UNC5A

Chr 5

unc-5 netrin receptor A

Also known as: UNC5H1

NCBI Gene: 90249 ENSG00000113763 UniProt: Q6ZN44

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.

ResearchSummary from RefSeq, UniProt

UNC5A belongs to a family of netrin-1 (MIM 601614) receptors thought to mediate the chemorepulsive effect of netrin-1 on specific axons. For more information on UNC5 proteins, see UNC5C (MIM 603610).[supplied by OMIM, Apr 2004]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.20

Clinical Summary— UNC5A

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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.

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ClinVar Variants

88 VUS of 100 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.20LOEUF

pLI 1.000

Z-score 5.26

OE 0.08 (0.04–0.20)

Highly constrained

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

Missense Constraint?

2.75Z-score

OE missense 0.66 (0.61–0.73)

354 obs / 532.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.08 (0.04–0.20)

0≤0.351.4

Missense OE?0.66 (0.61–0.73)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 3 / 38.0Missense obs/exp: 354 / 532.5Syn Z: 0.42

This gene — mechanism propensity

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

100 submitted variants in ClinVar

ClinVar

Classification Summary

VUS88

Likely Benign2

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	88	0	88
Likely Benign	1	1	2
Benign	0	0	0
Total	89	1	90

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

View in ClinVar →

56 pathogenic / likely-pathogenic (of 62) ClinVar copy-number / structural variants overlap UNC5A — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →