PLXNB2

Summary

PLXNB2 (plexin B2, HGNC:9104) is a protein-coding gene on chromosome 22q13.33, encoding Plexin-B2 (O15031). Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling.

Members of the B class of plexins, such as PLXNB2 are transmembrane receptors that participate in axon guidance and cell migration in response to semaphorins (Perrot et al. (2002) [PubMed 12183458]).

Source: NCBI Gene 23654 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic disease (Strong, GenCC)
• GWAS associations: 14
• Clinical variants (ClinVar): 378 total — 8 pathogenic
• MANE Select transcript: NM_012401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9104
Approved symbol	PLXNB2
Name	plexin B2
Location	22q13.33
Locus type	gene with protein product
Status	Approved
Aliases	MM1, KIAA0315, PLEXB2, lncFAL
Ensembl gene	ENSG00000196576
Ensembl biotype	protein_coding
OMIM	604293
Entrez	23654

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 31 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000359337, ENST00000411680, ENST00000425954, ENST00000427829, ENST00000432455, ENST00000434732, ENST00000449103, ENST00000463165, ENST00000479701, ENST00000479818, ENST00000492578, ENST00000496720, ENST00000890232, ENST00000890233, ENST00000890234, ENST00000890235, ENST00000890236, ENST00000890237, ENST00000890238, ENST00000890239, ENST00000890240, ENST00000890241, ENST00000890242, ENST00000930907, ENST00000930908, ENST00000930909, ENST00000930910, ENST00000930911, ENST00000930912, ENST00000930913, ENST00000930914, ENST00000930915, ENST00000930916, ENST00000930917, ENST00000930918, ENST00000949258

RefSeq mRNA: 24 — MANE Select: NM_012401 NM_001376864, NM_001376865, NM_001376866, NM_001376867, NM_001376868, NM_001376869, NM_001376870, NM_001376871, NM_001376872, NM_001376873, NM_001376874, NM_001376875, NM_001376876, NM_001376877, NM_001376878, NM_001376879, NM_001376880, NM_001376881, NM_001376882, NM_001376883, NM_001376884, NM_001376885, NM_001376886, NM_012401

CCDS: CCDS43035

Canonical transcript exons

ENST00000359337 — 37 exons

Exon	Start	End
ENSE00001554120	50294719	50294778
ENSE00001713579	50307553	50307646
ENSE00003462491	50280489	50280670
ENSE00003472038	50274979	50275808
ENSE00003472831	50276842	50276906
ENSE00003491667	50279630	50279776
ENSE00003511714	50283602	50283750
ENSE00003519429	50275889	50275963
ENSE00003526700	50278855	50279011
ENSE00003544458	50284573	50284665
ENSE00003550502	50281566	50281742
ENSE00003551841	50281360	50281499
ENSE00003569937	50281089	50281189
ENSE00003592828	50278596	50278696
ENSE00003604803	50278117	50278271
ENSE00003614828	50276629	50276704
ENSE00003620792	50277591	50277738
ENSE00003629293	50281854	50282081
ENSE00003636088	50285800	50285901
ENSE00003650155	50283833	50283990
ENSE00003651937	50280005	50280071
ENSE00003662568	50285990	50286098
ENSE00003663439	50278435	50278519
ENSE00003678823	50280744	50280973
ENSE00003692572	50277853	50278013
ENSE00003715024	50282711	50282881
ENSE00003754814	50282184	50282313
ENSE00003888682	50288960	50289142
ENSE00003889274	50287111	50287264
ENSE00003891649	50287937	50288037
ENSE00003891790	50284132	50284213
ENSE00003893219	50289517	50290597
ENSE00003893270	50283050	50283186
ENSE00003893683	50283337	50283445
ENSE00003893692	50287667	50287793
ENSE00003893901	50288743	50288871
ENSE00003895569	50286173	50286287

Expression profiles

Bgee: expression breadth ubiquitous, 276 present calls, max score 99.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 47.8590 / max 357.9644, expressed in 1784 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194732	33.1159	1776
194731	12.2158	1716
194726	1.2308	335
194728	0.8537	170
194727	0.2649	131
194729	0.1779	62

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.41	gold quality
metanephros cortex	UBERON:0010533	99.07	gold quality
lower esophagus mucosa	UBERON:0035834	98.91	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.80	gold quality
cerebellar hemisphere	UBERON:0002245	98.79	gold quality
cerebellar cortex	UBERON:0002129	98.74	gold quality
right lobe of thyroid gland	UBERON:0001119	98.72	gold quality
left lobe of thyroid gland	UBERON:0001120	98.71	gold quality
stromal cell of endometrium	CL:0002255	98.60	gold quality
adenohypophysis	UBERON:0002196	98.60	gold quality
nasal cavity epithelium	UBERON:0005384	98.55	gold quality
body of stomach	UBERON:0001161	98.50	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.43	gold quality
decidua	UBERON:0002450	98.37	gold quality
left ovary	UBERON:0002119	98.31	gold quality
fundus of stomach	UBERON:0001160	98.27	gold quality
cerebellum	UBERON:0002037	98.26	gold quality
right ovary	UBERON:0002118	98.26	gold quality
minor salivary gland	UBERON:0001830	98.23	gold quality
right adrenal gland cortex	UBERON:0035827	98.23	gold quality
pituitary gland	UBERON:0000007	98.22	gold quality
thyroid gland	UBERON:0002046	98.18	gold quality
spleen	UBERON:0002106	98.18	gold quality
right adrenal gland	UBERON:0001233	98.16	gold quality
pylorus	UBERON:0001166	98.15	gold quality
right coronary artery	UBERON:0001625	98.08	gold quality
endocervix	UBERON:0000458	98.06	gold quality
left adrenal gland cortex	UBERON:0035825	98.05	gold quality
renal medulla	UBERON:0000362	98.02	gold quality
body of uterus	UBERON:0009853	98.02	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	14.63
E-GEOD-81608	yes	7.29
E-MTAB-9801	yes	6.05
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): JDP2, MYC

miRNA regulators (miRDB)

31 targeting PLXNB2, 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-4283	100.00	66.42	2097
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4489	99.50	65.56	785
HSA-MIR-1324	99.46	66.57	1302
HSA-MIR-133A-5P	99.28	69.13	941
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-1294	98.91	69.26	1030
HSA-MIR-9986	98.91	69.28	1024
HSA-MIR-548Q	98.71	65.35	563
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-138-5P	98.43	70.49	1292
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-6759-3P	96.94	68.31	823
HSA-MIR-8071	95.69	64.93	484
HSA-MIR-885-3P	95.14	63.08	448

Literature-anchored findings (GeneRIF, showing 27)

• Plexin B2 associates directly with two members of a recently identified family of Dbl homology/pleckstrin homology containing guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and Leukemia-associated Rho GEF (LARG). (PMID:12183458)
• cleavage by proprotein convertases is a novel regulatory step for semaphorin receptors localized at the cell surface. (PMID:12533544)
• High PLEXIN B2 expression is associated with high-grade gliomas. (PMID:24158112)
• In endometrial luminal epithelium, cadherin 6, desmoglein 2 and plexin b2 were surprisingly found in the apical as well as the lateral membrane domain; their knock-down compromised epithelial integrity. (PMID:25237006)
• Plexin-B2 promotes glioma invasion and vascularization (PMID:25762646)
• Results show that decreased expression of Sema4D, plexin-B1 and -B2 was associated with local recurrence and poor prognosis of breast neoplasm. (PMID:26035216)
• Blocking of CD100, plexin B1 and/or B2 in adhesion experiments have shown that both CD100 and plexins act as adhesion molecules involved in monocyte-endothelial cell binding. (PMID:26275342)
• Two related guanine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B plexins and play critical roles in signaling. (PMID:26627240)
• plexin-B2 is a downstream target for Rnd3, which contributes to its cellular function. (PMID:27656111)
• Study data showed that cooperation of CD100 and PlxnB2 promoted the inflammatory responses in keratinocytes by activating NF-kappaB and the NLRP3 inflammasome and participated in the pathogenesis of psoriasis. (PMID:28927892)
• Analysis of the interaction of Plexin-B1 and Plexin-B2 with Rnd family proteins shows lack of binding specificity. (PMID:29040270)
• Study shows that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. (PMID:29100074)
• data indicate that Sema4C/PlexinB2 signaling is essential for the growth of breast carcinoma cells, featuring a novel potential therapeutic target. In addition, elevated Sema4C expression enables indolent luminal-type tumors to become resistant to estrogen deprivation, invasive and metastatic in vivo (PMID:29555978)
• Knocking down of PLXNB2 with PLXNB2 siRNA results in repressed ovarian cancer cell proliferation and invasion, and decreased phosphorylation of AKT and ERK1/2 (PMID:30054097)
• PLEXIN-B2 promotes the osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the RhoA signaling pathway. (PMID:31176746)
• Plexin B2 Is a Regulator of Monocyte Apoptotic Cell Disassembly. (PMID:31722200)
• Plexin-B2 in psoriasis; a clinical and immunohistochemical study. (PMID:32186222)
• Myeloid cells protect intestinal epithelial barrier integrity through the angiogenin/plexin-B2 axis. (PMID:32510170)
• Plexin-B2 facilitates glioblastoma infiltration by modulating cell biomechanics. (PMID:33514835)
• Increased airway epithelial cell-derived exosomes activate macrophage-mediated allergic inflammation via CD100 shedding. (PMID:34414666)
• Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion. (PMID:34650052)
• Angiogenin and plexin-B2 axis promotes glioblastoma progression by enhancing invasion, vascular association, proliferation and survival. (PMID:35418212)
• CircPLXNB2 regulates acute myeloid leukemia progression through miR-654-3p/CCND1 axis. (PMID:37272581)
• Expression analysis, clinical significance and potential function of PLXNB2 in acute myeloid leukaemia. (PMID:37632633)
• Colorectal Cancer-Associated Myofibroblasts Exhibit Enhanced Angiogenin Expression and Signaling via the PLXNB2 Receptor. (PMID:38295715)
• Biallelic variants in Plexin B2 (PLXNB2) cause amelogenesis imperfecta, hearing loss and intellectual disability. (PMID:38458752)
• In vivo interaction screening reveals liver-derived constraints to metastasis. (PMID:39048831)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	plxnb2a.1	ENSDARG00000003811
danio_rerio	plxnb2b	ENSDARG00000036985
danio_rerio	plxnb2a.2	ENSDARG00000077090
danio_rerio	plxnb2a.3	ENSDARG00000079892
danio_rerio	si:dkey-183c2.5	ENSDARG00000094799
mus_musculus	Plxnb2	ENSMUSG00000036606
rattus_norvegicus	Plxnb2	ENSRNOG00000007133
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), PLXNB1 (ENSG00000164050), PLXNB3 (ENSG00000198753), PLXNA4 (ENSG00000221866)

Protein

Protein identifiers

Plexin-B2 — O15031 (reviewed: O15031)

Alternative names: MM1

All UniProt accessions (6): A6QRG9, A6QRH1, E2PU09, O15031, H0Y6J7, H0Y7X5

UniProt curated annotations — full annotation on UniProt →

Function. Cell surface receptor for SEMA4C, SEMA4D and SEMA4G that plays an important role in cell-cell signaling. Plays a role in glutamatergic synapse development and is required for SEMA4A-mediated excitatory synapse development. Binding to class 4 semaphorins promotes downstream activation of RHOA and phosphorylation of ERBB2 at ‘Tyr-1248’. Also acts as a cell surface receptor for angiogenin (ANG); promoting ANG endocytosis and translocation to the cytoplasm or nucleus. Required for normal differentiation and migration of neuronal cells during brain corticogenesis and for normal embryonic brain development. Regulates the migration of cerebellar granule cells in the developing brain. Plays a role in RHOA activation and subsequent changes of the actin cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. May modulate the activity of RAC1 and CDC42.

Subunit / interactions. Monomer, and heterodimer with PLXNB1. Interacts with SEMA4C, SEMA4D and SEMA4G. Interacts with MET. Interacts with ARHGEF11 and ARHGEF12. May also interact with MST1R.

Subcellular location. Cell membrane.

Similarity. Belongs to the plexin family.

RefSeq proteins (24): NP_001363793, NP_001363794, NP_001363795, NP_001363796, NP_001363797, NP_001363798, NP_001363799, NP_001363800, NP_001363801, NP_001363802, NP_001363803, NP_001363804, NP_001363805, NP_001363806, NP_001363807, NP_001363808, NP_001363809, NP_001363810, NP_001363811, NP_001363812, NP_001363813, NP_001363814, NP_001363815, NP_036533* (*=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
IPR046800	Plexin_RBD	Domain
IPR057533	PSI_Plexin-B	Domain

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

UniProt features (46 total): glycosylation site 13, disulfide bond 10, strand 4, domain 4, modified residue 3, topological domain 2, sequence variant 2, helix 2, signal peptide 1, chain 1, transmembrane region 1, mutagenesis site 1, sequence conflict 1, site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4E71	X-RAY DIFFRACTION	2.26

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15031-F1	82.70	0.30

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 (1): 1164–1165 (cleavage; by proprotein convertases)

Post-translational modifications (3): 1236, 1244, 1570

Disulfide bonds (10): 78–87, 112–120, 250–364, 266–312, 330–351, 469–486, 475–518, 478–495, 489–501, 555–574

Glycosylation sites (13): 127, 242, 391, 402, 528, 733, 759, 795, 844, 1002, 1049, 1068, 1099

Mutagenesis-validated functional residues (1):

Position	Phenotype
1161–1164	abolishes cleavage by proprotein convertases.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 323 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SYNAPSE_ASSEMBLY, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOCC_CELL_SURFACE, HUMMERICH_BENIGN_SKIN_TUMOR_DN, HUMMERICH_MALIGNANT_SKIN_TUMOR_DN, GOBP_NEUROGENESIS, GOBP_NEURAL_TUBE_DEVELOPMENT

GO Biological Process (24): neural tube closure (GO:0001843), regulation of protein phosphorylation (GO:0001932), receptor-mediated endocytosis (GO:0006898), homophilic cell-cell adhesion (GO:0007156), negative regulation of cell adhesion (GO:0007162), neuroblast proliferation (GO:0007405), synapse assembly (GO:0007416), brain development (GO:0007420), regulation of cell shape (GO:0008360), positive regulation of neuron projection development (GO:0010976), regulation of cell migration (GO:0030334), regulation of GTPase activity (GO:0043087), positive regulation of translation (GO:0045727), positive regulation of axonogenesis (GO:0050772), semaphorin-plexin signaling pathway (GO:0071526), excitatory synapse assembly (GO:1904861), regulation of neuron migration (GO:2001222), cytoplasmic translation (GO:0002181), regulation of neuron projection development (GO:0010975), positive regulation of cell projection organization (GO:0031346), negative regulation of translation in response to stress (GO:0032055), cellular response to stress (GO:0033554), tRNA stabilization (GO:0036416), regulation of protein metabolic process (GO:0051246)

GO Molecular Function (4): transmembrane signaling receptor activity (GO:0004888), semaphorin receptor activity (GO:0017154), signaling receptor activity (GO:0038023), protein binding (GO:0005515)

GO Cellular Component (5): semaphorin receptor complex (GO:0002116), plasma membrane (GO:0005886), cell surface (GO:0009986), extracellular exosome (GO:0070062), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
neuron projection development	2
positive regulation of cell projection organization	2
translation	2
cellular anatomical structure	2
primary neural tube formation	1
tube closure	1
protein phosphorylation	1
regulation of protein modification process	1
regulation of phosphorylation	1
endocytosis	1
cell-cell adhesion	1
cell adhesion	1
regulation of cell adhesion	1
negative regulation of cellular process	1
generation of neurons	1
neural precursor cell proliferation	1
nervous system development	1
cell junction assembly	1
synapse organization	1
central nervous system development	1
animal organ development	1
head development	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of neuron projection development	1
cell migration	1
regulation of cell motility	1
GTPase activity	1
regulation of hydrolase activity	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
axonogenesis	1
positive regulation of neurogenesis	1
regulation of axonogenesis	1
cell surface receptor signaling pathway	1
synapse assembly	1
neuron migration	1
regulation of cell migration	1
regulation of plasma membrane bounded cell projection organization	1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLXNB2	SEMA4D	Q92854	998
PLXNB2	SEMA4C	Q9C0C4	957
PLXNB2	ARHGEF12	Q9NZN5	927
PLXNB2	PTN	P21246	902
PLXNB2	ARHGEF11	O15085	885
PLXNB2	JAML	Q86YT9	815
PLXNB2	RND3	P52199	803
PLXNB2	ANG	P03950	802
PLXNB2	SEMA4G	Q9NTN9	741
PLXNB2	MAPK12	P53778	675
PLXNB2	RRAS	P10301	651
PLXNB2	MAPK11	Q15759	635
PLXNB2	SEMA3C	Q99985	629
PLXNB2	CD72	P21854	624
PLXNB2	RND2	P52198	620

IntAct

150 interactions, top by confidence:

A	B	Type	Score
CD9	ADAM10	psi-mi:“MI:0914”(association)	0.750
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
RHOD	PLXNB2	psi-mi:“MI:0914”(association)	0.640
PDGFRB	PIK3R2	psi-mi:“MI:0914”(association)	0.610
SEMA4C	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.590
RND1	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.560
RND2	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.560
RND3	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.560
SEMA4D	PLXNB2	psi-mi:“MI:0407”(direct interaction)	0.560
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
DEFA5	NUDT19	psi-mi:“MI:0914”(association)	0.530
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
TMX1	NRP1	psi-mi:“MI:0914”(association)	0.530
LMAN2	PLXNB2	psi-mi:“MI:0914”(association)	0.530
LYPD6	PLXNB2	psi-mi:“MI:0914”(association)	0.530
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
BTNL3	FAM171A2	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530

BioGRID (238): PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS), PLXNB2 (Affinity Capture-MS)

ESM2 similar proteins: A0M8R7, A0M8S8, A1X150, B2RXS4, B3DK56, E2RK30, O15031, O45657, O60486, P08581, P08F94, 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, Q2QLH6, Q60PR7

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, A7MB70, D3ZTD8, O08665, O09126, O15041, O35464, O42237, O75326

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 148 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	7	6.8×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
semaphorin-plexin signaling pathway	5	15.2×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	8
Likely pathogenic	0
Uncertain significance	258
Likely benign	54
Benign	8

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
1071720	NC_000022.10:g.(?50297466)(51066227_?)del	Pathogenic
1895421	NM_012401.4(PLXNB2):c.2413A>T (p.Ile805Phe)	Pathogenic
1895422	NM_012401.4(PLXNB2):c.2248G>A (p.Asp750Asn)	Pathogenic
1895423	NM_012401.4(PLXNB2):c.750C>A (p.Cys250Ter)	Pathogenic
1895425	NM_012401.4(PLXNB2):c.2606del (p.Phe869fs)	Pathogenic
1895426	NM_012401.4(PLXNB2):c.3982_3986del (p.Phe1328fs)	Pathogenic
1895427	NM_012401.4(PLXNB2):c.5197-337_5310del	Pathogenic
1895428	NM_012401.4(PLXNB2):c.4609G>A (p.Gly1537Ser)	Pathogenic

SpliceAI

6835 predictions. Top by Δscore:

Variant	Effect	Δscore
22:50275805:TGAT:T	acceptor_gain	1.0000
22:50275807:AT:A	acceptor_gain	1.0000
22:50275807:ATC:A	acceptor_loss	1.0000
22:50275808:TCT:T	acceptor_loss	1.0000
22:50275809:C:CC	acceptor_gain	1.0000
22:50275810:T:G	acceptor_loss	1.0000
22:50275884:CCTA:C	donor_loss	1.0000
22:50275885:CTAC:C	donor_loss	1.0000
22:50275886:TACCT:T	donor_loss	1.0000
22:50275888:CCT:C	donor_gain	1.0000
22:50275901:CTT:C	donor_gain	1.0000
22:50275903:T:TA	donor_gain	1.0000
22:50276623:CCTTA:C	donor_loss	1.0000
22:50276624:CTTAC:C	donor_loss	1.0000
22:50276625:TTA:T	donor_loss	1.0000
22:50276626:TA:T	donor_loss	1.0000
22:50276627:A:AC	donor_gain	1.0000
22:50276627:AC:A	donor_gain	1.0000
22:50276627:ACCCG:A	donor_loss	1.0000
22:50276628:C:A	donor_loss	1.0000
22:50276628:C:CC	donor_gain	1.0000
22:50276628:CC:C	donor_gain	1.0000
22:50276703:AA:A	acceptor_gain	1.0000
22:50276703:AAC:A	acceptor_loss	1.0000
22:50276704:ACTG:A	acceptor_loss	1.0000
22:50276705:C:CC	acceptor_gain	1.0000
22:50276706:T:G	acceptor_loss	1.0000
22:50276839:TA:T	donor_loss	1.0000
22:50276840:A:AC	donor_gain	1.0000
22:50276840:ACT:A	donor_gain	1.0000

AlphaMissense

12046 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:50276878:G:T	A1742D	1.000
22:50276884:A:G	L1740P	1.000
22:50276884:A:T	L1740Q	1.000
22:50276887:A:G	L1739P	1.000
22:50276887:A:T	L1739Q	1.000
22:50276889:C:A	K1738N	1.000
22:50276889:C:G	K1738N	1.000
22:50278006:A:G	L1632P	1.000
22:50278117:C:A	K1629N	1.000
22:50278117:C:G	K1629N	1.000
22:50278127:A:G	L1626P	1.000
22:50278127:A:T	L1626H	1.000
22:50278130:A:G	L1625P	1.000
22:50278139:A:G	L1622P	1.000
22:50278139:A:T	L1622Q	1.000
22:50278518:A:T	V1550D	1.000
22:50278609:A:T	L1545H	1.000
22:50278694:A:G	W1517R	1.000
22:50278694:A:T	W1517R	1.000
22:50279676:A:G	L1448P	1.000
22:50279676:A:T	L1448H	1.000
22:50279748:A:G	L1424P	1.000
22:50280970:A:G	L1256P	1.000
22:50281093:G:C	F1253L	1.000
22:50281093:G:T	F1253L	1.000
22:50281094:A:C	F1253C	1.000
22:50281094:A:G	F1253S	1.000
22:50281095:A:G	F1253L	1.000
22:50281105:G:C	C1249W	1.000
22:50281107:A:G	C1249R	1.000

dbSNP variants (sampled 300 via entrez): RS1000023005 (22:50303056 C>T), RS1000051783 (22:50303309 G>A), RS1000095053 (22:50280860 C>T), RS1000106239 (22:50275462 G>A), RS1000176906 (22:50307333 C>A,G), RS1000205626 (22:50301480 G>A), RS1000307844 (22:50306584 G>A), RS1000353689 (22:50296338 G>A), RS1000411692 (22:50286529 C>T), RS1000491111 (22:50307500 C>A,T), RS1000503800 (22:50277241 C>T), RS1000534411 (22:50302557 G>A), RS1000660318 (22:50297394 C>G,T), RS1000681817 (22:50301267 C>G), RS1000786781 (22:50297227 C>A)

Disease associations

OMIM: gene MIM:604293 | disease phenotypes: MIM:607143

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic disease	Strong	Autosomal recessive

Mondo (2): ALG12-congenital disorder of glycosylation (MONDO:0011783), syndromic disease (MONDO:0002254)

Orphanet (1): ALG12-CDG (Orphanet:79324)

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST002481_12	Acne (severe)	4.000000e-06
GCST006585_1117	Blood protein levels	2.000000e-216
GCST006585_961	Blood protein levels	9.000000e-27
GCST006624_41	Systolic blood pressure	4.000000e-14
GCST006988_132	Blond vs. brown/black hair color	5.000000e-10
GCST009310_5	Sensorimotor dexterity	3.000000e-06
GCST010302_44	Cutaneous melanoma or hair colour	2.000000e-19
GCST010303_61	Nevus count or cutaneous melanoma	9.000000e-09
GCST010304_55	Cutaneous malignant melanoma	9.000000e-09
GCST90002385_585	High light scatter reticulocyte count	5.000000e-14
GCST90002386_497	High light scatter reticulocyte percentage of red cells	6.000000e-14
GCST90002388_273	Lymphocyte count	7.000000e-10
GCST90002405_424	Reticulocyte count	3.000000e-12
GCST90002406_575	Reticulocyte fraction of red cells	5.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0003924	hair color
EFO:0008354	cognitive function measurement
EFO:0004632	nevus count
EFO:0007986	reticulocyte count
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D013577	Syndrome	C23.550.288.500
C535745	Congenital disorder of glycosylation type 1G (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, increases expression, increases methylation, affects expression	4
Acetaminophen	decreases expression, increases expression	3
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	2
Air Pollutants	increases oxidation, decreases expression, affects cotreatment, increases abundance	2
Arsenic	increases abundance, affects methylation, affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, increases expression	2
Lead	decreases expression, affects splicing	2
Tobacco Smoke Pollution	decreases expression, affects expression	2
Valproic Acid	increases expression, decreases expression	2
Aflatoxin B1	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
bisphenol F	increases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
beta-lapachone	decreases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
perfluorooctanoic acid	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
isobutyl alcohol	affects cotreatment, increases abundance, increases expression	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1BD	Abcam HEK293 PLXNB2 KO	Transformed cell line	Female
CVCL_D1U0	Abcam U-87MG PLXNB2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00027456	PHASE2	COMPLETED	Leptin to Treat Severe Insulin Resistance - Pilot Study
NCT00213447	Not specified	COMPLETED	T Cell Response in Hypersensitivity Syndrome
NCT02240888	Not specified	COMPLETED	Vaccination in Inflammatory Rheumatic Disease (VACCIMIL). The Impact of Antirheumatic Treatment on Antibody Response
NCT02526082	Not specified	ACTIVE_NOT_RECRUITING	Long-term Follow-up of the Helsinki Businessmen Study
NCT02637518	Not specified	UNKNOWN	Comprehensive Validation of Frailty Assessment Tools in Older Adults in Different Clinical and Social Settings
NCT02971072	Not specified	COMPLETED	Neurophysiology of Weakness and Exercise in Rotator Cuff Tendinopathy
NCT02974569	Not specified	COMPLETED	Improving Symptom Self-management in Adolescents & Young Adults With Cancer
NCT03265561	Not specified	COMPLETED	Spinal Infection Management With Structural Allograft
NCT04190342	Not specified	COMPLETED	Effects of a Traditional Chinese Exercise Program on Symptom Cluster in Breast Cancer Patients
NCT04874584	Not specified	COMPLETED	Culturally Tailored Nurse Coaching Study for Cancer Symptom Management
NCT04909489	Not specified	UNKNOWN	PDR and SKYD of Dyslipidemia’s Characteristics From the Oxidative Stress Enhancement Caused by Inhibition of Serine Metabolic Pathway
NCT05218122	Not specified	UNKNOWN	Characteristics of LKDS and PBSS of KOA Based on the Enhancement of Inflammatory Response by TGF-β/Smad Pathway Inhibited
NCT05266118	Not specified	COMPLETED	Patient Reported Symptoms the First Week After Intensive Care Unit Discharge and up to Hospital Discharge
NCT05321966	Not specified	COMPLETED	The Effect of Video Training on Symptom Burden Patients Undergoing Hemodialysis Treatment
NCT05818748	Not specified	UNKNOWN	Effect Of Virtual Reality Distraction on Symptom Control and Anxiety in Children With Leukemia
NCT05837988	Not specified	UNKNOWN	Construction of Symptom Network in Maintenance Hemodialysis Patients
NCT06143436	Not specified	UNKNOWN	TCM Constitution, Pattern Types, and Disease Factors in Primary Lung Cancer.
NCT06222008	Not specified	UNKNOWN	Study on Symptom Clusters During Chemotherapy in Ovarian Cancer Patients With Different Chinese Medicine Constitution
NCT06412107	Not specified	COMPLETED	Somatic Acupressure for Symptom Cluster Management in Breast Cancer Survivors
NCT06847360	Not specified	RECRUITING	Home-based Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) for IBS Pain
NCT07281300	Not specified	RECRUITING	Mindfulness-Oriented Respiratory Distress Symptom Intervention for Lung Cancer
NCT07315672	Not specified	RECRUITING	Acupressure for Cough in Lung Cancer Survivors
NCT07479654	Not specified	NOT_YET_RECRUITING	AI-Enabled Frailty Risk Prediction in Adult Congenital Heart Disease
NCT07495358	Not specified	NOT_YET_RECRUITING	Development and Usability Evaluation of a Knowledge Graph-Based Symptom Management System for Patients With Breast Cancer Undergoing Chemotherapy
NCT07576114	Not specified	RECRUITING	Comparison of Gluteal Muscle Activation and Core Strengthening in Dead Butt Syndrome Syndrome