PLXNC1

Summary

PLXNC1 (plexin C1, HGNC:9106) is a protein-coding gene on chromosome 12q22, encoding Plexin-C1 (O60486). Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein.

This gene encodes a member of the plexin family. Plexins are transmembrane receptors for semaphorins, a large family of proteins that regulate axon guidance, cell motility and migration, and the immune response. The encoded protein and its ligand regulate melanocyte adhesion, and viral semaphorins may modulate the immune response by binding to this receptor. The encoded protein may be a tumor suppressor protein for melanoma. Alternatively spliced transcript variants have been observed for this gene.

Source: NCBI Gene 10154 — RefSeq curated summary.

At a glance

• Gene–disease (curated): cerebral cortical dysplasia (Limited, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 133 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• MANE Select transcript: NM_005761

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9106
Approved symbol	PLXNC1
Name	plexin C1
Location	12q22
Locus type	gene with protein product
Status	Approved
Aliases	VESPR, CD232
Ensembl gene	ENSG00000136040
Ensembl biotype	protein_coding
OMIM	604259
Entrez	10154

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000258526, ENST00000545312, ENST00000546659, ENST00000546733, ENST00000547057, ENST00000549187, ENST00000549217, ENST00000549810, ENST00000550080, ENST00000551495, ENST00000551850

RefSeq mRNA: 1 — MANE Select: NM_005761 NM_005761

CCDS: CCDS9049

Canonical transcript exons

ENST00000258526 — 31 exons

Exon	Start	End
ENSE00000922624	94148577	94150033
ENSE00000922627	94186373	94186473
ENSE00000922628	94209590	94209704
ENSE00000922629	94220016	94220163
ENSE00000922630	94224228	94224315
ENSE00000922631	94226605	94226707
ENSE00000922632	94227149	94227235
ENSE00000922634	94240485	94240664
ENSE00000922641	94259337	94259375
ENSE00000922642	94259610	94259734
ENSE00000922647	94294486	94294540
ENSE00000922648	94297189	94297220
ENSE00000922649	94297316	94297423
ENSE00000922650	94298632	94298795
ENSE00000922653	94303977	94304051
ENSE00000937599	94243938	94244025
ENSE00000937600	94247903	94248106
ENSE00000937601	94248227	94248412
ENSE00001197827	94237664	94237803
ENSE00002428526	94305181	94307675
ENSE00003469481	94265079	94265225
ENSE00003514711	94300910	94301057
ENSE00003531933	94255193	94255296
ENSE00003540327	94282298	94282401
ENSE00003550296	94251426	94251528
ENSE00003552328	94303756	94303896
ENSE00003565947	94181446	94181580
ENSE00003629594	94254787	94254888
ENSE00003648026	94169153	94169293
ENSE00003658394	94279472	94279649
ENSE00003677234	94260642	94260840

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.6808 / max 1487.4810, expressed in 955 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127397	7.9440	721
127394	3.9766	645
127396	1.7265	538
127395	0.6022	216
127415	0.3640	208
127399	0.3523	157
127398	0.2527	95
127400	0.1790	87
127392	0.1421	44
127393	0.0672	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.34	gold quality
blood	UBERON:0000178	96.98	gold quality
bone marrow cell	CL:0002092	96.14	gold quality
monocyte	CL:0000576	95.33	gold quality
mononuclear cell	CL:0000842	94.86	gold quality
trabecular bone tissue	UBERON:0002483	94.68	gold quality
leukocyte	CL:0000738	94.62	gold quality
periodontal ligament	UBERON:0008266	94.26	gold quality
bone marrow	UBERON:0002371	94.17	gold quality
middle temporal gyrus	UBERON:0002771	92.52	gold quality
Brodmann (1909) area 23	UBERON:0013554	91.48	gold quality
visceral pleura	UBERON:0002401	91.00	gold quality
epithelium of nasopharynx	UBERON:0001951	89.55	gold quality
germinal epithelium of ovary	UBERON:0001304	89.08	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.53	gold quality
vermiform appendix	UBERON:0001154	88.28	gold quality
secondary oocyte	CL:0000655	88.13	gold quality
upper leg skin	UBERON:0004262	88.08	gold quality
paraflocculus	UBERON:0005351	88.04	gold quality
superficial temporal artery	UBERON:0001614	87.99	gold quality
ventricular zone	UBERON:0003053	87.79	gold quality
trigeminal ganglion	UBERON:0001675	87.33	gold quality
pleura	UBERON:0000977	87.08	gold quality
lymph node	UBERON:0000029	86.63	gold quality
skin of hip	UBERON:0001554	86.57	gold quality
endothelial cell	CL:0000115	86.54	gold quality
granulocyte	CL:0000094	86.35	gold quality
ganglionic eminence	UBERON:0004023	86.13	gold quality
orbitofrontal cortex	UBERON:0004167	85.94	gold quality
caecum	UBERON:0001153	85.58	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.34
E-CURD-11	no	88.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

266 targeting PLXNC1, 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-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-150-5P	99.99	66.69	1976

Literature-anchored findings (GeneRIF, showing 11)

• GTP-bound form of Rab7 promotes melanogenesis through the regulation of gp100 maturation in melanoma cells. (PMID:17671519)
• Plexin C1, a receptor for semaphorin 7a, inactivates cofilin and is a potential tumor suppressor for melanoma progression. (PMID:18987670)
• significant loss of Plexin C1 in metastatic melanoma compared with primary melanoma, suggesting the possibility that the Plexin C1 receptor is a tumor suppressor protein for melanoma (PMID:19318806)
• Study reports the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1; both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers. (PMID:20727575)
• loss of Plexin C1 in melanoma may promote early steps in melanoma progression through suppression of migration and proliferation (PMID:23160370)
• Plexin C1 deficiency permits synaptotagmin 7-mediated macrophage migration and enhances mammalian lung fibrosis (PMID:27609773)
• Results indicate that long non-coding RNA (lncRNA) CASC2 can promote PLXNC1 expression by sponging miR-181a, thereby inhibiting the proliferation and invasion of melanoma cells. (PMID:29514220)
• Results indicated that PLXNC1 was a direct target of miR-4500. Its knockdown inhibits proliferation and invasion of papillary thyroid cancer (PTC) cells. On the contrary, its overexpression of impairs miR-4500-induced inhibition of PTC malignancy. (PMID:31317324)
• The Relationship Between Plexin C1 Overexpression and Survival in Hepatocellular Carcinoma: a Turkish Oncology Group (TOG) Study. (PMID:33656690)
• PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1beta-exposed chondrocytes via suppressing GRP78 expression. (PMID:37853395)
• Semaphorin 7A promotes endothelial permeability and inflammation via plexin C1 and integrin beta1 in Kawasaki disease. (PMID:38678170)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxnc1	ENSDARG00000015278
mus_musculus	Plxnc1	ENSMUSG00000074785
rattus_norvegicus	Plxnc1	ENSRNOG00000007970
drosophila_melanogaster	PlexB	FBGN0025740
drosophila_melanogaster	PlexA	FBGN0025741
caenorhabditis_elegans		WBGENE00004047
caenorhabditis_elegans		WBGENE00004048

Paralogs (8): PLXND1 (ENSG00000004399), PLXNA2 (ENSG00000076356), PLXNA1 (ENSG00000114554), PLXNA3 (ENSG00000130827), PLXNB1 (ENSG00000164050), PLXNB2 (ENSG00000196576), PLXNB3 (ENSG00000198753), PLXNA4 (ENSG00000221866)

Protein

Protein identifiers

Plexin-C1 — O60486 (reviewed: O60486)

Alternative names: Virus-encoded semaphorin protein receptor

All UniProt accessions (6): B4DHQ7, O60486, F5H3A2, F8VUW4, F8W095, F8W1K6

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8.

Subunit / interactions. Monomer. Homodimer. Interacts with SEMA7A.

Subcellular location. Membrane.

Tissue specificity. Detected in heart, brain, lung, spleen and placenta.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the plexin family.

RefSeq proteins (1): NP_005752* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR002909	IPT_dom	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR013548	Plexin_cytoplasmic_RasGAP_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR031148	Plexin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR041853	Plexin-C1_Sema	Domain
IPR046800	Plexin_RBD	Domain

Pfam: PF01437, PF01833, PF08337, PF20170

UniProt features (128 total): strand 76, glycosylation site 16, helix 12, disulfide bond 8, turn 7, topological domain 2, signal peptide 1, chain 1, transmembrane region 1, sequence variant 1, sequence conflict 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3NVN	X-RAY DIFFRACTION	2.26
3KUZ	X-RAY DIFFRACTION	2.3
3NVQ	X-RAY DIFFRACTION	2.4
6VXK	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60486-F1	79.55	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 978

Disulfide bonds (8): 64–87, 156–194, 226–354, 283–329, 455–472, 461–506, 464–481, 475–487

Glycosylation sites (16): 241, 252, 386, 407, 548, 582, 653, 692, 771, 796, 821, 871, 890, 86, 141, 149

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-416700	Other semaphorin interactions

MSigDB gene sets: 407 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, TURASHVILI_BREAST_LOBULAR_CARCINOMA_VS_DUCTAL_NORMAL_UP, JI_RESPONSE_TO_FSH_UP, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, CCAWYNNGAAR_UNKNOWN, GOBP_SYNAPSE_ASSEMBLY, JAEGER_METASTASIS_DN, REACTOME_OTHER_SEMAPHORIN_INTERACTIONS, GOBP_NEUROGENESIS, RACCACAR_AML_Q6, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, AP2_Q3

GO Biological Process (8): cell adhesion (GO:0007155), negative regulation of cell adhesion (GO:0007162), synapse assembly (GO:0007416), regulation of cell shape (GO:0008360), regulation of cell migration (GO:0030334), positive regulation of axonogenesis (GO:0050772), semaphorin-plexin signaling pathway (GO:0071526), regulation of synapse pruning (GO:1905806)

GO Molecular Function (3): signaling receptor binding (GO:0005102), semaphorin receptor activity (GO:0017154), protein binding (GO:0005515)

GO Cellular Component (4): semaphorin receptor complex (GO:0002116), plasma membrane (GO:0005886), membrane (GO:0016020), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Semaphorin interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
nervous system development	1
cell junction assembly	1
synapse organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
cell migration	1
regulation of cell motility	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
cell surface receptor signaling pathway	1
regulation of synapse organization	1
synapse pruning	1
protein binding	1
transmembrane signaling receptor activity	1
semaphorin-plexin signaling pathway	1
binding	1
signaling receptor complex	1
membrane	1
cell periphery	1
cellular anatomical structure	1
asymmetric, glutamatergic, excitatory synapse	1

Protein interactions and networks

STRING

1084 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXNC1	SEMA7A	O75326	999
PLXNC1	SEMA4D	Q92854	848
PLXNC1	SEMA3B	Q13214	787
PLXNC1	NRP2	O60462	785
PLXNC1	SEMA6A	Q9H2E6	770
PLXNC1	SEMA3E	O15041	719
PLXNC1	NRP1	O14786	692
PLXNC1	SEMA6C	Q9H3T2	622
PLXNC1	SEMA3A	Q14563	598
PLXNC1	SEMA3F	Q13275	568
PLXNC1	SEMA4C	Q9C0C4	522
PLXNC1	SEMA5A	Q13591	517
PLXNC1	SEMA4G	Q9NTN9	516
PLXNC1	SEMA6D	Q8NFY4	486
PLXNC1	RRAS	P10301	472

IntAct

19 interactions, top by confidence:

A	B	Type	Score
PLXNC1	SEMA7A	psi-mi:“MI:0915”(physical association)	0.720
SEMA7A	PLXNC1	psi-mi:“MI:0407”(direct interaction)	0.720
PLXNC1	SEMA7A	psi-mi:“MI:0407”(direct interaction)	0.720
PLXNC1	EVM139	psi-mi:“MI:0407”(direct interaction)	0.610
EVM139	PLXNC1	psi-mi:“MI:0407”(direct interaction)	0.610
	PLXNC1	psi-mi:“MI:0915”(physical association)	0.400
PLXNC1	HSPA5	psi-mi:“MI:0915”(physical association)	0.400
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PLXNC1	POTEF	psi-mi:“MI:0914”(association)	0.350
CEMP1	PABPN1L	psi-mi:“MI:0914”(association)	0.350
FAM163B	TSPY2	psi-mi:“MI:0914”(association)	0.350
GDF11	TSPY2	psi-mi:“MI:0914”(association)	0.350
LHX3	TSPY2	psi-mi:“MI:0914”(association)	0.350
CFAP54	TSPY2	psi-mi:“MI:0914”(association)	0.350
PDC	TSPY2	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): PLXNC1 (Proximity Label-MS), PLXNC1 (Affinity Capture-MS), HLA-DPA1 (Affinity Capture-MS), PLXNC1 (Affinity Capture-MS), MANEA (Affinity Capture-MS), TMEM205 (Affinity Capture-MS), PLXNC1 (Affinity Capture-MS), PLXNC1 (Affinity Capture-MS), PLXNC1 (Affinity Capture-MS), POTEF (Affinity Capture-MS), FBXO2 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), PLXNC1 (Affinity Capture-MS), PLXNC1 (Cross-Linking-MS (XL-MS)), PLXNC1 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, A0M8R7, A0M8S8, A1X150, E2RK30, O60486, O62446, P08581, P08F94, P10643, P16056, P97523, Q00PJ8, Q07DV8, Q07DY1, Q07DZ1, Q07E01, Q07E24, Q07E37, Q07E48, Q09YH7, Q09YI9, Q09YK0, Q09YL1, Q09YN5, Q108U6, Q2IBA6, Q2IBC0, Q2IBD8, Q2IBF2, Q2IBG7, Q2QL89, Q2QLA9, Q2QLC0, Q2QLE0, Q2QLF1, Q2QLG5

Diamond homologs: B0S5N4, B2RXS4, D3ZLH5, D3ZPX4, O15031, O43157, O60486, O75051, P51805, P70206, P70207, P70208, Q3UH93, Q6BEA0, Q80UG2, Q8CJH3, Q9HCM2, Q9NTN9, Q9QY40, Q9QZC2, Q9UIW2, Q9ULL4, Q9V4A7, Q9WUH7, Q9Y4D7, Q09YN5, Q80ZA4, Q60519, Q9P283, O42236, Q13591, Q9C0C4, Q62190, Q626H5, Q9H2E6, O95754, Q64151, Q9Z123, Q9Z143, Q90665

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
MARCHF9	“down-regulates quantity by destabilization”	PLXNC1	ubiquitination
SEMA7A	up-regulates	PLXNC1	binding

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — MEL.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

5101 predictions. Top by Δscore:

Variant	Effect	Δscore
12:94181578:GAG:G	donor_gain	1.0000
12:94220161:AAGGT:A	donor_loss	1.0000
12:94220162:AGG:A	donor_loss	1.0000
12:94220163:GGT:G	donor_loss	1.0000
12:94220165:T:G	donor_loss	1.0000
12:94224227:GAT:G	acceptor_gain	1.0000
12:94224314:GA:G	donor_gain	1.0000
12:94224316:G:GG	donor_gain	1.0000
12:94227231:TACAG:T	donor_loss	1.0000
12:94227232:ACAG:A	donor_loss	1.0000
12:94227233:CAGG:C	donor_loss	1.0000
12:94227234:AG:A	donor_loss	1.0000
12:94227235:GGT:G	donor_loss	1.0000
12:94227237:T:G	donor_loss	1.0000
12:94237661:TA:T	acceptor_loss	1.0000
12:94237799:GA:G	donor_gain	1.0000
12:94237799:GATGT:G	donor_gain	1.0000
12:94237800:ATGT:A	donor_gain	1.0000
12:94237802:GT:G	donor_gain	1.0000
12:94237804:G:GG	donor_gain	1.0000
12:94247900:CA:C	acceptor_loss	1.0000
12:94247901:A:AC	acceptor_loss	1.0000
12:94247901:A:AG	acceptor_gain	1.0000
12:94247902:G:GA	acceptor_loss	1.0000
12:94247902:G:GG	acceptor_gain	1.0000
12:94247902:GGTCT:G	acceptor_gain	1.0000
12:94248092:G:GT	donor_gain	1.0000
12:94248092:G:T	donor_gain	1.0000
12:94248102:TTCAA:T	donor_gain	1.0000
12:94248104:CAAGT:C	donor_loss	1.0000

AlphaMissense

10320 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:94255195:T:C	F996L	1.000
12:94255197:T:A	F996L	1.000
12:94255197:T:G	F996L	1.000
12:94255205:T:C	L999P	1.000
12:94255256:T:C	L1016P	1.000
12:94260653:C:A	A1088D	1.000
12:94260662:T:C	L1091P	1.000
12:94260770:G:C	R1127T	1.000
12:94260797:T:C	L1136P	1.000
12:94260808:T:A	W1140R	1.000
12:94260808:T:C	W1140R	1.000
12:94260824:T:C	L1145P	1.000
12:94260836:T:C	L1149P	1.000
12:94265107:T:C	L1160P	1.000
12:94265119:T:C	L1164P	1.000
12:94265179:T:A	L1184H	1.000
12:94265194:T:C	L1189P	1.000
12:94297401:T:A	L1351Q	1.000
12:94297401:T:C	L1351P	1.000
12:94297410:T:C	L1354P	1.000
12:94297413:T:A	L1355Q	1.000
12:94297413:T:C	L1355P	1.000
12:94297423:G:C	K1358N	1.000
12:94297423:G:T	K1358N	1.000
12:94298782:T:A	W1409R	1.000
12:94298782:T:C	W1409R	1.000
12:94298784:G:C	W1409C	1.000
12:94298784:G:T	W1409C	1.000
12:94298787:A:C	K1410N	1.000
12:94298787:A:T	K1410N	1.000

dbSNP variants (sampled 300 via entrez): RS1000004509 (12:94293142 A>T), RS1000013022 (12:94276830 C>T), RS1000019017 (12:94251956 G>A), RS1000019866 (12:94210687 C>G), RS1000030506 (12:94252202 GAC>G), RS1000068777 (12:94292968 T>C), RS1000079787 (12:94250484 G>A), RS1000096846 (12:94191268 A>G), RS1000129783 (12:94300104 C>T), RS1000149819 (12:94149575 G>A,T), RS1000160019 (12:94165335 G>C), RS1000179822 (12:94297885 C>T), RS1000180054 (12:94276773 T>A), RS1000188961 (12:94241230 C>A,T), RS1000207050 (12:94186584 C>G,T)

Disease associations

OMIM: gene MIM:604259 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
cerebral cortical dysplasia	Limited	Autosomal dominant

Mondo (1): cerebral cortical dysplasia (MONDO:0017094)

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST004866_26	Alopecia areata	5.000000e-06
GCST005231_36	Major depressive disorder	6.000000e-06
GCST005835_5	Remission after SSRI treatment in MDD or neuroticism	8.000000e-10
GCST006277_4	Response to ranibizumab in age-related macular degeneration (exudative)	7.000000e-06
GCST006585_550	Blood protein levels	2.000000e-28
GCST007268_45	Diastolic blood pressure	1.000000e-09
GCST007269_319	Pulse pressure	9.000000e-21
GCST008359_5	Response to cognitive-behavioural therapy in anxiety disorder	2.000000e-06
GCST009597_175	Multiple sclerosis	2.000000e-08
GCST009798_83	Asthma	6.000000e-11
GCST010042_3	Asthma	4.000000e-10
GCST010043_60	Asthma	8.000000e-12
GCST012490_330	Femur bone mineral density x serum urate levels interaction	2.000000e-09
GCST90014325_54	Asthma	7.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0007660	neuroticism measurement
EFO:0008348	response to ranibizumab
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0007820	cognitive behavioural therapy
EFO:0004531	urate measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D054220	Malformations of Cortical Development	C10.500.507; C16.131.666.507

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	6
Valproic Acid	affects cotreatment, decreases expression	6
Aflatoxin B1	affects expression, decreases expression, increases expression, increases methylation	4
trichostatin A	decreases expression, increases expression, affects cotreatment	3
Tretinoin	decreases expression, increases expression	3
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Vorinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Cyclosporine	decreases methylation, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
pentanal	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases expression	1
incobotulinumtoxinA	increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02261753	Not specified	TERMINATED	Evaluating Dietary Intervention Before surgicaL Treatment for Epilepsy
NCT02654340	Not specified	TERMINATED	Biomarkers for Tuberous Sclerosis Complex (BioTuScCom)
NCT06915649	Not specified	RECRUITING	Exploration and Evaluation of Amygdalo-Hippocampectomy According to Prof. Coubes’ Technique: An Anatomical, Clinical, and Educational Approach