EXOC2

Summary

EXOC2 (exocyst complex component 2, HGNC:24968) is a protein-coding gene on chromosome 6p25.3, encoding Exocyst complex component 2 (Q96KP1). 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: 27.1% of cell lines).

The protein encoded by this gene is a component of the exocyst complex, a multi-protein complex essential for the polarized targeting of exocytic vesicles to specific docking sites on the plasma membrane. Though best characterized in yeast, the component proteins and the functions of the 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. This interaction has been shown to mediate filopodia formation in fibroblasts. This protein has been shown to interact with the Ral subfamily of GTPases and thereby mediate exocytosis by tethering vesicles to the plasma membrane. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 55770 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 61
• Clinical variants (ClinVar): 243 total — 4 pathogenic
• Phenotypes (HPO): 37
• Cancer dependency (DepMap): dependent in 27.1% of screened cell lines
• MANE Select transcript: NM_018303

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24968
Approved symbol	EXOC2
Name	exocyst complex component 2
Location	6p25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ11026, Sec5
Ensembl gene	ENSG00000112685
Ensembl biotype	protein_coding
OMIM	615329
Entrez	55770

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 25 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000230449, ENST00000443083, ENST00000475028, ENST00000870874, ENST00000870875, ENST00000870876, ENST00000870877, ENST00000870878, ENST00000870879, ENST00000930287, ENST00000930288, ENST00000930289, ENST00000930290, ENST00000930291, ENST00000930292, ENST00000930293, ENST00000930294, ENST00000930295, ENST00000930296, ENST00000949686, ENST00000949687, ENST00000949688, ENST00000949689, ENST00000949690, ENST00000949691, ENST00000949692

RefSeq mRNA: 1 — MANE Select: NM_018303 NM_018303

CCDS: CCDS34327

Canonical transcript exons

ENST00000230449 — 28 exons

Exon	Start	End
ENSE00000679928	637701	637861
ENSE00000847761	632941	633117
ENSE00001275977	485154	486764
ENSE00001961245	592469	592587
ENSE00001962595	572520	572644
ENSE00001963937	610098	610178
ENSE00001964901	564033	564154
ENSE00001966837	617711	617835
ENSE00001968959	549175	549291
ENSE00001970714	488979	489038
ENSE00001971092	562784	562845
ENSE00001971333	499645	499700
ENSE00001975259	532469	532610
ENSE00001976768	564864	564929
ENSE00001977261	555954	556013
ENSE00001977911	619430	619543
ENSE00001978306	556484	556564
ENSE00001979168	491125	491186
ENSE00001979195	598021	598123
ENSE00001983308	564545	564702
ENSE00001983943	555227	555288
ENSE00001985443	553854	553920
ENSE00001986055	497367	497489
ENSE00001987451	599080	599225
ENSE00001988149	598860	598941
ENSE00003643190	576757	576882
ENSE00003789881	629835	629961
ENSE00003846072	693019	693139

Expression profiles

Bgee: expression breadth ubiquitous, 255 present calls, max score 90.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.4902 / max 112.4891, expressed in 1810 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
71331	17.8023	1809
71330	0.3632	165
71332	0.3247	148

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.57	gold quality
middle temporal gyrus	UBERON:0002771	90.36	gold quality
cortical plate	UBERON:0005343	89.19	gold quality
secondary oocyte	CL:0000655	87.93	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.93	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.15	gold quality
islet of Langerhans	UBERON:0000006	86.22	gold quality
oocyte	CL:0000023	86.16	gold quality
ganglionic eminence	UBERON:0004023	85.90	gold quality
calcaneal tendon	UBERON:0003701	85.53	gold quality
stromal cell of endometrium	CL:0002255	84.77	gold quality
primary visual cortex	UBERON:0002436	84.52	gold quality
granulocyte	CL:0000094	84.23	gold quality
leukocyte	CL:0000738	84.03	gold quality
monocyte	CL:0000576	83.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	83.91	gold quality
ventricular zone	UBERON:0003053	83.82	gold quality
mononuclear cell	CL:0000842	83.79	gold quality
colonic epithelium	UBERON:0000397	83.35	gold quality
spinal cord	UBERON:0002240	82.42	gold quality
corpus callosum	UBERON:0002336	82.33	gold quality
prefrontal cortex	UBERON:0000451	82.21	gold quality
rectum	UBERON:0001052	82.18	gold quality
testis	UBERON:0000473	82.06	gold quality
esophagus mucosa	UBERON:0002469	82.04	gold quality
mucosa of stomach	UBERON:0001199	81.96	gold quality
right testis	UBERON:0004534	81.88	gold quality
gastrocnemius	UBERON:0001388	81.84	gold quality
popliteal artery	UBERON:0002250	81.67	gold quality
tibial artery	UBERON:0007610	81.67	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.66
E-MTAB-4850	no	584.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting EXOC2, 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-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-3618	99.69	68.57	1012
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-1224-5P	99.48	65.59	803
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4311	99.31	70.47	3041

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 27.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 12)

• SEC5 has been identified as a binding partner of deafness locus putative guanine nucleotide exchange factor. (PMID:12459492)
• Functional study of the Drosophila homolog. (PMID:12575951)
• evidence that mammalian exocyst components are present as distinct subcomplexes on vesicles and the plasma membrane and that Ral GTPases regulate the assembly interface of a full octameric exocyst complex through interaction with Sec5 and Exo84 (PMID:14525976)
• These observations define the mechanistic contribution of RalGTPases to cancer cell survival and reveal the RalB/Sec5 effector complex as a component of TBK1-dependent innate immune signaling. (PMID:17018283)
• Localization of Exocyst and, by extension, targeting of Exocyst-dependent cargo, is dependent on Ral GTPases, which control association between Sec5 and paxillin. (PMID:18697830)
• shRNA-mediated knockdown of the Ral effector proteins Sec5 and Exo84, but less so in the case of RalBP1, reduced oncogenic RalGEF-mediated transformation and oncogenic Ras-driven tumorigenic growth of human cells. (PMID:20145037)
• Data show that Mc1R, HERC2, IRF4, TYR and EXOC2 are ranked highest in hair color prediction analysis. (PMID:21197618)
• We identified interactions between RalA and its effectors sec5 and exo84 in the Exocyst complex as directly necessary for migration and invasion of prostate cancer tumor cells. (PMID:22761837)
• Exocyst sec5 regulates exocytosis of newcomer insulin granules underlying biphasic insulin secretion. (PMID:23844030)
• data suggest that the induction of SGK1 through treatment with dexamethasone alters MT dynamics to increase Sec5-GEF-H1 interactions, which promote GEF-H1 targeting to adhesion sites. (PMID:26359301)
• Mutations in the exocyst component EXOC2 cause severe defects in human brain development. (PMID:32639540)
• The exocyst subunit EXOC2 regulates the toxicity of expanded GGGGCC repeats in C9ORF72-ALS/FTD. (PMID:38935506)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exoc2	ENSDARG00000055610
mus_musculus	Exoc2	ENSMUSG00000021357
rattus_norvegicus	Exoc2	ENSRNOG00000060266
drosophila_melanogaster	Sec5	FBGN0266670
caenorhabditis_elegans		WBGENE00004752

Protein

Protein identifiers

Exocyst complex component 2 — Q96KP1 (reviewed: Q96KP1)

Alternative names: Exocyst complex component Sec5

All UniProt accessions (2): Q96KP1, Q2MDF5

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 EXOC3L1. Interacts with GNEFR/DELGEF; this interaction occurs only in the presence of magnesium or manganese and is stimulated by dCTP or GTP. Interacts with RALA and RALB. Interacts with ARL13B; regulates ARL13B localization to the cilium membrane.

Subcellular location. Midbody. Midbody ring.

Tissue specificity. Widely expressed with highest levels in brain and placenta.

Disease relevance. Neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia (NEDFACH) [MIM:619306] An autosomal recessive disorder characterized by global developmental delay, intellectual disability, facial dysmorphism, and abnormalities of the cerebellum observed on brain imaging. Disease severity is variable. Some affected individuals have poor overall growth with microcephaly, delayed walking, spasticity, and poor or absent speech. Others may achieve more significant developmental milestones. Additional variable manifestations may include cardiac ventricular septal defect, spasticity, cataracts, optic nerve hypoplasia, seizures, and joint contractures. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Interacts with RALA through the TIG domain.

Similarity. Belongs to the SEC5 family.

RefSeq proteins (1): NP_060773* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002909	IPT_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR029175	EXOC2/Sec5	Family
IPR039481	EXOC2/Sec5_N_dom	Domain

Pfam: PF01833, PF15469

UniProt features (16 total): modified residue 6, sequence variant 4, sequence conflict 2, chain 1, domain 1, mutagenesis site 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KP1-F1	80.82	0.46

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 (6): 431, 432, 435, 440, 454, 888

Mutagenesis-validated functional residues (1):

Position	Phenotype
11	impaired cytokinesis. loss of rala-binding. no change in localization to the midbody during cytokinesis.

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: 249 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_MITOTIC_CYTOKINESIS, GOBP_VESICLE_LOCALIZATION, GOBP_VESICLE_TARGETING, CAFFAREL_RESPONSE_TO_THC_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, REACTOME_MEMBRANE_TRAFFICKING, GOMF_GTPASE_BINDING, GOBP_MEMBRANE_DOCKING, chr6p25, GOBP_EXOCYTOSIS, GOBP_GOLGI_TO_PLASMA_MEMBRANE_TRANSPORT, MODULE_205, GOBP_VESICLE_DOCKING_INVOLVED_IN_EXOCYTOSIS

GO Biological Process (8): mitotic cytokinesis (GO:0000281), exocytosis (GO:0006887), Golgi to plasma membrane transport (GO:0006893), obsolete vesicle docking involved in exocytosis (GO:0006904), protein transport (GO:0015031), membrane fission (GO:0090148), obsolete vesicle tethering involved in exocytosis (GO:0090522), regulation of entry of bacterium into host cell (GO:2000535)

GO Molecular Function (3): protein kinase binding (GO:0019901), small GTPase binding (GO:0031267), protein binding (GO:0005515)

GO Cellular Component (5): exocyst (GO:0000145), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), Flemming body (GO:0090543)

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	3
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
transport	1
intracellular protein localization	1
establishment of protein localization	1
membrane organization	1
entry of bacterium into host cell	1
modulation by symbiont of entry into host	1
kinase binding	1
GTPase binding	1
binding	1
cell cortex	1
vesicle tethering complex	1
cytoplasm	1
membrane	1
cell periphery	1
midbody	1

Protein interactions and networks

STRING

2306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOC2	EXOC3	O60645	999
EXOC2	RALB	P11234	999
EXOC2	EXOC6	Q8TAG9	999
EXOC2	EXOC1	Q9NV70	999
EXOC2	EXOC5	O00471	998
EXOC2	EXOC8	Q8IYI6	998
EXOC2	EXOC4	Q96A65	998
EXOC2	EXOC7	Q9UPT5	998
EXOC2	RALA	P11233	993
EXOC2	ARHGEF2	Q92974	908
EXOC2	TBK1	Q9UHD2	902
EXOC2	SSR2	P43308	827
EXOC2	SERGEF	Q9UGK8	814
EXOC2	DPH3	Q96FX2	788
EXOC2	RAB11A	P24410	784

IntAct

106 interactions, top by confidence:

A	B	Type	Score
EXOC1	EXOC2	psi-mi:“MI:0407”(direct interaction)	0.880
EXOC1	EXOC2	psi-mi:“MI:0915”(physical association)	0.880
EXOC2	EXOC1	psi-mi:“MI:0915”(physical association)	0.880
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
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
SCN2B	EXOC5	psi-mi:“MI:0914”(association)	0.640
GYPA	TCAF2	psi-mi:“MI:0914”(association)	0.640
APLNR	METTL15	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CXCR4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
CHRM3	PLD2	psi-mi:“MI:0914”(association)	0.530
IL1R2	EXOC5	psi-mi:“MI:0914”(association)	0.530

BioGRID (175): EXOC2 (Affinity Capture-RNA), EXOC2 (Affinity Capture-RNA), EXOC2 (Affinity Capture-RNA), EXOC2 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), EXOC2 (Affinity Capture-MS), EXOC2 (Co-fractionation), EXOC2 (Co-fractionation), EXOC2 (Co-fractionation), EXOC3 (Co-fractionation), EXOC4 (Co-fractionation), EXOC6 (Co-fractionation)

ESM2 similar proteins: A0JN62, A2RT67, A2RUS2, A2VDU2, A4IFB6, A4IIM3, A7MBL8, B1H2P5, B4F779, O94967, P48553, Q08CL8, Q0VEJ0, Q14161, Q15650, Q3TLI0, Q4R350, Q5RAQ5, Q5RCP7, Q5RDV5, Q5TKA1, Q5XIA4, Q5ZIW2, Q5ZJK1, Q68CZ1, Q6AYF1, Q6QD73, Q7TSG1, Q7ZYH1, Q8BH15, Q8BIK4, Q8BKH7, Q8C735, Q8CG73, Q8CGF6, Q8IWR0, Q8IZQ1, Q8N6S4, Q8N960, Q8NEU8

Diamond homologs: O54921, Q96KP1, Q9D4H1, Q9VQQ9, Q22706

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EXOC2	“form complex”	“Exocyst_EXOC6B variant”	binding
EXOC2	“form complex”	“Exocyst_EXOC6 variant”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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
VxPx cargo-targeting to cilium	7	56.8×	8e-09
Insulin processing	7	50.0×	1e-08
Translocation of SLC2A4 (GLUT4) to the plasma membrane	8	19.3×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
obsolete vesicle docking involved in exocytosis	8	60.6×	2e-10
Golgi to plasma membrane transport	6	37.9×	1e-06
membrane fission	8	37.0×	1e-08
mitotic cytokinesis	8	23.3×	4e-07
exocytosis	9	15.3×	1e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	179
Likely benign	18
Benign	9

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1074298	NM_018303.6(EXOC2):c.1739T>C (p.Leu580Ser)	Pathogenic
2506536	GRCh37/hg19 6p25.3(chr6:491126-1624775)	Pathogenic
2685193	GRCh37/hg19 6p25.3(chr6:647204-1716710)x1	Pathogenic
443497	GRCh37/hg19 6p25.3-q27(chr6:156975-170919482)	Pathogenic

SpliceAI

6767 predictions. Top by Δscore:

Variant	Effect	Δscore
6:488977:A:AC	donor_gain	1.0000
6:488978:C:CC	donor_gain	1.0000
6:491118:CACTT:C	donor_loss	1.0000
6:491119:ACTTA:A	donor_loss	1.0000
6:491120:CTTA:C	donor_loss	1.0000
6:491123:A:AC	donor_gain	1.0000
6:491124:C:CC	donor_gain	1.0000
6:491124:C:CT	donor_loss	1.0000
6:491124:CTTG:C	donor_gain	1.0000
6:491187:C:CC	acceptor_gain	1.0000
6:497361:TGTTA:T	donor_loss	1.0000
6:497362:GTTAC:G	donor_loss	1.0000
6:497363:TTA:T	donor_loss	1.0000
6:497364:TACCT:T	donor_loss	1.0000
6:497366:C:A	donor_loss	1.0000
6:497495:T:C	acceptor_gain	1.0000
6:497495:T:TC	acceptor_gain	1.0000
6:499698:CAC:C	acceptor_gain	1.0000
6:499707:T:C	acceptor_gain	1.0000
6:499707:T:TC	acceptor_gain	1.0000
6:532466:TAC:T	donor_loss	1.0000
6:532467:A:AC	donor_gain	1.0000
6:532467:AC:A	donor_gain	1.0000
6:532467:ACCTG:A	donor_loss	1.0000
6:532468:C:CA	donor_gain	1.0000
6:532468:CC:C	donor_gain	1.0000
6:532468:CCT:C	donor_gain	1.0000
6:532468:CCTG:C	donor_gain	1.0000
6:532468:CCTGT:C	donor_gain	1.0000
6:532606:CTAAC:C	acceptor_gain	1.0000

AlphaMissense

6088 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:532493:A:G	W786R	1.000
6:532493:A:T	W786R	1.000
6:598925:A:T	V302D	1.000
6:599111:A:G	L286P	1.000
6:599122:A:C	F282L	1.000
6:599122:A:T	F282L	1.000
6:599124:A:G	F282L	1.000
6:599147:A:G	L274P	1.000
6:599169:C:G	A267P	1.000
6:633009:A:T	V76D	1.000
6:532491:C:A	W786C	0.999
6:532491:C:G	W786C	0.999
6:572557:A:G	L469P	0.999
6:592573:A:G	L363P	0.999
6:592582:A:G	L360P	0.999
6:598078:A:G	L339P	0.999
6:598895:A:G	L312P	0.999
6:598904:G:T	A309D	0.999
6:598905:C:G	A309P	0.999
6:599117:A:G	F284S	0.999
6:599123:A:C	F282C	0.999
6:599123:A:G	F282S	0.999
6:599128:A:C	F280L	0.999
6:599128:A:T	F280L	0.999
6:599130:A:G	F280L	0.999
6:599132:C:G	R279P	0.999
6:599138:A:G	L277P	0.999
6:599151:C:G	A273P	0.999
6:599155:T:A	R271S	0.999
6:599155:T:G	R271S	0.999

dbSNP variants (sampled 300 via entrez): RS1000027784 (6:630616 A>G), RS1000029113 (6:691698 C>A), RS1000030068 (6:673623 T>A,C), RS1000063788 (6:554090 G>A), RS1000084503 (6:609410 A>G,T), RS1000086600 (6:504331 T>C), RS1000089012 (6:548788 G>A), RS1000097354 (6:586078 C>T), RS1000098195 (6:491904 C>A,T), RS1000098625 (6:569972 A>C), RS1000117800 (6:625151 C>T), RS1000137325 (6:609830 G>A,C), RS1000184071 (6:665447 G>A), RS1000186707 (6:549846 C>T), RS1000208191 (6:580145 G>A)

Disease associations

OMIM: gene MIM:615329 | disease phenotypes: MIM:619306, MIM:602482, MIM:616270

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	AR

Mondo (4): neurodevelopmental disorder with dysmorphic facies and cerebellar hypoplasia (MONDO:0859141), prostate cancer (MONDO:0008315), Axenfeld-Rieger syndrome type 3 (MONDO:0011233), amelogenesis imperfecta type 1F (MONDO:0014560)

Orphanet (3): Familial prostate cancer (Orphanet:1331), Axenfeld-Rieger syndrome (Orphanet:782), Amelogenesis imperfecta (Orphanet:88661)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000300	Oval face
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000340	Sloping forehead
HP:0000343	Long philtrum
HP:0000369	Low-set ears
HP:0000431	Wide nasal bridge
HP:0000437	Depressed nasal tip
HP:0000582	Upslanted palpebral fissure
HP:0000958	Dry skin
HP:0001250	Seizure
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001371	Flexion contracture
HP:0001629	Ventricular septal defect
HP:0001747	Accessory spleen
HP:0002079	Hypoplasia of the corpus callosum
HP:0002198	Dilated fourth ventricle
HP:0002263	Exaggerated cupid’s bow
HP:0002365	Hypoplasia of the brainstem
HP:0002419	Molar tooth sign on MRI
HP:0002510	Spastic tetraplegia
HP:0002870	Obstructive sleep apnea
HP:0003429	CNS hypomyelination
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0005484	Secondary microcephaly
HP:0006610	Wide intermamillary distance

GWAS associations

61 associations (top):

Study	Trait	p-value
GCST000119_1	Freckles	4.000000e-18
GCST000190_7	Black vs. blond hair color	6.000000e-08
GCST000191_3	Black vs. red hair color	5.000000e-07
GCST000371_4	Tanning	5.000000e-14
GCST001124_2	Basal cell carcinoma	1.000000e-09
GCST001657_10	Schizophrenia	4.000000e-06
GCST001657_2	Schizophrenia	3.000000e-06
GCST001713_5	Dental caries	3.000000e-06
GCST001940_2	Non-melanoma skin cancer	5.000000e-08
GCST002626_4	Vertical cup-disc ratio	1.000000e-09
GCST002636_2	Diffuse large B cell lymphoma	2.000000e-21
GCST002738_14	Psoriasis	3.000000e-07
GCST002740_74	Inflammatory skin disease	6.000000e-08
GCST002874_23	Psoriasis	6.000000e-06
GCST003726_3	Basal cell carcinoma	1.000000e-51
GCST004142_23	Melanoma	9.000000e-14
GCST004600_167	Eosinophil percentage of white cells	8.000000e-18
GCST004606_147	Eosinophil count	5.000000e-21
GCST004617_19	Eosinophil percentage of granulocytes	4.000000e-17
GCST004623_15	Neutrophil percentage of granulocytes	7.000000e-16
GCST004624_104	Sum eosinophil basophil counts	4.000000e-19
GCST004749_14	Lung cancer in ever smokers	3.000000e-06
GCST004866_25	Alopecia areata	9.000000e-07
GCST005334_6	Limited cutaneous systemic scleroderma	9.000000e-06
GCST005527_25	Psoriasis	2.000000e-11
GCST005580_60	Intraocular pressure	3.000000e-12
GCST005580_86	Intraocular pressure	4.000000e-11
GCST006065_33	Glaucoma (primary open-angle)	2.000000e-15
GCST006067_4	Glaucoma (primary open-angle)	3.000000e-10
GCST006394_2	Intraocular pressure	3.000000e-12

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0003963	freckles
EFO:0003924	hair color
EFO:0004279	suntan
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:1001017	limited scleroderma
EFO:0004695	intraocular pressure measurement
EFO:0009944	Antiglaucoma preparations and miotics use measurement
EFO:0006939	cup-to-disc ratio measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, affects methylation	4
bisphenol A	increases methylation, increases expression, affects cotreatment	2
Cadmium	decreases expression, increases expression, decreases reaction	2
Particulate Matter	increases abundance, increases expression, affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	increases expression	1
kojic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
butyraldehyde	decreases expression	1
tetrabromobisphenol A	increases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1
nickel sulfate	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
bisphenol B	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
asparanin A	decreases expression	1
bisphenol S	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A9N7	GIST-R5	Cancer cell line
CVCL_B1RN	Abcam HeLa EXOC2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer