ULK3

Chr 15

unc-51 like kinase 3

NCBI Gene: 25989 ENSG00000140474 UniProt: Q6PHR2 OMIM: 613472

Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

OMIM Research

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

0.58

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.58LOEUF

pLI 0.002

Z-score 3.28

OE 0.34 (0.21–0.58)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.24Z-score

OE missense 0.79 (0.70–0.88)

215 obs / 272.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.34 (0.21–0.58)

0≤0.351.4

Missense OE?0.79 (0.70–0.88)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 10 / 29.1Missense obs/exp: 215 / 272.5Syn Z: 1.22

Background carrier burden — how many people carry a rare variant somewhere in ULK3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

651 rare PASS variants

Rare truncating (LoF)

1 in 1,100

129 rare PASS variants

Rare synonymous (reference)

1 in 120

274 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ULK3. 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 120	1 in 1,300
South Asian	~43k	1 in 98	1 in 610
Remaining (unassigned)	~30k	1 in 120	1 in 680
European (Finnish)	~27k	1 in 670	≈ 1 in 8,500
Admixed American	~22k	1 in 77	1 in 700
African / African American	~21k	1 in 79	1 in 390
East Asian	~20k	1 in 83	1 in 800
Ashkenazi Jewish	~13k	1 in 150	≈ 1 in 5,800
Middle Eastern	~2,884	1 in 88	1 in 480

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 16 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 16.? see exons ↓