DNAJC14

Summary

DNAJC14 (DnaJ heat shock protein family (Hsp40) member C14, HGNC:24581) is a protein-coding gene on chromosome 12q13.2, encoding DnaJ homolog subfamily C member 14 (Q6Y2X3). Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface.

Predicted to enable dopamine receptor binding activity. Predicted to be involved in protein transport. Located in membrane.

Source: NCBI Gene 85406 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 101 total
• MANE Select transcript: NM_032364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24581
Approved symbol	DNAJC14
Name	DnaJ heat shock protein family (Hsp40) member C14
Location	12q13.2
Locus type	gene with protein product
Status	Approved
Aliases	DNAJ, DRIP78, HDJ3, LIP6, FLJ32792
Ensembl gene	ENSG00000135392
Ensembl biotype	protein_coding
OMIM	606092
Entrez	85406

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 10 protein_coding

ENST00000317287, ENST00000357606, ENST00000546957, ENST00000547445, ENST00000678005, ENST00000920411, ENST00000920412, ENST00000920413, ENST00000920414, ENST00000955944

RefSeq mRNA: 5 — MANE Select: NM_032364 NM_001394687, NM_001394688, NM_001394689, NM_001394690, NM_032364

CCDS: CCDS8894

Canonical transcript exons

ENST00000678005 — 7 exons

Exon	Start	End
ENSE00002230984	55827252	55828714
ENSE00003506707	55822373	55822475
ENSE00003581032	55823070	55823189
ENSE00003581441	55823402	55823508
ENSE00003645641	55822572	55822732
ENSE00003910771	55820985	55822187
ENSE00003912722	55829489	55829587

Expression profiles

Bgee: expression breadth ubiquitous, 216 present calls, max score 91.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.6802 / max 58.5584, expressed in 1805 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131436	9.9791	1792
131437	2.7019	1510
131438	1.3128	968
131440	0.6034	398
131439	0.0831	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
islet of Langerhans	UBERON:0000006	91.85	gold quality
ileal mucosa	UBERON:0000331	91.43	gold quality
stromal cell of endometrium	CL:0002255	88.00	gold quality
granulocyte	CL:0000094	86.02	gold quality
leukocyte	CL:0000738	85.91	gold quality
smooth muscle tissue	UBERON:0001135	85.88	gold quality
monocyte	CL:0000576	85.69	gold quality
tibialis anterior	UBERON:0001385	85.01	silver quality
vermiform appendix	UBERON:0001154	84.79	gold quality
pancreas	UBERON:0001264	84.39	gold quality
rectum	UBERON:0001052	84.22	gold quality
prefrontal cortex	UBERON:0000451	83.63	gold quality
bone marrow cell	CL:0002092	83.44	gold quality
gall bladder	UBERON:0002110	83.39	gold quality
right adrenal gland cortex	UBERON:0035827	83.37	gold quality
right adrenal gland	UBERON:0001233	83.32	gold quality
left adrenal gland	UBERON:0001234	82.88	gold quality
right testis	UBERON:0004534	82.86	gold quality
left testis	UBERON:0004533	82.69	gold quality
cortical plate	UBERON:0005343	82.68	gold quality
testis	UBERON:0000473	82.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	82.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.34	gold quality
adrenal gland	UBERON:0002369	82.23	gold quality
left adrenal gland cortex	UBERON:0035825	82.23	gold quality
left uterine tube	UBERON:0001303	82.17	gold quality
lymph node	UBERON:0000029	81.99	gold quality
mucosa of stomach	UBERON:0001199	81.95	gold quality
upper lobe of left lung	UBERON:0008952	81.91	gold quality
spleen	UBERON:0002106	81.78	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting DNAJC14, 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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4273	99.45	67.93	1206

Literature-anchored findings (GeneRIF, showing 5)

• DNAJC14 is required for yellow fever virus replication. (PMID:21249176)
• a molecular chaperone, DRiP78, that interacts with both CXCR4 and CCR5, but not the heterodimer formed by these receptors (PMID:22815758)
• These findings support a novel model of DNAJC14 action that includes specific membrane targeting of both DNAJC14 and yellow fever virus replication proteins. (PMID:22915803)
• This suggests that DNAJC14’s folding activity normally modulates yellow fever virus NS3/4A/2K cleavage events to liberate appropriate levels of NS3 and NS4A and promote replication complex formation. (PMID:26739057)
• Hsc70 and DNAJC14 are required for the unconventional trafficking of H723R-pendrin. (PMID:27109633)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajc14	ENSDARG00000105398
mus_musculus	Dnajc14	ENSMUSG00000025354
rattus_norvegicus	Dnajc14	ENSRNOG00000006844
drosophila_melanogaster	CG10565	FBGN0037051
drosophila_melanogaster	P58IPK	FBGN0037718
drosophila_melanogaster	l(3)80Fg	FBGN0287183
caenorhabditis_elegans		WBGENE00001020
caenorhabditis_elegans		WBGENE00001025
caenorhabditis_elegans		WBGENE00001026
caenorhabditis_elegans		WBGENE00001029
caenorhabditis_elegans	dnj-28	WBGENE00001046
caenorhabditis_elegans		WBGENE00008122

Paralogs (20): DNAJC11 (ENSG00000007923), DNAJC25 (ENSG00000059769), DNAJC10 (ENSG00000077232), DNAJC5 (ENSG00000101152), DNAJC3 (ENSG00000102580), DNAJC17 (ENSG00000104129), DNAJC2 (ENSG00000105821), DNAJC12 (ENSG00000108176), DNAJC4 (ENSG00000110011), DNAJC16 (ENSG00000116138), 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 14 — Q6Y2X3 (reviewed: Q6Y2X3)

Alternative names: DnaJ protein homolog 3, Dopamine receptor-interacting protein of 78 kDa, Human DnaJ protein 3

All UniProt accessions (3): Q6Y2X3, F8VNT6, F8VYY5

UniProt curated annotations — full annotation on UniProt →

Function. Regulates the export of target proteins, such as DRD1, from the endoplasmic reticulum to the cell surface.

Subunit / interactions. Interacts with the FxxxFxxxF motif of DRD1 via its C-terminal domain.

Subcellular location. Endoplasmic reticulum membrane.

Tissue specificity. Highly expressed in pancreas and selectively expressed in brain, lung, liver, skeletal muscle and kidney.

RefSeq proteins (5): NP_001381616, NP_001381617, NP_001381618, NP_001381619, NP_115740* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR032843	Jiv	Domain
IPR036869	J_dom_sf	Homologous_superfamily
IPR052317	Viral_replicn-host_int_reg	Family

Pfam: PF00226, PF14901

UniProt features (19 total): compositionally biased region 9, transmembrane region 3, region of interest 3, sequence conflict 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6Y2X3-F1	60.30	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 97 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GGGTGGRR_PAX4_03, CATRRAGC_UNKNOWN, TGACATY_UNKNOWN, DODD_NASOPHARYNGEAL_CARCINOMA_UP, RYTTCCTG_ETS2_B, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING, AML1_01, GOMF_SIGNALING_RECEPTOR_BINDING, ACEVEDO_LIVER_CANCER_UP, MODULE_207, AP4_01, ACTWSNACTNY_UNKNOWN, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK

GO Biological Process (1): protein transport (GO:0015031)

GO Molecular Function (3): dopamine receptor binding (GO:0050780), G protein-coupled receptor binding (GO:0001664), protein binding (GO:0005515)

GO Cellular Component (3): endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	1
intracellular protein localization	1
establishment of protein localization	1
G protein-coupled receptor binding	1
signaling receptor binding	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJC14	DRD1	P21728	717
DNAJC14	CANX	P27824	701
DNAJC14	HSPA5	P11021	617
DNAJC14	TMUB2	Q71RG4	580
DNAJC14	CHRM2	P08172	550
DNAJC14	DNAJC28	Q9NX36	532
DNAJC14	SLC26A4	O43511	529
DNAJC14	PCBP4	P57723	526
DNAJC14	PDCL	Q13371	522
DNAJC14	TBC1D10B	Q4KMP7	502
DNAJC14	TLK2	Q86UE8	499
DNAJC14	AMMECR1L	Q6DCA0	476
DNAJC14	ZNF521	Q96K83	476
DNAJC14	CNRIP1	Q96F85	459
DNAJC14	DNAJC9	Q8WXX5	459

IntAct

20 interactions, top by confidence:

A	B	Type	Score
DNAJC14	SARNP	psi-mi:“MI:0915”(physical association)	0.640
DNAJC14	SARNP	psi-mi:“MI:0914”(association)	0.640
IGSF8	CLGN	psi-mi:“MI:0914”(association)	0.530
REG1A	NAA25	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
DNAJC14	espY1	psi-mi:“MI:0915”(physical association)	0.370
espY1	DNAJC14	psi-mi:“MI:0915”(physical association)	0.370
DNAJC14	ADRB2	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
IGSF8	CD9	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
BSCL2	TMEM223	psi-mi:“MI:0914”(association)	0.350
IGSF8	SCAMP3	psi-mi:“MI:0914”(association)	0.350
BSCL2	QSOX1	psi-mi:“MI:0914”(association)	0.350
GDPD5	TMEM120B	psi-mi:“MI:0914”(association)	0.350
IGSF8	HIP1R	psi-mi:“MI:0914”(association)	0.350
SLC27A6	NBAS	psi-mi:“MI:0914”(association)	0.350
BTG3	DNAJC14	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (63): DNAJC14 (Affinity Capture-MS), SARNP (Affinity Capture-MS), CPVL (Affinity Capture-MS), DNAJC14 (Affinity Capture-MS), SARNP (Affinity Capture-MS), DNAJC14 (Affinity Capture-RNA), DNAJC14 (Affinity Capture-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS), DNAJC14 (Proximity Label-MS)

ESM2 similar proteins: A0A096P2H6, A0A0D9S1R4, A2APA5, A9CBA0, P06740, P06759, P0DKU6, P0DKW1, P0DKW2, P0DKW3, P0DKW4, P0DKY3, P0DML4, P0DML5, P0DML6, P0DMN8, P0DOC4, P0DP53, P0DTG9, P0DTH0, P0DTH1, P0DTH2, P0DTH3, P0DTH4, P0DUP5, P0DUP6, P22749, P33622, P35225, P55056, P55057, P55797, Q0VCT2, Q13790, Q3SYR5, Q3ZRW9, Q5HZE8, Q5JTB6, Q5JX69, Q5JX71

Diamond homologs: A1BHL1, A1JJD6, A1TLH8, A1WAR7, A3MA88, A5IDK7, A5N6M3, A5WBF8, A6LRN5, A6Q486, A6QBG7, A9BNG6, A9IGC5, B0S1F7, B0VA24, B0VQ00, B2I2G6, B2RLJ0, B2TLZ8, B2V2I6, B3EE31, B3PXH2, B3R6G6, B5ENA2, B7GV08, B7I2B2, B7J7X8, B9FHF3, B9MDJ8, C5BQ32, F4JIN3, O13633, O25890, O33529, O59731, O67623, O74746, O75190, O75937, P25303

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DNAJC14	down-regulates	ROS

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	91
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

983 predictions. Top by Δscore:

Variant	Effect	Δscore
12:55821994:T:TA	donor_gain	1.0000
12:55821999:A:AC	donor_gain	1.0000
12:55822000:C:CC	donor_gain	1.0000
12:55822000:CTTT:C	donor_gain	1.0000
12:55822003:T:A	donor_gain	1.0000
12:55822029:C:CA	donor_gain	1.0000
12:55822183:TGGCT:T	acceptor_gain	1.0000
12:55822184:GGCT:G	acceptor_gain	1.0000
12:55822186:CT:C	acceptor_gain	1.0000
12:55822187:TC:T	acceptor_loss	1.0000
12:55822188:C:CC	acceptor_gain	1.0000
12:55822189:T:A	acceptor_loss	1.0000
12:55822193:G:C	acceptor_gain	1.0000
12:55822193:G:GC	acceptor_gain	1.0000
12:55822199:C:CT	acceptor_gain	1.0000
12:55822200:A:T	acceptor_gain	1.0000
12:55822569:TA:T	donor_loss	1.0000
12:55822570:AC:A	donor_loss	1.0000
12:55822570:ACCT:A	donor_loss	1.0000
12:55822728:ACCTC:A	acceptor_gain	1.0000
12:55822729:CCTCC:C	acceptor_gain	1.0000
12:55822730:CTC:C	acceptor_gain	1.0000
12:55822731:TC:T	acceptor_gain	1.0000
12:55822731:TCCTG:T	acceptor_loss	1.0000
12:55822732:CC:C	acceptor_gain	1.0000
12:55822732:CCTGC:C	acceptor_loss	1.0000
12:55822733:C:CC	acceptor_gain	1.0000
12:55822733:CTGCA:C	acceptor_loss	1.0000
12:55822740:C:CT	acceptor_gain	1.0000
12:55822740:C:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000070111 (12:55826304 G>A,T), RS1000584101 (12:55830680 C>G,T), RS1000872070 (12:55829992 C>G,T), RS1000931554 (12:55825575 G>A,C,T), RS1001283510 (12:55829526 G>A), RS1001473614 (12:55829760 C>T), RS1001819695 (12:55829928 A>G), RS1001923313 (12:55825023 T>G), RS1002070031 (12:55829201 C>T), RS1002693364 (12:55830635 A>G), RS1002844851 (12:55821222 T>C), RS1002875932 (12:55821433 A>C), RS1002880268 (12:55830750 TC>T,TCC), RS1002936475 (12:55826656 C>T), RS1003345099 (12:55827834 G>A,T)

Disease associations

OMIM: gene MIM:606092 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_217	Refractive error	6.000000e-174

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, decreases expression	2
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
2-palmitoylglycerol	increases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
Bortezomib	decreases expression	1
Arsenic	affects methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	increases methylation	1
Copper Sulfate	decreases expression	1
Acrylamide	decreases expression	1
Vitamin K 3	affects expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1QA	Abcam HeLa DNAJC14 KO	Cancer cell line	Female
CVCL_LI03	GHOST(3)-CCR5 DRiP78 and NHERF1 knockdown	Cancer cell line	Female
CVCL_LI04	GHOST(3)-CXCR4 DRiP78 and NHERF1 knockdown	Cancer cell line	Female

Clinical trials (associated diseases)

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