DNAJB14

Summary

DNAJB14 (DnaJ heat shock protein family (Hsp40) member B14, HGNC:25881) is a protein-coding gene on chromosome 4q23, encoding DnaJ homolog subfamily B member 14 (Q8TBM8). Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway.

Enables Hsp70 protein binding activity. Involved in chaperone cofactor-dependent protein refolding and protein-containing complex assembly. Located in endoplasmic reticulum.

Source: NCBI Gene 79982 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001031723

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25881
Approved symbol	DNAJB14
Name	DnaJ heat shock protein family (Hsp40) member B14
Location	4q23
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14281
Ensembl gene	ENSG00000164031
Ensembl biotype	protein_coding
OMIM	617487
Entrez	79982

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 6 protein_coding, 5 nonsense_mediated_decay, 3 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000334223, ENST00000398991, ENST00000420137, ENST00000426476, ENST00000442697, ENST00000455208, ENST00000469942, ENST00000471101, ENST00000471738, ENST00000474664, ENST00000493110, ENST00000610281, ENST00000875636, ENST00000875637, ENST00000875638, ENST00000953796

RefSeq mRNA: 3 — MANE Select: NM_001031723 NM_001031723, NM_001278310, NM_001278311

CCDS: CCDS34035, CCDS75171

Canonical transcript exons

ENST00000442697 — 8 exons

Exon	Start	End
ENSE00001677945	99896248	99901152
ENSE00001737845	99946439	99946618
ENSE00003491208	99906517	99906611
ENSE00003510242	99930450	99930621
ENSE00003531618	99905597	99905706
ENSE00003547842	99903726	99903898
ENSE00003562576	99923040	99923185
ENSE00003593891	99908711	99908896

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.3958 / max 330.1331, expressed in 1761 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53299	9.3132	1715
53302	1.6014	869
53303	1.1077	630
53301	0.6920	415
53300	0.6814	356

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lateral nuclear group of thalamus	UBERON:0002736	97.36	gold quality
substantia nigra pars compacta	UBERON:0001965	96.51	gold quality
calcaneal tendon	UBERON:0003701	96.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	95.60	gold quality
cauda epididymis	UBERON:0004360	95.53	gold quality
caput epididymis	UBERON:0004358	95.44	gold quality
lateral globus pallidus	UBERON:0002476	95.29	gold quality
superficial temporal artery	UBERON:0001614	95.26	gold quality
dorsal root ganglion	UBERON:0000044	95.13	gold quality
lower lobe of lung	UBERON:0008949	95.06	gold quality
corpus epididymis	UBERON:0004359	94.98	gold quality
postcentral gyrus	UBERON:0002581	94.82	gold quality
cerebellar vermis	UBERON:0004720	94.82	gold quality
parietal lobe	UBERON:0001872	94.75	gold quality
superior vestibular nucleus	UBERON:0007227	94.55	gold quality
ventral tegmental area	UBERON:0002691	94.17	gold quality
adrenal tissue	UBERON:0018303	94.05	gold quality
corpus callosum	UBERON:0002336	93.80	gold quality
mucosa of paranasal sinus	UBERON:0005030	93.78	gold quality
inferior vagus X ganglion	UBERON:0005363	93.56	gold quality
trigeminal ganglion	UBERON:0001675	93.48	gold quality
pylorus	UBERON:0001166	93.46	gold quality
pons	UBERON:0000988	93.36	gold quality
urethra	UBERON:0000057	93.19	gold quality
renal medulla	UBERON:0000362	93.00	gold quality
mammary duct	UBERON:0001765	92.96	gold quality
nipple	UBERON:0002030	92.92	gold quality
superior frontal gyrus	UBERON:0002661	92.84	gold quality
blood vessel layer	UBERON:0004797	92.82	gold quality
entorhinal cortex	UBERON:0002728	92.52	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.60
E-MTAB-6678	yes	7.15

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Over-expression of DNAJB12 or DNAJB14 causes the formation of elaborate membranous structures within cell nuclei, designated DJANGOS for DNAJ-associated nuclear globular structures. (PMID:24732912)
• ER-located J-protein chaperones were identified as key regulators for the iogenesis and physiological function of ERG K+ channels. They regulate two distinct aspects of K+ channel biogenesis, the stabilization and assembly of channel subunits. (PMID:27916661)
• DNAJB12 and DNJB14 are non-redundant Hsp40 redox chaperones involved in endoplasmic reticulum protein reflux. (PMID:37925033)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnajb14	ENSDARG00000069996
mus_musculus	Dnajb14	ENSMUSG00000074212
rattus_norvegicus	Dnajb14	ENSRNOG00000060107
drosophila_melanogaster	CG2887	FBGN0030207
drosophila_melanogaster	CG5001	FBGN0031322
drosophila_melanogaster	CG3061	FBGN0038195
drosophila_melanogaster	CG30156	FBGN0050156
drosophila_melanogaster	DnaJ-1	FBGN0263106
caenorhabditis_elegans		WBGENE00001019
caenorhabditis_elegans		WBGENE00001044

Paralogs (11): DNAJB11 (ENSG00000090520), DNAJB6 (ENSG00000105993), DNAJB9 (ENSG00000128590), DNAJB1 (ENSG00000132002), DNAJB2 (ENSG00000135924), DNAJB5 (ENSG00000137094), DNAJB12 (ENSG00000148719), DNAJB4 (ENSG00000162616), DNAJB7 (ENSG00000172404), DNAJB8 (ENSG00000179407), DNAJB13 (ENSG00000187726)

Protein

Protein identifiers

DnaJ homolog subfamily B member 14 — Q8TBM8 (reviewed: Q8TBM8)

All UniProt accessions (6): A0A087WWX2, Q8TBM8, F2Z2L8, H7BZG5, H7BZK3, H7C494

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway. Acts by determining HSPA8/Hsc70’s ATPase and polypeptide-binding activities. Can also act independently of HSPA8/Hsc70: together with DNAJB12, acts as a chaperone that promotes maturation of potassium channels KCND2 and KCNH2 by stabilizing nascent channel subunits and assembling them into tetramers. While stabilization of nascent channel proteins is dependent on HSPA8/Hsc70, the process of oligomerization of channel subunits is independent of HSPA8/Hsc70. When overexpressed, forms membranous structures together with DNAJB12 and HSPA8/Hsc70 within the nucleus; the role of these structures, named DJANGOs, is still unclear. (Microbial infection) In case of infection by polyomavirus, involved in the virus endoplasmic reticulum membrane penetration and infection.

Subunit / interactions. Interacts (via J domain) with HSPA8/Hsc70. Forms a multiprotein complex, at least composed of DNAJB12, DNAJB14, HSPA8/Hsc70 and SGTA; interaction with DNAJB14 and HSPA8/Hsc70 is direct.

Subcellular location. Endoplasmic reticulum membrane. Nucleus membrane.

Similarity. Belongs to the DnaJ family. DNAJB12/DNAJB14 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TBM8-1	1	yes
Q8TBM8-2	2

RefSeq proteins (3): NP_001026893, NP_001265239, NP_001265240 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001623	DnaJ_domain	Domain
IPR015399	DUF1977_DnaJ-like	Domain
IPR018253	DnaJ_domain_CS	Conserved_site
IPR036869	J_dom_sf	Homologous_superfamily
IPR051100	DnaJ_subfamily_B/C	Family

Pfam: PF00226, PF09320

UniProt features (13 total): topological domain 2, sequence conflict 2, region of interest 2, splice variant 2, chain 1, mutagenesis site 1, transmembrane region 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBM8-F1	76.45	0.39

Functional residue map

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

Mutagenesis-validated functional residues (1):

Position	Phenotype
136	abolishes interaction with hspa8/hsc70.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 178 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GCM_MAP4K4, GCM_PTPRD, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GTGCCTT_MIR506, GOBP_PROTEIN_MATURATION, GOBP_PROTEIN_FOLDING, SENESE_HDAC1_TARGETS_UP, CUI_TCF21_TARGETS_2_DN, GOBP_RESPONSE_TO_MISFOLDED_PROTEIN, GOBP_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, GOCC_NUCLEAR_ENVELOPE, GCM_PTK2, MOREAUX_MULTIPLE_MYELOMA_BY_TACI_DN, MARSON_BOUND_BY_FOXP3_STIMULATED

GO Biological Process (3): protein folding (GO:0006457), protein-containing complex assembly (GO:0065003), cellular response to misfolded protein (GO:0071218)

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

GO Cellular Component (5): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nuclear membrane (GO:0031965), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	2
organelle membrane	2
cellular process	1
protein maturation	1
cellular component assembly	1
protein-containing complex organization	1
cellular response to topologically incorrect protein	1
response to misfolded protein	1
heat shock protein binding	1
protein-folding chaperone binding	1
binding	1
cytoplasm	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
nucleus	1
nuclear envelope	1

Protein interactions and networks

STRING

2595 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJB14	SGTA	O43765	735
DNAJB14	HSPH1	Q92598	677
DNAJB14	HSPA8	P11142	657
DNAJB14	EMC1	Q8N766	587
DNAJB14	DNAJC2	Q99543	483
DNAJB14	EMC3	Q9P0I2	448
DNAJB14	RFFL	Q8WZ73	428
DNAJB14	DNAJB12	Q9NXW2	408
DNAJB14	BCAP31	P51572	406
DNAJB14	DNAJC18	Q9H819	385
DNAJB14	DNAJC22	Q8N4W6	380
DNAJB14	NDUFA6	P56556	378
DNAJB14	EMC6	Q9BV81	375
DNAJB14	UQCC6	Q69YU5	374
DNAJB14	DNAJC28	Q9NX36	367

IntAct

27 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	DNAJB14	psi-mi:“MI:0915”(physical association)	0.550
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
DNAJB14	KHK	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350
RIPK4	VWA8	psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CCDC47	ESYT2	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
FOXRED2	VWA8	psi-mi:“MI:0914”(association)	0.350
GPR45	VWA8	psi-mi:“MI:0914”(association)	0.350
ECEL1	ADAM10	psi-mi:“MI:0914”(association)	0.350
TUSC2	HGS	psi-mi:“MI:0914”(association)	0.350
MAP2K2	FANCA	psi-mi:“MI:0914”(association)	0.350
HDAC6	DNAJB14	psi-mi:“MI:0914”(association)	0.350
SLC12A9	PGRMC1	psi-mi:“MI:0914”(association)	0.350
SLC19A2	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC6A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC9A4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SLC9C2	PSMD11	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
DNAJB14	RXRB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (89): DNAJB14 (Affinity Capture-MS), HSPA2 (Co-fractionation), HSPA8 (Co-fractionation), HSPA9 (Co-fractionation), KHK (Affinity Capture-MS), DNAJB14 (Affinity Capture-MS), DNAJB14 (Affinity Capture-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS), DNAJB14 (Proximity Label-MS)

ESM2 similar proteins: A0A0D1E2P6, A0A0D2XVZ5, A0A0P0VG31, A0A0P1AAU8, A0A287B8J2, A2WYG9, A4QP73, B9EHT4, B9F2Y7, D0NCC1, J9VKM5, O08788, O59739, P0C7L7, P0CP26, P0CP27, P14725, P28023, P39742, P82874, P92792, Q10MW6, Q13217, Q14203, Q149L6, Q27968, Q28I38, Q54M21, Q54NS3, Q58DR2, Q5JJI4, Q5JNB5, Q5R686, Q5R6H3, Q5ZI13, Q6PCJ1, Q6YUL8, Q7ZXQ8, Q8TBM8, Q91YW3

Diamond homologs: A1BHL1, A1V0U8, A2S563, A3MN97, A3ND66, A3NYX5, A4G8D1, A4SFR5, A5CD86, A5IDK7, A5UYW4, A5W9A2, A5WBF8, A6LJ63, A6Q486, A6T225, A6VNB0, A7GT07, A7NS65, A8FFD1, B0JW23, B0KIS4, B1J255, B1WVR2, B1YTK1, B2J3J3, B3CVD9, B3EE31, B4S9D0, B5YAR4, B7IFE0, B7JY68, B8HLD2, C4K3I5, C4L424, C4L8Y4, J9VP29, O06431, O13633, O27352

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2319 predictions. Top by Δscore:

Variant	Effect	Δscore
4:99901030:ATCCT:A	donor_gain	1.0000
4:99901031:T:TA	donor_gain	1.0000
4:99901034:T:TA	donor_gain	1.0000
4:99903720:ACTT:A	donor_loss	1.0000
4:99903721:CTTA:C	donor_gain	1.0000
4:99903722:TTACT:T	donor_loss	1.0000
4:99903723:TAC:T	donor_loss	1.0000
4:99903724:A:AC	donor_gain	1.0000
4:99903724:AC:A	donor_loss	1.0000
4:99903725:C:CT	donor_gain	1.0000
4:99903725:CT:C	donor_gain	1.0000
4:99903725:CTT:C	donor_gain	1.0000
4:99903725:CTTT:C	donor_gain	1.0000
4:99903725:CTTTG:C	donor_gain	1.0000
4:99903894:TTCCA:T	acceptor_gain	1.0000
4:99903895:TCCA:T	acceptor_gain	1.0000
4:99903896:CCA:C	acceptor_gain	1.0000
4:99903896:CCAC:C	acceptor_gain	1.0000
4:99903896:CCACT:C	acceptor_loss	1.0000
4:99903897:CA:C	acceptor_gain	1.0000
4:99903897:CAC:C	acceptor_gain	1.0000
4:99903898:AC:A	acceptor_loss	1.0000
4:99903899:C:CC	acceptor_gain	1.0000
4:99903900:T:A	acceptor_loss	1.0000
4:99906465:A:AC	donor_gain	1.0000
4:99906466:C:CC	donor_gain	1.0000
4:99906470:T:A	donor_gain	1.0000
4:99906512:CGTA:C	donor_loss	1.0000
4:99906513:GTA:G	donor_loss	1.0000
4:99906515:A:AC	donor_gain	1.0000

AlphaMissense

2512 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:99901071:C:G	C366S	1.000
4:99901072:A:G	C366R	1.000
4:99901072:A:T	C366S	1.000
4:99903745:G:C	C332W	1.000
4:99903746:C:G	C332S	1.000
4:99903746:C:T	C332Y	1.000
4:99903747:A:G	C332R	1.000
4:99903747:A:T	C332S	1.000
4:99908730:A:C	F206L	1.000
4:99908730:A:T	F206L	1.000
4:99908732:A:G	F206L	1.000
4:99908742:A:C	F202L	1.000
4:99908742:A:T	F202L	1.000
4:99908743:A:C	F202C	1.000
4:99908743:A:G	F202S	1.000
4:99908744:A:G	F202L	1.000
4:99908746:A:G	L201S	1.000
4:99908854:C:G	R165P	1.000
4:99908872:A:G	L159S	1.000
4:99908882:A:C	Y156D	1.000
4:99908884:G:T	A155D	1.000
4:99908885:C:G	A155P	1.000
4:99908890:C:T	G153E	1.000
4:99908891:C:G	G153R	1.000
4:99908891:C:T	G153R	1.000
4:99908893:A:T	I152N	1.000
4:99923041:T:A	K150N	1.000
4:99923041:T:G	K150N	1.000
4:99923043:T:C	K150E	1.000
4:99923044:A:C	F149L	1.000

dbSNP variants (sampled 300 via entrez): RS1000004218 (4:99942295 C>A,T), RS1000081328 (4:99908114 T>C), RS1000091835 (4:99913524 C>G,T), RS1000163952 (4:99913923 A>G), RS1000210780 (4:99919234 T>C), RS1000244519 (4:99921882 T>C), RS1000269871 (4:99947648 C>T), RS1000297988 (4:99914244 C>A), RS1000408431 (4:99906207 A>C), RS1000419378 (4:99929537 C>T), RS1000444884 (4:99905807 C>A), RS1000523720 (4:99936969 C>T), RS1000579544 (4:99919923 C>A,T), RS1000850152 (4:99898190 T>G), RS1000865519 (4:99906722 G>C,T)

Disease associations

OMIM: gene MIM:617487 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
bufotalin	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
arsenite	affects binding, increases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
fenpyroximate	increases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	increases expression	1
torcetrapib	increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	affects cotreatment, increases expression	1
Carbamazepine	affects expression	1
Diclofenac	affects expression	1
Gold	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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