DNAJC2

Summary

DNAJC2 (DnaJ heat shock protein family (Hsp40) member C2, HGNC:13192) is a protein-coding gene on chromosome 7q22.1, encoding DnaJ homolog subfamily C member 2 (Q99543). Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus.

This gene is a member of the M-phase phosphoprotein (MPP) family. The gene encodes a phosphoprotein with a J domain and a Myb DNA-binding domain which localizes to both the nucleus and the cytosol. The protein is capable of forming a heterodimeric complex that associates with ribosomes, acting as a molecular chaperone for nascent polypeptide chains as they exit the ribosome. This protein was identified as a leukemia-associated antigen and expression of the gene is upregulated in leukemic blasts. Also, chromosomal aberrations involving this gene are associated with primary head and neck squamous cell tumors. This gene has a pseudogene on chromosome 6. Alternatively spliced variants which encode different protein isoforms have been described.

Source: NCBI Gene 27000 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 84 total
• GTEx eGene: eQTL in 11 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
• MANE Select transcript: NM_014377
• Interaction hub: 2,022 STRING partners (top 7% of genes corpus-wide)
• Notable: 84 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13192
Approved symbol	DNAJC2
Name	DnaJ heat shock protein family (Hsp40) member C2
Location	7q22.1
Locus type	gene with protein product
Status	Approved
Aliases	MPP11, MPHOSPH11, ZUO1, zuotin
Ensembl gene	ENSG00000105821
Ensembl biotype	protein_coding
OMIM	605502
Entrez	27000

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 protein_coding, 5 retained_intron, 4 nonsense_mediated_decay

MANE Select: ENST00000379263

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 6, TSL 2: 1, TSL 3: 1, TSL 5: 3

ENST00000379263, ENST00000249270, ENST00000379257, ENST00000412522, ENST00000426036, ENST00000454277, ENST00000464253, ENST00000475065, ENST00000475090, ENST00000483637, ENST00000492497, ENST00000915316, ENST00001017200, ENST00001017201, ENST00001058857, ENST00001129054, ENST00001142962

RefSeq mRNA: 4 — MANE Select: NM_014377 NM_001129887, NM_001362667, NM_001362668, NM_014377

CCDS: CCDS43628, CCDS47679

Canonical transcript exons

ENST00000379263 — 17 exons

Exon	Start	End
ENSE00000881669	103341764	103341954
ENSE00001530457	103344559	103344767
ENSE00001600304	103322511	103322632
ENSE00001628196	103322703	103322794
ENSE00003460086	103326543	103326684
ENSE00003464847	103312289	103312643
ENSE00003497042	103315988	103316088
ENSE00003500195	103316830	103317014
ENSE00003501070	103327656	103327754
ENSE00003594972	103337736	103337811
ENSE00003613992	103323598	103323663
ENSE00003625802	103312947	103313101
ENSE00003628578	103315764	103315871
ENSE00003650531	103321932	103322081
ENSE00003656999	103319609	103319678
ENSE00003671914	103319756	103319844
ENSE00003686219	103324482	103324562

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 96.10.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.4374 / max 383.0341, expressed in 1819 samples.

Highest expression (Bgee): sural nerve, tendon of biceps brachii, gluteal muscle, nasal cavity epithelium, cartilage tissue.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DNAJC2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	7.5e-24	-0.35	7:103344764:C:G
Muscle Skeletal	eqtl	1.8e-08	+0.10	7:103344764:C:G
Thyroid	eqtl	4.3e-04	+0.12	7:103307593:T:C
Cells Cultured fibroblasts	eqtl	7.5e-03	-0.10	7:103159690:T:C
Whole Blood	eqtl	8.9e-03	-0.22	7:104084676:A:G
Brain Caudate basal ganglia	eqtl	1.2e-02	+0.37	7:102633821:C:T
Brain Frontal Cortex BA9	eqtl	2.8e-02	+0.43	7:103539663:G:A
Prostate	eqtl	3.1e-02	+0.64	7:104010968:G:A
Esophagus Gastroesophageal Junction	eqtl	3.7e-02	-0.23	7:103181620:T:G
Brain Hippocampus	eqtl	3.8e-02	-1.10	7:103512901:G:A
Skin Sun Exposed Lower leg	eqtl	4.0e-02	-0.44	7:103940314:A:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
85375	27.6253	1817
85376	1.8121	944

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.10	gold quality
tendon of biceps brachii	UBERON:0008188	94.33	gold quality
gluteal muscle	UBERON:0002000	93.92	gold quality
nasal cavity epithelium	UBERON:0005384	93.77	gold quality
cartilage tissue	UBERON:0002418	93.47	gold quality
hair follicle	UBERON:0002073	93.45	gold quality
tongue squamous epithelium	UBERON:0006919	93.43	gold quality
cervix squamous epithelium	UBERON:0006922	93.38	gold quality
tendon	UBERON:0000043	93.09	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	92.90	gold quality
cervix epithelium	UBERON:0004801	92.42	gold quality
calcaneal tendon	UBERON:0003701	92.39	gold quality
sperm	CL:0000019	92.24	gold quality
monocyte	CL:0000576	92.05	gold quality
mononuclear cell	CL:0000842	92.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.02	gold quality
epithelial cell of pancreas	CL:0000083	92.00	gold quality
superficial temporal artery	UBERON:0001614	92.00	gold quality
male germ cell	CL:0000015	91.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.96	gold quality
left testis	UBERON:0004533	91.89	gold quality
testis	UBERON:0000473	91.84	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.79	gold quality
mucosa of urinary bladder	UBERON:0001259	91.78	gold quality
gastrocnemius	UBERON:0001388	91.55	gold quality
nasal cavity mucosa	UBERON:0001826	91.45	gold quality
leukocyte	CL:0000738	91.44	gold quality
oviduct epithelium	UBERON:0004804	91.36	gold quality
colonic epithelium	UBERON:0000397	91.29	gold quality
epithelium of nasopharynx	UBERON:0001951	91.28	gold quality
right testis	UBERON:0004534	91.17	gold quality
colonic mucosa	UBERON:0000317	91.02	gold quality
deltoid	UBERON:0001476	91.02	gold quality
bone marrow	UBERON:0002371	90.72	gold quality
muscle of leg	UBERON:0001383	90.52	gold quality
parotid gland	UBERON:0001831	90.48	gold quality
myocardium	UBERON:0002349	90.47	gold quality
pericardium	UBERON:0002407	90.47	gold quality
biceps brachii	UBERON:0001507	90.38	gold quality
body of pancreas	UBERON:0001150	90.34	gold quality
cortical plate	UBERON:0005343	90.31	gold quality
adrenal tissue	UBERON:0018303	90.27	gold quality
left ventricle myocardium	UBERON:0006566	90.23	gold quality
muscle organ	UBERON:0001630	90.20	gold quality
triceps brachii	UBERON:0001509	90.07	gold quality
endometrium	UBERON:0001295	90.06	gold quality
ventricular zone	UBERON:0003053	89.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.96	gold quality
embryo	UBERON:0000922	89.89	gold quality
heart right ventricle	UBERON:0002080	89.70	gold quality
jejunum	UBERON:0002115	89.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.46	gold quality
left ovary	UBERON:0002119	89.45	gold quality
trabecular bone tissue	UBERON:0002483	89.45	gold quality
ovary	UBERON:0000992	89.41	gold quality
fallopian tube	UBERON:0003889	89.37	gold quality
tonsil	UBERON:0002372	89.34	gold quality
uterine cervix	UBERON:0000002	89.33	gold quality
skeletal muscle tissue	UBERON:0001134	89.33	gold quality
rectum	UBERON:0001052	89.30	gold quality
tibia	UBERON:0000979	89.29	gold quality
skin of abdomen	UBERON:0001416	89.29	gold quality
right ovary	UBERON:0002118	89.22	gold quality
jejunal mucosa	UBERON:0000399	89.20	gold quality
lymph node	UBERON:0000029	89.17	gold quality
vastus lateralis	UBERON:0001379	89.12	gold quality
quadriceps femoris	UBERON:0001377	89.08	gold quality
ganglionic eminence	UBERON:0004023	89.05	gold quality
uterus	UBERON:0000995	88.96	gold quality
placenta	UBERON:0001987	88.95	gold quality
adenohypophysis	UBERON:0002196	88.91	gold quality
zone of skin	UBERON:0000014	88.87	gold quality
middle temporal gyrus	UBERON:0002771	88.87	gold quality
skin of leg	UBERON:0001511	88.85	gold quality
epithelium of bronchus	UBERON:0002031	88.85	gold quality
muscle tissue	UBERON:0002385	88.85	gold quality
bronchus	UBERON:0002185	88.80	gold quality
superior surface of tongue	UBERON:0007371	88.75	gold quality
peritoneum	UBERON:0002358	88.70	gold quality
female reproductive system	UBERON:0000474	88.69	gold quality
omental fat pad	UBERON:0010414	88.69	gold quality
pancreas	UBERON:0001264	88.64	gold quality
parietal pleura	UBERON:0002400	88.61	gold quality
tibialis anterior	UBERON:0001385	88.59	gold quality
gingival epithelium	UBERON:0001949	88.59	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.59	gold quality
duodenum	UBERON:0002114	88.58	gold quality
minor salivary gland	UBERON:0001830	88.57	gold quality
bone marrow cell	CL:0002092	88.55	gold quality
visceral pleura	UBERON:0002401	88.55	gold quality
pylorus	UBERON:0001166	88.51	gold quality
bronchial epithelial cell	CL:0002328	88.47	gold quality
pleura	UBERON:0000977	88.47	gold quality
mouth mucosa	UBERON:0003729	88.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.42	gold quality
vermiform appendix	UBERON:0001154	88.31	gold quality
sigmoid colon	UBERON:0001159	88.30	gold quality
granulocyte	CL:0000094	88.28	gold quality
saliva-secreting gland	UBERON:0001044	88.28	gold quality
urinary bladder	UBERON:0001255	88.27	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7606	no	1175.72
E-MTAB-11011	no	229.98
E-MTAB-6386	no	142.11
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)
Bone marrow	tissue	39.6	medium
Caudate putamen	tissue	38.1
Testis	tissue	29.3	high
Frontal cortex	tissue	23.5
Putamen	tissue	23.4
Basal ganglia	tissue	18.6	medium
Urinary bladder	tissue	17.5	high
Postcentral gyrus	tissue	15.8
Lymph node	tissue	15.7	high
Nucleus accumbens	tissue	15.0
Choroid plexus	tissue	15.0
Septum	tissue	15.0
Ventral forebrain	tissue	14.7
Liver	tissue	14.6	medium
Cerebral cortex	tissue	14.5	high
Occipital cortex	tissue	14.5
Skeletal muscle	tissue	14.2	low
Locus coeruleus	tissue	14.1
Prefrontal cortex	tissue	13.9
Duodenum	tissue	13.8	high
Hippocampal formation	tissue	13.7
Motor cortex	tissue	13.5
Retrosplenial and cingulate cortex	tissue	13.2
Somatosensory cortex	tissue	13.2
Cerebellum	tissue	13.1	high
Olfactory bulb	tissue	12.8
Retrosplenial cortex	tissue	12.7
Pancreas	tissue	12.5	high
Temporal cortex	tissue	12.5
Hippocampus	tissue	12.4	high
Tonsil	tissue	12.4	high
Entorhinal cortex	tissue	12.4
Stomach 1	tissue	12.1
Breast	tissue	11.9	medium
Hypothalamus	tissue	11.9
Tongue	tissue	11.8
Pons	tissue	11.6
Skin 1	tissue	11.5	high
Vagina	tissue	11.5	medium
Substantia nigra	tissue	11.5
Thyroid gland	tissue	11.5	high
Thymus	tissue	11.5
Appendix	tissue	11.5	high
Pituitary gland	tissue	11.4
Amygdala	tissue	11.4
Midbrain	tissue	11.4
Spinal cord	tissue	11.4
Placenta	tissue	11.2	high
Rectum	tissue	11.1	high
Small intestine	tissue	11.1	high
Spleen	tissue	11.0	high
Endometrium 1	tissue	10.8	high
Medulla oblongata	tissue	10.8
Periaqueductal gray	tissue	10.7
Colon	tissue	10.4	high
Thalamus	tissue	10.4
Superior colliculi	tissue	10.4
Insular cortex	tissue	10.4
Adrenal gland	tissue	10.2	high
Ovary	tissue	10.1	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Vermis (19.1), Flocculonodular lobe (18.9), Cerebellar cortex (17.7), Temporal white matter (17.4), Parieto-temporal junction (white matter) (17.1).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets:

Target	Regulation
PRC1

Functional genomics

gnomAD constraint: pLI 0.997, LOEUF 0.466, missense Z 2.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000379263 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
7:103,312,572–103,319,843	271 / 302.6	0.90	no
7:103,319,844–103,344,622	279 / 416.9	0.67	no

Literature-anchored findings (GeneRIF, showing 16)

• concluded that Mpp11, an ortholog of yeast Zuo, is a ribosome-associated J protein; proposed that in metazoans, ribosome-associated Zuo and Mpp11 orthologs recruit cytosolic Hsc70 to short ribosome-bound nascent chains as they exit the ribosome (PMID:15802566)
• MPP11 is localized to the cytosol and with Hsp70L1, forms the mammalian ribosome-associated complex. (PMID:16002468)
• describe a novel epitope derived from the MPP11 antigen that has been recognized by human CD8+ CTL (PMID:20231810)
• At the onset of differentiation, ZRF1 specifically displaces polycomb-repressive complex 1 (PRC1) from chromatin and facilitates transcriptional activation (PMID:21179169)
• the majority of AML patients elicited a humoral immune response against the tumor antigen MPP11 (PMID:22433847)
• ZRF1 regulates the INK4-ARF locus during cellular proliferation and senescence, and alterations in ZRF1 may contribute to tumorigenesis. (PMID:22733129)
• our data reveal that ZRF1 is a key transcriptional regulator in leukemia progression (PMID:24292673)
• Zrf1 plays an essential role in neural progenitor cell generation and maintenance (PMID:24449271)
• Zrf1 is transcriptional regulator of neural fate downstream of Id1 in embryonic stem cells.During embryonic stem cell differentiation, Id1 levels decrease allowing Zrf1 to activate neural genes. (PMID:25361733)
• ZRF1 mediates remodeling of this E3 ligase complex directly at the DNA lesion site. (PMID:27091446)
• Unexplored functions of ZRF1-mediated remodeling in replication and double strand break repair are discussed. (PMID:27599465)
• The antibody response to ZRF1 was higher in sera of patients with invasive ductal carcinoma than in sera of patients with other histological types of breast tumors. (PMID:27847402)
• In response to UV irradiation, DICER is recruited to chromatin in a ZRF1-mediated manner. The H2A-ubiquitin binding protein ZRF1 and DICER together impact on the chromatin conformation via PARP1. (PMID:28402505)
• These findings suggest that ZRF1 plays a crucial role in tumor malignant potential through its overexpression and highlight its usefulness as a prognostic factor and potential therapeutic target in gastric cancer (PMID:29228320)
• DNAJC2 is reversely regulated by miR6273p, promoting the proliferation of colorectal cancer. (PMID:34165158)
• p113 isoform encoded by CUX1 circular RNA drives tumor progression via facilitating ZRF1/BRD4 transactivation. (PMID:34579723)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc2	ENSDARG00000070477
mus_musculus	Dnajc2	ENSMUSG00000029014
rattus_norvegicus	Dnajc2	ENSRNOG00000012392
drosophila_melanogaster	CG10565	FBGN0037051
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), DNAJC12 (ENSG00000108176), DNAJC4 (ENSG00000110011), DNAJC16 (ENSG00000116138), DNAJC14 (ENSG00000135392), DNAJC1 (ENSG00000136770), DNAJC13 (ENSG00000138246), DNAJC5B (ENSG00000147570), DNAJC5G (ENSG00000163793), DNAJC7 (ENSG00000168259), DNAJC21 (ENSG00000168724), DNAJC18 (ENSG00000170464), DNAJC24 (ENSG00000170946), DNAJC30 (ENSG00000176410), DNAJC9 (ENSG00000213551)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:99470) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased circulating calcium level	1
increased leukocyte cell number	1
increased circulating triglyceride level	1
embryonic lethality at implantation, complete penetrance	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	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
Macaca fascicularis	Q4R8H2	98.7%	Diamond
Bos taurus	Q1RMH9	97.7%	Diamond
Xenopus tropicalis	Q6P2Y3	84.4%	Diamond
Arabidopsis thaliana	Q1G3C4	74.7%	Diamond
Antirrhinum majus	Q8S9H7	71.8%	Diamond
Schizosaccharomyces pombe 972h-	Q9Y7I8	50.3%	Diamond
Saccharomyces cerevisiae S288C	P32527	50.2%	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
SLC26A5-AS1	ncRNA	101927870
SLC26A5	protein-coding	375611
RELN	protein-coding	5649
PSMC2	protein-coding	5701
PMPCB	protein-coding	9512
ORC5	protein-coding	5001
FBXL13	protein-coding	222235
NAPEPLD	protein-coding	222236
NFE4	ncRNA	58160
ARMC10	protein-coding	83787

Protein

Protein identifiers

DnaJ homolog subfamily C member 2 — Q99543 (reviewed: Q99543)

Alternative names: M-phase phosphoprotein 11, Zuotin-related factor 1

All UniProt accessions (5): C9IZ83, Q99543, F2Z3H0, F2Z3N9, H7C3L7

UniProt curated annotations — full annotation on UniProt →

Function. Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at ‘Lys-119’ (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation.

Subunit / interactions. Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2. Interacts (via ZRF1-UBD region) with ID1.

Subcellular location. Nucleus. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated in M (mitotic) phase.

Domain organisation. The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub.

Induction. Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells.

Miscellaneous. Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99543-1	1	yes
Q99543-2	2

RefSeq proteins (4): NP_001123359, NP_001349596, NP_001349597, NP_055192* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR001623	DnaJ_domain	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR017930	Myb_dom	Domain
IPR018253	DnaJ_domain_CS	Conserved_site
IPR032003	RAC_head	Domain
IPR036869	J_dom_sf	Homologous_superfamily
IPR042569	RAC_head_sf	Homologous_superfamily
IPR044634	Zuotin/DnaJC2	Family
IPR054076	ZUO1-like_ZHD	Domain

Pfam: PF00226, PF16717, PF21884, PF23082

UniProt features (28 total): helix 7, modified residue 5, region of interest 4, sequence conflict 3, domain 3, chain 2, initiator methionine 1, splice variant 1, mutagenesis site 1, turn 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
2M2E	Solution NMR structure of the SANT domain of human DNAJC2, Northeast structural genomics …	SOLUTION NMR
6CGH	Solution structure of the four-helix bundle region of human J-protein Zuotin, a component …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99543-F1	85.51	0.56

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Transcription factors, Helix-turn-helix domains, Cancer-related genes, Candidate cancer biomarkers

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · 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 (5)

Type	Positions
N-acetylmethionine	1
Phosphoserine	47, 49, 60, 63

Mutagenesis-validated functional residues (1)

Position	Phenotype
512–513	loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

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

4 pathways:

ID	Pathway	Evidence
R-HSA-3371556	Cellular response to heat stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-3371453	Regulation of HSF1-mediated heat shock response	—

MSigDB gene sets: 173 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_HEAT, PUJANA_CHEK2_PCC_NETWORK, GOBP_PROTEIN_MATURATION, ONKEN_UVEAL_MELANOMA_UP, GOBP_NEGATIVE_REGULATION_OF_DNA_BIOSYNTHETIC_PROCESS, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, DER_IFN_BETA_RESPONSE_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN, GOBP_PROTEIN_FOLDING, GOBP_DNA_BIOSYNTHETIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_HEAT, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, GOBP_RESPONSE_TO_ABIOTIC_STIMULUS

GO Biological Process (7): DNA-templated transcription (GO:0006351), regulation of translational fidelity (GO:0006450), protein folding (GO:0006457), positive regulation of DNA-templated transcription (GO:0045893), ‘de novo’ cotranslational protein folding (GO:0051083), regulation of cellular response to heat (GO:1900034), chromatin organization (GO:0006325)

GO Molecular Function (8): ATPase activator activity (GO:0001671), chromatin binding (GO:0003682), RNA binding (GO:0003723), Hsp70 protein binding (GO:0030544), histone binding (GO:0042393), ribosome binding (GO:0043022), ubiquitin-modified histone reader activity (GO:0061649), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Cellular response to heat stress	1
Cellular responses to stimuli	1
Cellular responses to stress	1

GO top-level categories

28 GO namespaces:

Category	Terms
cellular anatomical structure	3
binding	2
nuclear lumen	2
gene expression	1
RNA biosynthetic process	1
regulation of biological quality	1
cellular process	1
protein maturation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
‘de novo’ protein folding	1
cellular response to heat	1
regulation of cellular response to stress	1
cellular component organization	1
ATP-dependent activity	1
molecular function activator activity	1
nucleic acid binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
protein binding	1
ribonucleoprotein complex binding	1
ubiquitin-modified protein reader activity	1
histone reader activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 20 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of DNA-templated transcription	BP	direct assay
cytoplasm	CC	direct assay
cytosol	CC	direct assay
nucleolus	CC	direct assay
nucleus	CC	direct assay
Hsp70 protein binding	MF	physical interaction
RNA binding	MF	high-throughput assay
chromatin binding	MF	direct assay
histone binding	MF	direct assay
ubiquitin-modified histone reader activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,022 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC2	DNAJB4	Q9UDY4	952
DNAJC2	HSPA4	P34932	919
DNAJC2	DNAJB1	P25685	891
DNAJC2	HSPA14	Q0VDF9	891
DNAJC2	DNAJC24	Q6P3W2	871
DNAJC2	SEC63	Q9UGP8	852
DNAJC2	DNAJC19	Q96DA6	833
DNAJC2	HSCB	Q8IWL3	821
DNAJC2	BLZF1	Q9H2G9	775
DNAJC2	HSPA8	P11142	650
DNAJC2	ZPR1	O75312	619
DNAJC2	MYB	P10242	583
DNAJC2	CCNB1	P14635	551
DNAJC2	DNAJC9	Q8WXX5	538
DNAJC2	DNAJA1	P31689	519

IntAct

Human interaction partners of DNAJC2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

5 partners by confidence:

Partner	Interaction type	MIscore	Records
HSPA14	physical association	0.670	3
H2AC11	physical association	0.500	1
H2BC10	physical association	0.400	1
ID1	physical association	0.400	1
RPS3A	association	0.350	1

BioGRID (288 interactions; top human partners by supporting records): HSPA14 (Co-fractionation; 12 records), DRG1 (Affinity Capture-Western; 6 records), DRG2 (Affinity Capture-Western; 5 records), DICER1 (Proximity Label-MS; 3 records), RPL30 (Affinity Capture-MS; 3 records), RWDD1 (Affinity Capture-MS; 3 records), ZC3H15 (Affinity Capture-MS; 3 records), GNL3 (Affinity Capture-MS; 2 records), GTF2E2 (Affinity Capture-MS; 2 records), H1FX (Affinity Capture-MS; 2 records), HIST2H2AA3 (Affinity Capture-Western; 2 records), HSPA8 (Co-fractionation; 2 records), LTV1 (Proximity Label-MS; 2 records), MTDH (Affinity Capture-MS; 2 records), PPP6R1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
DNAJC2	“form complex”	“Ribosome-associated complex”	binding

Disease & clinical

Genetic variants

Variant evidence for DNAJC2: 84 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	62
Likely benign	0
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 1,128):

Position(s)	Effect	Δscore	Sites
7:103312937	donor_gain	1.0000
7:103315762–103315763	donor_loss	1.0000	5
7:103315873	acceptor_loss	1.0000
7:103315879	acceptor_gain	1.0000
7:103316046	acceptor_gain	1.0000
7:103319607–103319608	donor_loss	1.0000	5
7:103321930–103321931	donor_loss	1.0000	4
7:103321955	donor_gain	1.0000
7:103321960	donor_gain	1.0000
7:103322082–103322083	acceptor_loss	1.0000	5

AlphaMissense

1,684 missense substitutions predicted likely pathogenic (of 4,130 scored), across 395 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
D121	8	0.998	0.999
H119	8	0.997	1.000
D277	8	0.996	0.998
N251	8	0.995	0.999
D231	8	0.990	0.998
D271	8	0.990	0.999
H487	8	0.982	1.000
F138	8	0.981	0.999
D161	8	0.981	0.994
D88	8	0.976	0.997
D136	8	0.974	0.993
F469	8	0.970	0.999
F214	8	0.933	0.992
S159	8	0.931	0.999
H118	8	0.925	0.999
H89	8	0.896	0.991
N189	8	0.892	0.996
F186	8	0.888	0.993
F164	8	0.837	0.989
W477	7	1.000	1.000

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
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	4.66e-05
Liver Hepatocellular Carcinoma (validation)	unfavorable	0.00049

Disease associations

OMIM: gene MIM:605502 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST009391_869	Metabolite levels	9e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0010402	triacylglycerol 46:2 measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
sodium arsenite	increases activity, affects cotreatment, increases abundance, increases expression, decreases expression	2
Estradiol	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
methylmercuric chloride	increases expression	1
trichostatin A	affects expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	decreases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	increases phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Mustard Gas	increases phosphorylation	1
Phenobarbital	affects expression	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2W0	Abcam HEK293T DNAJC2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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