DNAJC4

Summary

DNAJC4 (DnaJ heat shock protein family (Hsp40) member C4, HGNC:5271) is a protein-coding gene on chromosome 11q13.1, encoding DnaJ homolog subfamily C member 4 (Q9NNZ3).

Predicted to enable unfolded protein binding activity. Predicted to be involved in protein folding and response to unfolded protein. Predicted to be located in membrane.

Source: NCBI Gene 3338 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 62 total
• MANE Select transcript: NM_005528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5271
Approved symbol	DNAJC4
Name	DnaJ heat shock protein family (Hsp40) member C4
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Aliases	MCG18
Ensembl gene	ENSG00000110011
Ensembl biotype	protein_coding
OMIM	604189
Entrez	3338

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 16 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000321460, ENST00000321685, ENST00000355040, ENST00000535246, ENST00000536006, ENST00000537109, ENST00000538961, ENST00000540945, ENST00000542376, ENST00000543685, ENST00000543791, ENST00000628077, ENST00000861854, ENST00000861855, ENST00000861856, ENST00000861857, ENST00000861858, ENST00000861859, ENST00000861860, ENST00000861861, ENST00000914118, ENST00000914119, ENST00000964216

RefSeq mRNA: 3 — MANE Select: NM_005528 NM_001307980, NM_001307981, NM_005528

CCDS: CCDS41666, CCDS76424

Canonical transcript exons

ENST00000628077 — 6 exons

Exon	Start	End
ENSE00001242518	64232704	64232865
ENSE00001603451	64233894	64233980
ENSE00002321360	64234073	64234281
ENSE00003556559	64231871	64231964
ENSE00003557813	64232430	64232614
ENSE00003936045	64230548	64230940

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 99.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.9267 / max 270.6510, expressed in 1813 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
114880	37.0622	1809
114883	1.0845	763
114882	1.0632	790
114885	0.8069	502
114881	0.5737	328
114884	0.4891	258
114886	0.3868	181
114877	0.2511	11
114887	0.1801	79
114878	0.0291	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.28	gold quality
left testis	UBERON:0004533	99.24	gold quality
sperm	CL:0000019	98.64	gold quality
apex of heart	UBERON:0002098	98.15	gold quality
body of pancreas	UBERON:0001150	97.36	gold quality
testis	UBERON:0000473	97.21	gold quality
right adrenal gland cortex	UBERON:0035827	96.88	gold quality
left adrenal gland cortex	UBERON:0035825	96.75	gold quality
right adrenal gland	UBERON:0001233	96.73	gold quality
metanephros cortex	UBERON:0010533	96.71	gold quality
granulocyte	CL:0000094	96.69	gold quality
left adrenal gland	UBERON:0001234	96.57	gold quality
right lobe of thyroid gland	UBERON:0001119	96.52	gold quality
adenohypophysis	UBERON:0002196	96.51	gold quality
left lobe of thyroid gland	UBERON:0001120	96.37	gold quality
right atrium auricular region	UBERON:0006631	96.37	gold quality
body of stomach	UBERON:0001161	96.27	gold quality
lower esophagus mucosa	UBERON:0035834	96.24	gold quality
mucosa of transverse colon	UBERON:0004991	96.19	gold quality
small intestine Peyer’s patch	UBERON:0003454	96.05	gold quality
adrenal cortex	UBERON:0001235	96.02	gold quality
transverse colon	UBERON:0001157	95.86	gold quality
right lobe of liver	UBERON:0001114	95.85	gold quality
minor salivary gland	UBERON:0001830	95.83	gold quality
left ovary	UBERON:0002119	95.80	gold quality
right uterine tube	UBERON:0001302	95.75	gold quality
right ovary	UBERON:0002118	95.60	gold quality
male germ cell	CL:0000015	95.54	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.50	gold quality
skin of abdomen	UBERON:0001416	95.39	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31.58
E-ANND-3	yes	11.63
E-MTAB-4850	no	229.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting DNAJC4, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-1225-3P	97.29	64.60	876
HSA-MIR-5090	93.28	60.86	94
HSA-MIR-6775-5P	92.43	61.00	132

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc4	ENSDARG00000024090
mus_musculus	Dnajc4	ENSMUSG00000024963
rattus_norvegicus	Dnajc4	ENSRNOG00000043060
drosophila_melanogaster	CG10565	FBGN0037051
drosophila_melanogaster	P58IPK	FBGN0037718
drosophila_melanogaster	l(3)80Fg	FBGN0287183
caenorhabditis_elegans		WBGENE00001020
caenorhabditis_elegans		WBGENE00001025
caenorhabditis_elegans		WBGENE00001026
caenorhabditis_elegans		WBGENE00001029
caenorhabditis_elegans	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), DNAJC12 (ENSG00000108176), DNAJC16 (ENSG00000116138), DNAJC14 (ENSG00000135392), DNAJC1 (ENSG00000136770), DNAJC13 (ENSG00000138246), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC7 (ENSG00000168259), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC30 (ENSG00000176410), DNAJC9 (ENSG00000213551)

Protein

Protein identifiers

DnaJ homolog subfamily C member 4 — Q9NNZ3 (reviewed: Q9NNZ3)

Alternative names: DnaJ-like protein HSPF2, Multiple endocrine neoplasia type 1 candidate protein number 18

All UniProt accessions (5): Q9NNZ3, G3V1T1, H0YGV0, J3KNJ8, Q96FY5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (3): NP_001294909, NP_001294910, NP_005519* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR036869	J_dom_sf	Homologous_superfamily
IPR052763	DnaJ_C4	Family

Pfam: PF00226

UniProt features (7 total): region of interest 2, compositionally biased region 2, chain 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NNZ3-F1	77.83	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 89 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, chr11q13, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_PROTEIN_MATURATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_PROTEIN_FOLDING, GCM_DDX11, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, PAX2_02, GOMF_UNFOLDED_PROTEIN_BINDING, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, ONKEN_UVEAL_MELANOMA_DN

GO Biological Process (2): protein folding (GO:0006457), response to unfolded protein (GO:0006986)

GO Molecular Function (2): obsolete unfolded protein binding (GO:0051082), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC4	VEGFB	P49765	782
DNAJC4	DNAJC11	Q9NVH1	686
DNAJC4	NUDT22	Q9BRQ3	512
DNAJC4	DNAJC28	Q9NX36	504
DNAJC4	DNAJC24	Q6P3W2	503
DNAJC4	MTX1	Q13505	488
DNAJC4	DNAJC9	Q8WXX5	482
DNAJC4	C15orf62	A8K5M9	480
DNAJC4	SPATA21	Q7Z572	463
DNAJC4	DNAJC22	Q8N4W6	463
DNAJC4	C15orf61	A6NNL5	454
DNAJC4	DNAJC8	O75937	452
DNAJC4	MISO1	Q6P1S2	441
DNAJC4	DNAJC14	Q6Y2X3	441
DNAJC4	DNAJC13	O75165	432

IntAct

19 interactions, top by confidence:

A	B	Type	Score
HTT	DNAJC4	psi-mi:“MI:0915”(physical association)	0.670
DNAJC4	WFS1	psi-mi:“MI:0915”(physical association)	0.560
EGFR	DNAJC4	psi-mi:“MI:0915”(physical association)	0.550
DNAJC4	EGFR	psi-mi:“MI:0915”(physical association)	0.550
DNAJC4	PGAM2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (59): FAM9B (Two-hybrid), DNAJC4 (Affinity Capture-RNA), HAX1 (Affinity Capture-MS), EXOSC8 (Affinity Capture-MS), DLD (Affinity Capture-MS), CACTIN (Affinity Capture-MS), MCCC2 (Affinity Capture-MS), GRPEL1 (Affinity Capture-MS), HSPA9 (Affinity Capture-MS), LRPPRC (Proximity Label-MS), MRPS31 (Proximity Label-MS), SLC30A9 (Proximity Label-MS), MTX2 (Proximity Label-MS), AFG3L2 (Proximity Label-MS), IMMT (Proximity Label-MS)

ESM2 similar proteins: A0JPP8, A1A4P4, A2ALW5, D3ZSC8, J9VP29, O43278, O75064, P59041, P92029, Q0WTI8, Q1ECT8, Q2KHT9, Q2KI83, Q2KIL7, Q3U1Y4, Q3UJV1, Q3UMT1, Q4G0I0, Q4VBF2, Q5BJW9, Q5BKU9, Q5HZT9, Q5R7Q6, Q5RFR4, Q5T124, Q5XJW2, Q5ZJ07, Q6DGF9, Q6IPM2, Q6RUT7, Q75BG6, Q8JZP9, Q8K1S6, Q8SPE7, Q8TAE8, Q8VD26, Q8WWL2, Q91WT4, Q96AN5, Q96D70

Diamond homologs: A0KMI5, A1WX30, A3MA88, A4IX29, A4W6D6, A4XKA5, A5FZ18, A5W9A2, A6VCL7, A7I2G3, A7MIK3, A7ZHA5, A9IGC5, A9W6R8, B0B7R0, B0BBX5, B0U3J7, B0U833, B0VA24, B0VQ00, B1LZ52, B1ZGR2, B1ZUS0, B2I2G6, B2I6F5, B2IBR5, B2RLJ0, B3EE31, B3QPW8, B4S9D0, B7GV08, B7I2B2, B7KSZ5, B7UI60, B7V1H2, B8IHL2, B9KH92, B9MJZ0, C4Z1J3, C6BYN5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	46
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1174 predictions. Top by Δscore:

Variant	Effect	Δscore
11:64233891:CAGG:C	acceptor_loss	1.0000
11:64233893:G:T	acceptor_loss	1.0000
11:64230494:G:GT	donor_gain	0.9900
11:64230495:A:T	donor_gain	0.9900
11:64230517:G:GG	donor_gain	0.9900
11:64231962:GAG:G	donor_gain	0.9900
11:64232429:GCT:G	acceptor_gain	0.9900
11:64232429:GCTGC:G	acceptor_gain	0.9900
11:64233892:A:AG	acceptor_gain	0.9900
11:64233892:AG:A	acceptor_gain	0.9900
11:64233893:G:GG	acceptor_gain	0.9900
11:64233893:GG:G	acceptor_gain	0.9900
11:64233893:GGA:G	acceptor_gain	0.9900
11:64233893:GGAA:G	acceptor_gain	0.9900
11:64230513:GTCT:G	donor_gain	0.9800
11:64230938:GCG:G	donor_gain	0.9800
11:64231962:G:GT	donor_gain	0.9800
11:64232611:ACAGG:A	donor_loss	0.9800
11:64232612:CAG:C	donor_loss	0.9800
11:64232613:AG:A	donor_loss	0.9800
11:64232614:GG:G	donor_loss	0.9800
11:64232615:GTA:G	donor_loss	0.9800
11:64232616:T:G	donor_loss	0.9800
11:64230463:GAAT:G	donor_gain	0.9700
11:64230562:TCCCC:T	donor_gain	0.9700
11:64231720:G:GT	donor_gain	0.9700
11:64231961:AGAG:A	donor_loss	0.9700
11:64231963:AG:A	donor_loss	0.9700
11:64231964:GG:G	donor_loss	0.9700
11:64231965:G:GA	donor_loss	0.9700

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000136739 (11:64228904 A>G,T), RS1000299009 (11:64228632 T>A,C,G), RS1000475163 (11:64233150 G>A), RS1000548533 (11:64232920 C>T), RS1000579773 (11:64232713 AC>A,ACC), RS1002009338 (11:64233237 CT>C,CTT), RS1002629045 (11:64230473 G>C), RS1002747513 (11:64234487 G>A,C), RS1002884392 (11:64228554 C>T), RS1002932120 (11:64230670 C>A,G,T), RS1003015350 (11:64234485 C>A,G), RS1003263805 (11:64228908 G>A,T), RS1003822218 (11:64230471 G>A,C), RS1004349649 (11:64228965 C>G), RS1005284811 (11:64230754 G>A)

Disease associations

OMIM: gene MIM:604189 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004132_98	Crohn’s disease	5.000000e-06
GCST004603_60	Platelet count	4.000000e-09
GCST010136_47	Fruit consumption	9.000000e-10
GCST90002400_638	Plateletcrit	3.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0008111	diet measurement
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases methylation	3
Indomethacin	increases expression, affects cotreatment	2
Okadaic Acid	decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
beta-N-methylamino-L-alanine	increases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
ochratoxin A	increases acetylation, increases expression	1
dinophysistoxin 1	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
bisphenol S	affects cotreatment, increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Hydrogen Peroxide	affects cotreatment, decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Serine	increases expression	1
Smoke	decreases expression	1
Theophylline	affects cotreatment, decreases expression	1
Thimerosal	decreases expression	1
Thiram	decreases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery