UNC5A

Chr 5

unc-5 netrin receptor A

Also known as: UNC5H1

NCBI Gene: 90249 ENSG00000113763 UniProt: Q6ZN44 OMIM: 607869

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.

OMIM 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]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.20

LOEUF· LoF intol.

LOF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in UNC5A?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 83

944 rare PASS variants

Rare truncating (LoF)

1 in 4,000

59 rare PASS variants

Rare synonymous (reference)

1 in 68

500 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UNC5A. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 91	1 in 3,600
South Asian	~43k	1 in 58	1 in 6,000
Remaining (unassigned)	~30k	1 in 56	1 in 830
European (Finnish)	~27k	1 in 100	≈ 1 in 12,000
Admixed American	~22k	1 in 71	≈ 1 in 5,600
African / African American	~21k	1 in 50	≈ 1 in 4,600
East Asian	~20k	1 in 89	1 in 2,600
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 60	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 14 of 15 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 15.? see exons ↓