UNC5C

protein-coding

unc-5 netrin receptor C, the group of I-set domain containing

Gene summary

This gene product belongs to the UNC-5 family of netrin receptors. Netrins are secreted proteins that direct axon extension and cell migration during neural development. They are bifunctional proteins that act as attractants for some cell types and as repellents for others, and these opposite actions are thought to be mediated by two classes of receptors. The UNC-5 family of receptors mediate the repellent response to netrin; they are transmembrane proteins containing 2 immunoglobulin (Ig)-like domains and 2 type I thrombospondin motifs in the extracellular region. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003728.4

Inheritance

—

ClinVar variants

U:124B:20

Top phenotype

UNC5C-related disorder

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr4:95,162,504-95,549,206

External References & Databases

Ensembl (ENSG00000182168)

Transcript & Mutation Effects

hg38 • Region Span ~386.7 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 UNC5C variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 118

UNC5C-related disorderTotal: 18

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003728.4. 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				10 clinvar	2 clinvar	12
missense			121 clinvar	3 clinvar	5 clinvar	129
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	124	13	7	144

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003728.4	RefSeq	NP_003719.3	16	MANE Select
ENST00000453304.6	Ensembl	ENSP00000406022.1	16	MANE Select
ENST00000504962.1	Ensembl	ENSP00000425117.1	6	Standard
ENST00000504962.2	Ensembl	ENSP00000425117.1	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Axon guidance - Homo sapiens (human)
Developmental Biology
Netrin mediated repulsion signals
Netrin-1 signaling
Axon guidance

Biological Process

apoptotic process
axon guidance
brain development
regulation of cell migration
anterior/posterior axon guidance

Molecular Function

netrin receptor activity

Cellular Component

plasma membrane
integral component of membrane
cell junction
neuron projection
synapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000453304
Coding exons: 16
Length: 386703
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.983	471	535	0.880	0.0000296	6046
Missense (PolyPhen)		153	210.46	0.72698		2374
Synonymous	-2.26	257	215	1.20	0.0000128	1871
Loss of Function	4.23	14	44.5	0.315	0.00000223	505

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00028	0.00027	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000066	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding. Axon repulsion in growth cones may be caused by its association with DCC that may trigger signaling for repulsion. Also involved in corticospinal tract axon guidances independently of DCC. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. {ECO:0000250|UniProtKB:O08747}.;

Recessive Scores

pRec: 0.136

Intolerance Scores

LoFtool: 0.482
RVIS EVS: -0.44
RVIS percentile EVS: 24.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.281

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High