SEMA6C

Summary

SEMA6C (semaphorin 6C, HGNC:10740) is a protein-coding gene on chromosome 1q21.3, encoding Semaphorin-6C (Q9H3T2). Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro.

This gene encodes a member of the semaphorin family. Semaphorins represent important molecular signals controlling multiple aspects of the cellular response that follows CNS injury, and thus may play an important role in neural regeneration.

Source: NCBI Gene 10500 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_030913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10740
Approved symbol	SEMA6C
Name	semaphorin 6C
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1869, Sema-Y
Ensembl gene	ENSG00000143434
Ensembl biotype	protein_coding
OMIM	609294
Entrez	10500

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 32 protein_coding, 4 protein_coding_CDS_not_defined

ENST00000341697, ENST00000368912, ENST00000368913, ENST00000368914, ENST00000464018, ENST00000479820, ENST00000485745, ENST00000489944, ENST00000866869, ENST00000866870, ENST00000866871, ENST00000866872, ENST00000866873, ENST00000866874, ENST00000866875, ENST00000866876, ENST00000866877, ENST00000866878, ENST00000866879, ENST00000866880, ENST00000866881, ENST00000866882, ENST00000866883, ENST00000866884, ENST00000866885, ENST00000866886, ENST00000866887, ENST00000866888, ENST00000927933, ENST00000927934, ENST00000927935, ENST00000927936, ENST00000967242, ENST00000967243, ENST00000967244, ENST00000967245

RefSeq mRNA: 3 — MANE Select: NM_030913 NM_001178061, NM_001178062, NM_030913

CCDS: CCDS53363, CCDS53364, CCDS984

Canonical transcript exons

ENST00000368914 — 19 exons

Exon	Start	End
ENSE00000960008	151138316	151138406
ENSE00000960009	151137986	151138105
ENSE00000960010	151137711	151137799
ENSE00000960011	151136857	151137074
ENSE00000960012	151136448	151136579
ENSE00000960013	151136011	151136163
ENSE00000960014	151135591	151135764
ENSE00001044830	151139976	151140090
ENSE00001044836	151139425	151139481
ENSE00001044838	151135163	151135309
ENSE00001044850	151134401	151134445
ENSE00001044852	151139638	151139701
ENSE00001384481	151144385	151144434
ENSE00001402481	151131707	151133517
ENSE00001435855	151146433	151146631
ENSE00001448277	151142504	151142675
ENSE00003512606	151138630	151138731
ENSE00003636166	151134620	151134675
ENSE00003636361	151134798	151134875

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 98.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7335 / max 278.6237, expressed in 1271 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14404	5.4034	1108
14406	1.1325	543
14405	0.1976	78

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	98.02	gold quality
apex of heart	UBERON:0002098	96.81	gold quality
gastrocnemius	UBERON:0001388	96.49	gold quality
type B pancreatic cell	CL:0000169	95.56	gold quality
muscle of leg	UBERON:0001383	95.46	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.95	gold quality
cerebellar hemisphere	UBERON:0002245	94.82	gold quality
cerebellar cortex	UBERON:0002129	94.74	gold quality
right testis	UBERON:0004534	94.34	gold quality
olfactory bulb	UBERON:0002264	94.18	gold quality
ganglionic eminence	UBERON:0004023	94.05	gold quality
left testis	UBERON:0004533	93.91	gold quality
muscle organ	UBERON:0001630	93.73	gold quality
cortical plate	UBERON:0005343	93.03	gold quality
cerebellum	UBERON:0002037	93.02	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	92.17	gold quality
triceps brachii	UBERON:0001509	91.97	gold quality
heart left ventricle	UBERON:0002084	91.95	gold quality
cardiac ventricle	UBERON:0002082	91.68	gold quality
sural nerve	UBERON:0015488	91.17	gold quality
testis	UBERON:0000473	90.96	gold quality
parotid gland	UBERON:0001831	90.79	gold quality
right atrium auricular region	UBERON:0006631	90.74	gold quality
skeletal muscle tissue	UBERON:0001134	90.15	gold quality
cardiac atrium	UBERON:0002081	89.79	gold quality
gluteal muscle	UBERON:0002000	89.62	gold quality
vastus lateralis	UBERON:0001379	88.80	gold quality
heart	UBERON:0000948	88.73	gold quality
tibial nerve	UBERON:0001323	88.67	gold quality
tongue squamous epithelium	UBERON:0006919	88.42	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.42

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

25 targeting SEMA6C, 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-6798-5P	100.00	65.77	699
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4465	99.71	72.56	2096
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-3153	99.55	67.59	2337
HSA-MIR-4762-3P	99.43	69.72	2363
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3131	95.33	65.74	102
HSA-MIR-11400	94.03	67.12	81
HSA-MIR-611	93.79	64.24	81
HSA-MIR-744-5P	93.78	65.29	230

Literature-anchored findings (GeneRIF, showing 1)

• identification, characterization, and functional study of the two novel human members of the semaphorin gene family (PMID:12110693)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	sema6cb	ENSDARG00000000189
danio_rerio	sema6ca	ENSDARG00000002748
mus_musculus	Sema6c	ENSMUSG00000038777
rattus_norvegicus	Sema6c	ENSRNOG00000021101

Paralogs (19): SEMA3F (ENSG00000001617), SEMA3G (ENSG00000010319), SEMA3B (ENSG00000012171), SEMA3A (ENSG00000075213), SEMA3C (ENSG00000075223), SEMA5B (ENSG00000082684), SEMA6A (ENSG00000092421), SEMA4G (ENSG00000095539), SEMA5A (ENSG00000112902), SEMA4F (ENSG00000135622), SEMA6D (ENSG00000137872), SEMA7A (ENSG00000138623), SEMA3D (ENSG00000153993), SEMA6B (ENSG00000167680), SEMA4C (ENSG00000168758), SEMA3E (ENSG00000170381), SEMA4B (ENSG00000185033), SEMA4D (ENSG00000187764), SEMA4A (ENSG00000196189)

Protein

Protein identifiers

Semaphorin-6C — Q9H3T2 (reviewed: Q9H3T2)

Alternative names: Semaphorin-Y

All UniProt accessions (1): Q9H3T2

UniProt curated annotations — full annotation on UniProt →

Function. Shows growth cone collapsing activity on dorsal root ganglion (DRG) neurons in vitro. May be a stop signal for the DRG neurons in their target areas, and possibly also for other neurons. May also be involved in the maintenance and remodeling of neuronal connections.

Subcellular location. Cell membrane.

Tissue specificity. In adult tissues, expressed only in skeletal muscle.

Similarity. Belongs to the semaphorin family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9H3T2-1	1, Short 1	yes
Q9H3T2-2	2, Short 2
Q9H3T2-3	3, Long

RefSeq proteins (3): NP_001171532, NP_001171533, NP_112175* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001627	Semap_dom	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR027231	Semaphorin	Family
IPR036352	Semap_dom_sf	Homologous_superfamily

Pfam: PF01403

UniProt features (28 total): disulfide bond 8, region of interest 5, glycosylation site 3, topological domain 2, splice variant 2, sequence conflict 2, signal peptide 1, chain 1, compositionally biased region 1, sequence variant 1, transmembrane region 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3T2-F1	72.13	0.48

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 (8): 111–121, 139–148, 262–373, 287–332, 479–510, 519–537, 525–570, 529–545

Glycosylation sites (3): 70, 286, 437

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 185 (showing top): MODULE_52, 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, MODULE_45, GOBP_GROWTH, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT, MODULE_16, CHX10_01, GGGTGGRR_PAX4_03, GOBP_NEGATIVE_REGULATION_OF_NERVOUS_SYSTEM_DEVELOPMENT

GO Biological Process (8): neural crest cell migration (GO:0001755), axon guidance (GO:0007411), positive regulation of cell migration (GO:0030335), negative regulation of axon extension (GO:0030517), semaphorin-plexin signaling pathway (GO:0071526), nervous system development (GO:0007399), cell differentiation (GO:0030154), negative chemotaxis (GO:0050919)

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

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
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
cell surface receptor signaling pathway	1
system development	1
cellular developmental process	1
chemotaxis	1
signaling receptor binding	1
receptor ligand activity	1
negative chemotaxis	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEMA6C	PLXNA1	Q9UIW2	918
SEMA6C	PLXNA2	O75051	762
SEMA6C	PLXNA4	Q9HCM2	723
SEMA6C	PLXNA3	P51805	706
SEMA6C	PLXND1	Q9Y4D7	682
SEMA6C	PLXNC1	O60486	622
SEMA6C	NGF	P01138	492
SEMA6C	PRICKLE3	O43900	390
SEMA6C	PRICKLE2	Q7Z3G6	383
SEMA6C	CELSR2	Q9HCU4	379
SEMA6C	EFNB1	P98172	365
SEMA6C	BCL11B	Q9C0K0	365
SEMA6C	NUDT5	Q9UKK9	365
SEMA6C	CD19	P15391	353
SEMA6C	SLIT3	O75094	353

IntAct

2 interactions, top by confidence:

A	B	Type	Score
SEMA6C	HSPA5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): SEMA6C (Two-hybrid), SEMA6C (Affinity Capture-RNA), HSPA5 (Affinity Capture-MS), SEMA6C (Affinity Capture-RNA), SEMA6C (Protein-peptide)

ESM2 similar proteins: A0A5F4BST2, A0PJX4, A0RZB4, A1L515, A2A9Q0, A2BDG0, A6QQ85, A6XN32, A9JSM3, B0FP48, D3YZZ2, D4A2Q0, E5RIL1, F1SAM7, P01183, Q1RMK9, Q3UPR0, Q3ZCQ3, Q5BIV7, Q5BIV9, Q5BK01, Q5GH56, Q5GH64, Q5GH72, Q5SNT2, Q5T7M4, Q6IEE6, Q6PRD1, Q6UWJ8, Q70RD5, Q864V4, Q86UD0, Q8BWU1, Q8BX43, Q8CCB5, Q8IVY1, Q8K064, Q8K2Y3, Q8K5A9, Q8N9H8

Diamond homologs: A7MB70, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, G1FC92, O08665, O08721, O08722, O08747, O09126, O14514, O15041, O35464, O42236, O42237, O54951, O60242, O70141, O88632, O95025, O95185, O95754, P11680, P27918, P35441, P58397, P70275, Q13214, Q13275, Q13591, Q14563, Q17330, Q24322, Q24323, Q26261, Q26473

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

5906 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151137002:A:G	W277R	1.000
1:151137002:A:T	W277R	1.000
1:151136085:G:C	F395L	0.999
1:151136085:G:T	F395L	0.999
1:151136087:A:G	F395L	0.999
1:151136483:C:A	W357C	0.999
1:151136483:C:G	W357C	0.999
1:151136485:A:G	W357R	0.999
1:151136485:A:T	W357R	0.999
1:151136985:C:A	K282N	0.999
1:151136985:C:G	K282N	0.999
1:151136995:G:A	S279F	0.999
1:151137000:C:A	W277C	0.999
1:151137000:C:G	W277C	0.999
1:151137046:C:G	C262S	0.999
1:151137047:A:T	C262S	0.999
1:151137061:C:G	R257P	0.999
1:151137790:A:C	F226C	0.999
1:151137790:A:G	F226S	0.999
1:151138051:A:T	V201D	0.999
1:151138072:A:C	F194C	0.999
1:151138094:A:C	Y187D	0.999
1:151138351:A:C	F171C	0.999
1:151138358:A:G	C169R	0.999
1:151138643:C:G	C148S	0.999
1:151138644:A:G	C148R	0.999
1:151138644:A:T	C148S	0.999
1:151138670:C:T	C139Y	0.999
1:151138723:G:C	C121W	0.999
1:151138724:C:G	C121S	0.999

dbSNP variants (sampled 300 via entrez): RS1000098727 (1:151144463 G>A), RS1000135057 (1:151137940 T>C), RS1000369229 (1:151133279 C>G), RS1000400519 (1:151138198 C>A), RS1000514621 (1:151133766 T>G), RS1000654044 (1:151145257 C>G), RS1000885242 (1:151144644 G>A), RS1000906914 (1:151145584 G>A), RS1001004104 (1:151139911 T>C,G), RS1001099120 (1:151145929 G>A,C,T), RS1001180255 (1:151131786 G>A,C), RS1001209597 (1:151131532 GA>G), RS1001477370 (1:151133963 G>A,C,T), RS1001539867 (1:151139612 GC>G), RS1001780882 (1:151145679 C>G)

Disease associations

OMIM: gene MIM:609294 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002783_114	Body mass index	5.000000e-06
GCST002783_130	Body mass index	2.000000e-06
GCST002783_311	Body mass index	3.000000e-06
GCST90002394_81	Monocyte percentage of white cells	4.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0007989	monocyte percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	increases methylation	1
(+)-JQ1 compound	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Azacitidine	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Urethane	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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