DNAJB4

Summary

DNAJB4 (DnaJ heat shock protein family (Hsp40) member B4, HGNC:14886) is a protein-coding gene on chromosome 1p31.1, encoding DnaJ homolog subfamily B member 4 (Q9UDY4). Probable chaperone.

The protein encoded by this gene is a molecular chaperone, tumor suppressor, and member of the heat shock protein-40 family. The encoded protein binds the cell adhesion protein E-cadherin and targets it to the plasma membrane. This protein also binds incorrectly folded E-cadherin and targets it for endoplasmic reticulum-associated degradation. This gene is a strong tumor suppressor for colorectal carcinoma, and downregulation of it may serve as a good biomarker for predicting patient outcomes. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 11080 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital myopathy 21 with early respiratory failure (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 24
• Clinical variants (ClinVar): 46 total — 4 pathogenic
• Phenotypes (HPO): 19
• MANE Select transcript: NM_007034

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14886
Approved symbol	DNAJB4
Name	DnaJ heat shock protein family (Hsp40) member B4
Location	1p31.1
Locus type	gene with protein product
Status	Approved
Aliases	HLJ1
Ensembl gene	ENSG00000162616
Ensembl biotype	protein_coding
OMIM	611327
Entrez	11080

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000370763, ENST00000426517, ENST00000476396, ENST00000477671, ENST00000484662, ENST00000487931, ENST00000867099, ENST00000867100, ENST00000939131, ENST00000939132, ENST00000939133, ENST00000939134, ENST00000939135, ENST00000939136, ENST00000957220

RefSeq mRNA: 6 — MANE Select: NM_007034 NM_001317099, NM_001317100, NM_001317101, NM_001317102, NM_001317103, NM_007034

CCDS: CCDS684

Canonical transcript exons

ENST00000370763 — 3 exons

Exon	Start	End
ENSE00001453580	78016014	78017964
ENSE00001875037	78004939	78005321
ENSE00003580240	78013051	78013619

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.4619 / max 5628.5881, expressed in 1788 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
3647	59.7220	1685
3646	8.4710	1484
3640	3.3161	1338
3637	2.9005	1239
3636	2.1646	837
3644	2.1131	679
3645	1.3132	496
201556	1.2842	567
3638	0.7804	450
3641	0.3968	199

Top tissues by expression

295 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.59	gold quality
calcaneal tendon	UBERON:0003701	98.36	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.57	gold quality
biceps brachii	UBERON:0001507	97.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.31	gold quality
adrenal tissue	UBERON:0018303	96.27	gold quality
heart right ventricle	UBERON:0002080	96.10	gold quality
diaphragm	UBERON:0001103	95.81	gold quality
cauda epididymis	UBERON:0004360	95.17	gold quality
myocardium	UBERON:0002349	95.12	gold quality
vena cava	UBERON:0004087	95.09	gold quality
skeletal muscle tissue	UBERON:0001134	95.05	gold quality
right coronary artery	UBERON:0001625	95.05	gold quality
blood vessel layer	UBERON:0004797	94.99	gold quality
left ventricle myocardium	UBERON:0006566	94.72	gold quality
saphenous vein	UBERON:0007318	94.54	gold quality
gall bladder	UBERON:0002110	94.50	gold quality
muscle tissue	UBERON:0002385	94.36	gold quality
choroid plexus epithelium	UBERON:0003911	94.13	gold quality
ascending aorta	UBERON:0001496	93.84	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.83	gold quality
thoracic aorta	UBERON:0001515	93.81	gold quality
adrenal gland	UBERON:0002369	93.73	gold quality
left adrenal gland	UBERON:0001234	93.54	gold quality
left coronary artery	UBERON:0001626	93.52	gold quality
vastus lateralis	UBERON:0001379	93.41	gold quality
coronary artery	UBERON:0001621	93.39	gold quality
body of tongue	UBERON:0011876	93.37	gold quality
heart	UBERON:0000948	93.25	gold quality
muscle organ	UBERON:0001630	93.18	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	9.96
E-GEOD-84465	yes	6.90
E-MTAB-7249	yes	4.88
E-GEOD-124858	no	1766.07
E-MTAB-10137	no	574.06
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOSB, JUN, JUNB, JUND, YY1

miRNA regulators (miRDB)

175 targeting DNAJB4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
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

Literature-anchored findings (GeneRIF, showing 17)

• Results indicate that DjA1 and DjB4 of subfamilies A and B of human Hsp40 have different quaternary structures and chaperone functions. (PMID:15661747)
• The increase in HLJ1 and E-cadherin expression, as well as the suppression of invasion ability, can be reversed specifically by HLJ1 siRNA. (PMID:15782117)
• HLJ1 is a novel tumor suppressor in NSCLC, and high HLJ1 expression is associated with reduced cancer recurrence and prolonged survival of NSCLC patients. (PMID:16788156)
• Results show that curcumin induces HLJ1, through activation of the JNK/JunD pathway, and inhibits lung cancer cell invasion and metastasis by modulating E-cadherin expression. (PMID:18794131)
• HLJ1 switches the role of NPM1, which can act as tumor suppressor or oncogene, by modulating the oligomerization of NPM1 via HLJ1-NPM1 heterodimer formation and recruiting AP-2alpha to the MMP-2 promoter. (PMID:20145123)
• acidic stress increases the association between HLJ1 and beta-actin to modulate migration of human lung cancer cells (PMID:20615403)
• HBV could promote HLJ1 expression by up-regulating the transcription factor YY1. (PMID:21345358)
• Silencing of HLJ1 partially reverses the inhibition of cancer-cell invasion by andrographolide. (PMID:23306212)
• Low expression of DNAJB4 is associated with gastric carcinomas. (PMID:24293545)
• we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. (PMID:24318877)
• HLJ1 is a strong tumor suppressor for colorectal carcinoma (PMID:24696714)
• HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. (PMID:27065329)
• These new observations support the idea that HLJ1 is a tumor suppressor candidate and potential biomarker for breast cancer (PMID:28481734)
• The DNAJB4 is down-regulated in the three lines of metastatic melanoma cells relative to the corresponding primary melanoma cells. (PMID:29722524)
• DNAJB4 role as a metastasis inducer in the breast cancer. (PMID:31221721)
• A pleiotropic variant in DNAJB4 is associated with multiple myeloma risk. (PMID:36082445)
• Human Endogenous Retrovirus-H-Derived miR-4454 Inhibits the Expression of DNAJB4 and SASH1 in Non-Muscle-Invasive Bladder Cancer. (PMID:37510314)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajb4	ENSDARG00000038978
mus_musculus	Dnajb4	ENSMUSG00000028035
rattus_norvegicus	Dnajb4	ENSRNOG00000013011
drosophila_melanogaster	CG7130	FBGN0037151

Paralogs (11): DNAJB11 (ENSG00000090520), DNAJB6 (ENSG00000105993), DNAJB9 (ENSG00000128590), DNAJB1 (ENSG00000132002), DNAJB2 (ENSG00000135924), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB14 (ENSG00000164031), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Protein

Protein identifiers

DnaJ homolog subfamily B member 4 — Q9UDY4 (reviewed: Q9UDY4)

Alternative names: Heat shock 40 kDa protein 1 homolog, Human liver DnaJ-like protein

All UniProt accessions (2): C9JUL4, Q9UDY4

UniProt curated annotations — full annotation on UniProt →

Function. Probable chaperone. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro).

Subunit / interactions. Homodimer. The C-terminal section interacts with the C-terminal tail of OPRM1. Also interacts with SDIM1.

Subcellular location. Cytoplasm. Cell membrane. Myofibril. Sarcomere. Z line.

Tissue specificity. Expressed in heart, pancreas and skeletal muscle, and to a lesser extent in brain, placenta and liver.

Disease relevance. Congenital myopathy 21 with early respiratory failure (CMYO21) [MIM:620326] An autosomal recessive muscle disorder characterized by diaphragmatic weakness, respiratory impairment, and spinal rigidity. Disease onset ranges from early childhood to adulthood and severity is variable. Death from respiratory failure may occur in severe cases. Some affected individuals may show developmental delay and hypertrophic cardiomyopathy. The disease is caused by variants affecting the gene represented in this entry.

Induction. By heat shock.

RefSeq proteins (6): NP_001304028, NP_001304029, NP_001304030, NP_001304031, NP_001304032, NP_008965* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR002939	DnaJ_C	Domain
IPR008971	HSP40/DnaJ_pept-bd	Homologous_superfamily
IPR018253	DnaJ_domain_CS	Conserved_site
IPR036869	J_dom_sf	Homologous_superfamily
IPR051339	DnaJ_subfamily_B	Family

Pfam: PF00226, PF01556

UniProt features (9 total): sequence variant 4, modified residue 2, initiator methionine 1, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UDY4-F1	83.43	0.60

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): 122, 148

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 408 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, NKX25_02, ADDYA_ERYTHROID_DIFFERENTIATION_BY_HEMIN, CHX10_01, AAAYRNCTG_UNKNOWN, GOBP_PROTEIN_MATURATION, SRF_C, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, NF1_Q6_01, TGCTGAY_UNKNOWN, GROSS_HYPOXIA_VIA_ELK3_AND_HIF1A_UP, DELYS_THYROID_CANCER_DN, WTGAAAT_UNKNOWN, DAUER_STAT3_TARGETS_DN, TGACATY_UNKNOWN

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), protein folding (GO:0006457), response to unfolded protein (GO:0006986), response to heat (GO:0009408)

GO Molecular Function (4): ATPase activator activity (GO:0001671), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), Z disc (GO:0030018), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
response to stress	1
response to temperature stimulus	1
ATP-dependent activity	1
molecular function activator activity	1
protein binding	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
I band	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

2505 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB4	DNAJC2	Q99543	854
DNAJB4	DNAJC12	Q9UKB3	842
DNAJB4	HSPA4	P34932	839
DNAJB4	DNAJC19	Q96DA6	821
DNAJB4	TRIM21	P19474	814
DNAJB4	HSPA1A	P08107	813
DNAJB4	DNAJC6	O75061	798
DNAJB4	HSPA14	Q0VDF9	742
DNAJB4	HSPA6	P17066	722
DNAJB4	HSPA5	P11021	721
DNAJB4	HSPA8	P11142	664
DNAJB4	HSP90AA1	P07900	647
DNAJB4	HSP90AB1	P08238	620
DNAJB4	BAG2	O95816	570
DNAJB4	FAM149B1	Q96BN6	550

IntAct

140 interactions, top by confidence:

A	B	Type	Score
MLF1	DNAJB6	psi-mi:“MI:0914”(association)	0.750
DNAJB4	DNAJB5	psi-mi:“MI:0914”(association)	0.730
NUDC	DNAJB1	psi-mi:“MI:0914”(association)	0.640
TTLL1	CDC27	psi-mi:“MI:0914”(association)	0.640
MLF2	DNAJB6	psi-mi:“MI:0914”(association)	0.630
DNAJB4	RUVBL2	psi-mi:“MI:0915”(physical association)	0.560
HTT	DNAJB4	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	DNAJB4	psi-mi:“MI:0915”(physical association)	0.560
MLF1	HAX1	psi-mi:“MI:0914”(association)	0.560
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
DNAJB4	SYNM	psi-mi:“MI:0914”(association)	0.530
ANGPTL4	NMT2	psi-mi:“MI:0914”(association)	0.530
P2RX6	DNAJB5	psi-mi:“MI:0914”(association)	0.530
ABHD15	HSPA8	psi-mi:“MI:0914”(association)	0.530
PYCR3	RPL23	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
KLHL10	PXDNL	psi-mi:“MI:0914”(association)	0.530

BioGRID (232): DNAJB4 (Two-hybrid), DNAJB4 (Affinity Capture-RNA), DNAJB4 (Affinity Capture-RNA), DNAJB4 (Affinity Capture-Western), DNAJB4 (Affinity Capture-Western), DNAJB4 (Affinity Capture-MS), DNAJB5 (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), GLB1 (Affinity Capture-MS), SYNM (Affinity Capture-MS), C3orf38 (Affinity Capture-MS), TTLL12 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS), DNAJB4 (Affinity Capture-MS)

ESM2 similar proteins: A6QBG7, B9FHF3, O35824, O60884, O74752, O75953, O89114, O94625, O94657, P25294, P25303, P25491, P25685, P42824, P42825, P43644, P59910, P78004, P81999, Q03363, Q04960, Q09912, Q0JB88, Q24133, Q2HJ94, Q2KIT4, Q3AQP5, Q3MI00, Q3ZBA6, Q54ED3, Q5BIP8, Q5R8J8, Q5RAJ6, Q626I7, Q6MNG0, Q6TUG0, Q8A8C3, Q8GWW8, Q8MPX3, Q8TA83

Diamond homologs: A4W6D6, A5W9N6, A6ZQH0, A7GT07, A7MIK3, A7TGR0, A7ZKA5, A8AI78, A8G9K9, A8GR21, A9KE65, A9MH53, A9N6S2, A9NDK6, A9VHU0, B0BWH0, B0JW23, B0KK26, B1J5W7, B1WVR2, B4T2U5, B4TEN5, B4TSM3, B5BBH2, B5F1Z5, B5FR40, B5R049, B5R6G3, B5YU43, B7HPL2, B7JN38, B7KEJ8, B7LFA9, B7MIE6, B7NLC5, B7UNY3, B8CXL0, B9E6X0, B9IY80, C0Q893

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 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
Attenuation phase	6	24.0×	5e-05
Regulation of HSF1-mediated heat shock response	12	16.4×	5e-09
HCMV Infection	5	16.0×	2e-03
HSF1-dependent transactivation	5	15.6×	2e-03
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	6	11.4×	2e-03
Signaling by NOTCH	6	10.3×	2e-03
Translocation of SLC2A4 (GLUT4) to the plasma membrane	6	9.1×	4e-03
Cellular responses to stress	13	4.7×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
response to unfolded protein	7	15.3×	2e-04
protein folding	12	9.0×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2499482	NM_007034.5(DNAJB4):c.856A>T (p.Lys286Ter)	Pathogenic
2499483	NM_007034.5(DNAJB4):c.785T>C (p.Leu262Ser)	Pathogenic
2499484	NM_007034.5(DNAJB4):c.74G>A (p.Arg25Gln)	Pathogenic
2499485	NM_007034.5(DNAJB4):c.181A>G (p.Arg61Gly)	Pathogenic

SpliceAI

276 predictions. Top by Δscore:

Variant	Effect	Δscore
1:78005317:GGAAG:G	donor_gain	1.0000
1:78005318:GAAGG:G	donor_gain	1.0000
1:78005319:AAGG:A	donor_loss	1.0000
1:78005321:GGT:G	donor_loss	1.0000
1:78005318:GAAG:G	donor_gain	0.9900
1:78005319:AAG:A	donor_gain	0.9900
1:78005320:AG:A	donor_gain	0.9900
1:78005321:GG:G	donor_gain	0.9900
1:78005322:G:GG	donor_gain	0.9900
1:78013047:TTA:T	acceptor_loss	0.9900
1:78013048:TA:T	acceptor_loss	0.9900
1:78013049:A:AC	acceptor_loss	0.9900
1:78013049:A:AG	acceptor_gain	0.9900
1:78013049:AG:A	acceptor_gain	0.9900
1:78013050:G:A	acceptor_gain	0.9900
1:78013050:G:GG	acceptor_gain	0.9900
1:78013050:GGGTT:G	acceptor_gain	0.9900
1:78013575:G:T	donor_gain	0.9900
1:78016001:T:TA	acceptor_gain	0.9900
1:78016008:TTTTA:T	acceptor_loss	0.9900
1:78016009:TTTA:T	acceptor_loss	0.9900
1:78016010:TTAGG:T	acceptor_loss	0.9900
1:78016011:TA:T	acceptor_loss	0.9900
1:78016012:A:AC	acceptor_loss	0.9900
1:78016013:GGC:G	acceptor_gain	0.9900
1:78005323:T:G	donor_loss	0.9800
1:78013046:A:G	acceptor_gain	0.9800
1:78013177:G:GT	donor_gain	0.9800
1:78013617:GAG:G	donor_gain	0.9800
1:78015998:ATTT:A	acceptor_gain	0.9800

AlphaMissense

2228 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:78005180:T:C	Y24H	1.000
1:78005180:T:G	Y24D	1.000
1:78005184:G:C	R25P	1.000
1:78005193:C:A	A28D	1.000
1:78005196:T:A	L29H	1.000
1:78005196:T:C	L29P	1.000
1:78005204:C:A	H32N	1.000
1:78005204:C:G	H32D	1.000
1:78005205:A:G	H32R	1.000
1:78005206:T:A	H32Q	1.000
1:78005206:T:G	H32Q	1.000
1:78005243:T:C	F45L	1.000
1:78005244:T:C	F45S	1.000
1:78005245:T:A	F45L	1.000
1:78005245:T:G	F45L	1.000
1:78005255:G:C	A49P	1.000
1:78005261:G:C	A51P	1.000
1:78005274:T:C	L55S	1.000
1:78005274:T:G	L55W	1.000
1:78013131:T:C	F98L	1.000
1:78013133:T:A	F98L	1.000
1:78013133:T:G	F98L	1.000
1:78013143:T:C	F102L	1.000
1:78013145:C:A	F102L	1.000
1:78013145:C:G	F102L	1.000
1:78013370:A:C	K177N	1.000
1:78013370:A:T	K177N	1.000
1:78013438:T:C	L200P	1.000
1:78013458:G:A	G207R	1.000
1:78013458:G:C	G207R	1.000

dbSNP variants (sampled 300 via entrez): RS1000017085 (1:78002646 A>G), RS1000066176 (1:78011725 C>A,T), RS1000078153 (1:78000965 C>A), RS1000193945 (1:77991295 G>A), RS1000206876 (1:77984825 C>G), RS1000241890 (1:78004353 A>G), RS1000258857 (1:77984497 C>T), RS1000349186 (1:77997929 A>G), RS1000434517 (1:77983906 T>G), RS1000526011 (1:77992521 A>C), RS1000528499 (1:78006687 A>G), RS1000539145 (1:77986169 T>G), RS1000674742 (1:77999255 A>T), RS1000814969 (1:77990994 G>A), RS1000890026 (1:77984212 C>A,G)

Disease associations

OMIM: gene MIM:611327 | disease phenotypes: MIM:620326

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital myopathy 21 with early respiratory failure	Strong	Autosomal recessive
distal myopathy	Strong	Autosomal dominant
congenital myopathy	Limited	Autosomal dominant

Mondo (3): congenital myopathy 21 with early respiratory failure (MONDO:0957224), congenital myopathy (MONDO:0019952), distal myopathy (MONDO:0018949)

Orphanet (0):

HPO phenotypes

19 total (19 of 19 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0001249	Intellectual disability
HP:0001270	Motor delay
HP:0001511	Intrauterine growth retardation
HP:0001639	Hypertrophic cardiomyopathy
HP:0002094	Dyspnea
HP:0002877	Nocturnal hypoventilation
HP:0002878	Respiratory failure
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003306	Spinal rigidity
HP:0003458	EMG: myopathic abnormalities
HP:0003596	Middle age onset
HP:0009113	Diaphragmatic weakness
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0012444	Brain atrophy
HP:0033364	Lipoid pneumonia
HP:0033725	Thin corpus callosum

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004065_12	Waist circumference	3.000000e-10
GCST004065_9	Waist circumference	1.000000e-06
GCST004557_148	Body mass index	5.000000e-10
GCST004557_254	Body mass index	1.000000e-09
GCST004557_6	Body mass index	1.000000e-09
GCST004557_75	Body mass index	2.000000e-10
GCST004558_117	Body mass index (joint analysis main effects and physical activity interaction)	6.000000e-10
GCST004558_190	Body mass index (joint analysis main effects and physical activity interaction)	3.000000e-08
GCST004558_201	Body mass index (joint analysis main effects and physical activity interaction)	1.000000e-09
GCST004558_48	Body mass index (joint analysis main effects and physical activity interaction)	5.000000e-09
GCST004559_145	Body mass index in physically active individuals	9.000000e-07
GCST004559_176	Body mass index in physically active individuals	2.000000e-06
GCST004559_37	Body mass index in physically active individuals	2.000000e-06
GCST004559_65	Body mass index in physically active individuals	8.000000e-07
GCST004744_59	Lung adenocarcinoma	4.000000e-08
GCST004748_66	Lung cancer	2.000000e-10
GCST004749_59	Lung cancer in ever smokers	7.000000e-08
GCST006630_86	Diastolic blood pressure	5.000000e-21
GCST008595_7	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-09
GCST010302_4	Cutaneous melanoma or hair colour	2.000000e-12
GCST010988_241	Adult body size	2.000000e-31
GCST010989_177	Body size at age 10	2.000000e-10
GCST90000025_929	Appendicular lean mass	6.000000e-48
GCST90013406_54	Liver enzyme levels (alkaline phosphatase)	7.000000e-15

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0006336	diastolic blood pressure
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0003924	hair color
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004980	appendicular lean mass
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects expression, increases expression	8
sodium arsenite	increases expression, affects binding, increases reaction, affects cotreatment, increases abundance	6
Tobacco Smoke Pollution	affects expression, increases expression	5
Arsenic Trioxide	increases expression	4
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	4
bisphenol A	decreases methylation, decreases expression, affects expression, affects cotreatment	3
cobaltous chloride	increases expression	3
Thiram	increases expression	3
Cyclosporine	decreases expression, increases expression	3
Cadmium Chloride	increases abundance, increases expression	3
captax	increases expression	2
cinnamaldehyde	increases expression	2
4-phenylenediamine	increases expression	2
isoeugenol	increases expression	2
1,2-dibromo-2,4-dicyanobutane	increases expression	2
celastrol	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Cadmium	increases abundance, increases expression	2
Copper	affects binding, increases expression	2
Dinitrochlorobenzene	increases expression, affects reaction	2
Eugenol	increases expression	2
Formaldehyde	increases expression	2
Glyoxal	increases expression	2
Silver	increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
tungsten carbide	affects cotreatment, increases expression	1
3,3’,4’,5-tetrachlorosalicylanilide	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Q7	Abcam HeLa DNAJB4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

13 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02020187	Not specified	COMPLETED	Aerobic Training in Patients With Congenital Myopathies
NCT03018184	Not specified	COMPLETED	Contractile Cross Sectional Areas and Muscle Strength in Patients With Congenital Myopathies
NCT04733976	Not specified	COMPLETED	Bullying in Youth With Muscular Dystrophy and Congenital Myopathies
NCT05099107	Not specified	COMPLETED	Changes of Motor Function Tests in Congenital Myopathy Subjects Treated With Oral Salbutamol as Compared to no Treatment
NCT05199246	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Lower-limb Powered Dermoskeleton in Patients With Neuromuscular Disorders
NCT05200702	Not specified	COMPLETED	Assessment of Safety and Acute Effects of a Knee-hip Powered Soft Exoskeleton in Patients With Neuromuscular Disorders
NCT05692349	Not specified	UNKNOWN	Magnetic Resonance Imaging and Ultrasonography in Evaluation of Muscle Diseases
NCT06791369	Not specified	NOT_YET_RECRUITING	The Prevalence of RYR1-related Disease
NCT06833489	Not specified	RECRUITING	Transcriptomic Analysis to Put an End to Misdiagnosis in Patients With Rare Muscle Diseases
NCT07138963	Not specified	RECRUITING	Phenotype - Genotype Correlation in a Sample of Egyptian Patients With Congenital Myopathies and Congenital Muscular Dystrophies
NCT07415837	Not specified	RECRUITING	Evaluation of the Role of miR-1 in the Pathogenesis and as a Biomarker in Muscular Dystrophies and Congenital Myopathies
NCT07502989	Not specified	RECRUITING	Muscle Health Measurements Using Electrical Impedance Myography
NCT07580365	Not specified	NOT_YET_RECRUITING	VirtualPark_Pediatric