PLXNC1

protein-coding

plexin C1, the group of CD molecules|Plexins|IPT domain containing

Gene summary

This gene encodes a member of the plexin family. Plexins are transmembrane receptors for semaphorins, a large family of proteins that regulate axon guidance, cell motility and migration, and the immune response. The encoded protein and its ligand regulate melanocyte adhesion, and viral semaphorins may modulate the immune response by binding to this receptor. The encoded protein may be a tumor suppressor protein for melanoma. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jan 2011]

MANE transcript

NM_005761.3

Inheritance

ClinVar variants

U:158B:20

Top phenotype

Anophthalmia-microphthalmia syndrome

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr12:94,148,577-94,307,675

External References & Databases

Ensembl (ENSG00000136040)

Transcript & Mutation Effects

hg38 • Region Span ~159.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral cortical dysplasiaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0017094

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLXNC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 151

not providedTotal: 19

Anophthalmia-microphthalmia syndromeTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005761.3. 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			4 clinvar	5 clinvar	1 clinvar	10
missense			145 clinvar	12 clinvar	2 clinvar	159
nonsense			3 clinvar			3
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	158	17	3	178

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005761.3	RefSeq	NP_005752.1	31	MANE Select
ENST00000258526.9	Ensembl	ENSP00000258526.4	31	MANE Select
ENST00000545312.1	Ensembl	ENSP00000439225.1	9	Standard
ENST00000545312.2	Ensembl	ENSP00000439225.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
Other semaphorin interactions
Semaphorin interactions
Axon guidance

Biological Process

cell adhesion
negative regulation of cell adhesion
regulation of cell shape
regulation of cell migration
regulation of GTPase activity

Molecular Function

signaling receptor binding
protein binding
semaphorin receptor activity

Cellular Component

semaphorin receptor complex
plasma membrane
integral component of plasma membrane
membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000258526
Coding exons: 31
Length: 158953
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.98	505	828	0.610	0.0000434	10198
Missense (PolyPhen)		134	310.62	0.43139		4049
Synonymous	0.176	331	335	0.988	0.0000191	3002
Loss of Function	6.67	13	75.6	0.172	0.00000352	952

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8 (By similarity). {ECO:0000250, ECO:0000269|PubMed:20727575}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.304
RVIS EVS: -0.33
RVIS percentile EVS: 30.92

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.247

Gene Damage Prediction

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