DOCK7

Summary

DOCK7 (dedicator of cytokinesis 7, HGNC:19190) is a protein-coding gene on chromosome 1p31.3, encoding Dedicator of cytokinesis protein 7 (Q96N67). Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP.

The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 85440 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 117
• Clinical variants (ClinVar): 1,879 total — 59 pathogenic, 34 likely-pathogenic
• Phenotypes (HPO): 47
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_001367561

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19190
Approved symbol	DOCK7
Name	dedicator of cytokinesis 7
Location	1p31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1771, ZIR2
Ensembl gene	ENSG00000116641
Ensembl biotype	protein_coding
OMIM	615730
Entrez	85440

Gene structure

Transcript identifiers

Ensembl transcripts: 47 — 21 protein_coding, 14 protein_coding_CDS_not_defined, 7 retained_intron, 4 nonsense_mediated_decay, 1 non_stop_decay

ENST00000251157, ENST00000340370, ENST00000404627, ENST00000454575, ENST00000464312, ENST00000467758, ENST00000479983, ENST00000489185, ENST00000614472, ENST00000634223, ENST00000634264, ENST00000634495, ENST00000634652, ENST00000634912, ENST00000634929, ENST00000635027, ENST00000635088, ENST00000635123, ENST00000635253, ENST00000635286, ENST00000635348, ENST00000635827, ENST00000635983, ENST00000636167, ENST00000636370, ENST00000636635, ENST00000636746, ENST00000637144, ENST00000637208, ENST00000637227, ENST00000637255, ENST00000637306, ENST00000637431, ENST00000637487, ENST00000637735, ENST00000637839, ENST00000638042, ENST00000895031, ENST00000895032, ENST00000895033, ENST00000912938, ENST00000912939, ENST00000912940, ENST00000912941, ENST00000941402, ENST00000941403, ENST00000941404

RefSeq mRNA: 7 — MANE Select: NM_001367561 NM_001271999, NM_001272000, NM_001272001, NM_001272002, NM_001330614, NM_001367561, NM_033407

CCDS: CCDS30734, CCDS60156, CCDS60157, CCDS81335, CCDS81336, CCDS81338, CCDS90964

Canonical transcript exons

ENST00000635253 — 50 exons

Exon	Start	End
ENSE00000857913	62488934	62489065
ENSE00000857914	62457538	62457705
ENSE00000857921	62505682	62505816
ENSE00000857926	62513444	62513606
ENSE00000857935	62539752	62539892
ENSE00000857936	62542608	62542703
ENSE00000906214	62539545	62539658
ENSE00000906217	62552732	62552901
ENSE00000956715	62544947	62545039
ENSE00000956716	62543656	62543745
ENSE00000956717	62529277	62529446
ENSE00000956718	62528151	62528305
ENSE00000956719	62513716	62513898
ENSE00001011066	62473982	62474088
ENSE00001011069	62492704	62492847
ENSE00001011086	62510577	62510673
ENSE00001011087	62507962	62508058
ENSE00001171158	62494275	62494467
ENSE00001171179	62496339	62496497
ENSE00001171184	62504630	62504782
ENSE00001224665	62535493	62535632
ENSE00001224673	62537891	62538061
ENSE00001364663	62561617	62561703
ENSE00001365553	62558989	62559220
ENSE00001371638	62578828	62578966
ENSE00001375459	62583184	62583254
ENSE00001378660	62577262	62577363
ENSE00001390793	62555825	62555989
ENSE00001454445	62477700	62477825
ENSE00001609612	62634773	62634922
ENSE00001626059	62653725	62653793
ENSE00001642806	62618706	62618868
ENSE00001652026	62495581	62495681
ENSE00001656921	62625259	62625401
ENSE00001668481	62619900	62619993
ENSE00001672788	62648106	62648318
ENSE00001678101	62487398	62487412
ENSE00001696248	62586507	62586624
ENSE00001709791	62636537	62636603
ENSE00001712470	62648415	62648544
ENSE00001713828	62663025	62663130
ENSE00001737563	62633498	62633578
ENSE00001779875	62653984	62654159
ENSE00001800119	62647691	62647776
ENSE00003546182	62475707	62475943
ENSE00003562389	62631240	62631405
ENSE00003612008	62476067	62476156
ENSE00003672862	62475208	62475351
ENSE00003891598	62688227	62688386
ENSE00003893362	62454726	62455456

Expression profiles

Bgee: expression breadth ubiquitous, 260 present calls, max score 97.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.3119 / max 147.4148, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
12631	15.2403	1779
12632	0.9412	491
12633	0.1304	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	97.24	gold quality
calcaneal tendon	UBERON:0003701	96.75	gold quality
sural nerve	UBERON:0015488	96.16	gold quality
tibia	UBERON:0000979	95.83	gold quality
ganglionic eminence	UBERON:0004023	95.49	gold quality
embryo	UBERON:0000922	95.48	gold quality
pigmented layer of retina	UBERON:0001782	95.04	gold quality
retina	UBERON:0000966	95.02	gold quality
upper arm skin	UBERON:0004263	95.02	gold quality
cortical plate	UBERON:0005343	94.83	gold quality
cartilage tissue	UBERON:0002418	94.69	gold quality
colonic epithelium	UBERON:0000397	93.70	gold quality
adrenal tissue	UBERON:0018303	93.22	gold quality
tibial nerve	UBERON:0001323	93.10	gold quality
corpus callosum	UBERON:0002336	93.05	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.96	gold quality
epithelial cell of pancreas	CL:0000083	92.86	gold quality
stromal cell of endometrium	CL:0002255	92.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.98	gold quality
kidney epithelium	UBERON:0004819	91.76	gold quality
buccal mucosa cell	CL:0002336	91.07	gold quality
pituitary gland	UBERON:0000007	91.07	gold quality
caudate nucleus	UBERON:0001873	90.54	gold quality
dorsal root ganglion	UBERON:0000044	90.50	gold quality
adenohypophysis	UBERON:0002196	90.50	gold quality
ileal mucosa	UBERON:0000331	90.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.82	gold quality
trigeminal ganglion	UBERON:0001675	89.72	gold quality
putamen	UBERON:0001874	89.72	gold quality
stomach	UBERON:0000945	89.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	63.49
E-ANND-3	yes	8.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting DOCK7, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4802-3P	99.72	70.13	1273
HSA-MIR-7152-5P	99.60	69.33	2094
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-513C-5P	99.50	68.42	1730
HSA-MIR-514B-5P	99.50	68.19	1766
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-122B-5P	99.46	70.81	1457

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 14)

• Dock7 functions as an intracellular substrate for ErbB2 to promote Schwann cell migration. (PMID:18426980)
• DOCK7 functions as an essential and downstream regulator of RAGE-mediated cellular migration through the formation of dendritic pseudopodia. (PMID:23254359)
• The action of DOCK7 in vivo may involve the coordinated integration of Cdc42/Rac signaling in the context of the membrane recruitment of a DOCK7 guanine nucleotide exchange factor (GEF) complex. (PMID:23718289)
• Dock7 mediates serum- and HGF-induced glioblastoma cell invasion. (PMID:24518591)
• These observations suggest that loss of DOCK7 function causes a syndromic form of epileptic encephalopathy by affecting multiple neuronal processes. (PMID:24814191)
• Possible inter-locus interactions among the DOCK7, PCSK9 and GALNT2 SNPs were also noted. (PMID:26493351)
• Differences in lipid profiles between the Jing and Han populations might partially attribute to the DOCK7, PCSK9 and GALNT2 gene polymorphisms and their haplotypes determining different risk for the development of cardiovascular diseases. (PMID:26744084)
• Interaction of myosin VI and its binding partner DOCK7 plays an important role in NGF-stimulated protrusion formation in PC12 cells. (PMID:27018747)
• Nbeal2 interacts with Dock7, Sec16a, and Vac14. (PMID:29187380)
• these results suggest that the DOCK-ANGPTL3 SNPs and their haplotypes were associated with the angiographic severity to coronary artery atherosclerosis and the risk of coronary artery disease (CAD) and ischemic stroke in the Southern Chinese Han population. (PMID:29454388)
• analysis of the crystal structure of the Cdc42-bound form of the DOCK7 DHR-2 domain of DOCK7 shows dual specificity for Rac1 and Cdc42 (PMID:30853411)
• Characteristic facial features and cortical blindness distinguish the DOCK7-related epileptic encephalopathy. (PMID:33471954)
• DOCK7 protects against replication stress by promoting RPA stability on chromatin. (PMID:33704464)
• Tumour-associated macrophage-derived DOCK7-enriched extracellular vesicles drive tumour metastasis in colorectal cancer via the RAC1/ABCA1 axis. (PMID:38385857)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dock7	ENSDARG00000078675
mus_musculus	Dock7	ENSMUSG00000028556
rattus_norvegicus	Dock7	ENSRNOG00000008298
drosophila_melanogaster	Zir	FBGN0031216
caenorhabditis_elegans		WBGENE00000419
caenorhabditis_elegans		WBGENE00018520

Paralogs (10): DOCK9 (ENSG00000088387), DOCK3 (ENSG00000088538), DOCK8 (ENSG00000107099), DOCK4 (ENSG00000128512), DOCK6 (ENSG00000130158), DOCK2 (ENSG00000134516), DOCK10 (ENSG00000135905), DOCK11 (ENSG00000147251), DOCK5 (ENSG00000147459), DOCK1 (ENSG00000150760)

Protein

Protein identifiers

Dedicator of cytokinesis protein 7 — Q96N67 (reviewed: Q96N67)

All UniProt accessions (10): Q96N67, A0A0C4DGY6, A0A0U1RQG7, A0A0U1RQJ5, A0A0U1RQT6, A0A0U1RR97, A0A0U1RRC1, A0A1B0GUE9, A0A1B0GVW2, A0A1B0GWE0

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a guanine nucleotide exchange factor (GEF), which activates Rac1 and Rac3 Rho small GTPases by exchanging bound GDP for free GTP. Does not have a GEF activity for CDC42. Required for STMN1 ‘Ser-15’ phosphorylation during axon formation and consequently for neuronal polarization. As part of the DISP complex, may regulate the association of septins with actin and thereby regulate the actin cytoskeleton. Has a role in pigmentation. Involved in the regulation of cortical neurogenesis through the control of radial glial cells (RGCs) proliferation versus differentiation; negatively regulates the basal-to-apical interkinetic nuclear migration of RGCs by antagonizing the microtubule growth-promoting function of TACC3.

Subunit / interactions. Component of the DOCK7-induced septin displacement/DISP complex, at least composed of DOCK7, LRCH3 and MYO6. Interacts with TSC1. Interacts with nucleotide-free RAC1 and RAC3. Interacts with TACC3 and CRY1. Interacts with NOD2.

Subcellular location. Cell projection. Axon.

Tissue specificity. Widely expressed.

Disease relevance. Developmental and epileptic encephalopathy 23 (DEE23) [MIM:615859] A severe disease characterized by early-onset intractable epilepsy, dysmorphic features, intellectual disability, and cortical blindness. Brain imaging shows an abnormally marked pontobulbar sulcus with mild pontine hypoplasia, white matter abnormalities, and atrophy in the occipital lobe. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The DOCKER domain mediates GEF activity.

Similarity. Belongs to the DOCK family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q96N67-1	1	yes
Q96N67-2	2
Q96N67-3	3
Q96N67-4	4
Q96N67-5	5
Q96N67-6	6
Q96N67-7	7

RefSeq proteins (7): NP_001258928, NP_001258929, NP_001258930, NP_001258931, NP_001317543, NP_001354490, NP_212132 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR021816	DOCK_C/D_N	Domain
IPR026791	DOCK	Family
IPR027007	C2_DOCK-type_domain	Domain
IPR027357	DOCKER_dom	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037808	C2_Dock-C	Domain
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

Pfam: PF06920, PF11878, PF14429, PF20421, PF20422

UniProt features (80 total): modified residue 37, strand 10, helix 10, sequence conflict 7, splice variant 5, domain 2, region of interest 2, coiled-coil region 2, compositionally biased region 2, chain 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6AJL	X-RAY DIFFRACTION	3.23
6AJ4	X-RAY DIFFRACTION	3.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96N67-F1	74.60	0.27

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 (37): 180, 182, 381, 450, 452, 862, 864, 882, 888, 896, 900, 905, 907, 909, 910, 929, 964, 1383, 1430, 1432 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8875555	MET activates RAP1 and RAC1
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 356 (showing top): GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, PAL_PRMT5_TARGETS_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOMF_GTPASE_BINDING, GOBP_CELL_PROLIFERATION_IN_FOREBRAIN, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_ASYMMETRIC_CELL_DIVISION, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_ESTABLISHMENT_OF_CELL_POLARITY, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_NUCLEUS_LOCALIZATION, GOBP_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_SMOOTH_MUSCLE_CELL_MIGRATION

GO Biological Process (13): microtubule cytoskeleton organization (GO:0000226), axonogenesis (GO:0007409), Rac protein signal transduction (GO:0016601), interkinetic nuclear migration (GO:0022027), neuron projection development (GO:0031175), regulation of Rho protein signal transduction (GO:0035023), establishment of neuroblast polarity (GO:0045200), regulation of neurogenesis (GO:0050767), negative regulation of cold-induced thermogenesis (GO:0120163), positive regulation of vascular associated smooth muscle cell migration (GO:1904754), small GTPase-mediated signal transduction (GO:0007264), nervous system development (GO:0007399), cell differentiation (GO:0030154)

GO Molecular Function (4): guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (7): focal adhesion (GO:0005925), axon (GO:0030424), growth cone (GO:0030426), neuron projection (GO:0043005), basal part of cell (GO:0045178), COP9 signalosome (GO:0008180), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
RHO GTPase cycle	2
MET promotes cell motility	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase regulator activity	2
cellular anatomical structure	2
cytoskeleton organization	1
microtubule-based process	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
axon development	1
small GTPase-mediated signal transduction	1
nuclear migration	1
cell proliferation in forebrain	1
neuron development	1
plasma membrane bounded cell projection organization	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
establishment of cell polarity	1
establishment or maintenance of neuroblast polarity	1
neurogenesis	1
regulation of nervous system development	1
regulation of cell development	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
positive regulation of smooth muscle cell migration	1
vascular associated smooth muscle cell migration	1
regulation of vascular associated smooth muscle cell migration	1
intracellular signaling cassette	1
system development	1
cellular developmental process	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
GTPase binding	1
binding	1
cell-substrate junction	1
neuron projection	1
site of polarized growth	1
distal axon	1
plasma membrane bounded cell projection	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DOCK7	LRCH3	Q96II8	847
DOCK7	CDC42	P21181	801
DOCK7	DHX37	Q8IY37	718
DOCK7	MYO6	Q9UM54	718
DOCK7	ANGPTL3	Q9Y5C1	679
DOCK7	STAP2	Q9UGK3	667
DOCK7	DOCK5	Q9H7D0	607
DOCK7	DHX8	Q14562	595
DOCK7	TACC3	Q9Y6A5	587
DOCK7	RHOJ	Q9H4E5	581
DOCK7	CRK	P46108	518
DOCK7	BCAR1	P56945	501
DOCK7	ATG4C	Q96DT6	493
DOCK7	KCTD20	Q7Z5Y7	479
DOCK7	YWHAB	P31946	471

IntAct

218 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
LRCH3	DOCK7	psi-mi:“MI:0914”(association)	0.840
LRCH3	DOCK7	psi-mi:“MI:0915”(physical association)	0.840
DOCK7	LRCH3	psi-mi:“MI:0914”(association)	0.840
LRCH3	DOCK7	psi-mi:“MI:0403”(colocalization)	0.840
MOB1B	LATS1	psi-mi:“MI:0914”(association)	0.840
LRCH1	DOCK7	psi-mi:“MI:0915”(physical association)	0.800
DOCK7	YWHAG	psi-mi:“MI:0915”(physical association)	0.750
LRCH3	DOCK6	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MYO6	GIPC1	psi-mi:“MI:0914”(association)	0.690
DOCK7	NBEAL2	psi-mi:“MI:0915”(physical association)	0.650
NBEAL2	DOCK7	psi-mi:“MI:2364”(proximity)	0.650
NBEAL2	VAC14	psi-mi:“MI:0914”(association)	0.650
SEC16A	NBEAL2	psi-mi:“MI:0914”(association)	0.640
NBEAL2	SEC16A	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
ARPC3	ARPC2	psi-mi:“MI:0914”(association)	0.640
DNAJC7	PLD2	psi-mi:“MI:0914”(association)	0.640
DOCK8	LRCH4	psi-mi:“MI:0914”(association)	0.620
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570

BioGRID (362): DOCK7 (Affinity Capture-RNA), DOCK7 (Affinity Capture-RNA), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Affinity Capture-MS), DOCK7 (Proximity Label-MS), DOCK7 (Affinity Capture-MS)

ESM2 similar proteins: A0JP85, A1A5H6, A2AGH6, A5GFY4, A5YKK6, B1AY13, B4KJ11, E9Q8I9, O75448, O94915, O95155, P55824, Q0KK59, Q23658, Q24134, Q2PW47, Q2QCI8, Q4V8B3, Q5F3M0, Q5RCU2, Q5RFA0, Q5TBA9, Q60PC0, Q6GLR7, Q6GYQ0, Q6PI53, Q6ZQ08, Q7ZYV9, Q80TJ1, Q80X82, Q80YV3, Q8BHR2, Q8BL99, Q8IXH7, Q8R0Z2, Q8R1A4, Q922L6, Q92797, Q93074, Q96N67

Diamond homologs: A2AF47, B0R034, Q5JSL3, Q63603, Q8BIK4, Q8BZN6, Q8C147, Q8NF50, Q8R1A4, Q8VDR9, Q96BY6, Q96HP0, Q96N67, Q9BZ29

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
ERBB2	up-regulates	DOCK7	phosphorylation
DOCK7	“up-regulates activity”	CDC42	“guanine nucleotide exchange factor”
DOCK7	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
NBEAL2	“up-regulates activity”	DOCK7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 204 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
Activation of BAD and translocation to mitochondria	8	42.3×	1e-09
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	37.3×	3e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	32.7×	1e-07
Activation of BH3-only proteins	8	27.6×	3e-08
Intrinsic Pathway for Apoptosis	10	20.3×	6e-09
Signaling by Hippo	5	18.9×	2e-04
RHO GTPases activate PKNs	8	17.6×	1e-06
RAF activation	7	16.3×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
substantia nigra development	7	13.9×	3e-04
response to calcium ion	7	12.0×	5e-04
protein targeting	6	11.9×	2e-03
endothelial cell migration	5	11.1×	1e-02
long-term synaptic potentiation	7	10.6×	1e-03
intracellular protein localization	14	7.9×	4e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

1879 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	59
Likely pathogenic	34
Uncertain significance	784
Likely benign	831
Benign	103

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069481	NC_000001.10:g.(?_62971367)_62980255del	Pathogenic
1073136	NM_001367561.1(DOCK7):c.1501C>T (p.Arg501Ter)	Pathogenic
1076823	NM_001367561.1(DOCK7):c.4682_4683del (p.His1560_Cys1561insTer)	Pathogenic
1338754	NM_001367561.1(DOCK7):c.2112+2T>C	Pathogenic
1387497	NM_001367561.1(DOCK7):c.5830_5834dup (p.Pro1946fs)	Pathogenic
139536	NM_001367561.1(DOCK7):c.2510del (p.Asp837fs)	Pathogenic
139537	NM_001367561.1(DOCK7):c.3709C>T (p.Arg1237Ter)	Pathogenic
139538	NM_001367561.1(DOCK7):c.983C>G (p.Ser328Ter)	Pathogenic
139539	NM_001367561.1(DOCK7):c.6265G>T (p.Glu2089Ter)	Pathogenic
1423192	NM_001367561.1(DOCK7):c.1725del (p.Arg576fs)	Pathogenic
1449770	NM_001367561.1(DOCK7):c.2683C>T (p.Arg895Ter)	Pathogenic
1452731	NM_001367561.1(DOCK7):c.556dup (p.Thr186fs)	Pathogenic
1453901	NM_001367561.1(DOCK7):c.4128del (p.Val1377fs)	Pathogenic
1454544	NM_001367561.1(DOCK7):c.5381_5382dup (p.Asn1795fs)	Pathogenic
1455206	NM_001367561.1(DOCK7):c.2106_2107dup (p.Pro703fs)	Pathogenic
1455645	NM_001367561.1(DOCK7):c.5059C>T (p.Arg1687Ter)	Pathogenic
1687530	NM_001367561.1(DOCK7):c.3132_3133del (p.Ile1045fs)	Pathogenic
1925575	NC_000001.11:g.62510670CT[1]	Pathogenic
1995558	NM_001367561.1(DOCK7):c.6101dup (p.Asn2034fs)	Pathogenic
2000115	NC_000001.11:g.62510670CT[2]	Pathogenic
2005938	NM_001367561.1(DOCK7):c.5338C>T (p.Gln1780Ter)	Pathogenic
2023278	NM_001367561.1(DOCK7):c.4675C>T (p.Arg1559Ter)	Pathogenic
2054099	NM_001367561.1(DOCK7):c.5619dup (p.Ser1874fs)	Pathogenic
2055243	NM_001367561.1(DOCK7):c.1083del (p.Tyr362fs)	Pathogenic
2101973	NM_001367561.1(DOCK7):c.5306_5310del (p.Tyr1768_Phe1769insTer)	Pathogenic
2127238	NM_001367561.1(DOCK7):c.6184C>T (p.Arg2062Ter)	Pathogenic
2500751	NM_001367561.1(DOCK7):c.453dup (p.Gly152fs)	Pathogenic
2727055	NM_001367561.1(DOCK7):c.2278C>T (p.Arg760Ter)	Pathogenic
2746325	NM_001367561.1(DOCK7):c.4141dup (p.Met1381fs)	Pathogenic
2755454	NM_001367561.1(DOCK7):c.2615del (p.Gly872fs)	Pathogenic

SpliceAI

8505 predictions. Top by Δscore:

Variant	Effect	Δscore
1:62455452:AATCT:A	acceptor_gain	1.0000
1:62455453:ATCT:A	acceptor_gain	1.0000
1:62455455:CT:C	acceptor_gain	1.0000
1:62455456:TC:T	acceptor_loss	1.0000
1:62455457:C:CC	acceptor_gain	1.0000
1:62455457:CTGGG:C	acceptor_loss	1.0000
1:62457533:CATA:C	donor_loss	1.0000
1:62457535:TA:T	donor_loss	1.0000
1:62457536:A:AC	donor_gain	1.0000
1:62457536:ACCTG:A	donor_loss	1.0000
1:62457537:C:CA	donor_loss	1.0000
1:62457537:C:CC	donor_gain	1.0000
1:62457562:G:GA	donor_gain	1.0000
1:62457701:CACAC:C	acceptor_gain	1.0000
1:62457702:ACAC:A	acceptor_gain	1.0000
1:62457703:CAC:C	acceptor_gain	1.0000
1:62457703:CACC:C	acceptor_gain	1.0000
1:62457704:AC:A	acceptor_gain	1.0000
1:62457705:CC:C	acceptor_gain	1.0000
1:62457706:C:CC	acceptor_gain	1.0000
1:62457707:T:C	acceptor_loss	1.0000
1:62475204:TAA:T	donor_loss	1.0000
1:62475205:AAC:A	donor_loss	1.0000
1:62475206:A:AC	donor_gain	1.0000
1:62475207:C:CC	donor_gain	1.0000
1:62475349:GATC:G	acceptor_loss	1.0000
1:62475351:TCT:T	acceptor_loss	1.0000
1:62475352:CTGA:C	acceptor_loss	1.0000
1:62475944:C:CC	acceptor_gain	1.0000
1:62476061:CTATA:C	donor_loss	1.0000

AlphaMissense

14113 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:62457604:A:G	L2105P	1.000
1:62457616:A:G	L2101P	1.000
1:62457637:A:G	L2094P	1.000
1:62474006:A:G	L2063P	1.000
1:62474009:C:G	R2062P	1.000
1:62474012:A:G	L2061P	1.000
1:62474060:A:G	L2045P	1.000
1:62474072:G:T	A2041D	1.000
1:62474088:C:G	G2036R	1.000
1:62474088:C:T	G2036R	1.000
1:62475234:C:G	G2027R	1.000
1:62475234:C:T	G2027R	1.000
1:62475239:A:G	L2025P	1.000
1:62475239:A:T	L2025H	1.000
1:62475245:A:G	M2023T	1.000
1:62475251:A:G	L2021P	1.000
1:62477752:A:T	V1861D	1.000
1:62477803:C:G	R1844P	1.000
1:62488965:A:G	L1821P	1.000
1:62492759:A:G	F1769S	1.000
1:62494422:C:A	W1690C	1.000
1:62494422:C:G	W1690C	1.000
1:62494424:A:G	W1690R	1.000
1:62494424:A:T	W1690R	1.000
1:62494435:A:G	L1686P	1.000
1:62494462:G:T	A1677D	1.000
1:62494463:C:G	A1677P	1.000
1:62495590:A:G	L1672P	1.000
1:62495641:T:A	D1655V	1.000
1:62495641:T:C	D1655G	1.000

dbSNP variants (sampled 300 via entrez): RS1000008208 (1:62609577 T>C), RS1000011674 (1:62671014 G>A), RS1000020965 (1:62579656 C>A,T), RS1000022770 (1:62516288 G>C,T), RS1000031014 (1:62649743 T>C), RS1000054359 (1:62497601 C>A), RS1000060073 (1:62687956 G>A), RS1000092391 (1:62471590 G>A), RS1000093340 (1:62565135 T>A,C), RS1000111095 (1:62526296 C>T), RS1000116276 (1:62677610 C>T), RS1000135330 (1:62502710 C>T), RS1000147764 (1:62589493 G>T), RS1000153247 (1:62635554 C>A), RS1000159010 (1:62458471 T>G)

Disease associations

OMIM: gene MIM:615730 | disease phenotypes: MIM:615859, MIM:603147, MIM:618389

GenCC curated gene-disease

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	Autosomal recessive
developmental and epileptic encephalopathy, 23	Strong	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AR

Mondo (4): developmental and epileptic encephalopathy, 23 (MONDO:0014371), ALG6-congenital disorder of glycosylation 1C (MONDO:0011291), fetal akinesia deformation sequence 3 (MONDO:0100103), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (2): Early-onset epileptic encephalopathy-cortical blindness-intellectual disability-facial dysmorphism syndrome (Orphanet:411986), ALG6-CDG (Orphanet:79320)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000232	Everted lower lip vermilion
HP:0000294	Low anterior hairline
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000377	Abnormal pinna morphology
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000506	Telecanthus
HP:0000527	Long eyelashes
HP:0000528	Anophthalmia
HP:0000574	Thick eyebrow
HP:0000629	Periorbital fullness
HP:0000664	Synophrys
HP:0000717	Autism
HP:0000733	Motor stereotypy
HP:0000817	Reduced eye contact
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001336	Myoclonus
HP:0001344	Absent speech
HP:0002069	Bilateral tonic-clonic seizure
HP:0002079	Hypoplasia of the corpus callosum
HP:0002121	Generalized non-motor (absence) seizure
HP:0002384	Focal impaired awareness seizure
HP:0002465	Poor speech
HP:0002521	Hypsarrhythmia

GWAS associations

117 associations (top):

Study	Trait	p-value
GCST000138_4	Triglycerides	2.000000e-08
GCST000282_12	LDL cholesterol	8.000000e-06
GCST000285_11	Cholesterol, total	4.000000e-12
GCST000289_4	Triglycerides	2.000000e-12
GCST000758_15	Triglycerides	9.000000e-43
GCST000759_19	LDL cholesterol	3.000000e-18
GCST000760_7	Cholesterol, total	5.000000e-41
GCST000809_6	Triglycerides	6.000000e-08
GCST001639_12	Metabolite levels	8.000000e-15
GCST002321_11	Lipid traits	6.000000e-10
GCST002321_7	Lipid traits	5.000000e-07
GCST002690_1	Very long-chain saturated fatty acid levels (fatty acid 20:0)	7.000000e-07
GCST002896_5	Cholesterol, total	2.000000e-34
GCST002897_11	Triglycerides	6.000000e-34
GCST002898_2	LDL cholesterol	2.000000e-11
GCST003649_5	Pneumococcal bacteremia	5.000000e-06
GCST004132_95	Crohn’s disease	4.000000e-06
GCST004209_2	Cholesterol, total	2.000000e-10
GCST004616_108	Platelet distribution width	9.000000e-33
GCST005780_1	Triglyceride levels	2.000000e-08
GCST006003_5	Triglyceride levels	4.000000e-32
GCST006034_27	Total cholesterol levels	4.000000e-10
GCST006611_71	HDL cholesterol	9.000000e-12
GCST006612_45	LDL cholesterol	6.000000e-22
GCST006614_116	Total cholesterol levels	6.000000e-112
GCST006920_5	Regular attendance at a gym or sports club	1.000000e-08
GCST007931_87	Medication use (HMG CoA reductase inhibitors)	3.000000e-37
GCST008074_21	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	2.000000e-12
GCST008074_30	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	3.000000e-123
GCST008074_64	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	9.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004574	total cholesterol measurement
EFO:0004723	coronary artery calcification
EFO:0006796	very long-chain saturated fatty acid measurement
EFO:1001925	pneumococcal bacteremia
EFO:0007984	platelet component distribution width
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009592	social interaction measurement
EFO:0009932	HMG CoA reductase inhibitor use measurement
EFO:0004329	alcohol drinking
EFO:0010449	3-methyladipic acid measurement
EFO:0010524	pimelic acid measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004615	apolipoprotein B measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535741	Congenital disorder of glycosylation type 1C (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	6
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
Particulate Matter	affects expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	decreases expression	1
perfluorooctanoic acid	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation	1
CGP 52608	increases reaction, affects binding	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT06719141	PHASE3	RECRUITING	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathies (DEE)
NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT05626634	PHASE2	COMPLETED	Open-label, Long-term Safety Study of LP352 in Subjects With Developmental and Epileptic Encephalopathy
NCT06700811	PHASE1	RECRUITING	Ketogenic Diet for Prevention of Epileptic Spasms in Infantile Onset Genetic Epilepsies
NCT05364021	PHASE1/PHASE2	COMPLETED	Study to Investigate LP352 in Subjects With Developmental and Epileptic Encephalopathies
NCT06983158	PHASE1/PHASE2	SUSPENDED	A Clinical Trial of CAP-002 Gene Therapy in Pediatric Patients With Syntaxin-Binding Protein 1 (STXBP1) Encephalopathy
NCT04937062	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	Phenylbutyrate for Monogenetic Developmental and Epileptic Encephalopathy
NCT06149663	Not specified	AVAILABLE	Intermediate-Size Expanded Access Protocol (EAP) for LP352
NCT06380192	Not specified	RECRUITING	Developmental and Epileptic Encephalopathy of Genetic Etiology: Natural History Through Reuse of Clinical Data
NCT07396883	Not specified	NOT_YET_RECRUITING	Developmental and Epileptic Encephalopathies Diagnosed Via Long-read Genome Sequencing
NCT07531511	Not specified	NOT_YET_RECRUITING	SLC6A1-NDD Prospective Longitudinal Natural History Study
NCT07585643	Not specified	NOT_YET_RECRUITING	IBIS - Investigating Reliability of BIS and SEDLINE Monitoring in Children With Developmental and Epileptic Encephalopathies (DEE).