UNC5CL

protein-coding

unc-5 family C-terminal like

Gene summary

Enables peptidase activity. Acts upstream of or within positive regulation of JNK cascade and positive regulation of canonical NF-kappaB signal transduction. Located in cytosol and membrane. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_173561.3

Inheritance

—

ClinVar variants

U:86B:4

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr6:41,026,895-41,039,221

External References & Databases

Ensembl (ENSG00000124602)

Transcript & Mutation Effects

hg38 • Region Span ~12.3 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 UNC5CL variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 86

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_173561.3. 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			1 clinvar			1
missense			83 clinvar	4 clinvar		87
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	86	4	0	90

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_173561.3	RefSeq	NP_775832.2	8	MANE Select
ENST00000244565.8	Ensembl	ENSP00000244565.3	8	MANE Select
ENST00000373164.1	Ensembl	ENSP00000362258.1	8	Standard
ENST00000373164.2	Ensembl	ENSP00000362258.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

TNFalpha

Biological Process

proteolysis
netrin-activated signaling pathway
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of JNK cascade

Molecular Function

netrin receptor activity
peptidase activity

Cellular Component

cytoplasm
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000244565
Coding exons: 8
Length: 12157
Individuals with no LoFs: 125556
Homozygous LoFs: 0
Heterozygous LoFs: 192
Defined: 125748
p: 0.000764

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.830	275	317	0.869	0.0000186	3328
Missense (PolyPhen)		80	99.976	0.80019		1139
Synonymous	0.251	131	135	0.973	0.00000766	1068
Loss of Function	0.476	21	23.5	0.894	0.00000114	242

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00088	0.00086	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.0016	0.0016	notable
East Asian	0.00076	0.00076	rare
Finnish	0.0028	0.0027	notable
European (Non-Finnish)	0.00059	0.00057	rare
South Asian	0.00020	0.00020	rare
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Inhibits NF-kappa-B-dependent transcription by impairing NF-kappa-B binding to its targets. {ECO:0000269|PubMed:14769797}.;

Recessive Scores

pRec: 0.0944

Intolerance Scores

LoFtool: 0.631
RVIS EVS: 1.51
RVIS percentile EVS: 95.47

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.895

Gene Damage Prediction

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