SEMA3G

Summary

SEMA3G (semaphorin 3G, HGNC:30400) is a protein-coding gene on chromosome 3p21.1, encoding Semaphorin-3G (Q9NS98). Has chemorepulsive activities for sympathetic axons.

The transcription of this gene is activated by PPAR-gamma, and the resulting protein product plays a role in endothelial cell migration. Expression of this gene also inhibits tumor cell migration and invasion.

Source: NCBI Gene 56920 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 394 total
• MANE Select transcript: NM_020163

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30400
Approved symbol	SEMA3G
Name	semaphorin 3G
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ00014, sem2
Ensembl gene	ENSG00000010319
Ensembl biotype	protein_coding
OMIM	620997
Entrez	56920

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000231721, ENST00000465657, ENST00000475739, ENST00000949100

RefSeq mRNA: 1 — MANE Select: NM_020163 NM_020163

CCDS: CCDS2856

Canonical transcript exons

ENST00000231721 — 16 exons

Exon	Start	End
ENSE00000421191	52439867	52440098
ENSE00000421192	52439680	52439771
ENSE00000421193	52437971	52438199
ENSE00000421194	52437527	52437666
ENSE00000770774	52433035	52436073
ENSE00000770788	52438920	52438961
ENSE00000770801	52440377	52440521
ENSE00000770824	52442559	52442621
ENSE00000770825	52442747	52442907
ENSE00000770827	52444913	52445103
ENSE00003505312	52440934	52441048
ENSE00003536670	52441574	52441690
ENSE00003590119	52441819	52441909
ENSE00003609782	52441264	52441409
ENSE00003651412	52442185	52442304
ENSE00003656317	52440754	52440823

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.68.

FANTOM5 (CAGE): breadth broad, TPM avg 3.6919 / max 191.3010, expressed in 524 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
42424	3.6919	524

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
renal glomerulus	UBERON:0000074	96.68	gold quality
metanephric glomerulus	UBERON:0004736	96.40	gold quality
parotid gland	UBERON:0001831	96.36	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.13	gold quality
adipose tissue	UBERON:0001013	94.86	gold quality
connective tissue	UBERON:0002384	93.60	gold quality
tendon of biceps brachii	UBERON:0008188	93.47	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.92	gold quality
omental fat pad	UBERON:0010414	92.64	gold quality
peritoneum	UBERON:0002358	92.59	gold quality
pericardium	UBERON:0002407	91.74	gold quality
right lung	UBERON:0002167	91.47	gold quality
cardia of stomach	UBERON:0001162	90.13	gold quality
vena cava	UBERON:0004087	90.02	gold quality
renal medulla	UBERON:0000362	89.99	gold quality
mammary gland	UBERON:0001911	89.61	gold quality
thoracic mammary gland	UBERON:0005200	89.59	gold quality
mammary duct	UBERON:0001765	89.23	gold quality
diaphragm	UBERON:0001103	88.96	gold quality
dorsal root ganglion	UBERON:0000044	88.57	gold quality
apex of heart	UBERON:0002098	88.49	gold quality
epithelium of mammary gland	UBERON:0003244	88.09	gold quality
left ventricle myocardium	UBERON:0006566	88.08	gold quality
synovial joint	UBERON:0002217	88.02	gold quality
metanephros	UBERON:0000081	87.53	gold quality
triceps brachii	UBERON:0001509	87.18	gold quality
olfactory bulb	UBERON:0002264	87.04	gold quality
kidney epithelium	UBERON:0004819	86.68	gold quality
cortex of kidney	UBERON:0001225	86.36	gold quality
layer of synovial tissue	UBERON:0007616	86.11	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	669.87
E-ANND-3	yes	9.76
E-MTAB-10137	yes	5.36
E-MTAB-6678	no	2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

79 targeting SEMA3G, 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-6851-5P	100.00	65.63	1294
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-4719	99.73	72.10	3329
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459

Literature-anchored findings (GeneRIF, showing 10)

• In gliomas, SEMA3B, SEMA3G and NRP2 expressions were related to prolonged survival (PMID:18781179)
• Sema3G inhibits tumor progression from MDA-MB-435 but not from MDA-MB-231 cancer cells. It inhibits tumor angiogenesis in MDA-MB-231 cells. (PMID:18818766)
• Identify Sema3G as a primarily endothelial cell-expressed class 3 semaphorin that controls endothelial and smooth muscle cell functions in autocrine and paracrine manners. (PMID:20947821)
• overexpressed SEMA3G inhibited the migratory and invasive behavior of U251MG cancer cells (PMID:22562223)
• Results identify Sema3g as one of the downstream effectors of PPAR-gamma, which is centrally involved in regulating endothelial cell migration. (PMID:25335934)
• Results indicate that Sema3G protein is secreted by podocytes and protects them from inflammatory kidney diseases and diabetic nephropathy. (PMID:27180624)
• Identification of a four immune-related genes signature based on an immunogenomic landscape analysis of clear cell renal cell carcinoma. (PMID:32452055)
• Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating beta-catenin-dependent vascular remodeling. (PMID:33586674)
• SEMA3G functions as a novel prognostic biomarker associated with Wnt pathway in clear cell renal cell carcinoma. (PMID:37633476)
• SEMA3G regulates BMP9 inhibition of VEGF-mediated migration and network formation in pulmonary endothelial cells. (PMID:38795838)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema3bl	ENSDARG00000007560
mus_musculus	Sema3g	ENSMUSG00000021904
rattus_norvegicus	Sema3g	ENSRNOG00000018952

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), 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-3G — Q9NS98 (reviewed: Q9NS98)

Alternative names: Semaphorin sem2

All UniProt accessions (3): Q9NS98, C9JXB2, H7C5M7

UniProt curated annotations — full annotation on UniProt →

Function. Has chemorepulsive activities for sympathetic axons. Ligand of NRP2.

Subcellular location. Secreted.

Similarity. Belongs to the semaphorin family.

RefSeq proteins (1): NP_064548* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR007110	Ig-like_dom	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR016201	PSI	Domain
IPR027231	Semaphorin	Family
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF00047, PF01403

UniProt features (15 total): disulfide bond 6, sequence variant 3, domain 2, glycosylation site 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NS98-F1	83.30	0.64

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 (6): 522–540, 603–655, 105–116, 134–143, 270–382, 294–342

Glycosylation sites (2): 44, 127

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_NEGATIVE_REGULATION_OF_AXON_EXTENSION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_GROWTH, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_AMEBOIDAL_TYPE_CELL_MIGRATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_TAXIS

GO Biological Process (7): neural crest cell migration (GO:0001755), axon guidance (GO:0007411), positive regulation of cell migration (GO:0030335), negative regulation of axon extension (GO:0030517), forebrain development (GO:0030900), negative chemotaxis (GO:0050919), semaphorin-plexin signaling pathway (GO:0071526)

GO Molecular Function (5): signaling receptor binding (GO:0005102), semaphorin receptor binding (GO:0030215), neuropilin binding (GO:0038191), chemorepellent activity (GO:0045499), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signaling receptor binding	2
neural crest cell development	1
mesenchymal cell migration	1
axonogenesis	1
neuron projection guidance	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
negative regulation of cell growth	1
regulation of axon extension	1
negative regulation of developmental growth	1
axon extension	1
negative regulation of axonogenesis	1
brain development	1
anatomical structure development	1
chemotaxis	1
cell surface receptor signaling pathway	1
protein binding	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA3G	NRP1	O14786	930
SEMA3G	NRP2	O60462	812
SEMA3G	PLXNA3	P51805	809
SEMA3G	SEM1	Q6ZVN7	669
SEMA3G	PLXNA4	Q9HCM2	601
SEMA3G	PLXND1	Q9Y4D7	595
SEMA3G	PLXNA1	Q9UIW2	590
SEMA3G	EFNB2	P52799	521
SEMA3G	ARHGEF15	O94989	489
SEMA3G	FN1	P02751	469
SEMA3G	SEMG2	Q02383	445
SEMA3G	CRIM1	Q9NZV1	439
SEMA3G	SCARF1	Q14162	437
SEMA3G	TNC	P24821	435
SEMA3G	SEMG1	P04279	432

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DESI2	SEMA3G	psi-mi:“MI:0915”(physical association)	0.560
FCGR2A	SEMA3G	psi-mi:“MI:0915”(physical association)	0.400
GP6	SEMA3G	psi-mi:“MI:0915”(physical association)	0.400
SEMA3G	LILRA3	psi-mi:“MI:0915”(physical association)	0.400
SEMA3G	DESI2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (6): SEMA3G (Reconstituted Complex), DESI2 (Two-hybrid), SEMA3G (Affinity Capture-RNA), SEMA3G (Affinity Capture-MS), SEMA3G (Negative Genetic), SEMA3G (Affinity Capture-MS)

ESM2 similar proteins: A2BD09, B0BNI5, B5MFE9, D3Z7H8, O70624, O75326, O88632, P09531, P42917, P82350, Q0P3W2, Q0V9V5, Q0VCP3, Q13275, Q16586, Q25C36, Q28686, Q29RB4, Q2HJE5, Q2KHV9, Q2PT31, Q3UH93, Q4LFA9, Q594P2, Q64255, Q66H86, Q68BL7, Q6UWY5, Q6ZMI3, Q80WF4, Q80WL1, Q863A3, Q866N2, Q8BH02, Q8BHP7, Q8BK62, Q8BMF8, Q8IUL8, Q8IYS2, Q91X21

Diamond homologs: A7MB70, D3ZTD8, O08665, O09126, O15041, O35464, O42236, O42237, O88632, O95025, O95754, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24322, Q24323, Q26473, Q26972, Q4LFA9, Q5EA85, Q5R7F5, Q5RE75, Q60519, Q62177, Q62178, Q62179, Q62181, Q62217, Q63548, Q64151, Q76KF0, Q8BH34, Q8NFY4, Q90607, Q90663, Q90665, Q92854

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	245
Likely benign	133
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2305 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52437524:CACC:C	donor_loss	1.0000
3:52437525:ACC:A	donor_loss	1.0000
3:52437526:C:CT	donor_loss	1.0000
3:52437662:CTCTT:C	acceptor_gain	1.0000
3:52437664:CTT:C	acceptor_gain	1.0000
3:52437665:TT:T	acceptor_gain	1.0000
3:52437666:TCTGG:T	acceptor_loss	1.0000
3:52437667:C:CC	acceptor_gain	1.0000
3:52437966:CTCA:C	donor_loss	1.0000
3:52437968:CA:C	donor_loss	1.0000
3:52437969:A:AC	donor_gain	1.0000
3:52437969:AC:A	donor_gain	1.0000
3:52437969:ACCTT:A	donor_gain	1.0000
3:52437970:C:CC	donor_gain	1.0000
3:52437970:CC:C	donor_gain	1.0000
3:52437970:CCTT:C	donor_gain	1.0000
3:52437970:CCTTC:C	donor_gain	1.0000
3:52437973:T:TA	donor_gain	1.0000
3:52438195:ATTTG:A	acceptor_gain	1.0000
3:52438196:TTTG:T	acceptor_gain	1.0000
3:52438197:TTG:T	acceptor_gain	1.0000
3:52438198:TG:T	acceptor_gain	1.0000
3:52438199:GC:G	acceptor_loss	1.0000
3:52438200:C:CC	acceptor_gain	1.0000
3:52438200:C:T	acceptor_loss	1.0000
3:52438201:T:A	acceptor_loss	1.0000
3:52438914:TCTTA:T	donor_loss	1.0000
3:52438915:CTTA:C	donor_loss	1.0000
3:52438916:TTAC:T	donor_loss	1.0000
3:52438917:TACC:T	donor_loss	1.0000

AlphaMissense

5036 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52438083:C:A	W542C	0.998
3:52438083:C:G	W542C	0.998
3:52435987:G:C	C655W	0.997
3:52435995:A:C	Y653D	0.997
3:52441012:A:G	W284R	0.997
3:52441012:A:T	W284R	0.997
3:52435988:C:G	C655S	0.995
3:52435988:C:T	C655Y	0.995
3:52435989:A:T	C655S	0.995
3:52437563:C:A	W614C	0.995
3:52437563:C:G	W614C	0.995
3:52437597:C:G	C603S	0.995
3:52437598:A:T	C603S	0.995
3:52438090:C:G	C540S	0.995
3:52438091:A:T	C540S	0.995
3:52437565:A:G	W614R	0.994
3:52437565:A:T	W614R	0.994
3:52437598:A:G	C603R	0.994
3:52441007:G:C	S285R	0.994
3:52441007:G:T	S285R	0.994
3:52441009:T:G	S285R	0.994
3:52441400:A:C	F226C	0.994
3:52438089:A:C	C540W	0.993
3:52438090:C:T	C540Y	0.993
3:52439752:T:A	K465N	0.993
3:52439752:T:G	K465N	0.993
3:52440494:A:C	C342W	0.993
3:52441010:C:A	W284C	0.993
3:52441010:C:G	W284C	0.993
3:52435989:A:G	C655R	0.992

dbSNP variants (sampled 300 via entrez): RS1000261205 (3:52434626 C>A,T), RS1000329877 (3:52446654 T>C), RS1000421456 (3:52435404 G>A,C), RS1000628660 (3:52440655 G>A,C), RS1001184700 (3:52446579 A>G), RS1001577298 (3:52434650 C>A,T), RS1001693268 (3:52434202 T>C), RS1001778038 (3:52440578 C>A,G,T), RS1001893668 (3:52436549 C>T), RS1001977183 (3:52445756 G>T), RS1002608598 (3:52443391 G>A), RS1002644840 (3:52443087 G>A,T), RS1003252821 (3:52433085 C>T), RS1003467824 (3:52438973 G>A), RS1003646696 (3:52444338 T>C)

Disease associations

OMIM: gene MIM:620997 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001241_15	Bipolar disorder	2.000000e-06
GCST002149_14	Schizophrenia	1.000000e-08
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_201	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST006585_249	Blood protein levels	2.000000e-14
GCST90020029_1192	Waist circumference adjusted for body mass index	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
Benzo(a)pyrene	increases expression, increases methylation	3
bisphenol S	decreases expression, increases expression, affects cotreatment	2
Dexamethasone	increases expression, affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
dicrotophos	increases expression	1
bisphenol A	decreases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
dimethylselenide	increases expression, increases oxidation	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, 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
nutlin 3	affects cotreatment, increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
2,6-dichloro-(1,4)benzoquinone	decreases expression	1
Arsenic Trioxide	decreases expression	1
Leflunomide	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Hexachlorocyclohexane	decreases expression	1
Carbamazepine	affects expression	1
Dactinomycin	affects cotreatment, increases expression	1
Diazinon	decreases methylation	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, decreases expression, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_ZD03	Mel 04.01	Cancer cell line	Male

Clinical trials (associated diseases)

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