DNAJC8

Summary

DNAJC8 (DnaJ heat shock protein family (Hsp40) member C8, HGNC:15470) is a protein-coding gene on chromosome 1p35.3, encoding DnaJ homolog subfamily C member 8 (O75937). Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells. It is a common-essential gene (DepMap: required in 94.8% of cancer cell lines).

Enables Hsp70 protein binding activity. Located in cytosol; intercellular bridge; and nucleoplasm.

Source: NCBI Gene 22826 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 37 total
• Cancer dependency (DepMap): dependent in 94.8% of screened cell lines (common-essential)
• MANE Select transcript: NM_014280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15470
Approved symbol	DNAJC8
Name	DnaJ heat shock protein family (Hsp40) member C8
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	SPF31
Ensembl gene	ENSG00000126698
Ensembl biotype	protein_coding
Entrez	22826

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000263697, ENST00000470967, ENST00000482674, ENST00000488868, ENST00000489277, ENST00000603289, ENST00000919815, ENST00000919816, ENST00000919817, ENST00000919818, ENST00000919819

RefSeq mRNA: 1 — MANE Select: NM_014280 NM_014280

CCDS: CCDS41292

Canonical transcript exons

ENST00000263697 — 9 exons

Exon	Start	End
ENSE00001207742	28200278	28201370
ENSE00003476609	28203747	28203822
ENSE00003486826	28209972	28210066
ENSE00003522355	28214940	28214996
ENSE00003555786	28228922	28229023
ENSE00003560989	28205258	28205349
ENSE00003561310	28210571	28210637
ENSE00003605362	28208342	28208413
ENSE00003633284	28232921	28233029

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.8438 / max 864.2320, expressed in 1813 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11348	30.8438	1813

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	97.45	gold quality
embryo	UBERON:0000922	97.44	gold quality
lymph node	UBERON:0000029	97.41	gold quality
ventricular zone	UBERON:0003053	97.41	gold quality
smooth muscle tissue	UBERON:0001135	97.40	gold quality
islet of Langerhans	UBERON:0000006	97.39	gold quality
placenta	UBERON:0001987	97.17	gold quality
endometrium	UBERON:0001295	97.13	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.11	gold quality
hypothalamus	UBERON:0001898	97.03	gold quality
substantia nigra	UBERON:0002038	97.00	gold quality
calcaneal tendon	UBERON:0003701	96.93	gold quality
popliteal artery	UBERON:0002250	96.86	gold quality
tibial artery	UBERON:0007610	96.86	gold quality
artery	UBERON:0001637	96.81	gold quality
amygdala	UBERON:0001876	96.79	gold quality
monocyte	CL:0000576	96.78	gold quality
leukocyte	CL:0000738	96.78	gold quality
uterus	UBERON:0000995	96.77	gold quality
body of uterus	UBERON:0009853	96.74	gold quality
temporal lobe	UBERON:0001871	96.72	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.68	gold quality
prefrontal cortex	UBERON:0000451	96.66	gold quality
anterior cingulate cortex	UBERON:0009835	96.66	gold quality
superior frontal gyrus	UBERON:0002661	96.63	gold quality
myometrium	UBERON:0001296	96.59	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.58	gold quality
vermiform appendix	UBERON:0001154	96.56	gold quality
cerebral cortex	UBERON:0000956	96.54	gold quality
nucleus accumbens	UBERON:0001882	96.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-106540	no	794.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

80 targeting DNAJC8, 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-3163	100.00	77.23	8605
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.8% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• TIG1 interacted with DNAJC8 in the cytosol, and this interaction completely blocked DNAJC8-mediated PKM2 translocation and inhibited glucose uptake. Furthermore, increased glycose uptake was observed in cells in which TIG1 was silenced. (PMID:29902837)
• DNAJC8: a prognostic marker and potential therapeutic target for hepatocellular carcinoma. (PMID:38274804)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc8	ENSDARG00000059373
mus_musculus	Dnajc8	ENSMUSG00000054405
rattus_norvegicus	Dnajc8	ENSRNOG00000013255
drosophila_melanogaster	CG10375	FBGN0039116
caenorhabditis_elegans	dnj-30	WBGENE00001048

Protein

Protein identifiers

DnaJ homolog subfamily C member 8 — O75937 (reviewed: O75937)

Alternative names: Splicing protein spf31

All UniProt accessions (3): O75937, A0AAA9YHT5, S4R3J5

UniProt curated annotations — full annotation on UniProt →

Function. Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells.

Subunit / interactions. Interacts with SRPK1. Interacts with HSP70 (HSPA1A or HSPA1B).

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

RefSeq proteins (1): NP_055095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR036869	J_dom_sf	Homologous_superfamily
IPR042858	DNAJC8	Family

Pfam: PF00226

UniProt features (16 total): modified residue 4, helix 2, region of interest 2, short sequence motif 2, compositionally biased region 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7VPX	ELECTRON MICROSCOPY	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75937-F1	84.60	0.59

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 (4): 35, 146, 222, 2

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9770562	mRNA Polyadenylation
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 148 (showing top): MORF_SNRP70, MORF_UBE2I, MORF_HDAC1, MORF_CDK2, MORF_HDAC2, MORF_TERF1, MORF_RAF1, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, MORF_CTBP1, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, MORF_BUB3, MORF_PRKDC, REACTOME_MRNA_SPLICING, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN

GO Biological Process (0):

GO Molecular Function (2): Hsp70 protein binding (GO:0030544), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), intercellular bridge (GO:0045171)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Splicing	1
mRNA 3’-end processing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
heat shock protein binding	1
protein-folding chaperone binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

1356 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC8	HSPB9	Q9BQS6	676
DNAJC8	DNAJC18	Q9H819	667
DNAJC8	DNAJC25	Q9H1X3	585
DNAJC8	HSPA4	P34932	561
DNAJC8	DNAJC9	Q8WXX5	558
DNAJC8	DNAJC28	Q9NX36	538
DNAJC8	DNAJC10	Q8IXB1	526
DNAJC8	DNAJC11	Q9NVH1	519
DNAJC8	DNAJC27	Q9NZQ0	512
DNAJC8	DNAJC21	Q5F1R6	503
DNAJC8	DNAJC22	Q8N4W6	495
DNAJC8	DNAJC24	Q6P3W2	467
DNAJC8	DNAJB1	P25685	460
DNAJC8	SRPK1	Q96SB4	453
DNAJC8	DNAJC4	Q9NNZ3	452

IntAct

80 interactions, top by confidence:

A	B	Type	Score
PIGS	GPAA1	psi-mi:“MI:0914”(association)	0.760
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
DNAJC8	SF3B1	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
DNAJC8	SF3A2	psi-mi:“MI:0915”(physical association)	0.560
SF3A1	DNAJC8	psi-mi:“MI:0914”(association)	0.530
AGTR1	DNAJC8	psi-mi:“MI:0915”(physical association)	0.510
DNAJC8	AGTR1	psi-mi:“MI:0915”(physical association)	0.510
	DNAJC8	psi-mi:“MI:0407”(direct interaction)	0.440
DNAJC8	SRPK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
DNAJC8	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
DNAJC8	HNRNPM	psi-mi:“MI:0915”(physical association)	0.400
TNFRSF21	DNAJC8	psi-mi:“MI:0915”(physical association)	0.400
Sf3a1	U2SURP	psi-mi:“MI:0915”(physical association)	0.400
	TK2	psi-mi:“MI:0915”(physical association)	0.400
OTUB1	EPM2A	psi-mi:“MI:0914”(association)	0.350
Kifc5b	KPNA3	psi-mi:“MI:0914”(association)	0.350
Dync1li1	SSR3	psi-mi:“MI:0914”(association)	0.350
Chmp3	DTL	psi-mi:“MI:0914”(association)	0.350
REEP5	CNOT1	psi-mi:“MI:0914”(association)	0.350
Psmb4	PSMD14	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
XRCC3	DERL1	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
MMGT1	DERL1	psi-mi:“MI:0914”(association)	0.350
EGR1	MAGEB2	psi-mi:“MI:0914”(association)	0.350
CNTROB	CENPX	psi-mi:“MI:0914”(association)	0.350

BioGRID (285): DNAJC8 (Affinity Capture-MS), DNAJC8 (Co-fractionation), DNAJC8 (Co-fractionation), DNAJC8 (Co-fractionation), DNAJC8 (Co-fractionation), HSPA4L (Co-fractionation), HYOU1 (Co-fractionation), NEDD8 (Co-fractionation), DNAJC8 (Proximity Label-MS), DNAJC8 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS), DNAJC8 (Affinity Capture-MS)

ESM2 similar proteins: A1Z3X3, A2AT37, A2VD00, A4GWN3, A4II09, A4VCH4, A7RWP6, B0W6N3, O43395, O49160, O75937, P23116, P32780, P46940, Q00004, Q14152, Q173M7, Q1JU68, Q2HJ41, Q2KIA6, Q40554, Q5EAV6, Q5R5F1, Q5RE03, Q5ZJ85, Q5ZMW3, Q62383, Q642C0, Q6DDM4, Q6GMH0, Q6GQ80, Q6NZB0, Q6PCR7, Q7KZ85, Q7ZY79, Q8BM39, Q8BMA6, Q8UVK2, Q8VZM1, Q922U1

Diamond homologs: A1BHL1, A1V9Q3, A3PNM0, A4SFR5, A4WW88, A6Q486, A6W2D1, A8LQ63, B3EE31, B3QPW8, B6IVA5, B8DQW8, B9KPP3, D2H417, D3ZD82, D3ZSC8, F1RTY8, O42196, O59731, O74746, O75937, P25686, P28616, P40564, P48353, P56101, P60904, P60905, P81999, Q03751, Q0IIE8, Q16D44, Q1GKS4, Q1H3B9, Q28VY4, Q29455, Q2KI83, Q2KIJ8, Q2VYT0, Q316U7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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
mRNA Splicing - Minor Pathway	8	23.3×	1e-07
mRNA Splicing	16	22.8×	8e-16
mRNA Polyadenylation	19	21.7×	2e-18
Processing of Capped Intron-Containing Pre-mRNA	19	20.3×	6e-18
CHD1 and CHD2 subfamily	14	19.8×	6e-13
mRNA Splicing - Major Pathway	24	17.0×	6e-21
SARS-CoV-2 modulates host translation machinery	5	14.5×	1e-03
Dengue Virus-Host Interactions	20	11.9×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	12	84.2×	2e-18
spliceosomal complex assembly	8	54.1×	3e-10
RNA splicing, via transesterification reactions	5	35.1×	4e-05
mRNA splicing, via spliceosome	20	20.6×	2e-18
regulation of DNA repair	5	15.5×	1e-03
RNA splicing	14	13.9×	3e-10
regulation of RNA splicing	5	12.3×	3e-03
mRNA processing	8	7.1×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1266 predictions. Top by Δscore:

Variant	Effect	Δscore
1:28201366:CTTTC:C	acceptor_gain	1.0000
1:28201367:TTTC:T	acceptor_gain	1.0000
1:28201368:TTC:T	acceptor_gain	1.0000
1:28201369:TC:T	acceptor_gain	1.0000
1:28201369:TCCTA:T	acceptor_loss	1.0000
1:28201370:CC:C	acceptor_gain	1.0000
1:28201371:C:CC	acceptor_gain	1.0000
1:28201375:G:C	acceptor_gain	1.0000
1:28201375:G:GC	acceptor_gain	1.0000
1:28201378:C:CT	acceptor_gain	1.0000
1:28201379:A:T	acceptor_gain	1.0000
1:28203744:TACC:T	donor_loss	1.0000
1:28203745:A:AG	donor_loss	1.0000
1:28203746:C:CA	donor_loss	1.0000
1:28203820:TTC:T	acceptor_gain	1.0000
1:28203820:TTCC:T	acceptor_loss	1.0000
1:28203821:TC:T	acceptor_gain	1.0000
1:28203822:CC:C	acceptor_gain	1.0000
1:28203823:C:CC	acceptor_gain	1.0000
1:28203824:T:C	acceptor_loss	1.0000
1:28203928:C:A	donor_gain	1.0000
1:28205253:TGTAC:T	donor_loss	1.0000
1:28205254:GTA:G	donor_loss	1.0000
1:28205255:TAC:T	donor_loss	1.0000
1:28205256:ACCTT:A	donor_loss	1.0000
1:28205257:C:T	donor_loss	1.0000
1:28205345:TTGAA:T	acceptor_gain	1.0000
1:28205346:TGAA:T	acceptor_gain	1.0000
1:28205347:GAA:G	acceptor_gain	1.0000
1:28205349:AC:A	acceptor_loss	1.0000

AlphaMissense

1680 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:28201332:G:C	F226L	1.000
1:28201332:G:T	F226L	1.000
1:28201333:A:C	F226C	1.000
1:28201333:A:G	F226S	1.000
1:28201334:A:G	F226L	1.000
1:28201339:C:G	R224P	1.000
1:28201341:C:A	W223C	1.000
1:28201341:C:G	W223C	1.000
1:28201342:C:G	W223S	1.000
1:28201343:A:G	W223R	1.000
1:28201343:A:T	W223R	1.000
1:28201354:C:A	R219L	1.000
1:28201354:C:G	R219P	1.000
1:28201355:G:A	R219C	1.000
1:28201355:G:C	R219G	1.000
1:28201355:G:T	R219S	1.000
1:28201363:C:G	R216P	1.000
1:28203750:A:C	F212L	1.000
1:28203750:A:T	F212L	1.000
1:28203751:A:C	F212C	1.000
1:28203752:A:G	F212L	1.000
1:28203817:C:G	R190P	1.000
1:28205303:A:G	L173P	1.000
1:28205309:G:T	A171E	1.000
1:28205310:C:G	A171P	1.000
1:28205315:A:G	L169P	1.000
1:28209994:C:T	G126E	1.000
1:28210042:A:G	L110P	1.000
1:28210054:G:T	A106D	1.000
1:28210055:C:G	A106P	1.000

dbSNP variants (sampled 300 via entrez): RS1000008142 (1:28206812 G>A), RS1000019079 (1:28221425 G>T), RS1000071480 (1:28221185 A>G), RS1000082193 (1:28220980 G>A,C,T), RS1000276010 (1:28211447 C>G,T), RS1000280040 (1:28213711 G>A), RS1000301633 (1:28225244 T>C), RS1000419744 (1:28218936 T>C), RS1000530360 (1:28232338 T>G), RS1000538020 (1:28227886 C>T), RS1000576688 (1:28233464 T>C), RS1000628991 (1:28233172 A>C), RS1000784570 (1:28201764 G>C), RS1000858043 (1:28201505 C>A,T), RS1000893486 (1:28218735 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002383_127	Hematocrit	4.000000e-10
GCST90011899_123	Aspartate aminotransferase levels	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	2
TAK-243	increases sumoylation	1
pirinixic acid	increases activity, affects binding, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
chloropicrin	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Diclofenac	affects expression	1
Diethylstilbestrol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Ivermectin	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Uranium Compounds	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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