UNC5D

Chr 8

unc-5 netrin receptor D

Also known as: PRO34692, Unc5h4

NCBI Gene: 137970 ENSG00000156687 UniProt: Q6UXZ4 OMIM: 616466

Predicted to enable netrin receptor activity. Involved in cell-cell adhesion. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

OMIM Research

Predicted to enable netrin receptor activity. Involved in cell-cell adhesion. Predicted to be located in plasma membrane. [provided by Alliance of Genome Resources, Jun 2026]

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

0.33

LOEUF· LoF intol.

LOF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.33LOEUF

pLI 0.929

Z-score 5.01

OE 0.18 (0.11–0.33)

Highly constrained

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

Missense Constraint?

2.25Z-score

OE missense 0.72 (0.66–0.79)

378 obs / 522.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.18 (0.11–0.33)

0≤0.351.4

Missense OE?0.72 (0.66–0.79)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 8 / 43.7Missense obs/exp: 378 / 522.6Syn Z: 0.27

Background carrier burden — how many people carry a rare variant somewhere in UNC5D?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 80

1,117 rare PASS variants

Rare truncating (LoF)

1 in 1,700

94 rare PASS variants

Rare synonymous (reference)

1 in 95

499 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for UNC5D. 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 100	1 in 2,800
South Asian	~43k	1 in 50	1 in 3,800
Remaining (unassigned)	~30k	1 in 64	1 in 1,300
European (Finnish)	~27k	1 in 230	1 in 4,400
Admixed American	~22k	1 in 88	1 in 1,500
African / African American	~21k	1 in 65	1 in 3,200
East Asian	~20k	1 in 68	≈ 1 in 6,300
Ashkenazi Jewish	~13k	1 in 160	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 76	≈ 1 in 2,900

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): 15 of 17 coding exons well covered in gnomAD exomes; exons 1, 8 marginal. Genomes: all 17.? see exons ↓