SEMA3C

protein-coding

semaphorin 3C, the group of I-set domain containing|Semaphorins

Gene summary

This gene encodes a secreted glycoprotein that belongs to the semaphorin class 3 family of neuronal guidance cues. The encoded protein contains an N-terminal sema domain, integrin and immunoglobulin-like domains, and a C-terminal basic domain. Homodimerization and proteolytic cleavage of the C-terminal propeptide are necessary for the function of the encoded protein. It binds a neuropilin co-receptor before forming a heterotrimeric complex with an associated plexin. An increase in the expression of this gene correlates with an increase in cancer cell invasion and adhesion. Naturally occurring mutations in this gene are associated with Hirschsprung disease. [provided by RefSeq, May 2017]

Previous symbols:

SEMAE

MANE transcript

NM_006379.5

Inheritance

—

ClinVar variants

U:224B:82

Top phenotype

SEMA3C-related disorder

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr7:80,742,538-80,922,359

External References & Databases

Ensembl (ENSG00000075223)

Transcript & Mutation Effects

hg38 • Region Span ~179.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SEMA3C variants in ClinVar

5 Conditions Cataloged

SEMA3C-related disorderTotal: 296

not specifiedTotal: 86

not providedTotal: 25

High myopiaTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_006379.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	70 clinvar	2 clinvar	73
missense			209 clinvar	7 clinvar	3 clinvar	219
nonsense			7 clinvar			7
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	224	77	5	306

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 45 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_006379.5	RefSeq	NP_006370.1	17	MANE Select
ENST00000265361.8	Ensembl	ENSP00000265361.3	17	MANE Select
NM_001350120.2	RefSeq	NP_001337049.1	18	Standard
NM_001350121.2	RefSeq	NP_001337050.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
sema3c	Danio rerio	Structure: enteric neuron Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

sema3c

Danio rerio

Structure: enteric neuron

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Plexin-D1 Signaling

Biological Process

neural crest cell migration
somitogenesis
blood vessel remodeling
outflow tract septum morphogenesis
cardiac right ventricle morphogenesis

Molecular Function

semaphorin receptor binding
neuropilin binding
chemorepellent activity

Cellular Component

extracellular space
integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265361
Coding exons: 17
Length: 179822
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.994	362	419	0.863	0.0000227	4945
Missense (PolyPhen)		148	206.94	0.71518		2347
Synonymous	0.647	138	148	0.932	0.00000792	1409
Loss of Function	3.96	13	40.0	0.325	0.00000223	477

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000088	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to plexin family members and plays an important role in the regulation of developmental processes. Required for normal cardiovascular development during embryogenesis. Functions as attractant for growing axons, and thereby plays an important role in axon growth and axon guidance (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.188

Intolerance Scores

LoFtool: 0.653
RVIS EVS: -0.62
RVIS percentile EVS: 17.4

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.507

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium