DNAJC10

Summary

DNAJC10 (DnaJ heat shock protein family (Hsp40) member C10, HGNC:24637) is a protein-coding gene on chromosome 2q32.1, encoding Endoplasmic reticulum disulfide reductase DNAJC10 (Q8IXB1). Endoplasmic reticulum disulfide reductase that collaborates directly with the chaperone BIP/HSPA5 (GRP78) to maintain protein quality control by facilitating either the correct folding or the targeted degradation of misfolded proteins.

This gene encodes an endoplasmic reticulum co-chaperone which is part of the endoplasmic reticulum-associated degradation complex involved in recognizing and degrading misfolded proteins. The encoded protein reduces incorrect disulfide bonds in misfolded glycoproteins. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

Source: NCBI Gene 54431 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 152 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018981

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24637
Approved symbol	DNAJC10
Name	DnaJ heat shock protein family (Hsp40) member C10
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	ERdj5, PDIA19
Ensembl gene	ENSG00000077232
Ensembl biotype	protein_coding
OMIM	607987
Entrez	54431

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 18 protein_coding, 10 nonsense_mediated_decay, 7 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264065, ENST00000418559, ENST00000444005, ENST00000459930, ENST00000469118, ENST00000491074, ENST00000494462, ENST00000537515, ENST00000616986, ENST00000640034, ENST00000650903, ENST00000679491, ENST00000679526, ENST00000679884, ENST00000680060, ENST00000680258, ENST00000680480, ENST00000680484, ENST00000680648, ENST00000680667, ENST00000681122, ENST00000681139, ENST00000681146, ENST00000681873, ENST00000874155, ENST00000874156, ENST00000874157, ENST00000874158, ENST00000874159, ENST00000874160, ENST00000874161, ENST00000929252, ENST00000960778, ENST00000960779, ENST00000960780, ENST00000960781

RefSeq mRNA: 2 — MANE Select: NM_018981 NM_001271581, NM_018981

CCDS: CCDS33345, CCDS74613

Canonical transcript exons

ENST00000264065 — 24 exons

Exon	Start	End
ENSE00000996054	182716257	182716483
ENSE00000996059	182717016	182717072
ENSE00001881622	182777121	182794464
ENSE00003460566	182756314	182756469
ENSE00003469668	182751658	182751785
ENSE00003482597	182736249	182736386
ENSE00003483062	182728863	182728994
ENSE00003488174	182722025	182722075
ENSE00003510897	182740299	182740388
ENSE00003513456	182728576	182728658
ENSE00003517059	182755003	182755104
ENSE00003519740	182758837	182758890
ENSE00003572568	182720007	182720169
ENSE00003573280	182741243	182741356
ENSE00003596994	182729848	182729941
ENSE00003604750	182752072	182752188
ENSE00003615337	182762682	182762801
ENSE00003637716	182759160	182759307
ENSE00003651176	182731030	182731107
ENSE00003667848	182775316	182775420
ENSE00003670669	182757692	182757825
ENSE00003672044	182743598	182743712
ENSE00003673068	182732499	182732542
ENSE00003673544	182717941	182718290

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 81.2945 / max 1179.9671, expressed in 1825 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24056	79.5336	1825
24055	1.1987	746
24057	0.3486	140
24058	0.2137	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.23	gold quality
right uterine tube	UBERON:0001302	97.70	gold quality
bronchial epithelial cell	CL:0002328	97.39	gold quality
stromal cell of endometrium	CL:0002255	97.21	gold quality
cauda epididymis	UBERON:0004360	97.02	gold quality
calcaneal tendon	UBERON:0003701	97.01	gold quality
endometrium	UBERON:0001295	96.91	gold quality
caput epididymis	UBERON:0004358	96.58	gold quality
seminal vesicle	UBERON:0000998	96.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.33	gold quality
islet of Langerhans	UBERON:0000006	96.02	gold quality
gall bladder	UBERON:0002110	95.72	gold quality
body of pancreas	UBERON:0001150	95.56	gold quality
smooth muscle tissue	UBERON:0001135	95.54	gold quality
right coronary artery	UBERON:0001625	95.40	gold quality
pancreas	UBERON:0001264	95.26	gold quality
colonic epithelium	UBERON:0000397	95.09	gold quality
descending thoracic aorta	UBERON:0002345	95.05	gold quality
germinal epithelium of ovary	UBERON:0001304	95.04	gold quality
left testis	UBERON:0004533	95.00	gold quality
epithelium of nasopharynx	UBERON:0001951	94.92	gold quality
thoracic aorta	UBERON:0001515	94.91	gold quality
nasopharynx	UBERON:0001728	94.90	gold quality
ascending aorta	UBERON:0001496	94.88	gold quality
ventricular zone	UBERON:0003053	94.79	gold quality
right testis	UBERON:0004534	94.79	gold quality
rectum	UBERON:0001052	94.77	gold quality
mucosa of stomach	UBERON:0001199	94.54	gold quality
left coronary artery	UBERON:0001626	94.49	gold quality
aorta	UBERON:0000947	94.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-10287	yes	49.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

128 targeting DNAJC10, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-570-3P	99.96	72.41	4910
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-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488

Literature-anchored findings (GeneRIF, showing 17)

• ERdj5 is a ubiquitous protein localized in the ER and is particularly abundant in secretory cells. Its transcription is induced during ER stress, suggesting potential roles for ERdj5 in protein folding and translocation across the ER membrane. (PMID:12411443)
• JPDI may have roles in folding of some proteins in the ER, chaperoning by BiP and formation of proper disulfide bonds (PMID:12446677)
• The organization of the functional motifs of hMTHr suggests that the protein might be a member of a molecular chaperone family. (PMID:14587667)
• ERdj4 and ERdj5 promote turnover of misfolded SP-C and this activity is dependent on their ability to stimulate BiP ATPase activity. (PMID:18400946)
• study found that an endoplasmic reticulum (ER) protein ERdj5 had a reductase activity, cleaved the disulfide bonds of misfolded proteins & accelerated ER-associated degradation through its physical and functional associations with EDEM & BiP (PMID:18653895)
• ERdj5 decreases neuroblastoma cell survival by down-regulating the UPR, raising the possibility that this protein could be a target for anti-tumor approaches. (PMID:19122239)
• ERdj5, by binding to Sel1L, triggers BiP-Cholera toxin interaction proximal to the Hrd1 complex; postulate this scenario enables the Hrd1-associated retrotranslocation machinery to capture the toxin efficiently once the toxin is released from BiP (PMID:23363602)
• ERdj5 acts as the endoplasmic reticulum reductase, both preparing misfolded proteins for degradation and catalyzing the folding of proteins that form obligatory non-native disulfides. (PMID:23769672)
• ERdj5 is a member of the proteostasis network that regulates rod opsin biogenesis and supports a role for disulfide bond formation/reduction in rod opsin biogenesis and disease. (PMID:25055872)
• Role of ERdj5 conformational dynamics in endoplasmic reticulum associated degradation (PMID:28479060)
• Ablation of the Chaperone Protein ERdj5 Results in a Sjogren’s Syndrome-Like Phenotype in Mice, Consistent With an Upregulated Unfolded Protein Response in Human Patients. (PMID:30967862)
• Downregulation of DNAJC10 (ERDJ5) is associated with poor survival in breast cancer. (PMID:31902119)
• AAV-mediated ERdj5 overexpression protects against P23H rhodopsin toxicity. (PMID:32196553)
• DNAJC10 correlates with tumor immune characteristics and predicts the prognosis of glioma patients. (PMID:34988580)
• DNAJC10 maintains survival and self-renewal of leukemia stem cells through PERK branch of the unfolded protein response. (PMID:37496439)
• Mechanistic characterization of disulfide bond reduction of an ERAD substrate mediated by cooperation between ERdj5 and BiP. (PMID:37739037)
• MCM8 promotes lung cancer progression through upregulating DNAJC10. (PMID:39031896)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc10	ENSDARG00000074727
mus_musculus	Dnajc10	ENSMUSG00000027006
rattus_norvegicus	Dnajc10	ENSRNOG00000006803
caenorhabditis_elegans	dnj-27	WBGENE00001045
caenorhabditis_elegans		WBGENE00022236

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), 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)

Protein

Protein identifiers

Endoplasmic reticulum disulfide reductase DNAJC10 — Q8IXB1 (reviewed: Q8IXB1)

Alternative names: DnaJ homolog subfamily C member 10, Endoplasmic reticulum DNA J domain-containing protein 5, Macrothioredoxin

All UniProt accessions (12): Q8IXB1, A0A494C1G5, A0A7P0T8Y3, A0A7P0T9B7, A0A7P0TAQ9, A0A7P0TB22, A0A7P0TB83, A0A7P0TB97, A0A7P0Z431, A0A7P0Z4F2, E7EP04, H7C1G0

UniProt curated annotations — full annotation on UniProt →

Function. Endoplasmic reticulum disulfide reductase that collaborates directly with the chaperone BIP/HSPA5 (GRP78) to maintain protein quality control by facilitating either the correct folding or the targeted degradation of misfolded proteins. Essential for efficient maturation of newly synthesized polypeptides in the endoplasmic reticulum, binds to substrate proteins and specifically catalyzes the reduction and removal of improper (non-native) disulfide bonds during the folding process. In endoplasmic reticulum-associated degradation (ERAD), DNAJC10 reduces incorrect disulfide bonds specifically in misfolded glycoproteins that have been recognized by EDEM1, a key component of the ERAD pathway, thereby enabling their retrotranslocation and degradation. Promotes apoptotic signaling pathway in response to endoplasmic reticulum stress.

Subunit / interactions. Interacts with EDEM1. Interacts (via its J domain) with HSPA5; this interaction is required for DNAJC10 activity in both protein folding and degradation. While not essential for its intrinsic disulfide reductase activity, HSPA5 binding may facilitate substrate release.

Subcellular location. Endoplasmic reticulum lumen.

Domain organisation. The J domain and more specifically the HPD motif mediates interaction with HSPA5. The thioredoxin-like regions Trxb 1 and 2 lack a redox-active CXXC motif. Thioredoxin domains 3 and 4 are the primary reductase domains. The thioredoxin domain 4 is the most efficient at reducing disulfide bonds.

Induction. By endoplasmic reticulum stress.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IXB1-1	1	yes
Q8IXB1-2	2
Q8IXB1-3	3

RefSeq proteins (2): NP_001258510, NP_061854* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR013766	Thioredoxin_domain	Domain
IPR017937	Thioredoxin_CS	Conserved_site
IPR021170	ERdj5	Family
IPR035673	ERdj5_TRX_N	Domain
IPR035674	ERdj5_TRX_C	Domain
IPR036249	Thioredoxin-like_sf	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily
IPR052460	ER_disulfide_reductase	Family

Pfam: PF00085, PF00226

Catalyzed reactions (Rhea), 1 shown:

• [protein]-disulfide + 2 glutathione = [protein]-dithiol + glutathione disulfide (RHEA:21064)

UniProt features (36 total): sequence conflict 8, domain 5, mutagenesis site 5, disulfide bond 4, sequence variant 4, splice variant 3, short sequence motif 2, region of interest 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IXB1-F1	89.42	0.65

Functional residue map

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

Disulfide bonds (4): 158–161, 480–483, 588–591, 700–703

Glycosylation sites (1): 530

Mutagenesis-validated functional residues (5):

Position	Phenotype
63	prevents interaction with hspa5, leading to prolonged interaction with substrate proteins.
161	abolishes disulfide reductase activity; when associated with a-483; a-591 and a-703.
483	abolishes disulfide reductase activity; when associated with a-161; a-591 and a-703.
591	abolishes disulfide reductase activity; when associated with a-161; a-483 and a-703.
703	abolishes disulfide reductase activity; when associated with a-161; a-483 and a-591.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9918432	Maturation of DENV proteins

MSigDB gene sets: 180 (showing top): SHEPARD_BMYB_MORPHOLINO_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, HORIUCHI_WTAP_TARGETS_DN, WANG_CLIM2_TARGETS_UP, GOBP_IRE1_MEDIATED_UNFOLDED_PROTEIN_RESPONSE, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, WANG_RECURRENT_LIVER_CANCER_UP, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, CHANDRAN_METASTASIS_DN, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, GOBP_PROTEIN_MATURATION, ONKEN_UVEAL_MELANOMA_UP

GO Biological Process (5): protein folding in endoplasmic reticulum (GO:0034975), response to endoplasmic reticulum stress (GO:0034976), IRE1-mediated unfolded protein response (GO:0036498), ERAD pathway (GO:0036503), intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress (GO:0070059)

GO Molecular Function (10): ATPase activator activity (GO:0001671), protein-disulfide reductase activity (GO:0015035), disulfide oxidoreductase activity (GO:0015036), oxidoreductase activity, acting on a sulfur group of donors, disulfide as acceptor (GO:0016671), Hsp70 protein binding (GO:0030544), protein-folding chaperone binding (GO:0051087), ATPase binding (GO:0051117), misfolded protein binding (GO:0051787), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum lumen (GO:0005788), membrane (GO:0016020), endoplasmic reticulum chaperone complex (GO:0034663)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Dengue Virus Genome Translation and Replication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
response to endoplasmic reticulum stress	2
oxidoreductase activity, acting on a sulfur group of donors	2
protein binding	2
protein folding	1
cellular response to stress	1
endoplasmic reticulum unfolded protein response	1
proteasomal protein catabolic process	1
response to chemical	1
intrinsic apoptotic signaling pathway	1
ATP-dependent activity	1
molecular function activator activity	1
disulfide oxidoreductase activity	1
catalytic activity, acting on a protein	1
heat shock protein binding	1
protein-folding chaperone binding	1
enzyme binding	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum	1
intracellular organelle lumen	1
cellular anatomical structure	1
endoplasmic reticulum protein-containing complex	1

Protein interactions and networks

STRING

6387 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC10	EDEM1	Q92611	997
DNAJC10	SEL1L	Q9UBV2	924
DNAJC10	HSPA5	P11021	891
DNAJC10	OS9	Q13438	883
DNAJC10	CANX	P27824	816
DNAJC10	CALR	P27797	803
DNAJC10	MTHFR	P42898	801
DNAJC10	HYOU1	Q9Y4L1	786
DNAJC10	FOXRED2	Q8IWF2	760
DNAJC10	TXN	P10599	743
DNAJC10	MAN1B1	Q9UKM7	716
DNAJC10	DERL2	Q9GZP9	703
DNAJC10	ERLEC1	Q96DZ1	693
DNAJC10	HSPA4	P34932	657
DNAJC10	HSP90B1	P14625	642
DNAJC10	ATF6	P18850	642

IntAct

114 interactions, top by confidence:

A	B	Type	Score
EGFR	HSP90AA1	psi-mi:“MI:0914”(association)	0.820
PRKCG	PRKCA	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
USE1	NBAS	psi-mi:“MI:0914”(association)	0.640
IGF1R	PIK3R2	psi-mi:“MI:2364”(proximity)	0.590
INSR	PIK3R2	psi-mi:“MI:2364”(proximity)	0.570
CSNK1E	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
HSPB8	VWA8	psi-mi:“MI:0914”(association)	0.530
ERBB2	NDUFA4	psi-mi:“MI:0914”(association)	0.530
FOXRED2	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
PRCC	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
DNAJC10	Edem1	psi-mi:“MI:0915”(physical association)	0.400
Edem2	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
Edem3	DNAJC10	psi-mi:“MI:0915”(physical association)	0.400
Cenpe	BBX	psi-mi:“MI:0914”(association)	0.350
Mis12		psi-mi:“MI:0914”(association)	0.350
CDC42	BBX	psi-mi:“MI:0914”(association)	0.350
OASL	LARP1	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC15A3		psi-mi:“MI:0914”(association)	0.350
UNC93B1		psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
CAND1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
CUL1	LGALS8	psi-mi:“MI:0914”(association)	0.350
CUL4A	HAX1	psi-mi:“MI:0914”(association)	0.350
DCUN1D1	RGSL1	psi-mi:“MI:0914”(association)	0.350
COPS5	FBLL1	psi-mi:“MI:0914”(association)	0.350
CUL2	ANXA2P2	psi-mi:“MI:0914”(association)	0.350

BioGRID (324): DNAJC10 (Affinity Capture-MS), DNAJC10 (Affinity Capture-MS), DNAJC10 (Two-hybrid), DNAJC10 (Two-hybrid), DNAJC10 (Affinity Capture-MS), DNAJC10 (Co-fractionation), DNAJC10 (Co-fractionation), TXNL1 (Co-fractionation), DNAJC10 (Affinity Capture-MS), DNAJC10 (Affinity Capture-MS), DNAJC10 (Proximity Label-MS), DNAJC10 (Proximity Label-MS), DNAJC10 (Affinity Capture-MS), DNAJC10 (Affinity Capture-MS), DNAJC10 (Affinity Capture-MS)

ESM2 similar proteins: A0A8M1N5Y4, A3KPF5, A8WG88, O22925, O80977, P08003, P11598, P13667, P30040, P30101, P32474, P38659, P52555, P52588, P57759, P81623, P81628, P93026, P93484, Q0E0I1, Q0JD42, Q0WL80, Q17688, Q2KIL5, Q43116, Q498R3, Q56ZQ3, Q5FVM7, Q5I0H9, Q5R5L3, Q5RDG4, Q5WA72, Q66GQ3, Q67IX6, Q6GNG3, Q6NRT6, Q6P5E4, Q7JW12, Q7XRB5, Q8IXB1

Diamond homologs: D3Z6P0, D4B2L8, O13704, O13811, O22263, O48773, O51890, P00275, P04785, P05307, P07237, P08003, P09102, P09103, P0A617, P0AGG4, P0AGG5, P0AGG6, P0AGG7, P10473, P11598, P13667, P21195, P23400, P27773, P29828, P30101, P34329, P38657, P38659, P38660, P38661, P46843, P52230, P52233, P52588, P52589, P54399, P55059, P73263

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 149 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
Neddylation	11	5.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	16.7×	4e-04
autophagosome maturation	6	16.3×	4e-04
mitophagy	5	12.3×	5e-03
G1/S transition of mitotic cell cycle	7	10.9×	7e-04
cell surface receptor protein tyrosine kinase signaling pathway	8	10.8×	4e-04
autophagosome assembly	6	10.4×	3e-03
insulin receptor signaling pathway	6	10.3×	3e-03
positive regulation of MAPK cascade	9	5.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	103
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4055 predictions. Top by Δscore:

Variant	Effect	Δscore
2:182720002:A:AG	acceptor_gain	1.0000
2:182720003:A:G	acceptor_gain	1.0000
2:182720003:ACAGA:A	acceptor_loss	1.0000
2:182720004:CAGA:C	acceptor_loss	1.0000
2:182720005:A:AG	acceptor_gain	1.0000
2:182720005:A:C	acceptor_loss	1.0000
2:182720006:G:GA	acceptor_gain	1.0000
2:182720006:GA:G	acceptor_gain	1.0000
2:182720006:GAA:G	acceptor_gain	1.0000
2:182720006:GAAT:G	acceptor_gain	1.0000
2:182720006:GAATA:G	acceptor_gain	1.0000
2:182720129:TGGC:T	donor_gain	1.0000
2:182720130:GGCC:G	donor_gain	1.0000
2:182720131:GCCA:G	donor_gain	1.0000
2:182720134:A:AG	donor_gain	1.0000
2:182720135:G:GG	donor_gain	1.0000
2:182720170:G:GG	donor_gain	1.0000
2:182728659:G:GG	donor_gain	1.0000
2:182728855:T:TA	acceptor_gain	1.0000
2:182728859:A:AG	acceptor_gain	1.0000
2:182728859:ATAGT:A	acceptor_gain	1.0000
2:182728860:T:G	acceptor_gain	1.0000
2:182728860:TA:T	acceptor_loss	1.0000
2:182728861:A:AG	acceptor_gain	1.0000
2:182728861:A:AT	acceptor_loss	1.0000
2:182728861:AGT:A	acceptor_gain	1.0000
2:182728861:AGTG:A	acceptor_gain	1.0000
2:182728861:AGTGG:A	acceptor_gain	1.0000
2:182728862:G:GA	acceptor_gain	1.0000
2:182728862:GT:G	acceptor_gain	1.0000

AlphaMissense

5271 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:182718254:G:C	K56N	0.999
2:182718254:G:T	K56N	0.999
2:182718273:C:G	H63D	0.999
2:182720031:T:C	F77L	0.999
2:182720032:T:C	F77S	0.999
2:182720032:T:G	F77C	0.999
2:182720033:T:A	F77L	0.999
2:182720033:T:G	F77L	0.999
2:182720062:T:A	L87H	0.999
2:182720062:T:C	L87P	0.999
2:182728638:T:C	C161R	0.999
2:182728639:G:A	C161Y	0.999
2:182728639:G:T	C161F	0.999
2:182728640:C:G	C161W	0.999
2:182728863:T:A	W168R	0.999
2:182728863:T:C	W168R	0.999
2:182728865:G:C	W168C	0.999
2:182728865:G:T	W168C	0.999
2:182728912:T:A	V184D	0.999
2:182728918:G:A	C186Y	0.999
2:182728938:T:A	C193S	0.999
2:182728939:G:A	C193Y	0.999
2:182728939:G:C	C193S	0.999
2:182718249:T:C	F55L	0.998
2:182718251:C:A	F55L	0.998
2:182718251:C:G	F55L	0.998
2:182718275:T:A	H63Q	0.998
2:182718275:T:G	H63Q	0.998
2:182720080:G:C	R93P	0.998
2:182720088:T:G	Y96D	0.998

dbSNP variants (sampled 300 via entrez): RS1000255161 (2:182746362 T>C), RS1000324934 (2:182759023 C>T), RS1000339815 (2:182734286 A>G), RS1000363722 (2:182753015 C>T), RS1000406672 (2:182752250 T>G), RS1000422377 (2:182758650 G>A), RS1000444764 (2:182741628 A>G), RS1000452824 (2:182721276 A>G), RS1000510736 (2:182771902 T>C), RS1000519697 (2:182788384 T>G), RS1000524382 (2:182738666 G>A), RS1000537066 (2:182745730 AT>A,ATT), RS1000577778 (2:182782567 C>T), RS1000581701 (2:182788931 C>A,G,T), RS1000585625 (2:182744163 T>C)

Disease associations

OMIM: gene MIM:607987 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003542_73	Night sleep phenotypes	5.000000e-06
GCST004582_3	Waist-to-hip circumference ratio (dietary energy interaction)	9.000000e-06
GCST004947_1	Pulmonary arterial hypertension	8.000000e-09
GCST006585_2592	Blood protein levels	8.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007827	nighttime rest measurement
EFO:0004343	waist-hip ratio
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725117 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

3 potent at pChembl≥5 of 4 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.49	Kd	3275	nM	CHEMBL5653589
5.49	ED50	3275	nM	CHEMBL5653589
5.00	IC50	1e+04	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 10 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148252: Binding affinity to human DNAJC10 incubated for 45 mins by Kinobead based pull down assay	kd	3.2749	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178987: Inhibition of DNAJC10 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, affects expression, increases expression	6
methylmercuric chloride	decreases expression	3
bisphenol A	affects expression, decreases expression, decreases methylation	3
sodium arsenite	decreases expression, increases expression	3
cobaltous chloride	decreases expression	2
Chenodeoxycholic Acid	affects cotreatment, increases expression, decreases expression	2
Deoxycholic Acid	affects cotreatment, increases expression, decreases expression	2
Glycochenodeoxycholic Acid	affects cotreatment, increases expression, decreases expression	2
Glycocholic Acid	affects cotreatment, increases expression, decreases expression	2
Glycodeoxycholic Acid	affects cotreatment, increases expression, decreases expression	2
Valproic Acid	decreases methylation, increases expression	2
Thapsigargin	increases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
6-hydroxy-5-((p- sulfophenyl)azo)-2-naphthalenesulfonic acid disodium salt	affects cotreatment, decreases expression	1
decabromobiphenyl ether	decreases expression	1
tetrabromobisphenol A	decreases expression	1
nefazodone	affects cotreatment, increases expression	1
dinophysistoxin 1	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
azaspiracid	affects expression	1
K 7174	increases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651294	Binding	Binding affinity to human DNAJC10 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1Q8	Abcam HeLa DNAJC10 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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