SEMA5B

Summary

SEMA5B (semaphorin 5B, HGNC:10737) is a protein-coding gene on chromosome 3q21.1, encoding Semaphorin-5B (Q9P283). May act as a positive axonal guidance cue.

This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 54437 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 210 total
• MANE Select transcript: NM_001031702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10737
Approved symbol	SEMA5B
Name	semaphorin 5B
Location	3q21.1
Locus type	gene with protein product
Status	Approved
Aliases	SemG, KIAA1445, FLJ10372
Ensembl gene	ENSG00000082684
Ensembl biotype	protein_coding
OMIM	609298
Entrez	54437

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 23 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000195173, ENST00000357599, ENST00000393583, ENST00000421053, ENST00000449546, ENST00000451055, ENST00000451541, ENST00000465147, ENST00000475244, ENST00000477001, ENST00000616742, ENST00000648990, ENST00000649167, ENST00000650207, ENST00000907744, ENST00000907745, ENST00000907746, ENST00000907747, ENST00000936472, ENST00000936473, ENST00000936474, ENST00000936475, ENST00000936476, ENST00000970352, ENST00000970353, ENST00000970354, ENST00000970355

RefSeq mRNA: 5 — MANE Select: NM_001031702 NM_001031702, NM_001256346, NM_001256347, NM_001256348, NM_001410801

CCDS: CCDS35491, CCDS58848, CCDS74995, CCDS93351

Canonical transcript exons

ENST00000357599 — 23 exons

Exon	Start	End
ENSE00001671469	122912172	122912342
ENSE00002218931	122943436	122943535
ENSE00002221720	122923617	122923752
ENSE00002224839	122912843	122913061
ENSE00002225017	122927790	122928003
ENSE00002237971	122913534	122913681
ENSE00002238433	122911491	122911535
ENSE00002254132	122928517	122928615
ENSE00002255386	122921915	122922122
ENSE00002256124	122939425	122939470
ENSE00002265679	122913858	122914001
ENSE00002274106	122911920	122912069
ENSE00002275204	122926392	122926677
ENSE00002276159	122922240	122922447
ENSE00002290525	122915773	122915890
ENSE00002292052	122913199	122913424
ENSE00002294974	122915440	122915621
ENSE00002308112	122928996	122929058
ENSE00003635623	122910840	122911045
ENSE00003644198	122961140	122961301
ENSE00003732253	122948506	122948709
ENSE00003835365	122909082	122910301
ENSE00003889764	123027464	123027763

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 98.59.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0342 / max 117.5357, expressed in 336 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44153	1.3738	291
44152	0.5194	224
44154	0.0736	45
44151	0.0248	11
44149	0.0236	5
44150	0.0190	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.59	gold quality
ganglionic eminence	UBERON:0004023	96.54	gold quality
tibialis anterior	UBERON:0001385	89.95	silver quality
upper arm skin	UBERON:0004263	89.17	gold quality
apex of heart	UBERON:0002098	86.37	gold quality
epithelial cell of pancreas	CL:0000083	85.97	gold quality
epithelium of nasopharynx	UBERON:0001951	84.69	gold quality
primary visual cortex	UBERON:0002436	84.22	gold quality
right frontal lobe	UBERON:0002810	83.61	gold quality
cardiac muscle of right atrium	UBERON:0003379	83.06	gold quality
occipital lobe	UBERON:0002021	82.73	gold quality
prefrontal cortex	UBERON:0000451	82.39	gold quality
amygdala	UBERON:0001876	82.05	gold quality
left ventricle myocardium	UBERON:0006566	81.99	gold quality
cerebellar vermis	UBERON:0004720	81.68	gold quality
ileal mucosa	UBERON:0000331	81.60	silver quality
frontal cortex	UBERON:0001870	81.25	gold quality
neocortex	UBERON:0001950	81.22	gold quality
cerebral cortex	UBERON:0000956	80.57	gold quality
Ammon’s horn	UBERON:0001954	80.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.19	gold quality
Brodmann (1909) area 9	UBERON:0013540	80.15	gold quality
anterior cingulate cortex	UBERON:0009835	80.02	gold quality
metanephros	UBERON:0000081	79.90	gold quality
deltoid	UBERON:0001476	79.28	gold quality
temporal lobe	UBERON:0001871	79.27	gold quality
myocardium	UBERON:0002349	79.26	gold quality
nucleus accumbens	UBERON:0001882	79.05	gold quality
middle temporal gyrus	UBERON:0002771	78.73	gold quality
caudate nucleus	UBERON:0001873	78.63	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.03

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXP1, RBPJ

miRNA regulators (miRDB)

52 targeting SEMA5B, 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-6867-5P	100.00	82.21	3464
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-3140-5P	99.39	69.04	1136
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-8070	99.07	69.30	1303
HSA-MIR-6889-3P	98.84	67.35	1198
HSA-MIR-4656	98.79	66.22	1306
HSA-MIR-6529-3P	98.68	66.76	1020

Literature-anchored findings (GeneRIF, showing 2)

• Sema5B regulates the development and maintenance of synapse size and number in hippocampal neurons. (PMID:19463192)
• SEMA5B could possibly serve as a candidate gene for alterations associated with asbestos exposure. (PMID:26463840)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema5ba	ENSDARG00000061471
danio_rerio	sema5bb	ENSDARG00000075648
mus_musculus	Sema5b	ENSMUSG00000052133
rattus_norvegicus	Sema5b	ENSRNOG00000002238

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA7A (ENSG00000138623), SEMA6C (ENSG00000143434), SEMA3D (ENSG00000153993), SEMA6B (ENSG00000167680), SEMA4C (ENSG00000168758), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-5B — Q9P283 (reviewed: Q9P283)

All UniProt accessions (9): Q9P283, A0A3B3IRP9, A0A3B3IT43, B5ME80, C9JKR3, C9JTV9, C9JTX2, F8WAT5, H0Y5U2

UniProt curated annotations — full annotation on UniProt →

Function. May act as a positive axonal guidance cue.

Subcellular location. Membrane.

Similarity. Belongs to the semaphorin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9P283-1	1	yes
Q9P283-2	2
Q9P283-3	3
Q9P283-4	4

RefSeq proteins (5): NP_001026872, NP_001243275, NP_001243276, NP_001243277, NP_001397730 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR001627	Semap_dom	Domain
IPR002165	Plexin_repeat	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR057563	Sema5A/B-like_TSP-1	Domain

Pfam: PF00090, PF01403, PF01437, PF23260

UniProt features (46 total): disulfide bond 16, domain 7, sequence variant 7, glycosylation site 5, splice variant 5, topological domain 2, sequence conflict 2, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P283-F1	75.50	0.36

Functional residue map

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

Disulfide bonds (16): 172–182, 199–208, 322–425, 346–388, 676–713, 680–719, 691–703, 734–765, 738–770, 749–755, 865–902, 869–907, 880–892, 922–959, 926–964, 937–949

Glycosylation sites (5): 153, 236, 345, 436, 788

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-1643685	Disease
R-HSA-3781865	Diseases of glycosylation
R-HSA-3906995	Diseases associated with O-glycosylation of proteins
R-HSA-392499	Metabolism of proteins
R-HSA-5173105	O-linked glycosylation
R-HSA-5668914	Diseases of metabolism
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 159 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GGGACCA_MIR133A_MIR133B, GOBP_NEURON_PROJECTION_EXTENSION, NKX25_02, GOBP_GROWTH, GOBP_NEUROGENESIS, CHX10_01, EFC_Q6, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_TAXIS, MODULE_205, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_SENSORY_PERCEPTION_OF_LIGHT_STIMULUS, IRF1_Q6, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN

GO Biological Process (11): neural crest cell migration (GO:0001755), axon guidance (GO:0007411), positive regulation of cell migration (GO:0030335), axon extension (GO:0048675), detection of light stimulus involved in visual perception (GO:0050908), semaphorin-plexin signaling pathway (GO:0071526), nervous system development (GO:0007399), cell differentiation (GO:0030154), negative chemotaxis (GO:0050919), neuron projection guidance (GO:0097485), neuron projection extension (GO:1990138)

GO Molecular Function (3): semaphorin receptor binding (GO:0030215), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
axonogenesis	2
neuron projection morphogenesis	2
neural crest cell development	1
mesenchymal cell migration	1
neuron projection guidance	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
neuron projection extension	1
visual perception	1
detection of light stimulus involved in sensory perception	1
cell surface receptor signaling pathway	1
system development	1
cellular developmental process	1
chemotaxis	1
neuron projection development	1
developmental cell growth	1
developmental growth involved in morphogenesis	1
signaling receptor binding	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

814 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA5B	PLXNA1	Q9UIW2	765
SEMA5B	PLXNA3	P51805	676
SEMA5B	PLXNB3	Q9ULL4	642
SEMA5B	SLIT3	O75094	594
SEMA5B	SLIT2	O94813	566
SEMA5B	PLXNB1	O43157	544
SEMA5B	PLXNB2	O15031	530
SEMA5B	EFNA5	P52803	506
SEMA5B	SEMA3A	Q14563	505
SEMA5B	EFNA1	P20827	487
SEMA5B	CCDC150	Q8NCX0	478
SEMA5B	SDK2	Q58EX2	473
SEMA5B	SLC49A4	Q96SL1	467
SEMA5B	SEMA3E	O15041	450
SEMA5B	IQCK	Q8N0W5	422

IntAct

9 interactions, top by confidence:

A	B	Type	Score
SEMA5B	ANXA7	psi-mi:“MI:0915”(physical association)	0.370
SEMA5B	SMAP	psi-mi:“MI:0915”(physical association)	0.370
SEMA5B	FAM118B	psi-mi:“MI:0915”(physical association)	0.370
SEMA5B	MRPL44	psi-mi:“MI:0915”(physical association)	0.370
NUDT21	SEMA5B	psi-mi:“MI:0915”(physical association)	0.370
SMN1	SEMA5B	psi-mi:“MI:0915”(physical association)	0.370
SEMA5B	SPRY2	psi-mi:“MI:0915”(physical association)	0.370
SEMA5B	TK1	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (10): SEMA5B (Affinity Capture-MS), SEMA5B (Affinity Capture-MS), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid), SEMA5B (Two-hybrid)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A4FV93, A6BM72, A6QR11, B2LW77, D3ZUK3, E9QJQ6, O70534, O75095, O88281, P07174, P15800, P23142, P55268, P80370, P97607, Q14162, Q2VWQ2, Q5ND28, Q5R3Z7, Q5VY43, Q60519, Q61220, Q61292, Q62918, Q62919, Q6DIB5, Q6UXH1, Q6UY11, Q75N90, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8K1E3, Q8MJJ9

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXP1	“down-regulates quantity by repression”	SEMA5B	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	177
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4325 predictions. Top by Δscore:

Variant	Effect	Δscore
3:122910299:GGT:G	acceptor_gain	1.0000
3:122910300:GTCT:G	acceptor_loss	1.0000
3:122910301:TC:T	acceptor_loss	1.0000
3:122910302:C:CC	acceptor_gain	1.0000
3:122910303:T:A	acceptor_loss	1.0000
3:122910308:G:C	acceptor_gain	1.0000
3:122910308:G:GC	acceptor_gain	1.0000
3:122910835:CCCAC:C	donor_loss	1.0000
3:122910836:CCACC:C	donor_loss	1.0000
3:122910839:C:CG	donor_loss	1.0000
3:122911042:AACCC:A	acceptor_loss	1.0000
3:122911043:ACCCT:A	acceptor_loss	1.0000
3:122911044:CC:C	acceptor_gain	1.0000
3:122911044:CCCT:C	acceptor_loss	1.0000
3:122911045:CC:C	acceptor_gain	1.0000
3:122911045:CCTAG:C	acceptor_loss	1.0000
3:122911046:C:CA	acceptor_loss	1.0000
3:122911046:C:CC	acceptor_gain	1.0000
3:122911047:T:G	acceptor_loss	1.0000
3:122911389:G:C	donor_gain	1.0000
3:122911533:TGA:T	acceptor_gain	1.0000
3:122911534:GA:G	acceptor_gain	1.0000
3:122911536:C:CC	acceptor_gain	1.0000
3:122911916:CTA:C	donor_loss	1.0000
3:122911917:TA:T	donor_loss	1.0000
3:122911918:A:AC	donor_gain	1.0000
3:122911918:ACCG:A	donor_loss	1.0000
3:122911919:C:CT	donor_gain	1.0000
3:122912065:GCCTT:G	acceptor_gain	1.0000
3:122912066:CCTTC:C	acceptor_gain	1.0000

AlphaMissense

7483 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:122912311:C:A	W919C	1.000
3:122912311:C:G	W919C	1.000
3:122912320:C:A	W916C	1.000
3:122912320:C:G	W916C	1.000
3:122912329:C:A	W913C	1.000
3:122912329:C:G	W913C	1.000
3:122913359:C:A	W782C	1.000
3:122913359:C:G	W782C	1.000
3:122913971:C:A	W673C	1.000
3:122913971:C:G	W673C	1.000
3:122913980:C:A	W670C	1.000
3:122913980:C:G	W670C	1.000
3:122923650:C:A	W413C	1.000
3:122923650:C:G	W413C	1.000
3:122923652:A:G	W413R	1.000
3:122923652:A:T	W413R	1.000
3:122926520:C:A	W336C	1.000
3:122926520:C:G	W336C	1.000
3:122926522:A:G	W336R	1.000
3:122926522:A:T	W336R	1.000
3:122926549:C:A	G327W	1.000
3:122926555:C:G	D325H	1.000
3:122926562:G:C	C322W	1.000
3:122926563:C:G	C322S	1.000
3:122926563:C:T	C322Y	1.000
3:122926564:A:G	C322R	1.000
3:122926564:A:T	C322S	1.000
3:122926569:C:G	R320P	1.000
3:122927795:A:G	L282P	1.000
3:122927797:C:A	W281C	1.000

dbSNP variants (sampled 300 via entrez): RS1000027337 (3:123026299 C>A), RS1000035081 (3:122966533 A>T), RS1000057489 (3:123027670 G>A), RS1000061661 (3:122989265 TC>T), RS1000087380 (3:122947297 C>T), RS1000104059 (3:122929406 C>T), RS1000108285 (3:122966608 G>A), RS1000119754 (3:122984981 A>C,G), RS1000122320 (3:122921563 T>A), RS1000125174 (3:122953308 A>G), RS1000143120 (3:123000903 A>C,G), RS1000165988 (3:122950579 A>C), RS1000175474 (3:122985283 A>G), RS1000204385 (3:122993176 C>G,T), RS1000228917 (3:122983301 C>T)

Disease associations

OMIM: gene MIM:609298 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001089_5	Esophageal cancer	1.000000e-07
GCST005988_1	Serum albumin levels	4.000000e-08
GCST009197_1	Cortex volume	1.000000e-06
GCST009263_4	Total grey matter volume	9.000000e-07
GCST90006992_5	Gut microbiota relative abundance (unclassified genus belonging to family Clostridiaceae)	3.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005420	grey matter volume measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Arsenic	decreases methylation, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	increases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
aristolochic acid I	decreases expression	1
methyleugenol	decreases expression	1
sodium arsenate	increases abundance, increases expression	1
O,O-diethyl O-3,5,6-trichloro-2-pyridyl phosphate	affects response to substance, affects expression	1
sodium arsenite	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	increases reaction, affects binding	1
entinostat	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
dorsomorphin	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	decreases expression	1
Atrazine	increases expression	1
Carbamazepine	affects expression	1
Cytarabine	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Silicon Dioxide	decreases expression	1

Clinical trials (associated diseases)

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