DOCK3

Summary

DOCK3 (dedicator of cytokinesis 3, HGNC:2989) is a protein-coding gene on chromosome 3p21.2, encoding Dedicator of cytokinesis protein 3 (Q8IZD9). Potential guanine nucleotide exchange factor (GEF).

This gene is specifically expressed in the central nervous system (CNS). It encodes a member of the DOCK (dedicator of cytokinesis) family of guanine nucleotide exchange factors (GEFs). This protein, dedicator of cytokinesis 3 (DOCK3), is also known as modifier of cell adhesion (MOCA) and presenilin-binding protein (PBP). The DOCK3 and DOCK1, -2 and -4 share several conserved amino acids in their DHR-2 (DOCK homology region 2) domains that are required for GEF activity, and bind directly to WAVE proteins [Wiskott-Aldrich syndrome protein (WASP) family Verprolin-homologous proteins] via their DHR-1 domains. The DOCK3 induces axonal outgrowth in CNS by stimulating membrane recruitment of the WAVE complex and activating the small G protein Rac1. This gene is associated with an attention deficit hyperactivity disorder-like phenotype by a complex chromosomal rearrangement.

Source: NCBI Gene 1795 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 45
• Clinical variants (ClinVar): 346 total — 10 pathogenic, 5 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_004947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2989
Approved symbol	DOCK3
Name	dedicator of cytokinesis 3
Location	3p21.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0299, MOCA, PBP
Ensembl gene	ENSG00000088538
Ensembl biotype	protein_coding
OMIM	603123
Entrez	1795

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000266037, ENST00000924010, ENST00000945458

RefSeq mRNA: 1 — MANE Select: NM_004947 NM_004947

CCDS: CCDS46835

Canonical transcript exons

ENST00000266037 — 53 exons

Exon	Start	End
ENSE00001081203	51350288	51350392
ENSE00001081206	51228661	51228832
ENSE00001081207	51333158	51333253
ENSE00001081208	51357758	51357841
ENSE00001081209	51341237	51341385
ENSE00001081210	51260156	51260326
ENSE00001081211	51246726	51246807
ENSE00001081213	51330138	51330223
ENSE00001081214	51236345	51236428
ENSE00001081215	51338359	51338419
ENSE00001081216	51237490	51237590
ENSE00001081217	51314980	51315128
ENSE00001081219	51270815	51271007
ENSE00001081220	51227982	51228088
ENSE00001081221	51354882	51355023
ENSE00001081222	51312844	51312902
ENSE00001081223	51361859	51361997
ENSE00001081224	51280106	51280204
ENSE00001081225	51356407	51356493
ENSE00001081226	51356962	51357141
ENSE00001081227	51333001	51333027
ENSE00001081228	51229512	51229609
ENSE00001081229	51312476	51312576
ENSE00001081232	51277608	51277754
ENSE00001081233	51227283	51227445
ENSE00001081234	51360511	51360632
ENSE00001081235	51348852	51348938
ENSE00001081236	51338935	51339028
ENSE00001081237	51357961	51358077
ENSE00001081238	51275079	51275206
ENSE00001081239	51312004	51312079
ENSE00001123743	51225649	51225773
ENSE00001129802	51090230	51090384
ENSE00001129810	51089243	51089284
ENSE00001129815	51075356	51075440
ENSE00001181109	51214122	51214247
ENSE00001181112	51208774	51208862
ENSE00001181117	51160555	51160702
ENSE00001181123	51159244	51159304
ENSE00001264658	51064448	51064596
ENSE00001305327	50841675	50841715
ENSE00001306510	51146549	51146630
ENSE00001306601	51356089	51356255
ENSE00001321925	51362527	51362674
ENSE00001327993	50933981	50934077
ENSE00001330779	51310232	51310326
ENSE00001550420	50674927	50675300
ENSE00001560831	50778675	50778758
ENSE00001601909	50890026	50890081
ENSE00001632085	51381050	51384198
ENSE00001678271	51375748	51375835
ENSE00001767756	51380125	51380207
ENSE00002695433	51374469	51374587

Expression profiles

Bgee: expression breadth ubiquitous, 203 present calls, max score 96.29.

FANTOM5 (CAGE): breadth broad, TPM avg 9.1225 / max 296.7693, expressed in 748 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36755	8.9532	747
36758	0.1370	59
36754	0.0323	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
frontal pole	UBERON:0002795	96.29	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.47	gold quality
paraflocculus	UBERON:0005351	94.38	gold quality
middle frontal gyrus	UBERON:0002702	94.24	gold quality
postcentral gyrus	UBERON:0002581	93.73	gold quality
parietal lobe	UBERON:0001872	92.98	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.53	gold quality
orbitofrontal cortex	UBERON:0004167	92.26	gold quality
superior frontal gyrus	UBERON:0002661	92.01	gold quality
prefrontal cortex	UBERON:0000451	91.24	gold quality
frontal cortex	UBERON:0001870	90.65	gold quality
frontal lobe	UBERON:0016525	90.65	gold quality
cerebellar vermis	UBERON:0004720	89.66	gold quality
neocortex	UBERON:0001950	89.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.26	gold quality
right frontal lobe	UBERON:0002810	88.45	gold quality
cerebral cortex	UBERON:0000956	88.40	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.32	gold quality
cortical plate	UBERON:0005343	88.03	gold quality
middle temporal gyrus	UBERON:0002771	87.82	gold quality
cerebellum	UBERON:0002037	87.62	gold quality
entorhinal cortex	UBERON:0002728	87.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	87.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.43	gold quality
cerebellar cortex	UBERON:0002129	87.35	gold quality
cerebellar hemisphere	UBERON:0002245	87.30	gold quality
occipital lobe	UBERON:0002021	86.62	gold quality
telencephalon	UBERON:0001893	86.51	gold quality
cingulate cortex	UBERON:0003027	86.17	gold quality
anterior cingulate cortex	UBERON:0009835	86.11	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.05
E-ENAD-17	no	100.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

236 targeting DOCK3, 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-3120-5P	100.00	65.56	965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-19A-3P	99.98	75.33	2762
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
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-MIR-5696	99.98	72.36	4487
HSA-MIR-4745-5P	99.98	65.95	1028

Literature-anchored findings (GeneRIF, showing 12)

• dOgg1 and RpS3 in mitochondria increase cell survival after exposure to the nitric oxide donor SNAP (PMID:16895796)
• We report that MOCA modulates cell-cell adhesion and morphology by increasing the accumulation of adherens junction proteins. (PMID:15647471)
• MOCA is a novel Wnt negative regulator and demonstrate that this screening approach can be a rapid means for isolation of new Wnt regulators. (PMID:18716063)
• Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex (PMID:20368433)
• MOCA is a key molecule of the Alzheimer disease-relevant neuronal death signals that links the presenilin-mediated death signal with the APP-mediated death signal at a point between Rac1 or Cdc42 and ASK1. (PMID:22115042)
• It plays a role in axonal regeneration. (review) (PMID:22746061)
• Results supported that miR-512-3p could inhibit tumor cell adhesion, migration, and invasion by regulating the RAC1 activity via DOCK3 in NSCLC A549 and H1299 cell lines. (PMID:25687035)
• Inhibition of Dock3 by Dock3 shRNA impaired the severity of status epilepticus in the acute stage and decreased the spontaneous recurrent seizures times in the chronic stage of lithium-pilocarpine model and decreased the expression of rac1-GTP. (PMID:26319681)
• Common features in both affected individuals include severe developmental disability, ataxic gait, and severe hypotonia, which recapitulates the Dock3 knockout mouse phenotype. We show that complete DOCK3 deficiency in humans leads to developmental disability with significant hypotonia and gait ataxia, probably due to abnormal axonal development (PMID:28195318)
• here we report a second case of biallelic DOCK3 mutation due to homozygous deletion. Given the clinical similarities among the cases with DOCK3 mutations, we provided further evidence that biallelic mutations of DOCK3 lead to a specific DOCK3-related neurodevelopmental syndrome (PMID:29130632)
• hree patients with genetic variants in the dedicator of cytokinesis 3 (DOCK3) who presented with global developmental delay (GDD), hypotonia, and wide-based or uncoordinated gait. (PMID:30976111)
• DOCK3 is a dosage-sensitive regulator of skeletal muscle and Duchenne muscular dystrophy-associated pathologies. (PMID:32766788)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dock3	ENSDARG00000063180
mus_musculus	Dock3	ENSMUSG00000039716
rattus_norvegicus	Dock3	ENSRNOG00000014576
drosophila_melanogaster	Zir	FBGN0031216
caenorhabditis_elegans		WBGENE00000419
caenorhabditis_elegans		WBGENE00018520

Paralogs (10): DOCK9 (ENSG00000088387), DOCK8 (ENSG00000107099), DOCK7 (ENSG00000116641), DOCK4 (ENSG00000128512), DOCK6 (ENSG00000130158), DOCK2 (ENSG00000134516), DOCK10 (ENSG00000135905), DOCK11 (ENSG00000147251), DOCK5 (ENSG00000147459), DOCK1 (ENSG00000150760)

Protein

Protein identifiers

Dedicator of cytokinesis protein 3 — Q8IZD9 (reviewed: Q8IZD9)

Alternative names: Modifier of cell adhesion, PS binding protein, Presenilin-binding protein

All UniProt accessions (1): Q8IZD9

UniProt curated annotations — full annotation on UniProt →

Function. Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP. Its interaction with presenilin proteins as well as its ability to stimulate Tau/MAPT phosphorylation suggest that it may be involved in Alzheimer disease. Ectopic expression in nerve cells decreases the secretion of amyloid-beta APBA1 protein and lowers the rate of cell-substratum adhesion, suggesting that it may affect the function of some small GTPase involved in the regulation of actin cytoskeleton or cell adhesion receptors.

Subunit / interactions. Interacts with PSEN1; this interaction mediates the membrane association of DOCK3. Interacts with PSEN2. Interacts with CRK.

Subcellular location. Cytoplasm.

Tissue specificity. In normal brains, it is localized in the neuropil, and occasionally in the pyramidal cells, while in Alzheimer disease brains, it is associated with neurofibrillary tangles.

Disease relevance. A chromosomal aberration involving DOCK3 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9. Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (NEDIDHA) [MIM:618292] An autosomal recessive disease characterized by global developmental delay, hypotonia, ataxic gait, hyporeflexia, poor or absent speech, and variable and mild dysmorphic features. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DOCKER domain may mediate some GEF activity.

Similarity. Belongs to the DOCK family.

RefSeq proteins (1): NP_004938* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001452	SH3_domain	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR026791	DOCK	Family
IPR026800	DHR2_DOCK3	Domain
IPR027007	C2_DOCK-type_domain	Domain
IPR027357	DOCKER_dom	Domain
IPR032376	DOCK_N	Domain
IPR035767	DOCK3_SH3	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR037811	C2_Dock-B	Domain
IPR042455	DOCK_N_sub1	Homologous_superfamily
IPR043161	DOCK_C_lobe_A	Homologous_superfamily
IPR043162	DOCK_C_lobe_C	Homologous_superfamily
IPR046769	DOCKER_Lobe_A	Domain
IPR046770	DOCKER_Lobe_B	Domain
IPR046773	DOCKER_Lobe_C	Domain
IPR056372	TPR_DOCK	Domain

Pfam: PF06920, PF07653, PF14429, PF16172, PF20421, PF20422, PF23554

UniProt features (20 total): compositionally biased region 6, sequence variant 4, region of interest 4, domain 3, chain 1, modified residue 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IZD9-F1	75.52	0.36

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 (1): 1658

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9032759	NTRK2 activates RAC1
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 271 (showing top): MORF_MTA1, GNF2_RTN1, LEE_NEURAL_CREST_STEM_CELL_DN, ACTACCT_MIR196A_MIR196B, FREAC2_01, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, MORF_CDK2, GCAAGGA_MIR502, MORF_HDAC2, GOMF_GTPASE_BINDING, GTACAGG_MIR486, CEBPB_01, TCF4_Q5, FOXJ2_01, MORF_BUB3

GO Biological Process (3): small GTPase-mediated signal transduction (GO:0007264), neurotrophin TRK receptor signaling pathway (GO:0048011), regulation of small GTPase mediated signal transduction (GO:0051056)

GO Molecular Function (5): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), SH3 domain binding (GO:0017124), small GTPase binding (GO:0031267), 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-3 pathways:

Category	Pathways
RHO GTPase cycle	3
Activated NTRK2 signals through FYN	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase regulator activity	2
cellular anatomical structure	2
intracellular signaling cassette	1
cell surface receptor protein tyrosine kinase signaling pathway	1
neurotrophin signaling pathway	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
protein domain specific binding	1
GTPase binding	1
binding	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1388 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK3	NEDD9	Q14511	919
DOCK3	SLC9A9	Q8IVB4	889
DOCK3	KIAA0319	Q5VV43	669
DOCK3	CRK	P46108	640
DOCK3	DHX8	Q14562	588
DOCK3	ARHGAP22	Q7Z5H3	542
DOCK3	DHX37	Q8IY37	527
DOCK3	WASF1	Q92558	516
DOCK3	LRRC73	Q5JTD7	510
DOCK3	RAC2	P15153	504
DOCK3	DIPK2A	Q8NDZ4	492
DOCK3	FYN	P06241	484
DOCK3	SLC9A8	Q9Y2E8	480
DOCK3	WASF2	Q9Y6W5	478
DOCK3	ELMO1	Q92556	470

IntAct

31 interactions, top by confidence:

A	B	Type	Score
ELMO1	DOCK1	psi-mi:“MI:0914”(association)	0.940
HOXA1	DOCK3	psi-mi:“MI:0915”(physical association)	0.560
DOCK3	PLEKHF2	psi-mi:“MI:0915”(physical association)	0.560
ELMO1	CALML3	psi-mi:“MI:0914”(association)	0.530
NEDD9	DOCK3	psi-mi:“MI:0915”(physical association)	0.520
DOCK3	NEDD9	psi-mi:“MI:0915”(physical association)	0.520
DOCK3	ARHGAP5	psi-mi:“MI:0915”(physical association)	0.500
DOCK3	ABL1	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	CRK	psi-mi:“MI:0915”(physical association)	0.400
SRC	DOCK3	psi-mi:“MI:0915”(physical association)	0.400
FYN	DOCK3	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	GRB2	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	NCK1	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	PIK3R1	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	PDIA4	psi-mi:“MI:0915”(physical association)	0.400
DOCK3	DDX21	psi-mi:“MI:0915”(physical association)	0.400
H3-4	DOCK3	psi-mi:“MI:0915”(physical association)	0.400
ELMO3	DOCK1	psi-mi:“MI:0914”(association)	0.350
ARHGAP5	KAZN	psi-mi:“MI:0914”(association)	0.350
DOCK3	SEC16A	psi-mi:“MI:0914”(association)	0.350
DOCK3	HS6ST3	psi-mi:“MI:0914”(association)	0.350
HOXA1	DOCK3	psi-mi:“MI:0915”(physical association)	0.000
PLEKHF2	DOCK3	psi-mi:“MI:0915”(physical association)	0.000
RSPH1	DOCK3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (62): DOCK3 (Affinity Capture-MS), DOCK3 (Biochemical Activity), DOCK3 (Two-hybrid), DOCK3 (Affinity Capture-MS), DOCK3 (Affinity Capture-MS), DOCK3 (PCA), HOXA1 (Two-hybrid), PLEKHF2 (Two-hybrid), DOCK3 (Proximity Label-MS), DOCK3 (Proximity Label-MS), DDX21 (Proximity Label-MS), ARHGAP5 (Affinity Capture-Western), DOCK3 (FRET), DOCK3 (Affinity Capture-MS), ABCD3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8J1LLF7, A0A974H8H3, A0MQH0, A4FUD6, A5HK05, B3DLA6, P11029, P11497, P42694, P54198, Q13085, Q25BN1, Q28559, Q4R4U1, Q504Q3, Q5R5F8, Q5R660, Q5R8I6, Q5RCC1, Q5SWU9, Q5ZIT8, Q6DFV5, Q6IE70, Q6NYU2, Q6P1X5, Q6TUI4, Q6TV19, Q80YV4, Q8BGF7, Q8BHL5, Q8BPU7, Q8C176, Q8CIQ7, Q8IZD9, Q8K0F1, Q8R418, Q8R5L3, Q8VHE0, Q923S8, Q92556

Diamond homologs: B2RY04, E7F1U2, P53281, P59764, Q14185, Q8BUR4, Q8C3J5, Q8CIQ7, Q8IZD9, Q8N1I0, Q92608, Q9H7D0, M0R4F8, Q09822, Q5TCX8, Q62662, Q6XZF7, Q8VDG6, Q91X43, Q922K9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
DOCK3	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 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	119.0×	3e-08
FCGR3A-mediated phagocytosis	8	93.6×	2e-12
Regulation of actin dynamics for phagocytic cup formation	6	69.1×	2e-08
VEGFA-VEGFR2 Pathway	7	60.9×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	78.2×	2e-06
response to endoplasmic reticulum stress	5	37.9×	3e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	5
Uncertain significance	235
Likely benign	42
Benign	4

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1335525	NM_004947.5(DOCK3):c.152_158dup (p.Gly55fs)	Pathogenic
1335526	NM_004947.5(DOCK3):c.214del (p.Arg72fs)	Pathogenic
144169	GRCh38/hg38 3p21.2(chr3:50818845-51207727)x3	Pathogenic
3504409	NM_004947.5(DOCK3):c.1766_1767del (p.Lys589fs)	Pathogenic
4279150	GRCh37/hg19 3p21.2(chr3:50951062-51018757)x1	Pathogenic
4293201	NM_004947.5(DOCK3):c.4231del (p.Leu1411fs)	Pathogenic
4848912	NM_004947.5(DOCK3):c.514dup (p.Ser172fs)	Pathogenic
520862	NM_004947.5(DOCK3):c.382C>T (p.Gln128Ter)	Pathogenic
599268	NM_004947.5(DOCK3):c.3107_3110del (p.Tyr1036fs)	Pathogenic
617489	NC_000003.11:g.51062402_51232768del	Pathogenic
2628392	NM_004947.5(DOCK3):c.1084C>T (p.Arg362Ter)	Likely pathogenic
2637227	NM_004947.5(DOCK3):c.1037+1G>A	Likely pathogenic
3350497	NM_004947.5(DOCK3):c.2535_2538dup (p.Ser847fs)	Likely pathogenic
4849416	NM_004947.5(DOCK3):c.6001C>T (p.Arg2001Ter)	Likely pathogenic
599269	NM_004947.5(DOCK3):c.1038-2A>G	Likely pathogenic

SpliceAI

4918 predictions. Top by Δscore:

Variant	Effect	Δscore
3:50675296:CGTAG:C	donor_loss	1.0000
3:50675300:GG:G	donor_loss	1.0000
3:50775265:G:GT	donor_gain	1.0000
3:50775265:G:T	donor_gain	1.0000
3:50778674:GT:G	acceptor_gain	1.0000
3:50778674:GTGAT:G	acceptor_gain	1.0000
3:50783705:G:GG	donor_gain	1.0000
3:50841670:TTTA:T	acceptor_loss	1.0000
3:50841671:TTA:T	acceptor_loss	1.0000
3:50841673:A:AG	acceptor_gain	1.0000
3:50841673:A:AT	acceptor_loss	1.0000
3:50841673:AG:A	acceptor_gain	1.0000
3:50841673:AGGTT:A	acceptor_gain	1.0000
3:50841674:G:GA	acceptor_gain	1.0000
3:50841674:GG:G	acceptor_gain	1.0000
3:50841674:GGT:G	acceptor_gain	1.0000
3:50841674:GGTT:G	acceptor_gain	1.0000
3:50841674:GGTTG:G	acceptor_gain	1.0000
3:50841713:AAG:A	donor_gain	1.0000
3:50841716:G:A	donor_loss	1.0000
3:50841717:T:A	donor_loss	1.0000
3:50890078:GGGG:G	donor_gain	1.0000
3:50890079:GGG:G	donor_gain	1.0000
3:50890079:GGGG:G	donor_gain	1.0000
3:50890080:GGG:G	donor_gain	1.0000
3:50933980:GGCA:G	acceptor_gain	1.0000
3:51064406:A:AG	acceptor_gain	1.0000
3:51064407:T:G	acceptor_gain	1.0000
3:51064417:A:AG	acceptor_gain	1.0000
3:51064422:A:AG	acceptor_gain	1.0000

AlphaMissense

13502 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:50778735:T:A	V33D	1.000
3:50934040:T:C	L93P	1.000
3:50934048:T:A	W96R	1.000
3:50934048:T:C	W96R	1.000
3:51064509:G:C	R126P	1.000
3:51064581:T:C	L150P	1.000
3:51064589:G:C	G153R	1.000
3:51064590:G:A	G153D	1.000
3:51225725:T:A	N443K	1.000
3:51225725:T:G	N443K	1.000
3:51227364:T:A	W487R	1.000
3:51227364:T:C	W487R	1.000
3:51227422:G:C	R506P	1.000
3:51260193:G:C	R741P	1.000
3:51270960:T:C	L834P	1.000
3:51275094:T:C	L855P	1.000
3:51275130:T:C	L867P	1.000
3:51275158:C:G	C876W	1.000
3:51310298:T:A	W997R	1.000
3:51310298:T:C	W997R	1.000
3:51312890:T:A	W1081R	1.000
3:51312890:T:C	W1081R	1.000
3:51338993:T:C	L1244P	1.000
3:51341252:T:C	L1261P	1.000
3:51341278:T:A	W1270R	1.000
3:51341278:T:C	W1270R	1.000
3:51341336:G:C	R1289P	1.000
3:51348855:T:A	W1307R	1.000
3:51348855:T:C	W1307R	1.000
3:51348886:T:C	L1317P	1.000

dbSNP variants (sampled 300 via entrez): RS1000000044 (3:51098200 G>A), RS1000006944 (3:51106034 A>G), RS1000012177 (3:51275740 T>G), RS1000013607 (3:50811777 T>C), RS1000015758 (3:51196396 T>A,C), RS1000023126 (3:51229171 C>A,T), RS1000028565 (3:50957795 T>C), RS1000029817 (3:51329165 G>A), RS1000030691 (3:51371917 C>G), RS1000031780 (3:51342620 G>A), RS1000032047 (3:50937472 G>A), RS1000035118 (3:50809687 C>T), RS1000041770 (3:51248340 G>A,C), RS1000043648 (3:50904768 C>G), RS1000046531 (3:50712679 C>A)

Disease associations

OMIM: gene MIM:603123 | disease phenotypes: MIM:618292

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia	Strong	Autosomal recessive
syndromic intellectual disability	Supportive	Autosomal dominant

Mondo (2): neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (MONDO:0032661), syndromic intellectual disability (MONDO:0000508)

Orphanet (0):

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000276	Long face
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000307	Pointed chin
HP:0000463	Anteverted nares
HP:0000494	Downslanted palpebral fissures
HP:0000689	Dental malocclusion
HP:0001182	Tapered finger
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001315	Reduced tendon reflexes
HP:0001344	Absent speech
HP:0002066	Gait ataxia
HP:0002317	Unsteady gait
HP:0003502	Mild short stature
HP:0003593	Infantile onset
HP:0004482	Relative macrocephaly
HP:0031936	Delayed ability to walk
HP:0100807	Long fingers

GWAS associations

45 associations (top):

Study	Trait	p-value
GCST000817_75	Height	4.000000e-10
GCST002514_1	Melanoma	8.000000e-06
GCST002647_11	Height	8.000000e-18
GCST003650_3	Bacteremia	4.000000e-06
GCST004500_109	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	8.000000e-11
GCST004501_22	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-10
GCST004504_40	Waist circumference adjusted for BMI in non-smokers	9.000000e-09
GCST004600_188	Eosinophil percentage of white cells	2.000000e-13
GCST004606_111	Eosinophil count	4.000000e-13
GCST004617_83	Eosinophil percentage of granulocytes	3.000000e-13
GCST004624_45	Sum eosinophil basophil counts	4.000000e-09
GCST005149_23	Colorectal cancer	1.000000e-07
GCST005150_20	Colorectal cancer	5.000000e-09
GCST005860_2	Cholangiocarcinoma in primary sclerosing cholangitis (time to event)	4.000000e-06
GCST007293_123	Body fat distribution (arm fat ratio)	8.000000e-08
GCST007293_25	Body fat distribution (arm fat ratio)	1.000000e-06
GCST007293_89	Body fat distribution (arm fat ratio)	3.000000e-11
GCST007294_19	Body fat distribution (trunk fat ratio)	3.000000e-08
GCST007294_38	Body fat distribution (trunk fat ratio)	8.000000e-09
GCST007565_86	Morning person	1.000000e-13
GCST008059_226	Estimated glomerular filtration rate	4.000000e-07
GCST008154_29	Trunk fat mass	4.000000e-06
GCST008157_68	Body fat mass	5.000000e-06
GCST008399_4	Cocaine dependence	7.000000e-06
GCST008843_1	Depressive symptom (appetite changes) (binary trait)	9.000000e-09
GCST008848_2	Depressive symptoms (sum-score)	1.000000e-09
GCST008849_3	Depressive symptoms (binary sum-score)	1.000000e-10
GCST010002_423	Refractive error	8.000000e-09
GCST010043_109	Asthma	1.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0007789	BMI-adjusted waist circumference
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004341	body fat distribution
EFO:0008328	chronotype measurement
EFO:0007006	depressive symptom measurement
EFO:0004346	neuroimaging measurement
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0009101	age at first birth measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
sodium arsenite	increases expression	2
daidzein	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
dimethylselenide	increases expression, increases oxidation	1
methylparaben	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
glycitein	affects cotreatment, decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
NSC 689534	affects binding, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Ethanol	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	affects binding, increases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Plant Oils	increases expression	1
Aflatoxin B1	increases methylation	1
Hydroxyl Radical	increases expression, increases oxidation	1
Cadmium Chloride	increases expression	1
Genistein	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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