EXOC4

Summary

EXOC4 (exocyst complex component 4, HGNC:30389) is a protein-coding gene on chromosome 7q33, encoding Exocyst complex component 4 (Q96A65). Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane. It is a selective cancer dependency (DepMap: 31.5% of cell lines).

The protein encoded by this gene is a component of the exocyst complex, a multiple protein complex essential for targeting exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and functions of exocyst complex have been demonstrated to be highly conserved in higher eukaryotes. At least eight components of the exocyst complex, including this protein, are found to interact with the actin cytoskeletal remodeling and vesicle transport machinery. The complex is also essential for the biogenesis of epithelial cell surface polarity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 60412 — RefSeq curated summary.

At a glance

• GWAS associations: 50
• Clinical variants (ClinVar): 207 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 31.5% of screened cell lines
• MANE Select transcript: NM_021807

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30389
Approved symbol	EXOC4
Name	exocyst complex component 4
Location	7q33
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1699, MGC27170, SEC8, Sec8p
Ensembl gene	ENSG00000131558
Ensembl biotype	protein_coding
OMIM	608185
Entrez	60412

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 16 protein_coding_CDS_not_defined, 7 protein_coding, 5 retained_intron

ENST00000253861, ENST00000393161, ENST00000459626, ENST00000460346, ENST00000462055, ENST00000463150, ENST00000466000, ENST00000469115, ENST00000472020, ENST00000478265, ENST00000479839, ENST00000480337, ENST00000480840, ENST00000481074, ENST00000482089, ENST00000483800, ENST00000484397, ENST00000486013, ENST00000486409, ENST00000489931, ENST00000492326, ENST00000494685, ENST00000498024, ENST00000850617, ENST00000852803, ENST00000933610, ENST00000933611, ENST00000941115

RefSeq mRNA: 2 — MANE Select: NM_021807 NM_001037126, NM_021807

CCDS: CCDS43648, CCDS5829

Canonical transcript exons

ENST00000253861 — 18 exons

Exon	Start	End
ENSE00001175682	134007676	134007835
ENSE00001175694	133997492	133997633
ENSE00003460580	133895599	133895735
ENSE00003463215	133305877	133306061
ENSE00003469399	133630045	133630141
ENSE00003484876	133475328	133475473
ENSE00003514754	133937891	133938069
ENSE00003539200	133274982	133275171
ENSE00003603116	133317284	133317390
ENSE00003607322	133917583	133917738
ENSE00003616578	133356330	133356573
ENSE00003648627	134004912	134005090
ENSE00003648683	133288922	133289116
ENSE00003658203	133480050	133480138
ENSE00003670987	133817325	133817544
ENSE00003675287	133374828	133375002
ENSE00004282337	134064291	134065761
ENSE00004282340	133253078	133253187

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.8493 / max 653.9018, expressed in 1823 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
81224	49.4463	1823
81239	0.1571	7
81232	0.0507	11
81250	0.0355	6
81233	0.0338	8
81234	0.0326	11
81238	0.0249	4
81236	0.0201	3
81235	0.0124	3
81251	0.0105	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	97.12	gold quality
cortical plate	UBERON:0005343	96.44	gold quality
calcaneal tendon	UBERON:0003701	96.41	gold quality
colonic epithelium	UBERON:0000397	95.64	gold quality
ventricular zone	UBERON:0003053	95.60	gold quality
ganglionic eminence	UBERON:0004023	95.57	gold quality
upper arm skin	UBERON:0004263	94.38	gold quality
adrenal tissue	UBERON:0018303	94.09	gold quality
deltoid	UBERON:0001476	94.08	gold quality
sural nerve	UBERON:0015488	92.95	gold quality
tibialis anterior	UBERON:0001385	92.92	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.74	gold quality
islet of Langerhans	UBERON:0000006	92.61	gold quality
skeletal muscle tissue	UBERON:0001134	92.58	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.58	gold quality
tonsil	UBERON:0002372	92.14	gold quality
vastus lateralis	UBERON:0001379	92.10	gold quality
muscle of leg	UBERON:0001383	92.10	gold quality
skeletal muscle organ	UBERON:0014892	92.08	gold quality
muscle tissue	UBERON:0002385	92.06	gold quality
sperm	CL:0000019	92.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.99	gold quality
endothelial cell	CL:0000115	91.91	gold quality
stromal cell of endometrium	CL:0002255	91.91	gold quality
quadriceps femoris	UBERON:0001377	91.74	gold quality
tendon	UBERON:0000043	91.52	gold quality
gastrocnemius	UBERON:0001388	91.49	gold quality
gingival epithelium	UBERON:0001949	91.35	gold quality
pancreatic ductal cell	CL:0002079	91.32	gold quality
smooth muscle tissue	UBERON:0001135	91.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.18
E-MTAB-6058	no	249.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXA2, NFE2L2

miRNA regulators (miRDB)

63 targeting EXOC4, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
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-371B-5P	99.99	75.34	4759
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-452-5P	99.65	69.63	1762
HSA-MIR-4676-3P	99.65	69.31	1733
HSA-MIR-892C-3P	99.65	69.38	1745
HSA-MIR-3177-5P	99.65	70.38	1174

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• EXOC4 is involved in insulin-stimulated glucose transport and may be a candidate for an association with type 2 diabetes. (PMID:18498660)
• The exocyst subunits Sec3 and Sec8 interact with the polarity protein IQGAP1 and that this interaction is triggered by active Cdc42 and RhoA, which are essential for matrix degradation. (PMID:18541705)
• Exome sequencing revealed a likely pathogenic mutation in three novel candidate MKS disease genes-C5orf42, EVC2 and SEC8 (also known as EXOC4), which encodes an exocyst protein with an established role in ciliogenesis (PMID:23169490)
• High Sec8 expression is associated with progression of oral squamous-cell carcinoma by secretion of matrix metalloproteinases. (PMID:23207790)
• knockdown of Sec8 enhances the binding of JIP4 to MAPK kinase 4, thereby decreasing the phosphorylation of MAPK kinase 4, JNK, and p38. (PMID:25244576)
• Sec8 knockdown in HSC3 cells resulted in reduced expressions of PAK1 and PAK2 by upregulating Pirh2 and Siah1 expression, which inhibited the ERK or p38 MAPK signalling pathway and cytokeratin8 phosphorylation and cell migration. (PMID:25725287)
• Sec8 regulates histone-modifying proteins ATF2 and RNF20. (PMID:26283729)
• Sec8 regulate Bcl-2 and Mcl-1 expressions but not Bcl-xl in malignant peripheral nerve sheath tumor cells. (PMID:26892009)
• Sec8 regulates N-cadherin expression by controlling Smad3 and Smad4 expression through CBP, thereby mediating the epithelial-mesenchymal transition. (PMID:27769780)
• LRRK2 Modulates the Exocyst Complex Assembly by Interacting with Sec8. (PMID:33498474)
• EXOC4 Promotes Diffuse-Type Gastric Cancer Metastasis via Activating FAK Signal. (PMID:35471457)
• Altered methylation pattern in EXOC4 is associated with stroke outcome: an epigenome-wide association study. (PMID:36180927)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exoc4	ENSDARG00000004336
mus_musculus	Exoc4	ENSMUSG00000029763
rattus_norvegicus	Exoc4	ENSRNOG00000046023
drosophila_melanogaster	Sec8	FBGN0266672
caenorhabditis_elegans	sec-8	WBGENE00004753

Protein

Protein identifiers

Exocyst complex component 4 — Q96A65 (reviewed: Q96A65)

Alternative names: Exocyst complex component Sec8

All UniProt accessions (1): Q96A65

UniProt curated annotations — full annotation on UniProt →

Function. Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.

Subunit / interactions. The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8. Interacts with BIRC6/bruce. Interacts with MYRIP. Interacts with SH3BP1; required for the localization of both SH3BP1 and the exocyst to the leading edge of migrating cells. Interacts with SLC6A9.

Subcellular location. Midbody. Midbody ring. Cell projection. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome.

Similarity. Belongs to the SEC8 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96A65-1	1	yes
Q96A65-2	2

RefSeq proteins (2): NP_001032203, NP_068579* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007191	Sec8_exocyst_N	Domain
IPR039682	Sec8/EXOC4	Family
IPR048630	Sec8_M	Domain

Pfam: PF04048, PF20652

UniProt features (16 total): modified residue 7, sequence variant 2, sequence conflict 2, initiator methionine 1, chain 1, splice variant 1, strand 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7PC5	X-RAY DIFFRACTION	1.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96A65-F1	79.22	0.45

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 (7): 2, 9, 32, 226, 233, 237, 468

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1445148	Translocation of SLC2A4 (GLUT4) to the plasma membrane
R-HSA-264876	Insulin processing
R-HSA-5620916	VxPx cargo-targeting to cilium

MSigDB gene sets: 243 (showing top): MORF_ITGA2, GOBP_MITOTIC_CYTOKINESIS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_VESICLE_LOCALIZATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_VESICLE_TARGETING, KEGG_TIGHT_JUNCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, MORF_RAD51L3, GOCC_MICROTUBULE_ORGANIZING_CENTER, GOBP_MACROAUTOPHAGY

GO Biological Process (11): mitotic cytokinesis (GO:0000281), exocytosis (GO:0006887), Golgi to plasma membrane transport (GO:0006893), obsolete vesicle docking involved in exocytosis (GO:0006904), chemical synaptic transmission (GO:0007268), regulation of macroautophagy (GO:0016241), paraxial mesoderm formation (GO:0048341), protein transmembrane transport (GO:0071806), membrane fission (GO:0090148), obsolete vesicle tethering involved in exocytosis (GO:0090522), protein transport (GO:0015031)

GO Molecular Function (2): PDZ domain binding (GO:0030165), protein binding (GO:0005515)

GO Cellular Component (14): exocyst (GO:0000145), cytoplasm (GO:0005737), centrosome (GO:0005813), cytosol (GO:0005829), plasma membrane (GO:0005886), microvillus (GO:0005902), membrane (GO:0016020), growth cone membrane (GO:0032584), myelin sheath abaxonal region (GO:0035748), synapse (GO:0045202), Flemming body (GO:0090543), cytoskeleton (GO:0005856), cell projection (GO:0042995), neuron projection (GO:0043005)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Membrane Trafficking	1
Peptide hormone metabolism	1
Cargo trafficking to the periciliary membrane	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	7
mitotic cell cycle	1
cytoskeleton-dependent cytokinesis	1
mitotic cell cycle process	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
post-Golgi vesicle-mediated transport	1
vesicle-mediated transport to the plasma membrane	1
anterograde trans-synaptic signaling	1
regulation of autophagy	1
macroautophagy	1
mesoderm formation	1
paraxial mesoderm morphogenesis	1
protein transport	1
transmembrane transport	1
membrane organization	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
protein domain specific binding	1
binding	1
cell cortex	1
vesicle tethering complex	1
intracellular anatomical structure	1
centriole	1
microtubule organizing center	1
cytoplasm	1
membrane	1
cell periphery	1
actin filament bundle	1
actin-based cell projection	1
plasma membrane	1
growth cone	1
myelin sheath	1
cell junction	1
midbody	1
intracellular membraneless organelle	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

2252 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOC4	EXOC5	O00471	999
EXOC4	EXOC3	O60645	999
EXOC4	EXOC6	Q8TAG9	999
EXOC4	EXOC1	Q9NV70	999
EXOC4	EXOC7	Q9UPT5	999
EXOC4	EXOC2	Q96KP1	998
EXOC4	EXOC8	Q8IYI6	998
EXOC4	IQGAP1	P46940	934
EXOC4	RHOQ	P17081	914
EXOC4	MYRIP	Q8NFW9	890
EXOC4	RALA	P11233	874
EXOC4	RAB11A	P24410	792
EXOC4	EXOC6B	Q9Y2D4	771
EXOC4	GRIN2B	Q13224	691
EXOC4	SLC2A4	P14672	675

IntAct

303 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
EXOC1	EXOC4	psi-mi:“MI:0407”(direct interaction)	0.890
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
EXOC6	EXOC5	psi-mi:“MI:0914”(association)	0.840
EXOC2	EXOC3	psi-mi:“MI:0914”(association)	0.790
EXOC6B	EXOC5	psi-mi:“MI:0914”(association)	0.790
EXOC3	EXOC5	psi-mi:“MI:0914”(association)	0.790
EXOC8	EXOC4	psi-mi:“MI:0914”(association)	0.790
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
EXOC8	EXOC5	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
IKBIP	SNAPIN	psi-mi:“MI:0914”(association)	0.670
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640

BioGRID (310): EXOC4 (Affinity Capture-MS), EXOC4 (Affinity Capture-MS), EXOC4 (Affinity Capture-MS), EXOC4 (Affinity Capture-MS), EXOC4 (Affinity Capture-MS), EXOC4 (Affinity Capture-Western), EXOC4 (Co-fractionation), EXOC4 (Co-fractionation), EXOC4 (Co-fractionation), EXOC4 (Co-fractionation), EXOC4 (Co-fractionation), EXOC6 (Co-fractionation), EXOC7 (Co-fractionation), EXOC4 (Affinity Capture-MS), EXOC4 (Proximity Label-MS)

ESM2 similar proteins: A0A098DRQ4, A1A4L0, A1CAN8, A1DF15, A1L1C7, A6RJQ7, A7E559, A7KAL4, B2AVN3, C8VDI2, C8VDQ4, I1RKA1, I1S4N7, O60749, O95219, P0C220, P83094, Q0WQF4, Q2TBW7, Q2U7R4, Q2UB56, Q4IR87, Q4WCV3, Q4WUE5, Q4WZF1, Q524W4, Q5AZC9, Q5R4C2, Q5R6M6, Q5R9A9, Q6NRZ4, Q6P3Q6, Q6PCS4, Q6VVX2, Q7SB54, Q7SB97, Q8J2R3, Q8K3H0, Q8VWF1, Q91VH2

Diamond homologs: O35382, Q62824, Q96A65, Q9VNH6, Q93YU5, Q9HE88, Q54P76

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EXOC4	“form complex”	“Exocyst_EXOC6B variant”	binding
EXOC4	“form complex”	“Exocyst_EXOC6 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 190 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
Insulin processing	8	29.0×	1e-07
VxPx cargo-targeting to cilium	7	28.8×	6e-07
Signaling by FGFR1 in disease	6	13.9×	2e-04
Translocation of SLC2A4 (GLUT4) to the plasma membrane	11	13.5×	1e-07
Loss of Nlp from mitotic centrosomes	9	11.3×	1e-05
Loss of proteins required for interphase microtubule organization from the centrosome	9	11.3×	1e-05
AURKA Activation by TPX2	9	10.9×	1e-05
Anchoring of the basal body to the plasma membrane	11	9.9×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
Golgi to plasma membrane transport	10	33.8×	1e-10
obsolete vesicle docking involved in exocytosis	8	32.5×	3e-08
membrane fission	8	19.8×	1e-06
mitotic cytokinesis	8	12.5×	4e-05
exocytosis	12	11.0×	3e-07
autophagosome maturation	5	10.6×	9e-03
endosome to lysosome transport	5	10.2×	1e-02
intermediate filament organization	6	8.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	167
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
183330	NM_021807.4(EXOC4):c.1733A>G (p.Gln578Arg)	Likely pathogenic

SpliceAI

4829 predictions. Top by Δscore:

Variant	Effect	Δscore
7:133274977:ACCAG:A	acceptor_gain	1.0000
7:133274978:CCAG:C	acceptor_loss	1.0000
7:133274979:CAG:C	acceptor_loss	1.0000
7:133274981:G:GT	acceptor_loss	1.0000
7:133274981:GGA:G	acceptor_gain	1.0000
7:133288917:TGTA:T	acceptor_loss	1.0000
7:133288918:GTAG:G	acceptor_loss	1.0000
7:133288919:TA:T	acceptor_loss	1.0000
7:133288920:A:AG	acceptor_gain	1.0000
7:133288920:A:AT	acceptor_loss	1.0000
7:133288921:G:GG	acceptor_gain	1.0000
7:133289112:TGTTG:T	donor_loss	1.0000
7:133289113:GTTG:G	donor_gain	1.0000
7:133289116:GGTAA:G	donor_loss	1.0000
7:133289117:G:GG	donor_gain	1.0000
7:133289117:G:T	donor_loss	1.0000
7:133289118:T:TC	donor_loss	1.0000
7:133305873:TCA:T	acceptor_loss	1.0000
7:133305874:CA:C	acceptor_loss	1.0000
7:133305875:A:AG	acceptor_gain	1.0000
7:133305875:AG:A	acceptor_gain	1.0000
7:133305875:AGGT:A	acceptor_gain	1.0000
7:133305876:G:A	acceptor_gain	1.0000
7:133305876:G:GT	acceptor_gain	1.0000
7:133305876:GGT:G	acceptor_gain	1.0000
7:133305876:GGTG:G	acceptor_gain	1.0000
7:133305876:GGTGT:G	acceptor_gain	1.0000
7:133306035:GC:G	donor_gain	1.0000
7:133306045:G:GT	donor_gain	1.0000
7:133306046:A:T	donor_gain	1.0000

AlphaMissense

6451 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:133275035:T:C	L47P	1.000
7:133275068:T:C	L58P	1.000
7:133275101:T:C	L69S	1.000
7:133275109:G:C	A72P	1.000
7:133275155:G:C	R87P	1.000
7:133288935:T:C	L97P	1.000
7:133288953:T:C	L103P	1.000
7:133288956:T:C	L104P	1.000
7:133288977:T:A	L111H	1.000
7:133288977:T:C	L111P	1.000
7:133288980:G:C	R112P	1.000
7:133288986:T:C	L114P	1.000
7:133289019:T:C	L125P	1.000
7:133305992:T:C	L196P	1.000
7:133374842:T:C	L341P	1.000
7:133630090:T:A	V488D	1.000
7:133895633:T:C	L590P	1.000
7:133895642:T:C	L593P	1.000
7:133895699:T:C	L612P	1.000
7:133917617:A:C	S636R	1.000
7:133917619:T:A	S636R	1.000
7:133917619:T:G	S636R	1.000
7:133917626:T:A	W639R	1.000
7:133917626:T:C	W639R	1.000
7:133937920:T:C	L686P	1.000
7:133937995:C:A	A711D	1.000
7:133938009:A:C	S716R	1.000
7:133938011:C:A	S716R	1.000
7:133938011:C:G	S716R	1.000
7:133997624:T:C	L780P	1.000

dbSNP variants (sampled 300 via entrez): RS1000002035 (7:133328050 C>G,T), RS1000002038 (7:133687555 C>G), RS1000002971 (7:133368904 A>C), RS1000007505 (7:133681634 C>A,G,T), RS1000007954 (7:133866697 T>C), RS1000009764 (7:133788110 G>T), RS1000010914 (7:133601158 G>A), RS1000011338 (7:133543629 A>G), RS1000016819 (7:133742924 T>C), RS1000020382 (7:133968008 G>A,T), RS1000022779 (7:134037194 T>C), RS1000031274 (7:133782779 GGA>G), RS1000031530 (7:133467838 G>A,T), RS1000035464 (7:134052763 A>C), RS1000038546 (7:133600877 G>A,C)

Disease associations

OMIM: gene MIM:608185 | disease phenotypes: MIM:249000, MIM:615083, MIM:615139, MIM:618336

GenCC curated gene-disease

Mondo (6): Meckel syndrome (MONDO:0018921), familial colorectal cancer type X (MONDO:0018604), Polymerase proofreading-related adenomatous polyposis (MONDO:0018653), colorectal cancer, susceptibility to, 12 (MONDO:0014038), facial dysmorphism-immunodeficiency-livedo-short stature syndrome (MONDO:0014058), intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency (MONDO:0032684)

Orphanet (5): Meckel syndrome (Orphanet:564), Familial colorectal cancer Type X (Orphanet:440437), Polymerase proofreading-related polyposis (Orphanet:447877), Attenuated familial adenomatous polyposis (Orphanet:220460), Facial dysmorphism-immunodeficiency-livedo-short stature syndrome (Orphanet:352712)

HPO phenotypes

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

GWAS associations

50 associations (top):

Study	Trait	p-value
GCST000107_3	Tonometry	8.000000e-06
GCST001915_21	Alzheimer’s disease (cognitive decline)	5.000000e-07
GCST004364_25	Intelligence	2.000000e-09
GCST004364_7	Intelligence	4.000000e-07
GCST005141_62	Cognitive ability (MTAG)	1.000000e-12
GCST005142_16	Cognitive ability	5.000000e-10
GCST005142_64	Cognitive ability	4.000000e-10
GCST005171_50	QT interval	5.000000e-07
GCST005316_15	Intelligence (MTAG)	1.000000e-10
GCST005316_16	Intelligence (MTAG)	3.000000e-11
GCST005316_17	Intelligence (MTAG)	3.000000e-09
GCST005316_18	Intelligence (MTAG)	4.000000e-10
GCST005316_19	Intelligence (MTAG)	2.000000e-16
GCST005316_20	Intelligence (MTAG)	1.000000e-11
GCST005316_21	Intelligence (MTAG)	5.000000e-08
GCST005316_22	Intelligence (MTAG)	3.000000e-12
GCST005316_23	Intelligence (MTAG)	1.000000e-11
GCST005316_24	Intelligence (MTAG)	8.000000e-16
GCST005316_25	Intelligence (MTAG)	2.000000e-14
GCST005316_400	Intelligence (MTAG)	9.000000e-13
GCST005316_450	Intelligence (MTAG)	2.000000e-10
GCST005316_451	Intelligence (MTAG)	2.000000e-09
GCST005316_452	Intelligence (MTAG)	4.000000e-15
GCST005316_76	Intelligence (MTAG)	6.000000e-09
GCST006038_5	Food allergy	3.000000e-06
GCST006039_5	Peanut allergy	4.000000e-07
GCST006097_2	Moderate to vigorous physical activity levels	1.000000e-11
GCST006098_4	Vigorous physical activity	9.000000e-11
GCST006267_1	Response to selective serotonin reuptake inhibitors in depression	7.000000e-06
GCST006269_1047	General cognitive ability	2.000000e-08

EFO canonical traits (13, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004682	QT interval
EFO:0007016	food allergy measurement
EFO:0007017	peanut allergy measurement
EFO:0008002	physical activity measurement
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0008328	chronotype measurement
EFO:0008475	mood instability measurement
EFO:0009695	household income
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067376 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs718656	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs718656	EXOC4	3	2.00	1	opioids

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.31	Kd	48.76	nM	CHEMBL5653589
7.31	ED50	48.76	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148350: Binding affinity to human EXOC4 incubated for 45 mins by Kinobead based pull down assay	kd	0.0488	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	5
Aflatoxin B1	affects expression, decreases expression, increases methylation	5
Air Pollutants	increases oxidation, affects expression, increases expression, affects cotreatment, increases abundance	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
bisphenol A	increases expression, decreases expression	2
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Acrolein	increases abundance, affects cotreatment, increases oxidation	2
Cisplatin	affects cotreatment, decreases expression	2
Quercetin	decreases expression, decreases phosphorylation	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
clothianidin	decreases expression	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651392	Binding	Binding affinity to human EXOC4 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01401998	Not specified	RECRUITING	ARPKD Database Study
NCT05367609	Not specified	RECRUITING	Personalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)