SEMA4C semaphorin 4C [Homo sapiens (human)] - Gene

Summary

Official Symbol: SEMA4Cprovided by HGNC
Official Full Name: semaphorin 4Cprovided by HGNC
Primary source: HGNC:HGNC:10731
See related: Ensembl:ENSG00000168758 MIM:604462; AllianceGenome:HGNC:10731
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SEMAF; SEMAI; SEMACL1; M-SEMA-F
Summary: Predicted to enable chemorepellent activity; neuropilin binding activity; and semaphorin receptor binding activity. Involved in muscle cell differentiation and positive regulation of stress-activated MAPK cascade. Located in extracellular space. [provided by Alliance of Genome Resources, Jul 2025]
Expression: Ubiquitous expression in placenta (RPKM 20.2), endometrium (RPKM 13.1) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2q11.2

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (96859718..96870830, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (97366349..97377098, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (97525455..97535817, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer.
Title: Serum semaphorin4C as an auxiliary diagnostic biomarker for breast cancer.
Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C.
Title: Effect of microrna-138 on epithelial-Mesenchymal transition and invasion of breast cancer cells by targeting semaphorin 4C.
High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma.
Title: High SEMA4C expression promotes the epithelial-mesenchymal transition and predicts poor prognosis in colorectal carcinoma.
SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis.
Title: SEMA4C is a novel target to limit osteosarcoma growth, progression, and metastasis.
Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells.
Title: Sema4C mediates EMT inducing chemotherapeutic resistance of miR-31-3p in cervical cancer cells.
Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-beta1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation.
Title: Downregulation of SEMA4C Inhibit Epithelial-Mesenchymal Transition (EMT) and the Invasion and Metastasis of Cervical Cancer Cells via Inhibiting Transforming Growth Factor-beta 1 (TGF-β1)-Induced Hela cells p38 Mitogen-Activated Protein Kinase (MAPK) Activation.
SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis.
Title: Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer.
Sema4D and 4C can contribute to tumor progression in human patients or experimental models, while the role of Sema4A has not yet been fully understood
Title: Semaphorin 4A, 4C, and 4D: Function comparison in the autoimmunity, allergy, and cancer.
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
Title: Sema4C/PlexinB2 signaling controls breast cancer cell growth, hormonal dependence and tumorigenic potential.
Tumor-associated LECs produce sSEMA4C to promote lymphatic metastasis of tumors.
Title: Tumor-associated Lymphatic Endothelial Cells Promote Lymphatic Metastasis By Highly Expressing and Secreting SEMA4C.

Submit: New GeneRIF Correction See all GeneRIFs (15)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

D2S2834 (e-PCR)
- UniSTS:16704

D1S1425 (e-PCR)
- UniSTS:149621

RH36905 (e-PCR)
- UniSTS:87932

D11S3114 (e-PCR)
- UniSTS:152207

SEMA4C_2477 (e-PCR)
- UniSTS:280989

SEMA4C (e-PCR)
- UniSTS:505018

Clone Names

FLJ20369, KIAA1739, MGC126382, MGC126383

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables chemorepellent activity	IBA Inferred from Biological aspect of Ancestor more info
enables neuropilin binding	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables semaphorin receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables semaphorin receptor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in axon guidance	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell migration in hindbrain	IEA Inferred from Electronic Annotation more info
involved_in cell migration in hindbrain	ISS Inferred from Sequence or Structural Similarity more info
involved_in cerebellum development	IEA Inferred from Electronic Annotation more info
involved_in muscle cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in negative chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in nervous system development	IEA Inferred from Electronic Annotation more info
involved_in neural crest cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in neural tube closure	IEA Inferred from Electronic Annotation more info
involved_in neural tube closure	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell migration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of stress-activated MAPK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of postsynapse assembly	IEA Inferred from Electronic Annotation more info
involved_in semaphorin-plexin signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in semaphorin-plexin signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in semaphorin-plexin signaling pathway	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cytoplasmic vesicle	IEA Inferred from Electronic Annotation more info
located_in extracellular space	HDA more info	PubMed
is_active_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
is_active_in synaptic vesicle membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in synaptic vesicle membrane	IEA Inferred from Electronic Annotation more info
located_in synaptic vesicle membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: semaphorin-4C

Names: M-Sema F; sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4C

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_017789.5 → NP_060259.4 semaphorin-4C precursor

See identical proteins and their annotated locations for NP_060259.4

Status: VALIDATED

Source sequence(s)

AC092636, BC017476, BC109104, BI518922

Consensus CDS

CCDS2029.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000306844.5, ENST00000305476.10

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

96859718..96870830 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047444831.1 → XP_047300787.1 semaphorin-4C isoform X1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567338.1, ENST00000897279.1
XM_011511380.2 → XP_011509682.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509682.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000584364.1, ENST00000914305.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_011511381.2 → XP_011509683.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509683.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567340.1, ENST00000897281.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_011511379.3 → XP_011509681.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509681.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567342.1, ENST00000897283.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_011511378.3 → XP_011509680.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509680.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567343.1, ENST00000897284.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_011511382.4 → XP_011509684.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509684.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567354.1, ENST00000897295.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_011511383.2 → XP_011509685.1 semaphorin-4C isoform X1

See identical proteins and their annotated locations for XP_011509685.1

UniProtKB/Swiss-Prot

Q32MJ3, Q7Z5X0, Q9C0C4

Related

ENSP00000567356.1, ENST00000897297.1

Conserved Domains (3) summary

cd11258
Location:42 → 498

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)

smart00423
Location:499 → 528

PSI; domain found in Plexins, Semaphorins and Integrins

cl11960
Location:560 → 647

Ig; Immunoglobulin domain
XM_017004393.3 → XP_016859882.1 semaphorin-4C isoform X2

Related

ENSP00000567355.1, ENST00000897296.1
XM_017004394.3 → XP_016859883.1 semaphorin-4C isoform X3

Related

ENST00000482925.5
XM_047444832.1 → XP_047300788.1 semaphorin-4C isoform X4
XM_047444834.1 → XP_047300790.1 semaphorin-4C isoform X4
XM_006712606.4 → XP_006712669.2 semaphorin-4C isoform X4

Conserved Domains (1) summary

cd11258
Location:42 → 480

Sema_4C; The Sema domain, a protein interacting module, of semaphorin 4C (Sema4C)