UNC5A

Chr 5

unc-5 netrin receptor A

Also known as: UNC5H1

UNC5A encodes a netrin-1 receptor that mediates axon guidance and repulsion during nervous system development, promoting neurite outgrowth and triggering apoptosis when not bound to its ligand. Mutations cause congenital mirror movements, a neurological condition characterized by involuntary mirroring movements of the opposite limb during voluntary unilateral movements. The condition follows an autosomal dominant inheritance pattern.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
56
P/LP submissions
0%
P/LP missense
0.20
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryUNC5A
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
54 unique Pathogenic / Likely Pathogenic· 93 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.20LOEUF
pLI 1.000
Z-score 5.26
OE 0.08 (0.040.20)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.75Z-score
OE missense 0.66 (0.610.73)
354 obs / 532.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.08 (0.040.20)
00.351.4
Missense OE0.66 (0.610.73)
00.61.4
Synonymous OE0.96
01.21.6
LoF obs/exp: 3 / 38.0Missense obs/exp: 354 / 532.5Syn Z: 0.42
DN
0.3793th %ile
GOF
0.4580th %ile
LOF
0.68top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.20

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

160 submitted variants in ClinVar

Classification Summary

Pathogenic52
Likely Pathogenic2
VUS93
Likely Benign3
52
Pathogenic
2
Likely Pathogenic
93
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
52
0
52
Likely Pathogenic
0
0
2
0
2
VUS
0
88
5
0
93
Likely Benign
0
1
1
1
3
Benign
0
0
0
0
0
Total089601150

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

View in ClinVar →

Protein Context — Lollipop Plot

UNC5A · 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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