UNC5C

Chr 4

unc-5 netrin receptor C

Also known as: UNC5H3

This gene encodes a netrin receptor that mediates axon repulsion during neural development by binding netrin-1 and triggering growth cone repulsion in the developing nervous system. The gene is highly constrained against loss-of-function variants (pLI ~0.0009, LOEUF 0.49), suggesting intolerance to haploinsufficiency. Mutations in UNC5C cause autosomal dominant neurodevelopmental disorders affecting the central nervous system, though specific phenotypes and age of onset require further characterization.

Summary from RefSeq, UniProt
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Primary Disease Associations & Inheritance

UniProtAlzheimer disease
0
Active trials
15
Pubs (1 yr)
18
P/LP submissions
0%
P/LP missense
0.49
LOEUF
Mechanism
Clinical SummaryUNC5C
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.31) despite low pLI — interpret in context.
📋
ClinVar Variants
18 unique Pathogenic / Likely Pathogenic· 127 VUS of 187 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.001
Z-score 4.23
OE 0.31 (0.210.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.98Z-score
OE missense 0.88 (0.820.95)
471 obs / 535.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.31 (0.210.49)
00.351.4
Missense OE0.88 (0.820.95)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 14 / 44.5Missense obs/exp: 471 / 535.0Syn Z: -2.26

ClinVar Variant Classifications

187 submitted variants in ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic4
VUS127
Likely Benign18
Benign13
14
Pathogenic
4
Likely Pathogenic
127
VUS
18
Likely Benign
13
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
14
0
14
Likely Pathogenic
0
0
4
0
4
VUS
0
118
9
0
127
Likely Benign
0
3
5
10
18
Benign
0
6
0
7
13
Total01273217176

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

UNC5C · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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