DNAJA2

Summary

DNAJA2 (DnaJ heat shock protein family (Hsp40) member A2, HGNC:14884) is a protein-coding gene on chromosome 16q11.2, encoding DnaJ homolog subfamily A member 2 (O60884). Co-chaperone of Hsc70.

The protein encoded by this gene belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus; a glycine/phenylalanine (G/F)-rich region; and a cysteine-rich domain containing 4 motifs resembling a zinc finger domain. The product of this gene works as a cochaperone of Hsp70s in protein folding and mitochondrial protein import in vitro.

Source: NCBI Gene 10294 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• GTEx eGene: eQTL in 18 tissues, sQTL in 1 (q < 0.05)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.26 (highly constrained)
• MANE Select transcript: NM_005880
• Interaction hub: 2,531 STRING partners (top 4% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14884
Approved symbol	DNAJA2
Name	DnaJ heat shock protein family (Hsp40) member A2
Location	16q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HIRIP4, DNAJ, CPR3, DNJ3
Ensembl gene	ENSG00000069345
Ensembl biotype	protein_coding
OMIM	611322
Entrez	10294

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 nonsense_mediated_decay, 7 protein_coding, 1 retained_intron

MANE Select: ENST00000317089

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 5: 1

ENST00000317089, ENST00000563158, ENST00000569553, ENST00000617000, ENST00000898901, ENST00000917412, ENST00000968499, ENST00000968500, ENST00000998868, ENST00001013965, ENST00001013966, ENST00001013967, ENST00001013968, ENST00001067703, ENST00001067704, ENST00001067706, ENST00001134761

RefSeq mRNA: 1 — MANE Select: NM_005880 NM_005880

CCDS: CCDS10726

Canonical transcript exons

ENST00000317089 — 9 exons

Exon	Start	End
ENSE00000682853	46971349	46971572
ENSE00000682855	46971896	46971955
ENSE00001308081	46955362	46957220
ENSE00002611132	46973495	46973674
ENSE00003473638	46968084	46968164
ENSE00003533248	46967513	46967646
ENSE00003614046	46959275	46959419
ENSE00003670389	46959003	46959130
ENSE00003690454	46964611	46964807

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 96.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 86.7471 / max 819.9124, expressed in 1825 samples.

Highest expression (Bgee): calcaneal tendon, gastrocnemius, muscle of leg, endothelial cell, sperm.

Genetic regulation across tissues (GTEx eQTL / sQTL)

DNAJA2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 18 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

19 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Not Sun Exposed Suprapubic	eqtl	8.4e-05	+0.19	16:47052286:CA:C
Thyroid	eqtl	2.4e-04	+0.17	16:47000728:C:T
Skin Sun Exposed Lower leg	eqtl	3.9e-04	+0.14	16:47043617:C:T
Brain Frontal Cortex BA9	eqtl	4.0e-03	+0.25	16:47019826:A:G
Artery Tibial	eqtl	6.8e-03	-0.18	16:47272133:T:C
Breast Mammary Tissue	eqtl	1.1e-02	+0.15	16:46981007:G:A
Brain Putamen basal ganglia	eqtl	1.2e-02	+0.19	16:47020178:G:T
Cells Cultured fibroblasts	eqtl	1.3e-02	-0.11	16:47907471:T:C
Brain Substantia nigra	eqtl	1.3e-02	-0.18	16:47862522:T:C
Lung	eqtl	1.4e-02	-0.29	16:46924397:G:A
Esophagus Muscularis	eqtl	1.7e-02	+0.11	16:46948904:G:C
Colon Transverse	eqtl	2.0e-02	+0.14	16:47052286:CA:C
Brain Nucleus accumbens basal ganglia	eqtl	2.1e-02	+0.13	16:47030240:T:TG
Nerve Tibial	eqtl	2.9e-02	-0.30	16:46688167:A:C
Adipose Visceral Omentum	eqtl	3.4e-02	+0.26	16:46611734:C:T
Testis	eqtl	3.5e-02	+0.12	16:47065484:A:T
Muscle Skeletal	eqtl	4.2e-02	+0.09	16:46746283:A:G
Adipose Subcutaneous	sqtl	4.2e-02	+0.50	16:47060939:A:G
Brain Cerebellar Hemisphere	eqtl	4.8e-02	-0.22	16:47571500:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
157232	85.1295	1825
157231	1.6176	998

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.68	gold quality
gastrocnemius	UBERON:0001388	95.65	gold quality
muscle of leg	UBERON:0001383	95.58	gold quality
endothelial cell	CL:0000115	95.56	gold quality
sperm	CL:0000019	95.52	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.51	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	95.43	gold quality
adrenal tissue	UBERON:0018303	95.22	gold quality
germinal epithelium of ovary	UBERON:0001304	95.15	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.13	gold quality
cortical plate	UBERON:0005343	95.03	gold quality
right atrium auricular region	UBERON:0006631	94.99	gold quality
prefrontal cortex	UBERON:0000451	94.84	gold quality
cardiac atrium	UBERON:0002081	94.82	gold quality
pigmented layer of retina	UBERON:0001782	94.61	gold quality
monocyte	CL:0000576	94.59	gold quality
heart left ventricle	UBERON:0002084	94.56	gold quality
cardiac ventricle	UBERON:0002082	94.51	gold quality
muscle organ	UBERON:0001630	94.47	gold quality
islet of Langerhans	UBERON:0000006	94.38	gold quality
heart	UBERON:0000948	94.38	gold quality
right adrenal gland	UBERON:0001233	94.38	gold quality
right adrenal gland cortex	UBERON:0035827	94.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.31	gold quality
mononuclear cell	CL:0000842	94.29	gold quality
biceps brachii	UBERON:0001507	94.27	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.23	gold quality
leukocyte	CL:0000738	94.20	gold quality
ganglionic eminence	UBERON:0004023	94.18	gold quality
left adrenal gland	UBERON:0001234	94.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	94.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	94.04	gold quality
primary visual cortex	UBERON:0002436	94.01	gold quality
nucleus accumbens	UBERON:0001882	94.00	gold quality
caudate nucleus	UBERON:0001873	93.95	gold quality
adrenal gland	UBERON:0002369	93.88	gold quality
esophagus	UBERON:0001043	93.80	gold quality
esophagus mucosa	UBERON:0002469	93.80	gold quality
left adrenal gland cortex	UBERON:0035825	93.79	gold quality
adrenal cortex	UBERON:0001235	93.78	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.76	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.76	gold quality
colonic mucosa	UBERON:0000317	93.75	gold quality
lower esophagus	UBERON:0013473	93.75	gold quality
male germ cell	CL:0000015	93.65	gold quality
stromal cell of endometrium	CL:0002255	93.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.49	gold quality
ventricular zone	UBERON:0003053	93.48	gold quality
sigmoid colon	UBERON:0001159	93.46	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.45	gold quality
gall bladder	UBERON:0002110	93.43	gold quality
right frontal lobe	UBERON:0002810	93.42	gold quality
popliteal artery	UBERON:0002250	93.14	gold quality
tibial artery	UBERON:0007610	93.14	gold quality
skin of leg	UBERON:0001511	93.10	gold quality
pons	UBERON:0000988	93.09	gold quality
myocardium	UBERON:0002349	93.07	gold quality
putamen	UBERON:0001874	93.04	gold quality
descending thoracic aorta	UBERON:0002345	93.04	gold quality
skin of abdomen	UBERON:0001416	93.03	gold quality
left ovary	UBERON:0002119	93.00	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.00	gold quality
body of uterus	UBERON:0009853	93.00	gold quality
penis	UBERON:0000989	92.95	gold quality
caput epididymis	UBERON:0004358	92.92	gold quality
ovary	UBERON:0000992	92.91	gold quality
right testis	UBERON:0004534	92.91	gold quality
neocortex	UBERON:0001950	92.84	gold quality
omental fat pad	UBERON:0010414	92.84	gold quality
peritoneum	UBERON:0002358	92.83	gold quality
colon	UBERON:0001155	92.81	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.80	gold quality
large intestine	UBERON:0000059	92.78	gold quality
frontal cortex	UBERON:0001870	92.78	gold quality
aorta	UBERON:0000947	92.77	gold quality
transverse colon	UBERON:0001157	92.76	gold quality
testis	UBERON:0000473	92.73	gold quality
telencephalon	UBERON:0001893	92.73	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.73	gold quality
cerebral cortex	UBERON:0000956	92.68	gold quality
jejunum	UBERON:0002115	92.67	gold quality
left testis	UBERON:0004533	92.63	gold quality
mucosa of transverse colon	UBERON:0004991	92.63	gold quality
rectum	UBERON:0001052	92.62	gold quality
lymph node	UBERON:0000029	92.60	gold quality
jejunal mucosa	UBERON:0000399	92.60	gold quality
right coronary artery	UBERON:0001625	92.57	gold quality
apex of heart	UBERON:0002098	92.55	gold quality
cingulate cortex	UBERON:0003027	92.55	gold quality
intestine	UBERON:0000160	92.53	gold quality
endometrium	UBERON:0001295	92.49	gold quality
amygdala	UBERON:0001876	92.49	gold quality
forebrain	UBERON:0001890	92.48	gold quality
zone of skin	UBERON:0000014	92.43	gold quality
upper leg skin	UBERON:0004262	92.43	gold quality
oral cavity	UBERON:0000167	92.42	gold quality
adipose tissue	UBERON:0001013	92.42	gold quality
right ovary	UBERON:0002118	92.41	gold quality
left uterine tube	UBERON:0001303	92.39	gold quality
epithelium of nasopharynx	UBERON:0001951	92.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	no	3.12
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	117.5
Caudate putamen	tissue	113.4
Spinal cord	tissue	77.2
Pons	tissue	72.1
Thalamus	tissue	72.1
Cerebral cortex	tissue	70.9	medium
Somatosensory cortex	tissue	70.9
Superior colliculi	tissue	68.9
Occipital cortex	tissue	66.5
Midbrain	tissue	64.8
Putamen	tissue	64.1
Medulla oblongata	tissue	60.9
Hippocampal formation	tissue	58.8
Motor cortex	tissue	58.7
Septum	tissue	56.8
Prefrontal cortex	tissue	56.5
Hypothalamus	tissue	56.3
Retrosplenial and cingulate cortex	tissue	55.5
Substantia nigra	tissue	54.7
Cerebellum	tissue	54.5	medium
Entorhinal cortex	tissue	54.5
Basal ganglia	tissue	53.5	medium
Periaqueductal gray	tissue	53.2
Ventral forebrain	tissue	52.9
Temporal cortex	tissue	51.2
Retrosplenial cortex	tissue	49.7
Olfactory bulb	tissue	44.7
Insular cortex	tissue	42.9
Amygdala	tissue	41.8
Corpus callosum	tissue	39.9
Postcentral gyrus	tissue	37.7
Tongue	tissue	36.0
Nucleus accumbens	tissue	35.2
Choroid plexus	tissue	35.0
Skeletal muscle	tissue	34.8	medium
Heart muscle	tissue	33.6	medium
Liver	tissue	33.6	low
Locus coeruleus	tissue	27.8
Hippocampus	tissue	27.7	medium
Parathyroid gland	tissue	27.4	low
Retina	tissue	27.3
Epididymis	tissue	26.9	medium
Kidney	tissue	26.2	high
Adrenal gland	tissue	23.8	high
Testis	tissue	23.3	high
Ovary	tissue	23.2	high
Bone marrow	tissue	22.5	low
Spleen	tissue	21.4	medium
Thyroid gland	tissue	20.8	medium
Endometrium 1	tissue	20.6	medium
Prostate	tissue	20.5	low
Urinary bladder	tissue	20.2	medium
Tonsil	tissue	20.1	medium
Seminal vesicle	tissue	19.4	medium
Adipose tissue	tissue	19.4	not detected
Small intestine	tissue	19.3	medium
Duodenum	tissue	18.9	high
Thymus	tissue	18.9
Placenta	tissue	18.7	medium
Lymph node	tissue	18.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (77.2), Dorsal hippocampus (58.8), Dorsal spinal cord (57.8), Ventral hippocampus (51.9), Subiculum (49.8).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting DNAJA2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 186 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
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-3646	100.00	73.56	5283
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.258, missense Z 2.87 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000317089 — one region, missense o/e 0.67.

Literature-anchored findings (GeneRIF, showing 12)

• Rdj2 modulates G protein signaling and further suggest that chaperoning G proteins is an emerging theme of the J protein network. (PMID:18595009)
• Bag1 NEF increased refolding by Hsc70 and DJA2, as did the newly characterized NEF Hsp110 (PMID:18684711)
• Hsp40 type 1 chaperones DJA1 (DNAJA1/Hdj2) and DJA2 (DNAJA2) as key modulators of hERG degradation (PMID:19940115)
• The DNAJA2 substrate release mechanism is essential for chaperone-mediated folding. (PMID:23091061)
• we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. (PMID:24318877)
• Study shows that Hsp40 and Hsp70 recognize a region of the androgen receptor (AR) N-terminal domain (NTD), including a FQNLF motif, that interacts with the AR ligand-binding domain (LBD) upon activation. This suggests that competition between molecular chaperones and the LBD for the FQNLF motif regulates AR activation. (PMID:31395886)
• overexpressing DNAJA2 but not DNAJA1 enhanced CFTR degradation at the endoplasmic reticulum by Hsc70/Hsp70 and the E3 ubiquitin ligase CHIP. Excess Hsp70 also promoted CFTR degradation, but this occurred through the lysosomal pathway and required CHIP but not complex formation with HOP and Hsp90. (PMID:31408507)
• Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles. (PMID:33229560)
• DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability. (PMID:37640708)
• The self-association equilibrium of DNAJA2 regulates its interaction with unfolded substrate proteins and with Hsc70. (PMID:37670029)
• Pseudophosphorylation of single residues of the J-domain of DNAJA2 regulates the holding/folding balance of the Hsc70 system. (PMID:39012012)
• DNAJA2 and Hero11 mediate similar conformational extension and aggregation suppression of TDP-43. (PMID:39117455)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnaja2b	ENSDARG00000010745
danio_rerio	dnaja2a	ENSDARG00000104066
mus_musculus	Dnaja2	ENSMUSG00000031701
rattus_norvegicus	Dnaja2	ENSRNOG00000016251
caenorhabditis_elegans		WBGENE00001037

Paralogs (3): DNAJA1 (ENSG00000086061), DNAJA3 (ENSG00000103423), DNAJA4 (ENSG00000140403)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1931882) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
female infertility	1
abnormal vitreous body morphology	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RAJ6	100.0%	Diamond
Bos taurus	Q5E954	99.7%	Diamond
Chlorocebus aethiops	Q95JF4	99.7%	Diamond
Canis lupus familiaris	P81999	98.0%	Diamond
Xenopus laevis	Q7ZXQ8	91.2%	Diamond
Allium ampeloprasum	P42824	88.9%	Diamond
Arabidopsis thaliana	P42825	88.9%	Diamond
Caenorhabditis briggsae	Q626I7	86.4%	Diamond
Cucumis sativus	Q04960	83.0%	Diamond
Atriplex nummularia	P43644	82.6%	Diamond
Oryza sativa Japonica Group	B9FHF3	74.5%	Diamond
Mycoplasmoides genitalium G37	P47248	67.0%	Diamond
Drosophila melanogaster	Q9VPQ2	63.8%	Diamond
Schizosaccharomyces pombe 972h-	Q09912	58.5%	Diamond
Saccharomyces cerevisiae S288C	P25491	55.7%	Diamond
Eremothecium gossypii ATCC 10895	Q757X4	54.0%	Diamond
Kluyveromyces lactis NRRL Y-1140	Q6CW35	50.0%	Diamond
Shewanella oneidensis MR-1	Q8EFW5	50.0%	Diamond
Dictyostelium discoideum	Q54ED3	40.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DNAJA2-DT	ncRNA	119545626
HDIP1	protein-coding	388272
GPT2	protein-coding	84706
SNORD148	snoRNA	109623466
ITFG1-AS1	ncRNA	101927102
NETO2	protein-coding	81831
ITFG1	protein-coding	81533

Protein

Protein identifiers

DnaJ homolog subfamily A member 2 — O60884 (reviewed: O60884)

Alternative names: Cell cycle progression restoration gene 3 protein, Dnj3, HIRA-interacting protein 4, Renal carcinoma antigen NY-REN-14

All UniProt accessions (3): A0A087WT48, I3L320, O60884

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone of Hsc70. Stimulates ATP hydrolysis and the folding of unfolded proteins mediated by HSPA1A/B (in vitro).

Subcellular location. Membrane.

RefSeq proteins (1): NP_005871* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001305	HSP_DnaJ_Cys-rich_dom	Domain
IPR001623	DnaJ_domain	Domain
IPR002939	DnaJ_C	Domain
IPR008971	HSP40/DnaJ_pept-bd	Homologous_superfamily
IPR012724	DnaJ	Family
IPR018253	DnaJ_domain_CS	Conserved_site
IPR036410	HSP_DnaJ_Cys-rich_dom_sf	Homologous_superfamily
IPR036869	J_dom_sf	Homologous_superfamily
IPR044713	DNJA1/2-like	Family

Pfam: PF00226, PF00684, PF01556

UniProt features (33 total): binding site 8, modified residue 8, sequence conflict 6, repeat 4, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1, cross-link 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
7ZHS	3D reconstruction of the cylindrical assembly of DnaJA2 delta G/F by imposing D5 symmetry	ELECTRON MICROSCOPY	6.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60884-F1	84.10	0.53

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol; nucleoli

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

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

Ligand- & substrate-binding residues (8)

Position	Role
146	Zn(2+)
159	Zn(2+)
162	Zn(2+)
186	Zn(2+)
189	Zn(2+)
202	Zn(2+)
205	Zn(2+)
143	Zn(2+)

Post-translational modifications (10)

Type	Positions
N6-acetyllysine	39, 152
Phosphoserine	78, 123, 394, 395
Phosphotyrosine	391
Cysteine methyl ester	409
S-farnesyl cysteine	409
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	134

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 4; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-9918487	Dengue Virus Genome Translation and Replication ⚕	curated
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	curated
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—

MSigDB gene sets: 265 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, SHEPARD_BMYB_MORPHOLINO_UP, TGCGCANK_UNKNOWN, GAANYNYGACNY_UNKNOWN, TGACCTY_ERR1_Q2, AAAYRNCTG_UNKNOWN, BONCI_TARGETS_OF_MIR15A_AND_MIR16_1, COUP_01, GOBP_PROTEIN_MATURATION, SOX9_B1, FOSTER_TOLERANT_MACROPHAGE_UP, HNF4_DR1_Q3, HNF4_01, GOBP_PROTEIN_FOLDING, PPAR_DR1_Q2

GO Biological Process (5): positive regulation of cell population proliferation (GO:0008284), cellular response to heat (GO:0034605), protein refolding (GO:0042026), protein folding (GO:0006457), response to heat (GO:0009408)

GO Molecular Function (8): ATPase activator activity (GO:0001671), ATP binding (GO:0005524), zinc ion binding (GO:0008270), Hsp70 protein binding (GO:0030544), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515), heat shock protein binding (GO:0031072), metal ion binding (GO:0046872)

GO Cellular Component (3): cytosol (GO:0005829), membrane (GO:0016020), extracellular exosome (GO:0070062)

Reactome top-level categories

3 top-level categories:

Category	Pathways
Cellular responses to stress	1
Dengue Virus Infection	1
Cellular responses to stimuli	1

GO top-level categories

24 GO namespaces:

Category	Terms
protein binding	2
cellular anatomical structure	2
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
response to heat	1
cellular response to stress	1
protein folding	1
cellular process	1
protein maturation	1
response to stress	1
response to temperature stimulus	1
ATP-dependent activity	1
molecular function activator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
transition metal ion binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
binding	1
cation binding	1
cytoplasm	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 5 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

5 experimentally-supported GO terms:

GO term	NS	Evidence
protein refolding	BP	direct assay
cytosol	CC	direct assay
extracellular exosome	CC	high-throughput assay
ATPase activator activity	MF	direct assay
protein-folding chaperone binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 2,531 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJA2	PRTN3	P15637	734
DNAJA2	IL32	P24001	640
DNAJA2	HSPA8	P11142	597
DNAJA2	HSPA4	P34932	563
DNAJA2	FASTKD4	Q969Z0	509
DNAJA2	BAG2	O95816	492
DNAJA2	HSP90AB1	P08238	491
DNAJA2	CSF3R	Q99062	486
DNAJA2	HSP90AA1	P07900	484
DNAJA2	HSPA9	P30036	477
DNAJA2	DNAJC6	O75061	469
DNAJA2	DNAJC8	O75937	459
DNAJA2	DNAJC10	Q8IXB1	445
DNAJA2	HSPA4L	O95757	442
DNAJA2	ELANE	P08246	439

IntAct

Human interaction partners of DNAJA2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 49 partners by confidence:

Partner	Interaction type	MIscore	Records
DNAJA4	physical association	0.710	2
NUDC	physical association	0.710	2
LLGL1	association	0.640	1
AICDA	physical association	0.570	3
DYNLT1	physical association	0.560	3
DCAF10	physical association	0.560	1
HSCB	physical association	0.550	1
DNAJA1	association	0.530	2
TAF1C	association	0.530	2
DDX11	association	0.530	1
DTL	association	0.530	1
ELP2	association	0.530	1
IFT122	association	0.530	1
TTLL5	association	0.530	1
PRR14L	physical association	0.400	1
SENP5	association	0.350	2
SFXN3	association	0.350	2
ABHD18	association	0.350	1
AXL	association	0.350	1
BLVRA	association	0.350	1
BRD2	association	0.350	1
DDB2	association	0.350	1
DENND11	association	0.350	1
DNAJC24	association	0.350	1
DNAJC5	association	0.350	1
DTWD2	association	0.350	1
EHD4	association	0.350	1
ENC1	association	0.350	1
ERCC3	association	0.350	1
GTF3C2	association	0.350	1

BioGRID (718 interactions; top human partners by supporting records in a sample of 600 records): DNAJA1 (Affinity Capture-MS; 7 records), DNAJC7 (Affinity Capture-MS; 4 records), HSPA1A (Affinity Capture-Western; 4 records), HSPA8 (Co-fractionation; 4 records), PARK2 (Affinity Capture-MS; 4 records), WDR76 (Affinity Capture-MS; 4 records), CCNF (Affinity Capture-MS; 3 records), DNAJA4 (Affinity Capture-MS; 3 records), DNAJB1 (Co-localization; 3 records), ENDOG (Affinity Capture-MS; 3 records), NTRK1 (Affinity Capture-MS; 3 records), STIP1 (Co-fractionation; 3 records), AKAP1 (Proximity Label-MS; 2 records), ANLN (Affinity Capture-MS; 2 records), ARAF (Affinity Capture-MS; 2 records)

Disease & clinical

Genetic variants

Variant evidence for DNAJA2: 46 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 679):

Position(s)	Effect	Δscore	Sites
16:46957226	acceptor_gain	1.0000
16:46959001–46959002	donor_loss	1.0000	4
16:46959273–46959274	donor_loss	1.0000	5
16:46959420–46959421	acceptor_loss	1.0000	5
16:46964609–46964610	donor_loss	1.0000	4
16:46964808–46964809	acceptor_loss	1.0000	4
16:46967511–46967512	donor_loss	1.0000	5
16:46968082–46968083	donor_loss	1.0000	5
16:46968165–46968166	acceptor_loss	1.0000	4
16:46971894–46971895	donor_loss	1.0000	5

AlphaMissense

1,524 missense substitutions predicted likely pathogenic (of 2,734 scored), across 333 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M225	9	0.972	0.995
M317	9	0.952	0.999
D38	8	0.999	1.000
H36	8	0.997	1.000
F47	8	0.995	1.000
F92	8	0.989	0.997
D290	8	0.987	0.998
F88	8	0.971	0.997
D238	8	0.969	0.993
F233	8	0.967	0.998
N40	8	0.961	0.995
D67	8	0.961	0.994
F333	8	0.961	0.998
F337	8	0.956	0.997
S51	8	0.935	0.999
D247	8	0.928	0.993
D86	8	0.924	0.992
H288	8	0.922	0.991
H118	8	0.910	0.997
F97	8	0.904	0.974

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	4.42e-05

Disease associations

OMIM: gene MIM:611322 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST007401_23	Factor VII activity	7e-7

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004619	factor VII measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295671 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
ochratoxin A	increases expression, decreases acetylation, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Particulate Matter	decreases expression, increases abundance, affects expression, increases reaction	2
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression, affects cotreatment	1
oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine	affects expression, increases reaction	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Vehicle Emissions	affects expression, increases reaction	1
Benzo(a)pyrene	increases expression	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, decreases expression	1
Dactinomycin	affects cotreatment, increases secretion	1
Diazinon	increases methylation	1
Diclofenac	affects expression	1
Hydrogen Peroxide	decreases expression	1
Indomethacin	decreases expression	1
Ivermectin	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Phenobarbital	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118575	Binding	Binding affinity to DNAJA2 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for DNAJA2 across ~30M SureChEMBL compounds — explore on Sugi Predict.