PLXNB1

Summary

PLXNB1 (plexin B1, HGNC:9103) is a protein-coding gene on chromosome 3p21.31, encoding Plexin-B1 (O43157). Receptor for SEMA4D.

Enables semaphorin receptor activity. Involved in several processes, including negative regulation of cell adhesion; regulation of cell shape; and semaphorin-plexin signaling pathway. Located in plasma membrane. Part of semaphorin receptor complex.

Source: NCBI Gene 5364 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 386 total
• MANE Select transcript: NM_001130082

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9103
Approved symbol	PLXNB1
Name	plexin B1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	SEP, KIAA0407
Ensembl gene	ENSG00000164050
Ensembl biotype	protein_coding
OMIM	601053
Entrez	5364

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 20 protein_coding, 11 retained_intron, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000296440, ENST00000358536, ENST00000449094, ENST00000456774, ENST00000461261, ENST00000462738, ENST00000464294, ENST00000465117, ENST00000466353, ENST00000467913, ENST00000470525, ENST00000473683, ENST00000473996, ENST00000478171, ENST00000483676, ENST00000483753, ENST00000484485, ENST00000485535, ENST00000497627, ENST00000859424, ENST00000859425, ENST00000859426, ENST00000859427, ENST00000934701, ENST00000934702, ENST00000934703, ENST00000934704, ENST00000934705, ENST00000934706, ENST00000934707, ENST00000948892, ENST00000948893, ENST00000948894, ENST00000948895, ENST00000948896, ENST00000948897

RefSeq mRNA: 2 — MANE Select: NM_001130082 NM_001130082, NM_002673

CCDS: CCDS2765

Canonical transcript exons

ENST00000296440 — 38 exons

Exon	Start	End
ENSE00001080893	48422331	48422459
ENSE00001080898	48422105	48422205
ENSE00001080902	48421228	48421384
ENSE00001080910	48421674	48421806
ENSE00001206107	48423505	48424617
ENSE00001326499	48419577	48420257
ENSE00001420712	48430008	48430086
ENSE00001428482	48425281	48425333
ENSE00001633158	48413069	48413169
ENSE00001788421	48413670	48413818
ENSE00001862797	48403854	48404590
ENSE00003460473	48420848	48420956
ENSE00003464962	48416346	48416451
ENSE00003467760	48415583	48415759
ENSE00003481305	48417911	48418062
ENSE00003483173	48413895	48414071
ENSE00003486134	48410296	48410380
ENSE00003493223	48420665	48420773
ENSE00003494184	48406823	48406898
ENSE00003502737	48409571	48409731
ENSE00003514633	48418449	48418542
ENSE00003515500	48409329	48409476
ENSE00003521920	48415176	48415347
ENSE00003541420	48412238	48412304
ENSE00003547101	48407027	48407091
ENSE00003550877	48418191	48418363
ENSE00003553054	48416031	48416167
ENSE00003574355	48414799	48415041
ENSE00003587431	48418917	48419039
ENSE00003602170	48405724	48405798
ENSE00003616359	48411863	48412009
ENSE00003619749	48419244	48419366
ENSE00003627953	48422765	48422947
ENSE00003639166	48410868	48411036
ENSE00003640901	48410455	48410558
ENSE00003663968	48409905	48410077
ENSE00003676753	48412442	48412620
ENSE00003681263	48412742	48412959

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 99.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.2144 / max 217.0966, expressed in 1340 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42105	1.9999	458
42109	1.3992	811
42112	1.2744	638
42110	1.0358	589
42108	0.7344	322
42106	0.4370	154
42113	0.1999	76
42107	0.1200	49
42114	0.0139	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.63	gold quality
metanephros cortex	UBERON:0010533	99.28	gold quality
right lobe of thyroid gland	UBERON:0001119	99.01	gold quality
left lobe of thyroid gland	UBERON:0001120	98.93	gold quality
popliteal artery	UBERON:0002250	98.62	gold quality
tibial artery	UBERON:0007610	98.62	gold quality
lower esophagus mucosa	UBERON:0035834	98.62	gold quality
mucosa of stomach	UBERON:0001199	98.58	gold quality
ventricular zone	UBERON:0003053	98.55	gold quality
skin of abdomen	UBERON:0001416	98.38	gold quality
lower esophagus	UBERON:0013473	98.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.36	gold quality
skin of leg	UBERON:0001511	98.30	gold quality
right coronary artery	UBERON:0001625	98.26	gold quality
ectocervix	UBERON:0012249	98.26	gold quality
body of pancreas	UBERON:0001150	98.25	gold quality
adenohypophysis	UBERON:0002196	98.25	gold quality
nerve	UBERON:0001021	98.24	gold quality
tibial nerve	UBERON:0001323	98.24	gold quality
aorta	UBERON:0000947	98.23	gold quality
left ovary	UBERON:0002119	98.23	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.21	gold quality
right ovary	UBERON:0002118	98.20	gold quality
right lobe of liver	UBERON:0001114	98.19	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	98.09	gold quality
ascending aorta	UBERON:0001496	98.00	gold quality
thoracic aorta	UBERON:0001515	97.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.95	gold quality
endocervix	UBERON:0000458	97.92	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.61
E-HCAD-25	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PLXNB1, 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-223-3P	99.99	70.14	1140
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-6744-3P	99.22	64.41	972
HSA-MIR-4757-5P	99.12	64.51	981
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-501-5P	98.77	68.88	1328
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-6793-3P	97.66	65.78	1084
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-6779-3P	97.51	65.82	789
HSA-MIR-3684	96.90	67.51	293
HSA-MIR-362-5P	95.87	66.02	554
HSA-MIR-500B-5P	95.87	66.04	557
HSA-MIR-6777-3P	95.35	64.30	699

Literature-anchored findings (GeneRIF, showing 40)

• The plexin-B1/Rac interaction inhibits PAK activation and enhances Sema4D ligand binding (PMID:11937491)
• LARG plays a critical role in plexin-B1 signaling to stimulate Rho activation and cytoskeletal reorganization. (PMID:12196628)
• Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors (PMID:12220504)
• Plexin-B1 is an easily accessible receptor for CD100 within the immune system. The crosstalk operated by the CD100/Plexin-B1 interaction is not malignancy related but reproduces a mechanism used by normal CD5+ B cells. (PMID:12406905)
• cleavage by proprotein convertases is a novel regulatory step for semaphorin receptors localized at the cell surface. (PMID:12533544)
• In some human neoplastic lines, PLXB1 is overexpressed, constitutively tyrosine phosphorylated, and associated with Scatter Factor Receptors. (PMID:15184888)
• ErbB-2-mediated phosphorylation of plexin-B1 is critically involved in Sema4D-induced RhoA activation. (PMID:15210733)
• demonstrate that Sema4D is angiogenic in vitro and in vivo and that this effect is mediated by its high-affinity receptor, Plexin B1, and that biologic effects elicited by Plexin B1 require coupling and activation of the Met tyrosine kinase (PMID:15632204)
• the minimal Rac1 GTPase binding domain of plexin-B1 has a ubiquitin fold, as shown by NMR (PMID:15929008)
• Semaphorin 4D/plexin-B1 induces endothelial cell migration through the activation of PYK2, Src, and the phosphatidylinositol 3-kinase-Akt pathway (PMID:16055703)
• Plexin-B1 contributes to trophoblast-endometrium interactions, most likely by enhancing adhesion properties. (PMID:17383649)
• plexin-B1 promotes endothelial cell motility through RhoA and ROK by regulating the integrin-dependent signaling networks that result in the activation of PI3K and Akt (PMID:17855350)
• Binding of Rac1, Rnd1, and RhoD to a novel Rho GTPase interaction motif destabilizes dimerization of the plexin-B1 effector domain (PMID:17916560)
• 13 somatic missense mutations in the cytoplasmic domain of the Plexin-B1 gene hinder Rac & R-Ras binding & R-RasGAP activity, & increase cell motility, invasion, adhesion, & lamellipodia extension. (PMID:18024597)
• a novel mechanism by which plexin-mediated signaling can be regulated and explains how Sema4D can exert different biological activities through the differential association of its receptor with ErbB-2 and Met. (PMID:18025083)
• NMR solution structure of the Rho GTPase binding domain; study suggests that the oncogenic behavior of the mutants can be rationalized with reference to the structure of the RBD of plexin-B1 (PMID:18275816)
• Plexin B1 protein is absent in more than 80% of renal cell carcinomas. when we have induced plexin B1 expression with an expression vector in the renal adenocarcinoma cell line ACHN, a marked reduction in proliferation rate was produced. (PMID:18279812)
• Mapping of the Rac1 GTPase surface that contacts the Rho GTPase binding domain of plexin-B1 by NMR confirms the plexin domain as a GTPase effector protein and regions neighboring the GTPase switch I and II regions are also involved in the interaction. (PMID:18321527)
• Plexin B1 expression is reduced in the group of “uncoupled” stem cell-like breast cancer tumors (PMID:18417270)
• Plexin-B1 is a dual functional GTPase activating protein for R-Ras and M-Ras, remodelling axon and dendrite morphology, respectively. (PMID:19444311)
• B-Raf/MKK/ERK provides a permissive environment for melanoma genesis by modulating plexin B1. (PMID:19483722)
• show here that activation of plexin-B1 by Semaphorin 4D and its subsequent tyrosine phosphorylation creates docking sites for the SH2 domains of phospholipase Cgamma. (PMID:19805522)
• the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation. (PMID:19843518)
• Data show that Plex-B1 assumes a predictive value for unfavourable outcome when co-expressed with Met. (PMID:19940359)
• In the endometrium, both Glycodelin and Plexin-B1 are exhibiting a cyclic pattern suggesting a possible steroid regulation and a role in endometrial receptivity (PMID:20040080)
• Plexin B1 may function as a tumor promoter in melanomas not driven by c-Met activation. (PMID:20164843)
• Sema4D/Plexin-B1 promotes the dephosphorylation and activation of PTEN through the R-Ras GAP activity, inducing growth cone collapse. (PMID:20610402)
• crystal structures of cognate complexes of the semaphorin-binding regions of plexins B1 and A2 with semaphorin ectodomains (human PLXNB1(1-2)-SEMA4D(ecto) and murine PlxnA2(1-4)-Sema6A(ecto)), plus unliganded structures of PlxnA2(1-4) and Sema6A(ecto) (PMID:20877282)
• Plexin B1 abrogates integrin-dependent migration and activation of pp125(FAK). (PMID:21029396)
• Plexin-B1 expression correlates with malignant phenotypes of serous ovarian tumors, probably via phosphorylation of AKT at Ser473 (PMID:21059203)
• plexin-B1, a target of miR-214, may function as an oncogene in human cervical cancer HeLa cells (PMID:21216304)
• The binding of Sema4D to plexinB1 induced small GTPase Ras homolog gene family, member A activation and resulted in the phosphorylation of MAPK and Akt. (PMID:21812859)
• Two crystal structures of the human Plexin-B1 cytoplasmic region in complex with a constitutively active RhoGTPase, Rac1, are reported. (PMID:21912513)
• ErbB-2 overexpression in human breast & ovarian cancer cell lines leads to phosphorylation & activation of Plexin-B1. This was required for ErbB-2-dependent activation of RhoA & RhoC & promoted invasive behavior. (PMID:22378040)
• PlexinB1 mutations block plexinB1-mediated signalling pathways that inhibit cell motility. (PMID:22404908)
• Data indicate that Rnd1 efficiently displaces Rac1 from its complex with Plexin-B1 but not vice versa. (PMID:23603360)
• Activation of endogenous plexin-B1 enhances cell migration and tumor invasiveness in prostate cancer cells. (PMID:23775445)
• results show that Sema4D/plexin-B1 signaling promotes the translocation of androgen receptor to the nucleus and thereby enhances AR transcriptional activity (PMID:25982277)
• Results show that decreased expression of Sema4D, plexin-B1 and -B2 was associated with local recurrence and poor prognosis of breast neoplasm. (PMID:26035216)
• Plexin-B1 induces cutaneous squamous cell carcinoma cell proliferation, migration, and invasion by interacting with Sema4D. Plexin-B1 might serve as a useful biomarker and/or as a novel therapeutic target for cSCC. (PMID:26051877)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxnb1b	ENSDARG00000017211
danio_rerio	plxnb1a	ENSDARG00000075821
mus_musculus	Plxnb1	ENSMUSG00000053646
rattus_norvegicus	Plxnb1	ENSRNOG00000029510
drosophila_melanogaster	PlexB	FBGN0025740
drosophila_melanogaster	PlexA	FBGN0025741
caenorhabditis_elegans		WBGENE00004047
caenorhabditis_elegans		WBGENE00004048

Paralogs (8): PLXND1 (ENSG00000004399), PLXNA2 (ENSG00000076356), PLXNA1 (ENSG00000114554), PLXNA3 (ENSG00000130827), PLXNC1 (ENSG00000136040), PLXNB2 (ENSG00000196576), PLXNB3 (ENSG00000198753), PLXNA4 (ENSG00000221866)

Protein

Protein identifiers

Plexin-B1 — O43157 (reviewed: O43157)

Alternative names: Semaphorin receptor SEP

All UniProt accessions (1): O43157

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for SEMA4D. Plays a role in GABAergic synapse development. Mediates SEMA4A- and SEMA4D-dependent inhibitory synapse development. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration.

Subunit / interactions. Monomer, and heterodimer with PLXNB2 after proteolytic processing. Binds RAC1 that has been activated by GTP binding. Interaction with SEMA4D promotes binding of cytoplasmic ligands. Interacts with PLXNA1. Interacts with ARHGEF11 and ARHGEF12. Interacts with ERBB2. Interacts with MET. Interacts with MST1R. Interacts with RRAS. Interacts with RHOD. Interacts with RND1. Interacts with NRP1 and NRP2.

Subcellular location. Cell membrane Secreted Secreted.

Tissue specificity. Highly expressed in fetal kidney, and at slightly lower levels in fetal brain, lung and liver.

Post-translational modifications. Phosphorylated on tyrosine residues by ERBB2 and MET upon SEMA4D binding. Proteolytic processing favors heterodimerization with PLXNB2 and SEMA4D binding.

Similarity. Belongs to the plexin family.

Isoforms (3)

UniProt ID	Names	Canonical?
O43157-1	1	yes
O43157-2	2, Isoform R
O43157-3	3

RefSeq proteins (2): NP_001123554, NP_002664 (=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
IPR014756	Ig_E-set	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR031148	Plexin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR041019	TIG1_plexin	Domain
IPR041362	TIG2_plexin	Domain
IPR046800	Plexin_RBD	Domain
IPR057533	PSI_Plexin-B	Domain

Pfam: PF01403, PF01437, PF01833, PF08337, PF17960, PF18020, PF20170, PF24317, PF24479

UniProt features (153 total): strand 60, helix 37, disulfide bond 10, turn 9, glycosylation site 6, compositionally biased region 4, mutagenesis site 4, domain 4, region of interest 3, splice variant 3, sequence variant 3, site 2, topological domain 2, sequence conflict 2, signal peptide 1, chain 1, coiled-coil region 1, transmembrane region 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
2R2O	X-RAY DIFFRACTION	2
7VF3	X-RAY DIFFRACTION	2.29
2REX	X-RAY DIFFRACTION	2.3
3HM6	X-RAY DIFFRACTION	2.4
7VG7	X-RAY DIFFRACTION	2.5
5B4W	X-RAY DIFFRACTION	2.6
8B3K	X-RAY DIFFRACTION	2.69
3OL2	X-RAY DIFFRACTION	2.99
3SU8	X-RAY DIFFRACTION	3.2
3SUA	X-RAY DIFFRACTION	4.39
2JPH	SOLUTION NMR
2OS6	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43157-F1	76.06	0.23

Functional residue map

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

Catalytic / active sites (2): 1305–1306 (cleavage; by proprotein convertases); 1815 (important for interaction with rac1 and rnd1)

Disulfide bonds (10): 79–88, 111–119, 252–377, 268–322, 340–364, 482–499, 488–533, 491–508, 502–514, 570–588

Glycosylation sites (6): 31, 334, 543, 1183, 1253, 1330

Mutagenesis-validated functional residues (4):

Position	Phenotype
139	strongly reduced interaction with sema4d.
1302–1305	abolishes cleavage by proprotein convertases.
1815	abolishes interaction with rac1 and rnd1.
1884–1885	loss of cytoskeleton remodeling in response to sema4d.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-416550	Sema4D mediated inhibition of cell attachment and migration
R-HSA-416572	Sema4D induced cell migration and growth-cone collapse
R-HSA-9013405	RHOD GTPase cycle

MSigDB gene sets: 208 (showing top): CREL_01, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_SYNAPSE_ASSEMBLY, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_POSITIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, MODULE_66, WATANABE_ULCERATIVE_COLITIS_WITH_CANCER_UP, GOBP_ANATOMICAL_STRUCTURE_MATURATION, GOBP_POSITIVE_REGULATION_OF_CATALYTIC_ACTIVITY

GO Biological Process (16): negative regulation of cell adhesion (GO:0007162), synapse assembly (GO:0007416), regulation of cell shape (GO:0008360), cell migration (GO:0016477), regulation of cell migration (GO:0030334), negative regulation of osteoblast proliferation (GO:0033689), positive regulation of Rho protein signal transduction (GO:0035025), intracellular signal transduction (GO:0035556), positive regulation of GTPase activity (GO:0043547), ossification involved in bone maturation (GO:0043931), neuron projection morphogenesis (GO:0048812), positive regulation of axonogenesis (GO:0050772), regulation of cytoskeleton organization (GO:0051493), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), semaphorin-plexin signaling pathway (GO:0071526), inhibitory synapse assembly (GO:1904862)

GO Molecular Function (6): transmembrane signaling receptor activity (GO:0004888), GTPase activator activity (GO:0005096), semaphorin receptor activity (GO:0017154), semaphorin receptor binding (GO:0030215), GTPase activating protein binding (GO:0032794), protein binding (GO:0005515)

GO Cellular Component (6): semaphorin receptor complex (GO:0002116), extracellular region (GO:0005576), plasma membrane (GO:0005886), postsynaptic membrane (GO:0045211), glutamatergic synapse (GO:0098978), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Sema4D in semaphorin signaling	2
GPCR downstream signalling	1
RHO GTPase cycle	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
GTPase activity	2
cellular anatomical structure	2
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 motility	1
cell migration	1
regulation of cell motility	1
negative regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
intracellular anatomical structure	1
signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
ossification	1
bone maturation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
axonogenesis	1
positive regulation of cell projection organization	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
cytoskeleton organization	1
regulation of organelle organization	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
cell surface receptor signaling pathway	1
synapse assembly	1
signaling receptor activity	1
enzyme activator activity	1

Protein interactions and networks

STRING

1268 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXNB1	SEMA4D	Q92854	999
PLXNB1	RND1	Q92730	990
PLXNB1	ARHGEF12	Q9NZN5	965
PLXNB1	ARHGEF11	O15085	952
PLXNB1	ERBB2	P04626	929
PLXNB1	RRAS	P10301	927
PLXNB1	MET	P08581	899
PLXNB1	RHOD	O00212	875
PLXNB1	RND2	P52198	853
PLXNB1	CD72	P21854	846
PLXNB1	SEMA3A	Q14563	813
PLXNB1	SEMA3B	Q13214	811
PLXNB1	SEMA4A	Q9H3S1	795
PLXNB1	SEMA5A	Q13591	739
PLXNB1	HGF	P14210	738

IntAct

152 interactions, top by confidence:

A	B	Type	Score
RND1	PLXNB1	psi-mi:“MI:0915”(physical association)	0.780
RND1	PLXNB1	psi-mi:“MI:0407”(direct interaction)	0.780
PLXNB1	MET	psi-mi:“MI:0915”(physical association)	0.780
MET	PLXNB1	psi-mi:“MI:0915”(physical association)	0.780
PLXNB1	MET	psi-mi:“MI:0217”(phosphorylation reaction)	0.780
PLXNB1	RND1	psi-mi:“MI:0915”(physical association)	0.780
PLXNB1	RND3	psi-mi:“MI:0915”(physical association)	0.680
RND3	PLXNB1	psi-mi:“MI:0407”(direct interaction)	0.680
PLXNB1	ARHGEF11	psi-mi:“MI:0915”(physical association)	0.610
PLXNB1	ARHGEF11	psi-mi:“MI:0407”(direct interaction)	0.610
RND2	PLXNB1	psi-mi:“MI:0407”(direct interaction)	0.560
PLXNB1	MST1R	psi-mi:“MI:0915”(physical association)	0.520
MST1R	PLXNB1	psi-mi:“MI:0915”(physical association)	0.520
PLXNB1	MAST2	psi-mi:“MI:0407”(direct interaction)	0.440
PLXNB1	ARHGEF12	psi-mi:“MI:0407”(direct interaction)	0.440
PLXNB1	MAGI2	psi-mi:“MI:0407”(direct interaction)	0.440
PLXNB1	SCRIB	psi-mi:“MI:0407”(direct interaction)	0.440
PLXNB1	PDZD7	psi-mi:“MI:0407”(direct interaction)	0.440
TAX1BP3	PLXNB1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (60): PLXNB1 (Two-hybrid), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Affinity Capture-MS), PLXNB1 (Two-hybrid), SMPX (Affinity Capture-MS), HBB (Affinity Capture-MS), HBA2 (Affinity Capture-MS), PLXNB1 (Two-hybrid), PLXNB1 (Two-hybrid), PLXNB1 (Two-hybrid)

ESM2 similar proteins: A0A1B0GTW7, A0A1D5NSK0, A0A1L8HYT7, A0A286YEC0, D3ZT86, D3ZWJ9, D4A929, F8W3R9, G7PWZ3, I6M4H4, O08852, O43157, O43278, O75074, O88204, P17813, P49000, P59383, Q04912, Q17R55, Q499Z3, Q4R3B7, Q4TUC0, Q5ND34, Q62190, Q63961, Q6AXX1, Q76MJ5, Q7TN88, Q7TQH7, Q7Z442, Q7Z4F1, Q80W87, Q80YN4, Q866Y3, Q86VZ4, Q8BHW9, Q8BMN4, Q8BYI8, Q8BZT7

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

1 interactions.

A	Effect	B	Mechanism
SEMA4D	up-regulates	PLXNB1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 91 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
Sema4D in semaphorin signaling	5	53.3×	1e-06
Sema4D induced cell migration and growth-cone collapse	5	45.3×	3e-06
Dopamine Neurotransmitter Release Cycle	5	39.4×	5e-06
Semaphorin interactions	6	37.5×	6e-07
Assembly and cell surface presentation of NMDA receptors	9	36.2×	3e-10
Neurexins and neuroligins	11	34.4×	3e-12
Protein-protein interactions at synapses	7	29.5×	3e-07
RND3 GTPase cycle	5	20.6×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	8	54.7×	7e-10
protein localization to synapse	6	54.1×	3e-07
receptor clustering	6	44.1×	5e-07
regulation of postsynaptic membrane neurotransmitter receptor levels	6	35.0×	2e-06
Rho protein signal transduction	5	14.6×	1e-03
protein-containing complex assembly	9	12.1×	5e-06
small GTPase-mediated signal transduction	5	10.8×	3e-03
cell-cell adhesion	9	10.8×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	261
Likely benign	40
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

7032 predictions. Top by Δscore:

Variant	Effect	Δscore
3:48404587:TGAT:T	acceptor_gain	1.0000
3:48404588:GATC:G	acceptor_loss	1.0000
3:48404590:TCTGA:T	acceptor_loss	1.0000
3:48404591:C:CC	acceptor_gain	1.0000
3:48404591:CTGA:C	acceptor_loss	1.0000
3:48404592:TGAAA:T	acceptor_loss	1.0000
3:48404597:C:CT	acceptor_gain	1.0000
3:48405719:CCCA:C	donor_loss	1.0000
3:48405721:CACC:C	donor_loss	1.0000
3:48405722:AC:A	donor_loss	1.0000
3:48405723:CCT:C	donor_loss	1.0000
3:48405735:A:AC	donor_gain	1.0000
3:48405736:C:CC	donor_gain	1.0000
3:48405794:TAGTT:T	acceptor_gain	1.0000
3:48405795:AGTT:A	acceptor_gain	1.0000
3:48405796:GTT:G	acceptor_gain	1.0000
3:48405797:TT:T	acceptor_gain	1.0000
3:48405797:TTCTA:T	acceptor_loss	1.0000
3:48405799:C:CC	acceptor_gain	1.0000
3:48405800:T:G	acceptor_loss	1.0000
3:48406817:CCTTA:C	donor_loss	1.0000
3:48406818:CTTAC:C	donor_loss	1.0000
3:48406819:TTAC:T	donor_loss	1.0000
3:48406820:TAC:T	donor_loss	1.0000
3:48406821:AC:A	donor_gain	1.0000
3:48406821:ACCCA:A	donor_loss	1.0000
3:48406822:C:CG	donor_loss	1.0000
3:48406822:CC:C	donor_gain	1.0000
3:48406896:TAC:T	acceptor_gain	1.0000
3:48406903:C:CT	acceptor_gain	1.0000

AlphaMissense

13755 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:48407072:A:G	L2036P	1.000
3:48409915:A:G	L1923P	1.000
3:48409918:A:G	L1922P	1.000
3:48409927:A:G	L1919P	1.000
3:48409933:A:C	I1917S	1.000
3:48409933:A:G	I1917T	1.000
3:48411894:A:G	L1739P	1.000
3:48412956:A:G	L1547P	1.000
3:48413073:G:C	F1544L	1.000
3:48413073:G:T	F1544L	1.000
3:48413075:A:G	F1544L	1.000
3:48413110:A:G	L1532P	1.000
3:48413119:A:G	L1529P	1.000
3:48407069:A:T	L2037Q	0.999
3:48407072:A:T	L2036H	0.999
3:48407074:T:A	K2035N	0.999
3:48407074:T:G	K2035N	0.999
3:48407075:T:A	K2035I	0.999
3:48407077:G:C	N2034K	0.999
3:48407077:G:T	N2034K	0.999
3:48409460:A:G	W1986R	0.999
3:48409460:A:T	W1986R	0.999
3:48409584:A:G	W1976R	0.999
3:48409584:A:T	W1976R	0.999
3:48409724:A:G	L1929P	0.999
3:48409905:C:A	K1926N	0.999
3:48409905:C:G	K1926N	0.999
3:48409915:A:T	L1923Q	0.999
3:48409918:A:T	L1922Q	0.999
3:48409921:C:G	R1921P	0.999

dbSNP variants (sampled 300 via entrez): RS1000065332 (3:48412139 C>G), RS1000097168 (3:48406760 A>C), RS1000265027 (3:48408161 C>T), RS1000436420 (3:48427236 G>A,C), RS1000566755 (3:48408460 A>C,G), RS1000856258 (3:48430095 A>G), RS1000900430 (3:48420461 T>A,C), RS1000930868 (3:48427583 G>T), RS1000952219 (3:48430467 G>A,T), RS1001059916 (3:48424716 C>T), RS1001137417 (3:48426675 G>A), RS1001168705 (3:48426440 C>T), RS1001169429 (3:48431565 G>A,C), RS1001493320 (3:48426311 C>T), RS1001501826 (3:48420252 C>G,T)

Disease associations

OMIM: gene MIM:601053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST004131_23	Inflammatory bowel disease	1.000000e-33
GCST004132_17	Crohn’s disease	3.000000e-23
GCST004133_11	Ulcerative colitis	8.000000e-20
GCST008058_247	Estimated glomerular filtration rate	3.000000e-13
GCST008059_49	Estimated glomerular filtration rate	1.000000e-13
GCST009067_4	Mosaic loss of chromosome Y (Y chromosome dosage)	5.000000e-08
GCST010698_80	Subcortical volume (min-P)	3.000000e-24
GCST010699_110	Brain morphology (min-P)	4.000000e-08
GCST010701_52	Cortical surface area (MOSTest)	1.000000e-16
GCST010702_36	Subcortical volume (MOSTest)	1.000000e-10
GCST010703_262	Brain morphology (MOSTest)	2.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007783	mosaic loss of chromosome Y measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
bisphenol A	decreases expression, increases methylation	2
bisphenol S	affects expression, affects cotreatment, decreases expression	2
Acetaminophen	decreases expression	2
Air Pollutants	decreases expression, increases abundance, increases expression	2
Methotrexate	increases expression	2
Smoke	decreases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
bisphenol F	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
cupric chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
jinfukang	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Acrolein	affects cotreatment, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance, increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Cisplatin	affects cotreatment, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ozone	affects cotreatment, increases expression	1
Phenobarbital	affects expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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