DNAJC17

Summary

DNAJC17 (DnaJ heat shock protein family (Hsp40) member C17, HGNC:25556) is a protein-coding gene on chromosome 15q15.1, encoding DnaJ homolog subfamily C member 17 (Q9NVM6). May negatively affect PAX8-induced thyroglobulin/TG transcription. It is a common-essential gene (DepMap: required in 99.3% of cancer cell lines).

Predicted to enable RNA binding activity. Predicted to be involved in spliceosomal complex disassembly. Predicted to act upstream of or within negative regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. Predicted to be part of spliceosomal complex.

Source: NCBI Gene 55192 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 270 total
• Cancer dependency (DepMap): dependent in 99.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_018163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25556
Approved symbol	DNAJC17
Name	DnaJ heat shock protein family (Hsp40) member C17
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10634
Ensembl gene	ENSG00000104129
Ensembl biotype	protein_coding
OMIM	616844
Entrez	55192

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 11 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000220496, ENST00000558727, ENST00000558769, ENST00000559238, ENST00000559310, ENST00000560065, ENST00000560301, ENST00000560645, ENST00000561018, ENST00000561044, ENST00000561110, ENST00000627802, ENST00000899497, ENST00000899498, ENST00000899499, ENST00000938175, ENST00000938176, ENST00000938177, ENST00000938178, ENST00000945868, ENST00000945869

RefSeq mRNA: 1 — MANE Select: NM_018163 NM_018163

CCDS: CCDS10065

Canonical transcript exons

ENST00000220496 — 11 exons

Exon	Start	End
ENSE00000883925	40765161	40768062
ENSE00001403544	40807369	40807473
ENSE00003497902	40774356	40774436
ENSE00003539612	40779928	40779997
ENSE00003586985	40779545	40779603
ENSE00003601494	40773727	40773837
ENSE00003611059	40776196	40776292
ENSE00003617200	40775553	40775596
ENSE00003635379	40775031	40775108
ENSE00003643453	40779223	40779310
ENSE00003650434	40776542	40776627

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7429 / max 211.4608, expressed in 1802 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
149507	16.6332	1802
149505	0.1097	54

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.20	gold quality
calcaneal tendon	UBERON:0003701	94.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.01	gold quality
lower esophagus mucosa	UBERON:0035834	93.55	gold quality
minor salivary gland	UBERON:0001830	93.40	gold quality
granulocyte	CL:0000094	93.04	gold quality
right lobe of liver	UBERON:0001114	92.73	gold quality
endocervix	UBERON:0000458	92.56	gold quality
mucosa of transverse colon	UBERON:0004991	92.54	gold quality
skin of leg	UBERON:0001511	91.92	gold quality
skin of abdomen	UBERON:0001416	91.52	gold quality
ectocervix	UBERON:0012249	91.46	gold quality
metanephros cortex	UBERON:0010533	91.39	gold quality
right ovary	UBERON:0002118	91.28	gold quality
right lobe of thyroid gland	UBERON:0001119	91.19	gold quality
body of uterus	UBERON:0009853	91.05	gold quality
esophagus mucosa	UBERON:0002469	91.03	gold quality
gall bladder	UBERON:0002110	91.00	gold quality
tibial nerve	UBERON:0001323	90.99	gold quality
left lobe of thyroid gland	UBERON:0001120	90.97	gold quality
left ovary	UBERON:0002119	90.84	gold quality
left uterine tube	UBERON:0001303	90.42	gold quality
saliva-secreting gland	UBERON:0001044	90.40	gold quality
omental fat pad	UBERON:0010414	90.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	90.23	gold quality
peritoneum	UBERON:0002358	90.22	gold quality
rectum	UBERON:0001052	89.98	gold quality
mouth mucosa	UBERON:0003729	89.81	gold quality
apex of heart	UBERON:0002098	89.80	gold quality
left adrenal gland cortex	UBERON:0035825	89.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	28.34
E-CURD-112	yes	9.29
E-ANND-3	yes	5.96

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 2)

• Our study expands the clinical and allelic spectrum of known Retinal dystrophies genes, and reveals AGBL5, CDH16, and DNAJC17 as novel disease candidates. (PMID:26355662)
• DNAJC17 mutations are not frequently present in patients with thyroid dysgenesis. (PMID:29159607)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc17	ENSDARG00000104959
mus_musculus	Dnajc17	ENSMUSG00000034278
rattus_norvegicus	Dnajc17	ENSRNOG00000012368
rattus_norvegicus		ENSRNOG00000069569
drosophila_melanogaster	CG17187	FBGN0037882
caenorhabditis_elegans		WBGENE00001020
caenorhabditis_elegans		WBGENE00001025
caenorhabditis_elegans	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), 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

DnaJ homolog subfamily C member 17 — Q9NVM6 (reviewed: Q9NVM6)

All UniProt accessions (5): Q9NVM6, H0YK99, H0YLQ7, H0YLV4, S4R343

UniProt curated annotations — full annotation on UniProt →

Function. May negatively affect PAX8-induced thyroglobulin/TG transcription.

Subcellular location. Cytoplasm. Nucleus.

RefSeq proteins (1): NP_060633* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001623	DnaJ_domain	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034254	DNAJC17_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily
IPR052094	Pre-mRNA-splicing_ERAD	Family

Pfam: PF00076, PF00226

UniProt features (14 total): strand 4, domain 2, helix 2, compositionally biased region 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D9O	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NVM6-F1	83.72	0.46

Functional residue map

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

Post-translational modifications (2): 112, 264

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): YANG_BREAST_CANCER_ESR1_LASER_UP, GCANCTGNY_MYOD_Q6, MARTINEZ_RB1_TARGETS_UP, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, GOBP_PROTEIN_RNA_COMPLEX_DISASSEMBLY, SOX5_01, PARENT_MTOR_SIGNALING_UP, ACTWSNACTNY_UNKNOWN, GOCC_SPLICEOSOMAL_COMPLEX, GOCC_RIBONUCLEOPROTEIN_COMPLEX, CASORELLI_ACUTE_PROMYELOCYTIC_LEUKEMIA_DN, RASHI_RESPONSE_TO_IONIZING_RADIATION_1, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_B

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), spliceosomal complex disassembly (GO:0000390)

GO Molecular Function (3): RNA binding (GO:0003723), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (3): spliceosomal complex (GO:0005681), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
mRNA splicing, via spliceosome	1
protein-RNA complex disassembly	1
nucleic acid binding	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC17	C15orf62	A8K5M9	586
DNAJC17	ZFYVE19	Q96K21	527
DNAJC17	ANKRD9	Q96BM1	495
DNAJC17	LRRC57	Q8N9N7	485
DNAJC17	DNAJC2	Q99543	450
DNAJC17	IBTK	Q9P2D0	443
DNAJC17	ABCB5	Q2M3G0	442
DNAJC17	DNAJC28	Q9NX36	434
DNAJC17	FRG1	Q14331	431
DNAJC17	DNAJC13	O75165	422
DNAJC17	SESN2	P58004	422
DNAJC17	C4orf17	Q53FE4	418
DNAJC17	NDRG2	Q9UN36	398
DNAJC17	ST13	P50502	397
DNAJC17	DNAJC6	O75061	397
DNAJC17	DNAJC19	Q96DA6	397

IntAct

19 interactions, top by confidence:

A	B	Type	Score
MEOX2	DNAJC17	psi-mi:“MI:0915”(physical association)	0.560
EFTUD2	DNAJC17	psi-mi:“MI:0915”(physical association)	0.560
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
DNAJC17	MTHFD1	psi-mi:“MI:0915”(physical association)	0.400
DNAJC17	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
PTH1R	DEGS1	psi-mi:“MI:0914”(association)	0.350
ENG	IGKV2-28	psi-mi:“MI:0914”(association)	0.350
DNAJC17	SNRNP200	psi-mi:“MI:0914”(association)	0.350
DNAJC2	RPS3A	psi-mi:“MI:0914”(association)	0.350
PLA2G4A	AHSA1	psi-mi:“MI:0914”(association)	0.350
SNRPC	DDX39A	psi-mi:“MI:0914”(association)	0.350
ATG16L1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DNAJC17	SYF2	psi-mi:“MI:0914”(association)	0.350
MILR1	SBNO1	psi-mi:“MI:0914”(association)	0.350
DNAJC17	AQR	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
DNAJC17	MEOX2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (160): DNAJC17 (Affinity Capture-MS), C1orf123 (Co-fractionation), DNAJC17 (Co-fractionation), DNAJC17 (Co-fractionation), DNAJC17 (Co-fractionation), DNAJC17 (Co-fractionation), DNAJC17 (Co-fractionation), DNAJC17 (Co-fractionation), HSPA14 (Co-fractionation), HSPA9 (Co-fractionation), HSPH1 (Co-fractionation), HYOU1 (Co-fractionation), DNAJC17 (Proximity Label-MS), DNAJC17 (Affinity Capture-MS), DNAJC17 (Affinity Capture-MS)

ESM2 similar proteins: A1YVX4, A3KMI0, A6QPH1, B1AVY7, D3ZSC8, E9Q8D0, F1M5N7, O43896, O55156, O75037, O93307, O95239, O95475, P41229, P41230, Q0II91, Q2KI83, Q38JA7, Q58G59, Q5F259, Q5I0E3, Q61712, Q674X7, Q6C3L4, Q6K687, Q6PGC1, Q6PH11, Q6UWE0, Q80ZI6, Q86YJ7, Q8CHP5, Q8TDY4, Q90640, Q91784, Q91WT4, Q96KC8, Q9BRP8, Q9CQR5, Q9CXL3, Q9FL54

Diamond homologs: A0K4S9, A1K4C4, A1KR91, A1U613, A1V0U8, A1WX30, A2S563, A3MA88, A3MN97, A3ND66, A3NYX5, A4JBS2, A4XYF5, A5WBF8, A6Q486, A6W2D1, A9IGC5, A9LZV9, B0VA24, B0VQ00, B1JW20, B1YTK1, B1ZUS0, B2I2G6, B2JGE1, B2UBP2, B4EDZ1, B7GV08, B7I2B2, B7V1H2, B8DQW8, C1DD87, C1DFM2, C4L8Y4, D2H417, D3ZSC8, F1RTY8, O54946, P56101, P60904

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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 - Major Pathway	6	19.3×	6e-05
Dengue Virus-Host Interactions	6	16.1×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	7	27.9×	7e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	147
Likely benign	108
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

2688 predictions. Top by Δscore:

Variant	Effect	Δscore
15:40765823:GCAG:G	acceptor_loss	1.0000
15:40765918:ACTT:A	donor_gain	1.0000
15:40765919:CTT:C	donor_gain	1.0000
15:40765922:G:GG	donor_gain	1.0000
15:40767956:T:TA	donor_gain	1.0000
15:40767965:T:TA	donor_gain	1.0000
15:40774355:CCG:C	donor_gain	1.0000
15:40774432:CCATA:C	acceptor_gain	1.0000
15:40774433:CATA:C	acceptor_gain	1.0000
15:40774433:CATAC:C	acceptor_gain	1.0000
15:40774435:TA:T	acceptor_gain	1.0000
15:40774437:C:CC	acceptor_gain	1.0000
15:40775548:CTCA:C	donor_loss	1.0000
15:40775550:CA:C	donor_loss	1.0000
15:40775606:T:C	acceptor_gain	1.0000
15:40775606:T:TC	acceptor_gain	1.0000
15:40776202:A:C	donor_gain	1.0000
15:40776216:T:A	donor_gain	1.0000
15:40776226:T:C	donor_gain	1.0000
15:40776537:CTCA:C	donor_loss	1.0000
15:40776538:TCA:T	donor_loss	1.0000
15:40776539:CACC:C	donor_loss	1.0000
15:40776540:A:AC	donor_gain	1.0000
15:40776540:ACC:A	donor_loss	1.0000
15:40776541:C:CC	donor_gain	1.0000
15:40776541:CCT:C	donor_gain	1.0000
15:40776623:CAGGT:C	acceptor_gain	1.0000
15:40776625:GGT:G	acceptor_gain	1.0000
15:40776627:TC:T	acceptor_loss	1.0000
15:40776628:C:CA	acceptor_loss	1.0000

AlphaMissense

1972 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:40779959:G:C	H39Q	1.000
15:40779959:G:T	H39Q	1.000
15:40779961:G:C	H39D	1.000
15:40779593:G:C	F53L	0.999
15:40779593:G:T	F53L	0.999
15:40779595:A:G	F53L	0.999
15:40779950:T:A	K42N	0.999
15:40779950:T:G	K42N	0.999
15:40779957:G:T	P40Q	0.999
15:40779958:G:A	P40S	0.999
15:40779960:T:C	H39R	0.999
15:40779961:G:T	H39N	0.999
15:40779980:C:A	R32S	0.999
15:40779980:C:G	R32S	0.999
15:40779981:C:A	R32M	0.999
15:40779981:C:G	R32T	0.999
15:40779594:A:G	F53S	0.998
15:40779952:T:C	K42E	0.998
15:40779972:G:T	A35D	0.998
15:40779985:A:C	Y31D	0.998
15:40779585:A:G	L56P	0.997
15:40779594:A:C	F53C	0.997
15:40779595:A:C	F53V	0.997
15:40779953:G:C	D41E	0.997
15:40779953:G:T	D41E	0.997
15:40779955:C:G	D41H	0.997
15:40779958:G:T	P40T	0.997
15:40779985:A:T	Y31N	0.997
15:40775102:A:G	W177R	0.996
15:40775102:A:T	W177R	0.996

dbSNP variants (sampled 300 via entrez): RS1000058877 (15:40793346 A>G), RS1000070858 (15:40775402 C>A,T), RS1000083715 (15:40793738 C>T), RS1000177756 (15:40795160 C>T), RS1000210800 (15:40771255 TG>T,TGG), RS1000278575 (15:40801610 G>A,C), RS1000324661 (15:40788645 G>A), RS1000381512 (15:40774087 GGGGTGCA>G), RS1000440650 (15:40788521 C>A), RS1000581857 (15:40768519 G>A,T), RS1000599079 (15:40771403 G>A), RS1000613408 (15:40794917 T>C), RS1000907851 (15:40783208 T>C), RS1000936706 (15:40807270 G>A,C), RS1000966483 (15:40797973 T>C,G)

Disease associations

OMIM: gene MIM:616844 | disease phenotypes: MIM:236600

GenCC curated gene-disease

Mondo (1): hydrocephalus, nonsyndromic, autosomal recessive 1 (MONDO:0009360)

Orphanet (1): Congenital hydrocephalus (Orphanet:2185)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST008559_8	Anxiety and stress-related disorders	7.000000e-07
GCST010725_23	Malaria	2.000000e-06
GCST010725_38	Malaria	3.000000e-06
GCST010725_80	Malaria	7.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010098	stress-related disorder

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance	2
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	increases expression	1
Sunitinib	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Coal	decreases expression, increases abundance	1
Estradiol	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	decreases expression	1
Lactic Acid	increases expression	1
Genistein	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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