DOK2

Summary

DOK2 (docking protein 2, HGNC:2991) is a protein-coding gene on chromosome 8p21.3, encoding Docking protein 2 (O60496). DOK proteins are enzymatically inert adaptor or scaffolding proteins.

The protein encoded by this gene is constitutively tyrosine phosphorylated in hematopoietic progenitors isolated from chronic myelogenous leukemia (CML) patients in the chronic phase. It may be a critical substrate for p210(bcr/abl), a chimeric protein whose presence is associated with CML. This encoded protein binds p120 (RasGAP) from CML cells.

Source: NCBI Gene 9046 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 107 total — 1 pathogenic
• Phenotypes (HPO): 1
• MANE Select transcript: NM_003974

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2991
Approved symbol	DOK2
Name	docking protein 2
Location	8p21.3
Locus type	gene with protein product
Status	Approved
Aliases	p56dok-2, Dok-2
Ensembl gene	ENSG00000147443
Ensembl biotype	protein_coding
OMIM	604997
Entrez	9046

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000276420, ENST00000517422, ENST00000518197, ENST00000522011, ENST00000523932, ENST00000524001, ENST00000852539, ENST00000852540, ENST00000964986

RefSeq mRNA: 4 — MANE Select: NM_003974 NM_001317800, NM_001401272, NM_003974, NM_201349

CCDS: CCDS6016

Canonical transcript exons

ENST00000276420 — 5 exons

Exon	Start	End
ENSE00001108735	21911901	21911988
ENSE00001283358	21908873	21909931
ENSE00003462262	21910673	21910857
ENSE00003589654	21913539	21913690
ENSE00003653632	21912229	21912510

Expression profiles

Bgee: expression breadth ubiquitous, 191 present calls, max score 98.95.

FANTOM5 (CAGE): breadth broad, TPM avg 4.7840 / max 133.3143, expressed in 434 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92189	3.9835	410
92187	0.3254	141
92188	0.2844	143
92190	0.1599	107
92186	0.0308	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	98.95	gold quality
monocyte	CL:0000576	98.60	gold quality
mononuclear cell	CL:0000842	98.37	gold quality
leukocyte	CL:0000738	98.29	gold quality
blood	UBERON:0000178	94.56	gold quality
spleen	UBERON:0002106	91.47	gold quality
lymph node	UBERON:0000029	88.03	gold quality
vermiform appendix	UBERON:0001154	87.70	gold quality
upper lobe of left lung	UBERON:0008952	86.44	gold quality
caecum	UBERON:0001153	86.37	gold quality
upper lobe of lung	UBERON:0008948	86.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.00	gold quality
lower lobe of lung	UBERON:0008949	84.08	gold quality
right lung	UBERON:0002167	83.84	gold quality
layer of synovial tissue	UBERON:0007616	82.89	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	82.71	gold quality
bone marrow	UBERON:0002371	82.68	gold quality
bone marrow cell	CL:0002092	82.57	gold quality
triceps brachii	UBERON:0001509	82.50	gold quality
vena cava	UBERON:0004087	82.28	silver quality
gluteal muscle	UBERON:0002000	82.18	gold quality
oocyte	CL:0000023	81.97	gold quality
lung	UBERON:0002048	81.83	gold quality
diaphragm	UBERON:0001103	81.68	gold quality
decidua	UBERON:0002450	81.15	gold quality
thymus	UBERON:0002370	80.85	silver quality
right coronary artery	UBERON:0001625	80.48	gold quality
omental fat pad	UBERON:0010414	80.29	gold quality
peritoneum	UBERON:0002358	80.28	gold quality
pericardium	UBERON:0002407	79.87	silver quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	96.85
E-HCAD-4	yes	79.50
E-MTAB-10287	yes	32.33
E-HCAD-10	yes	24.00
E-MTAB-6379	no	856.94
E-CURD-120	no	32.18
E-GEOD-130148	no	3.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting DOK2, 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-4715-3P	99.98	66.03	670
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-365A-3P	99.43	70.02	836
HSA-MIR-365B-3P	99.43	70.02	836
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-4795-5P	99.11	66.90	876
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-18B-3P	98.05	65.55	595
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-5685	97.02	64.34	1004
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-3677-5P	93.16	64.62	393

Literature-anchored findings (GeneRIF, showing 24)

• identified tyrosine residue 1106 on Tie2 as an Angiopoietin 1-dependent autophosphorylation site that mediates binding and phosphorylation of the downstream-of-kinase-related (Dok-R) docking protein (PMID:12665569)
• Dok-R and c-Abl interact in both a constitutive and inducible fashion and Dok-R influences the intracellular kinase and biological activity of c-Abl (PMID:12777393)
• Dok-2 tyrosine phosphorylation was also found to be involved in collagen receptor, glycoprotein VI (GPVI), signaling as well as in outside-in signaling through the major platelet integrin, alpha IIIb beta 3 (PMID:14645010)
• DOK1 and DOK2 interact with the Tec protein tyrosine kinase. (PMID:14647425)
• Dok-R acts as an EGFR-recruited scaffolding molecule that processively assembles c-Src and Csk to attenuate signaling from the EGFR. (PMID:15831486)
• Phosphotyrosine-binding mediated oligomerization of Dok-1 and Dok-2 represents an essential step for Dok phosphorylation and function. (PMID:16177091)
• The data provide evidence that DOK2 protein has a role in regulating cell proliferation and differentiation and is positive regulators of the MAPK signaling pathway in this context. (PMID:16823827)
• Dok-2 is a critical element of a linker for activation of T cells (LAT)-dependent negative feedback loop that attenuates early T-cell receptor (TCR) signal. (PMID:17043143)
• results demonstrate differential modes of regulation of Dok1 and Dok2 in platelets, and raise the possibility that Dok2 plays an important role in integrin outside-in signaling through a physical and functional interaction with integrin alphaIIbbeta3 (PMID:17092301)
• Dok-1/Dok-2 pleckstrin homology domains bind in vitro to the rare phosphoinositide species, phosphatidylinositol 5-phosphate (PMID:19299694)
• CD200R inhibits the activation of human myeloid cells through direct recruitment of Dok2 and subsequent activation of RAS p21 protein activator 1. (PMID:19786546)
• Identification of DOK genes as lung tumor suppressors. (PMID:20139980)
• Dok1 negatively regulates Dok2-mediated CD200R signaling through the recruitment of CrkL. (PMID:21078907)
• Data indicate there was no evidence of DOK2 somatic mutation in the leukemias analyzed. (PMID:21329978)
• data indicate that DOK2 is altered in gastric (GC) and colorectal cancers (CRC) by loss of expressions; data indicate that somatic mutation of DOK2 may be rare in GC, CRC, breast cancer, prostate cancer and liver cancer (PMID:21749457)
• DOK2 is a marker of poor prognosis in patients with gastric cancer after curative resection (PMID:22130622)
• DOK2 as a tumor suppressor in EGFR-mutant lung adenocarcinoma (PMID:24255704)
• Taken together, these results reveal that Dok1 and Dok2 proteins are involved in an intrinsic negative feedback loop downstream of natural killer-cell-activating receptors in mouse and human. (PMID:24963146)
• point mutations in DOK1 and DOK2 genes are detected with low frequency in chronic myelomonocytic leukemia but may have consequences for the function of the DOK2 PTB domain (PMID:25252871)
• DOK2 and DOK3 expression was significantly reduced in HTLV-1-infected T cells. (PMID:27265473)
• DOK2 overexpression in different brain regions is associated with poor prognosis in astrocytoma clinical cases. (PMID:27975172)
• In this report, the authors demonstrated that the cellular adaptor proteins Dok-2 and Dok-1 are tyrosine phosphorylated upon herpes simplex virus 1 infection. In addition, herpes simplex virus 1 induced the selective degradation of Dok-2. Finally, Dok-2 interacts with herpes simplex virus 1 VP11/12, and that herpes simplex virus 1-induced tyrosine phosphorylation and degradation of Dok-2 require VP11/12. (PMID:28841444)
• Decreased DOK1/2 expressions associated with their promoter hypermethylations predict adverse prognosis in AML. (PMID:29150948)
• Introduction to DOK2 and its potential role in cancer. (PMID:34505522)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dok2	ENSDARG00000075818
danio_rerio		ENSDARG00000116593
mus_musculus	Dok2	ENSMUSG00000022102
rattus_norvegicus	Dok2	ENSRNOG00000013922
drosophila_melanogaster	Dok	FBGN0029944
drosophila_melanogaster	CG13398	FBGN0032042
caenorhabditis_elegans		WBGENE00018819

Paralogs (7): DOK5 (ENSG00000101134), DOK1 (ENSG00000115325), DOK4 (ENSG00000125170), FRS3 (ENSG00000137218), DOK3 (ENSG00000146094), FRS2 (ENSG00000166225), DOK6 (ENSG00000206052)

Protein

Protein identifiers

Docking protein 2 — O60496 (reviewed: O60496)

Alternative names: Downstream of tyrosine kinase 2, p56(dok-2)

All UniProt accessions (4): O60496, E5RIG9, E5RJ11, G3V114

UniProt curated annotations — full annotation on UniProt →

Function. DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK2 may modulate the cellular proliferation induced by IL-4, as well as IL-2 and IL-3. May be involved in modulating Bcr-Abl signaling. Attenuates EGF-stimulated MAP kinase activation.

Subunit / interactions. Interacts with phosphorylated RASGAP and EGFR. Interacts with RET and NCK. Interacts (via PH domain) with TEK/TIE2 (tyrosine phosphorylated). (Microbial infection) Interacts with Herpes simplex virus 1 (HHV-1) protein UL46; this interaction induces DOK2 phosphorylation and subsequent degradation.

Tissue specificity. Highly expressed in peripheral blood leukocytes, lymph nodes and spleen. Lower expression in thymus, bone marrow and fetal liver.

Post-translational modifications. On immunoreceptor stimulation, phosphorylated on C-terminal tyrosine residues. Phosphorylation on Tyr-345 is required for binding to the SH2 domain of NCK. Phosphorylation on both Tyr-271 and Tyr-299 is required for interaction with RASGAP. Phosphorylated on tyrosine residues by TEK/TIE2.

Domain organisation. PTB domain mediates receptor interaction.

Similarity. Belongs to the DOK family. Type A subfamily.

RefSeq proteins (4): NP_001304729, NP_001388201, NP_003965, NP_958728 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001849	PH_domain	Domain
IPR002404	IRS_PTB	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR037751	Dok1/2/3_PTB	Domain
IPR050996	Docking_Protein_DOK	Family

Pfam: PF02174

UniProt features (40 total): strand 18, helix 5, sequence conflict 4, sequence variant 3, modified residue 3, domain 2, region of interest 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2D9W	SOLUTION NMR
2DLW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60496-F1	70.72	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.

Post-translational modifications (3): 271, 299, 345

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-210993	Tie2 Signaling
R-HSA-8853659	RET signaling

MSigDB gene sets: 226 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GSE45365_NK_CELL_VS_BCELL_DN, MODULE_45, RACCACAR_AML_Q6, HUMMERICH_SKIN_CANCER_PROGRESSION_UP, REACTOME_TIE2_SIGNALING, PID_IL2_1PATHWAY, RICKMAN_METASTASIS_DN, chr8p21, AML_Q6, GNF2_S100A4, GOBP_RAS_PROTEIN_SIGNAL_TRANSDUCTION, BYSTROEM_CORRELATED_WITH_IL5_UP, GATA1_03, GNF2_CD97

GO Biological Process (4): signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), Ras protein signal transduction (GO:0007265)

GO Molecular Function (2): transmembrane receptor protein tyrosine kinase adaptor activity (GO:0005068), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cell surface interactions at the vascular wall	1
Axon guidance	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
enzyme-linked receptor protein signaling pathway	1
small GTPase-mediated signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
signaling receptor complex adaptor activity	1
receptor tyrosine kinase binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOK2	RASA1	P20936	963
DOK2	CD200R1	Q8TD46	943
DOK2	NCK1	P16333	820
DOK2	SHC1	P29353	763
DOK2	GRB2	P29354	711
DOK2	FYN	P06241	624
DOK2	CSK	P41240	621
DOK2	CRKL	P46109	606
DOK2	INPP5D	Q92835	593
DOK2	LCK	P06239	536
DOK2	GRAP	Q13588	533
DOK2	CD200	P41217	520
DOK2	EVPL	Q92817	519
DOK2	TEC	P42680	487
DOK2	CD84	Q9UIB8	486

IntAct

59 interactions, top by confidence:

A	B	Type	Score
DOK2	YES1	psi-mi:“MI:0915”(physical association)	0.560
DOK2	TXK	psi-mi:“MI:0915”(physical association)	0.560
KIFBP	DOK2	psi-mi:“MI:0915”(physical association)	0.550
DOK2	KIFBP	psi-mi:“MI:0915”(physical association)	0.550
PLEKHO1	UBA6	psi-mi:“MI:0914”(association)	0.530
DOK2	NCK2	psi-mi:“MI:0914”(association)	0.530
TMEM38A	DOK2	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
TMEM184B	INPPL1	psi-mi:“MI:0914”(association)	0.530
NCEH1	CLGN	psi-mi:“MI:0914”(association)	0.530
POT1	DOK2	psi-mi:“MI:0915”(physical association)	0.510
DOK3	DOK2	psi-mi:“MI:0915”(physical association)	0.490
DOK2	CRKL	psi-mi:“MI:0915”(physical association)	0.490
LCK	DOK2	psi-mi:“MI:0915”(physical association)	0.490
CRK	DOK2	psi-mi:“MI:0915”(physical association)	0.490
DOK2	CRK	psi-mi:“MI:0915”(physical association)	0.490
STAT3	DOK2	psi-mi:“MI:0915”(physical association)	0.490
DOK2	APPL1	psi-mi:“MI:0915”(physical association)	0.490
DOK2	DOK3	psi-mi:“MI:0915”(physical association)	0.490
DOK2	STAT3	psi-mi:“MI:0915”(physical association)	0.490
Numb	DOK2	psi-mi:“MI:0915”(physical association)	0.400
DOK2	SERPINA3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (130): DOK2 (Affinity Capture-MS), DOK2 (Affinity Capture-MS), DOK2 (Affinity Capture-MS), DOK2 (Affinity Capture-MS), DOK2 (Affinity Capture-MS), KIAA1279 (Two-hybrid), DOK2 (Two-hybrid), DOK3 (Two-hybrid), DOK2 (Two-hybrid), CRKL (Two-hybrid), DOK2 (Two-hybrid), LCK (Two-hybrid), PLCG1 (Affinity Capture-MS), LANCL2 (Affinity Capture-MS), NCK2 (Affinity Capture-MS)

ESM2 similar proteins: A3R064, A7MBB8, B2RYG7, D3ZZN9, E1BDF2, O60496, O70469, O94989, O95153, P97465, P97680, P98077, Q13671, Q14B98, Q1RMU7, Q3MIN7, Q3UR97, Q3UYI5, Q494U1, Q4QQV2, Q58EX7, Q5EA84, Q5FWH6, Q6ICB4, Q6PGG2, Q6ZW31, Q7L591, Q7TNF8, Q8BH49, Q8BWA8, Q8IW93, Q8IYJ3, Q8N878, Q8NAG6, Q8NFA2, Q91WA6, Q921Q7, Q92502, Q969H4, Q969T3

Diamond homologs: A3R064, A7MBB8, B2RYG7, O43559, O60496, O70469, P97465, Q4QQV2, Q52RG8, Q5EA84, Q7L591, Q8C180, Q8WU20, Q91WJ0, Q99704, Q9QZK7, Q5RA30, Q8TEW6, Q99KE3, Q2MHE5, Q6PKX4, Q91ZM9, Q9P104

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PTPRG	“up-regulates activity”	DOK2	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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
Downstream signal transduction	5	63.4×	3e-06
FCGR3A-mediated phagocytosis	5	31.2×	7e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	92
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
523288	GRCh37/hg19 8p23.1-21.2(chr8:12580104-25947329)	Pathogenic

SpliceAI

757 predictions. Top by Δscore:

Variant	Effect	Δscore
8:21909932:CT:C	acceptor_loss	1.0000
8:21910808:A:AC	donor_gain	1.0000
8:21910809:C:CC	donor_gain	1.0000
8:21910853:GCCGA:G	acceptor_gain	1.0000
8:21910854:CCGA:C	acceptor_gain	1.0000
8:21910854:CCGAC:C	acceptor_gain	1.0000
8:21910855:CGA:C	acceptor_gain	1.0000
8:21910855:CGAC:C	acceptor_gain	1.0000
8:21910856:G:T	acceptor_gain	1.0000
8:21910856:GA:G	acceptor_gain	1.0000
8:21910858:C:CC	acceptor_gain	1.0000
8:21912225:TCACG:T	donor_loss	1.0000
8:21912226:CACG:C	donor_loss	1.0000
8:21912227:A:AC	donor_gain	1.0000
8:21912227:ACG:A	donor_loss	1.0000
8:21912228:C:CT	donor_gain	1.0000
8:21912228:CG:C	donor_gain	1.0000
8:21912228:CGG:C	donor_gain	1.0000
8:21912228:CGGGG:C	donor_gain	1.0000
8:21909927:GTTAC:G	acceptor_gain	0.9900
8:21909928:TTAC:T	acceptor_gain	0.9900
8:21909929:TAC:T	acceptor_gain	0.9900
8:21909938:C:CT	acceptor_gain	0.9900
8:21910669:TCAC:T	donor_loss	0.9900
8:21910672:C:CA	donor_loss	0.9900
8:21910809:CTGG:C	donor_gain	0.9900
8:21910855:CGACT:C	acceptor_gain	0.9900
8:21910856:GACTG:G	acceptor_gain	0.9900
8:21910857:ACTGG:A	acceptor_gain	0.9900
8:21910858:C:G	acceptor_gain	0.9900

AlphaMissense

2635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:21910685:A:C	F202L	0.997
8:21910685:A:T	F202L	0.997
8:21910687:A:G	F202L	0.997
8:21910711:A:G	W194R	0.997
8:21910711:A:T	W194R	0.997
8:21909879:A:G	F224S	0.996
8:21910709:C:A	W194C	0.996
8:21910709:C:G	W194C	0.996
8:21909873:A:G	F226S	0.995
8:21909924:A:G	F209S	0.995
8:21909918:A:G	F211S	0.994
8:21912507:A:G	W23R	0.994
8:21912507:A:T	W23R	0.994
8:21909849:A:G	I234T	0.993
8:21909878:A:C	F224L	0.993
8:21909878:A:T	F224L	0.993
8:21909880:A:G	F224L	0.993
8:21909901:A:G	C217R	0.993
8:21910689:C:G	R201P	0.993
8:21912505:C:A	W23C	0.993
8:21912505:C:G	W23C	0.993
8:21912259:C:A	W105C	0.992
8:21912259:C:G	W105C	0.992
8:21909849:A:C	I234S	0.991
8:21909886:C:G	G222R	0.991
8:21909899:G:C	C217W	0.991
8:21909907:G:T	R215S	0.991
8:21910710:C:G	W194S	0.991
8:21910776:A:G	L172P	0.991
8:21910838:A:C	F151L	0.991

dbSNP variants (sampled 300 via entrez): RS1000358438 (8:21910189 C>T), RS1000526442 (8:21913361 G>C), RS1000615997 (8:21911242 C>A), RS1000730205 (8:21911030 C>A,G,T), RS1000817263 (8:21910085 G>A,T), RS1001308440 (8:21915273 T>C), RS1001339429 (8:21914966 C>A,T), RS1001569538 (8:21910470 C>G), RS1001601520 (8:21913951 C>G,T), RS1002371399 (8:21910432 C>G,T), RS1002404281 (8:21910174 G>A,T), RS1002635337 (8:21914933 C>A,T), RS1003014058 (8:21915151 G>C), RS1003410663 (8:21911159 C>A,T), RS1003817294 (8:21912627 G>A,C)

Disease associations

OMIM: gene MIM:604997 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000585_8	Mean corpuscular volume	3.000000e-08
GCST000894_2	Entorhinal cortical thickness	7.000000e-06
GCST002507_1	Neuropathic pain in type 2 diabetes	2.000000e-07
GCST002701_26	Verbal declarative memory	2.000000e-06
GCST009391_725	Metabolite levels	5.000000e-07
GCST009895_2	Pancreatic cancer	4.000000e-09
GCST010002_271	Refractive error	2.000000e-17
GCST010796_4381	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-11
GCST010796_4382	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4383	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4384	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-09
GCST010796_4385	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_4386	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4387	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-10
GCST010796_4388	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-10
GCST010796_4389	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4390	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4391	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST90002388_237	Lymphocyte count	2.000000e-14
GCST90002393_563	Monocyte count	4.000000e-13
GCST90002394_321	Monocyte percentage of white cells	2.000000e-13
GCST90002395_6	Mean platelet volume	2.000000e-26
GCST90002399_193	Neutrophil percentage of white cells	4.000000e-11
GCST90002401_505	Platelet distribution width	1.000000e-14
GCST90002401_506	Platelet distribution width	4.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004840	cortical thickness
EFO:0005762	neuropathic pain
EFO:0004874	memory performance
EFO:0006805	word list delayed recall measurement
EFO:0009774	serine measurement
EFO:0004327	electrocardiography
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0007989	monocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression	2
bisphenol A	decreases methylation, affects cotreatment, increases methylation	1
sodium arsenite	affects splicing, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	increases expression	1
Diuron	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Nickel	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms