DNAJA1

Summary

DNAJA1 (DnaJ heat shock protein family (Hsp40) member A1, HGNC:5229) is a protein-coding gene on chromosome 9p21.1, encoding DnaJ homolog subfamily A member 1 (P31689). Co-chaperone for HSPA8/Hsc70. It is a selective cancer dependency (DepMap: 38.7% of cell lines).

This gene encodes a member of the DnaJ family of proteins, which act as heat shock protein 70 cochaperones. Heat shock proteins facilitate protein folding, trafficking, prevention of aggregation, and proteolytic degradation. Members of this family are characterized by a highly conserved N-terminal J domain, a glycine/phenylalanine-rich region, four CxxCxGxG zinc finger repeats, and a C-terminal substrate-binding domain. The J domain mediates the interaction with heat shock protein 70 to recruit substrates and regulate ATP hydrolysis activity. In humans, this gene has been implicated in positive regulation of virus replication through co-option by the influenza A virus. Several pseudogenes of this gene are found on other chromosomes.

Source: NCBI Gene 3301 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 48 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 38.7% of screened cell lines
• MANE Select transcript: NM_001539

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:5229
Approved symbol	DNAJA1
Name	DnaJ heat shock protein family (Hsp40) member A1
Location	9p21.1
Locus type	gene with protein product
Status	Approved
Aliases	HSPF4, hdj-2, dj-2, NEDD7
Ensembl gene	ENSG00000086061
Ensembl biotype	protein_coding
OMIM	602837
Entrez	3301

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 20 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000330899, ENST00000465677, ENST00000495015, ENST00000851558, ENST00000851559, ENST00000851560, ENST00000851561, ENST00000851562, ENST00000851563, ENST00000851564, ENST00000851565, ENST00000851566, ENST00000851567, ENST00000851568, ENST00000925271, ENST00000925272, ENST00000925273, ENST00000925274, ENST00000925275, ENST00000959509, ENST00000959510, ENST00000959511

RefSeq mRNA: 2 — MANE Select: NM_001539 NM_001314039, NM_001539

CCDS: CCDS6533

Canonical transcript exons

ENST00000330899 — 9 exons

Exon	Start	End
ENSE00001047034	33025273	33025383
ENSE00001225366	33026813	33026990
ENSE00001421214	33038685	33039907
ENSE00003463108	33036574	33036689
ENSE00003465110	33034216	33034330
ENSE00003536351	33029885	33029989
ENSE00003548015	33030440	33030667
ENSE00003592958	33037015	33037115
ENSE00003665323	33026475	33026616

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 99.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 210.4633 / max 5289.0448, expressed in 1828 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96421	207.6217	1828
96425	1.2637	627
96426	1.2315	648
96428	0.2069	76
96424	0.0953	17
96423	0.0443	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.64	gold quality
cortical plate	UBERON:0005343	99.26	gold quality
bronchial epithelial cell	CL:0002328	99.25	gold quality
ganglionic eminence	UBERON:0004023	99.06	gold quality
amniotic fluid	UBERON:0000173	98.95	gold quality
epithelium of bronchus	UBERON:0002031	98.95	gold quality
bronchus	UBERON:0002185	98.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.90	gold quality
secondary oocyte	CL:0000655	98.86	gold quality
embryo	UBERON:0000922	98.86	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.81	gold quality
ventricular zone	UBERON:0003053	98.75	gold quality
type B pancreatic cell	CL:0000169	98.61	gold quality
stromal cell of endometrium	CL:0002255	98.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	98.50	gold quality
adrenal tissue	UBERON:0018303	98.47	gold quality
lower lobe of lung	UBERON:0008949	98.45	gold quality
islet of Langerhans	UBERON:0000006	98.41	gold quality
cartilage tissue	UBERON:0002418	98.39	gold quality
colonic mucosa	UBERON:0000317	98.36	gold quality
right testis	UBERON:0004534	98.36	gold quality
left testis	UBERON:0004533	98.32	gold quality
superior vestibular nucleus	UBERON:0007227	98.30	gold quality
prefrontal cortex	UBERON:0000451	98.29	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.27	gold quality
adult organism	UBERON:0007023	98.27	gold quality
parietal pleura	UBERON:0002400	98.26	gold quality
substantia nigra pars compacta	UBERON:0001965	98.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.22	gold quality
endometrium	UBERON:0001295	98.17	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-GEOD-124472	yes	2931.67
E-HCAD-1	yes	45.92
E-CURD-122	yes	44.21
E-CURD-88	yes	41.67
E-MTAB-8142	yes	40.50
E-HCAD-4	yes	34.15
E-GEOD-135922	yes	20.78
E-MTAB-6678	yes	5.07
E-GEOD-125970	yes	4.62
E-MTAB-10137	no	7702.67
E-CURD-89	no	4036.69
E-MTAB-7037	no	352.91
E-CURD-46	no	11.26
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting DNAJA1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-3156-3P	99.76	66.72	939
HSA-MIR-3659	99.70	67.97	694
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-4804-3P	99.65	67.78	866

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 38.7% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 28)

• Mammalian, yeast, bacterial, and chemical chaperones reduce aggregate formation and death in a cell model of oculopharyngeal muscular dystrophy (PMID:11796717)
• HSP40 binding is the first step in the HSP90 chaperoning pathway for the progesterone receptor (PMID:11809754)
• sequence analysis of two isoforms (PMID:12974469)
• Multiple tissue polymerase chain reaction (PCR) results showed that nDnaJA1 expressed highly in testis and lung but low in thymus, prostate, colon and liver (PMID:15595953)
• Results indicate that DjA1 and DjB4 of subfamilies A and B of human Hsp40 have different quaternary structures and chaperone functions. (PMID:15661747)
• DJA1 was inhibitory of refolding with DJA2 and Hsc70. (PMID:18684711)
• Hsp40 type 1 chaperones DJA1 (DNAJA1/Hdj2) and DJA2 (DNAJA2) as key modulators of hERG degradation (PMID:19940115)
• Hsc70 and a dimer of DjA1 independently bind to an unfolded protein (PMID:20363747)
• Hdj2 directly associates with Japanese encephalitis virus nonstructural protein NS5 and facilitates viral replication. (PMID:21999493)
• Moreover, the levels of DnaJA1 and Hsp70 seem to play against each other with regard to tau: as DnaJA1 levels increase, tau levels are reduced, but this can be prevented if Hsp70 levels are simultaneously induced. (PMID:22343013)
• we combined the Hsp70-NEF pairs with cochaperones of the J protein family (DnaJA1, DnaJA2, DnaJB1, and DnaJB4) to generate 16 permutations. (PMID:24318877)
• structure and function of human DNAJA1 and its relationship to pancreatic cancer (PMID:24512202)
• Therefore, we propose that DnaJA1 is co-opted by the influenza A virus to enter the nucleus and to enhance its RNA polymerase activity in an Hsp70 cochaperone-independent manner. (PMID:25253355)
• that DNAJA1 controls the fate of misfolded stabilization of mutant p53 (PMID:27775703)
• DjA1 interacts with GRASP65 to enhance Golgi structure formation through the promotion of GRASP65 trans-oligomerization. (PMID:30566031)
• analysis of a a biallelic truncating variant in DNAJA1 gene (c.511C>T p.(Gln171*) in a multiplex Saudi consanguineous family (PMID:30972502)
• High level of DNAJA1 predicted poor prognosis for colorectal cancer (CRC) patients. Its expression was highly linked with E2F1 and CDC45 in CRC tissues. More importantly, KNK437 significantly suppressed the growth of DNAJA1 expressing tumor in vivo (PMID:31477839)
• HSP4 triggers epithelial-mesenchymal transition and promotes motility capacities of hepatocellular carcinoma cells via activating AKT. (PMID:32077551)
• Co-chaperones DNAJA1 and DNAJB6 are critical for regulation of polyglutamine aggregation. (PMID:32424160)
• Identification of a druggable protein-protein interaction site between mutant p53 and its stabilizing chaperone DNAJA1. (PMID:33208462)
• Hsp40 proteins phase separate to chaperone the assembly and maintenance of membraneless organelles. (PMID:33229560)
• Cereblon Regulates the Proteotoxicity of Tau by Tuning the Chaperone Activity of DNAJA1. (PMID:33972400)
• DNAJA1 promotes cancer metastasis through interaction with mutant p53. (PMID:34183772)
• High expression of DNAJA1 (HDJ2) predicts unfavorable survival outcomes in breast cancer. (PMID:34236236)
• DNAJA1 Dysregulates Metabolism Promoting an Antiapoptotic Phenotype in Pancreatic Ductal Adenocarcinoma. (PMID:34264680)
• Leveraging the Structure of DNAJA1 to Discover Novel Potential Pancreatic Cancer Therapies. (PMID:36291603)
• DNAJA1 promotes proliferation and metastasis of breast cancer by activating mutant P53/NF-kappaB pathway. (PMID:37977037)
• Novel insights into the post-translational modifications of Ydj1/DNAJA1 co-chaperones. (PMID:38309209)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dnaja1	ENSDARG00000030972
mus_musculus	Dnaja1	ENSMUSG00000028410
rattus_norvegicus	Dnaja1	ENSRNOG00000007029

Paralogs (3): DNAJA2 (ENSG00000069345), DNAJA3 (ENSG00000103423), DNAJA4 (ENSG00000140403)

Protein

Protein identifiers

DnaJ homolog subfamily A member 1 — P31689 (reviewed: P31689)

Alternative names: DnaJ protein homolog 2, HSDJ, Heat shock 40 kDa protein 4, Heat shock protein J2, Human DnaJ protein 2

All UniProt accessions (1): P31689

UniProt curated annotations — full annotation on UniProt →

Function. Co-chaperone for HSPA8/Hsc70. Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro). Plays a role in protein transport into mitochondria via its role as co-chaperone. Functions as a co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis. Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV.

Subunit / interactions. Identified in a complex with HSPA1B and BAX. Interacts with RNF207.

Subcellular location. Membrane. Cytoplasm. Microsome. Nucleus. Perinuclear region. Mitochondrion.

Tissue specificity. Ubiquitous. Isoform 2 is highly expressed in testis and lung, but detected at low levels in thymus, prostate, colon and liver.

Induction. Up-regulated by heat shock.

Isoforms (2)

UniProt ID	Names	Canonical?
P31689-1	1	yes
P31689-2	2, nDnaJA1

RefSeq proteins (2): NP_001300968, NP_001530* (*=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 (37 total): binding site 8, helix 7, modified residue 5, repeat 4, turn 2, chain 1, propeptide 1, domain 1, lipid moiety-binding region 1, splice variant 1, mutagenesis site 1, sequence conflict 1, strand 1, zinc finger region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6E8M	X-RAY DIFFRACTION	1.61
2LO1	SOLUTION NMR
2M6Y	SOLUTION NMR
8E2O	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P31689-F1	83.67	0.44

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): 134; 137; 150; 153; 177; 180; 193; 196

Post-translational modifications (6): 66, 83, 335, 381, 394, 394

Mutagenesis-validated functional residues (1):

Position	Phenotype
394	loss of farnesylation.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3371497	HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand
R-HSA-9841251	Mitochondrial unfolded protein response (UPRmt)

MSigDB gene sets: 391 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_NEGATIVE_REGULATION_OF_MAP_KINASE_ACTIVITY, ELVIDGE_HYPOXIA_DN, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, BROWNE_HCMV_INFECTION_8HR_UP, ENK_UV_RESPONSE_KERATINOCYTE_UP, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, KYNG_DNA_DAMAGE_DN, GOBP_NEGATIVE_REGULATION_OF_JUN_KINASE_ACTIVITY, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (12): protein folding (GO:0006457), response to unfolded protein (GO:0006986), response to heat (GO:0009408), negative regulation of protein ubiquitination (GO:0031397), protein refolding (GO:0042026), positive regulation of apoptotic process (GO:0043065), negative regulation of apoptotic process (GO:0043066), negative regulation of JUN kinase activity (GO:0043508), regulation of protein transport (GO:0051223), protein localization to mitochondrion (GO:0070585), negative regulation of protein localization to mitochondrion (GO:1903748), negative regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway (GO:1905259)

GO Molecular Function (14): G protein-coupled receptor binding (GO:0001664), ATPase activator activity (GO:0001671), ATP binding (GO:0005524), zinc ion binding (GO:0008270), Hsp70 protein binding (GO:0030544), Tat protein binding (GO:0030957), ubiquitin protein ligase binding (GO:0031625), low-density lipoprotein particle receptor binding (GO:0050750), obsolete unfolded protein binding (GO:0051082), protein-folding chaperone binding (GO:0051087), C3HC4-type RING finger domain binding (GO:0055131), protein binding (GO:0005515), heat shock protein binding (GO:0031072), metal ion binding (GO:0046872)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), cytoplasmic side of endoplasmic reticulum membrane (GO:0098554), endoplasmic reticulum (GO:0005783)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Cellular responses to stress	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	4
intracellular membrane-bounded organelle	3
apoptotic process	2
regulation of apoptotic process	2
protein binding	2
cellular process	1
protein maturation	1
response to topologically incorrect protein	1
response to stress	1
response to temperature stimulus	1
protein ubiquitination	1
regulation of protein ubiquitination	1
negative regulation of protein modification by small protein conjugation or removal	1
protein folding	1
positive regulation of programmed cell death	1
negative regulation of programmed cell death	1
JUN kinase activity	1
negative regulation of MAP kinase activity	1
regulation of JUN kinase activity	1
negative regulation of JNK cascade	1
protein transport	1
regulation of transport	1
regulation of establishment of protein localization	1
protein localization to organelle	1
protein localization to mitochondrion	1
regulation of protein localization to mitochondrion	1
negative regulation of protein localization	1
regulation of nitrosative stress-induced intrinsic apoptotic signaling pathway	1
intrinsic apoptotic signaling pathway in response to nitrosative stress	1
negative regulation of intrinsic apoptotic signaling pathway	1
signaling receptor binding	1
ATP-dependent activity	1
molecular function activator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
heat shock protein binding	1
protein-folding chaperone binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1

Protein interactions and networks

STRING

3995 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DNAJA1	HSPA4	P34932	978
DNAJA1	HSPA8	P11142	943
DNAJA1	HSP90AA1	P07900	935
DNAJA1	HSP90AB1	P08238	874
DNAJA1	STUB1	Q9UNE7	852
DNAJA1	STIP1	P31948	749
DNAJA1	HSPA1A	P08107	729
DNAJA1	AHSA1	O95433	722
DNAJA1	HSPH1	Q92598	704
DNAJA1	HSPBP1	Q9NZL4	683
DNAJA1	PARK7	Q99497	663
DNAJA1	ICMT	O60725	663
DNAJA1	ZMPSTE24	O75844	662
DNAJA1	CFTR	P13569	649
DNAJA1	RCE1	Q9Y256	642
DNAJA1	BAG1	Q99933	642

IntAct

362 interactions, top by confidence:

A	B	Type	Score
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
DNAJA1	HTT	psi-mi:“MI:0915”(physical association)	0.670
RAF1	CALU	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
Mad2l1	BUB1B	psi-mi:“MI:0915”(physical association)	0.560
PRKN	DNAJA1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (737): DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-Western), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-Western), DNAJA1 (Affinity Capture-Western), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS), DNAJA1 (Affinity Capture-MS)

ESM2 similar proteins: B2RLJ0, B9FHF3, O35824, O60884, O74752, O75953, O89114, O94657, P25491, P25685, P31689, P42824, P42825, P43644, P59910, P63036, P63037, P81999, Q03363, Q04960, Q0JB88, Q24133, Q2HJ94, Q2KIT4, Q3MI00, Q3ZBA6, Q54ED3, Q5BIP8, Q5E954, Q5NVI9, Q5R8J8, Q5RAJ6, Q626I7, Q6TUG0, Q8A8C3, Q8MPX3, Q8WW22, Q94AW8, Q95JF4, Q96EY1

Diamond homologs: A0A0D1E2P6, A0A0P0VG31, A0AIS3, A1A9Q7, A4XKA5, A7Z6W0, A7ZKA5, A7ZYV2, A8AI78, A8FFD1, A9MH53, A9N6S2, B1IV97, B1LJ04, B1X8V5, B1YKT0, B2TTP8, B4T2U5, B4TEN5, B4TSM3, B5BBH2, B5F1Z5, B5FR40, B5R049, B5R6G3, B5YU43, B6I976, B7LFA9, B7LP19, B7M8Y3, B7MIE6, B7MPT2, B7N3F5, B7NLC5, B7UNY3, B8I304, B9DNJ9, B9MJZ0, C0Q893, C1KVB9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 207 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
Microtubule-dependent trafficking of connexons from Golgi to the plasma membrane	6	24.2×	1e-05
Transport of connexons to the plasma membrane	6	24.2×	1e-05
Gap junction trafficking and regulation	6	21.1×	2e-05
Gap junction trafficking	6	21.1×	2e-05
Post-chaperonin tubulin folding pathway	6	21.1×	2e-05
Prefoldin mediated transfer of substrate to CCT/TriC	7	20.4×	6e-06
Activation of AMPK downstream of NMDARs	7	19.7×	6e-06
Formation of tubulin folding intermediates by CCT/TriC	6	18.8×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
intrinsic apoptotic signaling pathway	6	12.9×	3e-03
microtubule cytoskeleton organization	11	8.0×	2e-04
MAPK cascade	8	7.3×	4e-03
protein phosphorylation	12	4.9×	3e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	13	4.1×	5e-03
intracellular signal transduction	17	3.9×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1050 predictions. Top by Δscore:

Variant	Effect	Δscore
9:33026472:CAGGC:C	acceptor_loss	1.0000
9:33026473:A:AG	acceptor_gain	1.0000
9:33026473:AGG:A	acceptor_loss	1.0000
9:33026474:G:GA	acceptor_gain	1.0000
9:33026474:G:T	acceptor_loss	1.0000
9:33026474:GGC:G	acceptor_gain	1.0000
9:33026474:GGCA:G	acceptor_gain	1.0000
9:33026577:G:GT	donor_gain	1.0000
9:33026610:A:T	donor_gain	1.0000
9:33026613:GAAG:G	donor_gain	1.0000
9:33026614:AAGG:A	donor_loss	1.0000
9:33026616:GG:G	donor_loss	1.0000
9:33026617:G:GA	donor_loss	1.0000
9:33026618:T:G	donor_loss	1.0000
9:33026811:A:AG	acceptor_gain	1.0000
9:33026812:G:GA	acceptor_gain	1.0000
9:33026812:GT:G	acceptor_gain	1.0000
9:33026812:GTTT:G	acceptor_gain	1.0000
9:33026812:GTTTA:G	acceptor_gain	1.0000
9:33026988:GAG:G	donor_gain	1.0000
9:33026988:GAGGT:G	donor_loss	1.0000
9:33026989:AGGT:A	donor_loss	1.0000
9:33026991:G:A	donor_loss	1.0000
9:33026992:T:G	donor_loss	1.0000
9:33029878:GTTTT:G	acceptor_loss	1.0000
9:33029879:TTTTA:T	acceptor_loss	1.0000
9:33029880:TTTAG:T	acceptor_loss	1.0000
9:33029881:TTAG:T	acceptor_loss	1.0000
9:33029883:A:G	acceptor_loss	1.0000
9:33029884:G:A	acceptor_loss	1.0000

AlphaMissense

2634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:33026564:G:C	R27T	1.000
9:33026564:G:T	R27M	1.000
9:33026565:G:C	R27S	1.000
9:33026565:G:T	R27S	1.000
9:33026573:C:A	A30D	1.000
9:33026584:C:A	H34N	1.000
9:33026584:C:G	H34D	1.000
9:33026585:A:G	H34R	1.000
9:33026586:T:A	H34Q	1.000
9:33026586:T:G	H34Q	1.000
9:33026587:C:T	P35S	1.000
9:33026590:G:C	D36H	1.000
9:33026595:G:C	K37N	1.000
9:33026595:G:T	K37N	1.000
9:33026813:T:C	F45L	1.000
9:33026814:T:C	F45S	1.000
9:33026814:T:G	F45C	1.000
9:33026815:T:A	F45L	1.000
9:33026815:T:G	F45L	1.000
9:33026844:T:A	L55H	1.000
9:33029974:T:C	C134R	1.000
9:33029975:G:A	C134Y	1.000
9:33029983:T:C	C137R	1.000
9:33030472:T:C	C150R	1.000
9:33030481:T:A	C153S	1.000
9:33030481:T:C	C153R	1.000
9:33030482:G:C	C153S	1.000
9:33030483:C:G	C153W	1.000
9:33030553:T:C	C177R	1.000
9:33030554:G:A	C177Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000398217 (9:33027951 G>A,C), RS1000411612 (9:33024341 G>A,C), RS1000566336 (9:33034452 A>C,G,T), RS1000583178 (9:33031958 CA>C), RS1000682896 (9:33029308 T>C), RS1000865265 (9:33025254 G>A,T), RS1000914573 (9:33034656 C>G,T), RS1000922734 (9:33036878 G>A,C), RS1001125030 (9:33027289 G>T), RS1001231213 (9:33031824 C>T), RS1001357718 (9:33027217 G>A), RS1001411440 (9:33026847 C>G,T), RS1001577608 (9:33032091 A>G), RS1001605446 (9:33039274 CTG>C), RS1001617208 (9:33025074 A>G)

Disease associations

OMIM: gene MIM:602837 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal recessive
neurodevelopmental disorder	Limited	Autosomal recessive

Mondo (2): complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2189122 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 2,305 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL483158	ALISERTIB	3	2,305

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

ChEMBL bioactivities

5 potent at pChembl≥5 of 5 total, top 5 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	EC50	2	nM	CHEMBL52073
7.92	EC50	12	nM	CHEMBL159171
6.02	Kd	962	nM	ALISERTIB
5.54	Kd	2864	nM	CHEMBL5653589
5.54	ED50	2864	nM	CHEMBL5653589

PubChem BioAssay actives

4 with measured affinity, of 246 total; 4 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
3-oxo-18-oxa-2,5,9,11-tetrazahexacyclo[17.6.2.22,5.113,17.07,11.022,26]triaconta-1(25),7,9,13(28),14,16,19(27),20,22(26),23-decaene-16-carbonitrile	711468: Inhibition of HDJ2	ec50	0.0020	uM
4-(2-cyclohexylethyl)-23-oxo-8-oxa-1,15,17,21-tetrazapentacyclo[19.2.2.13,7.19,13.015,19]heptacosa-3,5,7(27),9,11,13(26),16,18-octaene-10-carbonitrile	711468: Inhibition of HDJ2	ec50	0.0120	uM
4-[[9-chloro-7-(2-fluoro-6-methoxyphenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]-2-methoxybenzoic acid	1424980: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.9620	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148247: Binding affinity to human DNAJA1 incubated for 45 mins by Kinobead based pull down assay	kd	2.8640	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, affects cotreatment, increases expression, affects binding, increases reaction (+2 more)	8
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	7
Aflatoxin B1	affects cotreatment, increases expression, increases methylation	3
Particulate Matter	decreases expression, increases abundance, affects cotreatment, affects expression, increases reaction	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol A	decreases expression, decreases methylation	2
pyrithione zinc	increases expression	2
Arsenic Trioxide	increases expression	2
Fulvestrant	decreases expression, increases methylation	2
Cadmium	increases expression	2
Cisplatin	affects reaction, decreases expression, affects cotreatment, increases expression	2
Copper	affects binding, decreases expression, increases expression	2
Estradiol	increases expression	2
Dronabinol	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	decreases expression	1
lead acetate	affects cotreatment, increases expression	1
potassium perchlorate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression	1
methylparaben	decreases expression	1
afimoxifene	decreases expression	1
aurin	increases expression	1
cobaltous chloride	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2208524	Binding	Inhibition of HDJ2	Macrocycles are great cycles: applications, opportunities, and challenges of synthetic macrocycles in drug discovery. — J Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2VY	Abcam HEK293T DNAJA1 KO	Transformed cell line	Female
CVCL_SL00	HAP1 DNAJA1 (-) 1	Cancer cell line	Male
CVCL_SL01	HAP1 DNAJA1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism