direct assay
negative regulation of inclusion body assembly	BP	direct assay
nervous system process	BP	direct assay
protein folding	BP	direct assay
regulation of protein localization	BP	mutant phenotype
Z disc	CC	direct assay
cytosol	CC	direct assay
membrane	CC	high-throughput assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay
ATPase activator activity	MF	direct assay
heat shock protein binding	MF	direct assay
identical protein binding	MF	physical interaction
protein-folding chaperone binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,985 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB6	HSPA4	P34932	744
DNAJB6	GRPEL1	Q9HAV7	725
DNAJB6	HSPA1A	P08107	705
DNAJB6	MYOT	Q9UBF9	667
DNAJB6	HSPA8	P11142	661
DNAJB6	BAG3	O95817	622
DNAJB6	HTT	P42858	593
DNAJB6	HSPB8	Q9UJY1	579
DNAJB6	CIC	Q96RK0	552
DNAJB6	RBM17	Q96I25	551
DNAJB6	ANO5	Q75V66	539
DNAJB6	DNAJC6	O75061	520
DNAJB6	LDB3	O75112	498
DNAJB6	CRYAB	P02511	498
DNAJB6	FLNC	Q14315	496

IntAct

Human interaction partners of DNAJB6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 57 partners by confidence:

Partner	Interaction type	MIscore	Records
MLF1	association	0.750	3
MLF2	physical association	0.630	4
KRT18	physical association	0.620	6
ASCL4	physical association	0.560	3
CBLB	physical association	0.560	3
CFAP100	physical association	0.560	3
FAM117B	physical association	0.560	3
IK	physical association	0.560	3
MAGEC3	physical association	0.560	3
RPP25	physical association	0.560	3
SPATA22	physical association	0.560	3
ZNF829	physical association	0.560	3
ZSCAN1	physical association	0.560	3
DNAJB8	association	0.530	2
BAG2	association	0.530	1
L3MBTL1	association	0.530	1
STUB1	association	0.530	1
BRMS1	physical association	0.510	2
HSPA8	physical association	0.480	2
DYSF	proximity	0.450	2
SGCG	proximity	0.450	2
AARSD1	physical association	0.400	1
GPX8	physical association	0.400	1
LRRK2	physical association	0.400	1
PSMD2	physical association	0.400	1
POLR1D	physical association	0.370	1
ANKK1	association	0.350	1
BAG1	association	0.350	1
BAG3	association	0.350	1
BAG4	association	0.350	1

BioGRID (460 interactions; top human partners by supporting records): MLF2 (Two-hybrid; 6 records), BAG2 (Affinity Capture-MS; 5 records), STUB1 (Affinity Capture-Western; 5 records), BAG3 (Affinity Capture-Western; 4 records), STIP1 (Affinity Capture-MS; 4 records), C12orf45 (Affinity Capture-MS; 3 records), CUL3 (Affinity Capture-MS; 3 records), DNAJB2 (Affinity Capture-MS; 3 records), FKBP5 (Affinity Capture-MS; 3 records), HDAC4 (Affinity Capture-Western; 3 records), HSPA8 (Affinity Capture-MS; 3 records), KRT18 (Affinity Capture-Western; 3 records), MLF1 (Affinity Capture-MS; 3 records), ALKBH1 (Affinity Capture-Western; 2 records), BAG1 (Affinity Capture-Luminescence; 2 records)

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of HSF1-mediated heat shock response	5	19.3×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
protein folding	7	12.9×	1e-04

Disease & clinical

Genetic variants

Variant evidence for DNAJB6: 551 ClinVar records (20 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	17
Likely pathogenic	3
Uncertain significance	259
Likely benign	155
Benign	51

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 20 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
31529	NM_058246.4(DNAJB6):c.279C>G (p.Phe93Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
31531	NM_058246.4(DNAJB6):c.265T>A (p.Phe89Ile)	Pathogenic	criteria provided, multiple submitters, no conflicts	8
225176	NM_058246.4(DNAJB6):c.273C>G (p.Phe91Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
31530	NM_058246.4(DNAJB6):c.279C>A (p.Phe93Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
30905	NM_058246.4(DNAJB6):c.287C>G (p.Pro96Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
1322758	NM_058246.4(DNAJB6):c.271T>C (p.Phe91Leu)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
30904	NM_058246.4(DNAJB6):c.277T>C (p.Phe93Leu)	Pathogenic	criteria provided, single submitter	2
225175	NM_058246.4(DNAJB6):c.271T>A (p.Phe91Ile)	Pathogenic	criteria provided, single submitter	2
2136635	NM_058246.4(DNAJB6):c.287C>T (p.Pro96Leu)	Pathogenic	criteria provided, single submitter	1
4737597	NM_058246.4(DNAJB6):c.290ATG[1] (p.Asp98del)	Pathogenic	criteria provided, single submitter	1
830317	NM_058246.4(DNAJB6):c.236G>A (p.Gly79Asp)	Likely pathogenic	criteria provided, single submitter	1
4854771	NM_058246.4(DNAJB6):c.298T>A (p.Phe100Ile)	Likely pathogenic	criteria provided, single submitter	1
3062957	GRCh37/hg19 7q36.3(chr7:155607058-159119707)x1	Pathogenic	criteria provided, single submitter	1
253366	GRCh37/hg19 7q36.3(chr7:156431577-157598312)x1	Likely pathogenic	criteria provided, single submitter	1
225174	NM_058246.4(DNAJB6):c.298T>G (p.Phe100Val)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore DNAJB6’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; 39 predictions of 2,062):

Position(s)	Effect	Δscore	Sites
7:157358638–157358639	donor_loss	1.0000	5
7:157363159	acceptor_gain	1.0000
7:157363159–157363160	acceptor_loss	1.0000	2
7:157363271–157363272	donor_loss	1.0000	5
7:157366500–157366501	acceptor_loss	1.0000	4
7:157366562–157366563	donor_loss	1.0000	5
7:157367371–157367372	acceptor_loss	1.0000	6
7:157367484–157367485	donor_loss	1.0000	5
7:157381946	donor_gain	1.0000
7:157382378–157382379	donor_loss	1.0000	5

AlphaMissense

1,010 missense substitutions predicted likely pathogenic (of 2,124 scored), across 227 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	0.999	1.000
D33	8	0.999	1.000
F46	8	0.998	1.000
F100	8	0.997	1.000
F104	8	0.995	1.000
N35	8	0.990	0.999
F93	8	0.989	1.000
D66	8	0.985	0.999
F110	8	0.985	0.998
D108	8	0.983	0.995
D58	8	0.976	0.996
F103	8	0.972	0.999
F91	8	0.970	1.000
D3	8	0.876	0.983
F175	8	0.849	0.976
D18	8	0.840	0.980
F119	8	0.789	0.891
D117	8	0.752	0.919
W30	7	0.999	1.000
E54	7	0.991	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	9.88e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000192

Disease associations

OMIM: gene MIM:611332 | disease phenotypes: MIM:603511, MIM:130000, MIM:130010

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6)	Strong	Autosomal dominant	3

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
muscular dystrophy, limb-girdle, autosomal dominant	Definitive	AD

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
Distal myopathies	green
Hypotonic infant	green
Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies	green
Other rare neuromuscular disorders	green

Mondo (3): autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6) (MONDO:0021018), Ehlers-Danlos syndrome, classic type, 1 (MONDO:0019567), Ehlers-Danlos syndrome, classic type, 2 (MONDO:0019568)

Orphanet (4): DNAJB6-related limb-girdle muscular dystrophy D1 (Orphanet:34516), Classical Ehlers-Danlos syndrome (Orphanet:287), OBSOLETE: Ehlers-Danlos syndrome type 2 (Orphanet:90318), OBSOLETE: Ehlers-Danlos syndrome type 1 (Orphanet:90309)

HPO phenotypes

29 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001260	Dysarthria
HP:0001283	Bulbar palsy
HP:0001371	Flexion contracture
HP:0002015	Dysphagia
HP:0002094	Dyspnea
HP:0002505	Loss of ambulation
HP:0002515	Waddling gait
HP:0003236	Elevated circulating creatine kinase activity
HP:0003324	Generalized muscle weakness
HP:0003326	Myalgia
HP:0003391	Gowers sign
HP:0003547	Shoulder girdle muscle weakness
HP:0003551	Difficulty climbing stairs
HP:0003555	Muscle fiber splitting
HP:0003557	Increased variability in muscle fiber diameter
HP:0003560	Muscular dystrophy
HP:0003677	Slowly progressive
HP:0003715	Myofibrillar myopathy
HP:0003749	Pelvic girdle muscle weakness
HP:0003805	Rimmed vacuoles
HP:0004303	Abnormal muscle fiber morphology
HP:0009046	Difficulty running
HP:0010548	Percussion myotonia
HP:0010628	Facial palsy
HP:0011462	Young adult onset
HP:0012548	Fatty replacement of skeletal muscle
HP:0030951	Skeletal muscle fibrosis
HP:0033383	Decreased compound muscle action potential amplitude

GWAS associations

4 associations:

Study	Trait	p-value
GCST008151_85	Waist circumference	3e-6
GCST008160_74	Waist circumference	3e-6
GCST009959_5	Retinal detachment or retinal break	3e-6
GCST008158_87	Body mass index	9e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010698	retinal break

MeSH disease descriptors

3 disease descriptors:

Descriptor	Name	Tree numbers
C536194	Ehlers-Danlos syndrome type 1 *(supp.)*
C536195	Ehlers-Danlos syndrome type 2 *(supp.)*
C566370	Muscular Dystrophy, Limb-Girdle, Type 1D *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295674 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, increases expression, decreases expression	4
Tobacco Smoke Pollution	increases expression	3
Valproic Acid	affects expression, increases expression	3
sodium arsenite	decreases expression, increases abundance, increases expression	2
cobaltous chloride	increases expression	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	increases oxidation, increases expression, affects cotreatment, increases abundance	2
Cadmium	increases expression	2
Copper	decreases expression, increases expression, affects binding	2
Silver	increases expression	2
aristolochic acid I	increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
beta-lapachone	decreases expression, increases expression	1
nickel chloride	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
coumarin	increases phosphorylation	1
cupric oxide	increases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
motexafin gadolinium	increases expression, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
candoxin	increases expression	1
darinaparsin	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118642	Binding	Binding affinity to DNAJB6 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2TF	GM27890	Transformed cell line	Female
CVCL_C7LZ	GM28910	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

14 trials:

NCT	Phase	Status	Title
NCT00455143	Phase 4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	Phase 4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT01807481	Phase 4	UNKNOWN	Phase IV Study to Evaluate the Efficacy and Safety of Mircera in PD
NCT07015671	Phase 3	COMPLETED	Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects
NCT03942458	Phase 1	COMPLETED	Pharmacokinetics and Pharmacodynamics of Vicagrel in Healthy Adult Subjects of Different CYP2C19
NCT07195825	Phase 1	RECRUITING	A Clinical Study to Evaluate the Safety, and Tolerability of BBM-P002 in the Treatment of Parkinson’s Disease
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments
NCT06566066	Not specified	RECRUITING	Register for Patients With Thyroid Hormone Resistance.
NCT04093349	Phase 1/2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT07282847	Phase 1/2	RECRUITING	A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late-Onset Pompe Disease (PROGRESS-GT LOPD)
NCT00105131	Not specified	COMPLETED	Genetic Characterization of Parkinson’s Disease
NCT03021408	Not specified	UNKNOWN	Effectiveness of Different Approaches for the Rehabilitation of Gait in Patients With Parkinson’s Disease
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
NCT05810454	Not specified	UNKNOWN	iPACES v3 MCI NIA Protocol Copied for iPACES v4 PD NINDS