ULK2

Chr 17

unc-51 like autophagy activating kinase 2

Also known as: ATG1B, Unc51.2

NCBI Gene: 9706ENSG00000083290UniProt: Q8IYT8

This gene encodes a protein that is similar to a serine/threonine kinase in C. elegans which is involved in axonal elongation. The structure of this protein is similar to the C. elegans protein in that both proteins have an N-terminal kinase domain, a central proline/serine rich (PS) domain, and a C-terminal (C) domain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Dec 2008]

258
ClinVar variants
99
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— ULK2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
99 Pathogenic / Likely Pathogenic· 146 VUS of 258 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.59LOEUF
pLI 0.000
Z-score 4.03
OE 0.42 (0.30–0.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.62Z-score
OE missense 0.81 (0.75–0.87)
451 obs / 559.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.42 (0.30–0.59)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.75–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.99
0≤1.21.6
LoF obs/exp: 23 / 55.4Missense obs/exp: 451 / 559.1Syn Z: 0.09

ClinVar Variant Classifications

258 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic96
Likely Pathogenic3
VUS146
Likely Benign8
Benign5
96
Pathogenic
3
Likely Pathogenic
146
VUS
8
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
96
0
96
Likely Pathogenic
0
1
2
0
3
VUS
0
130
16
0
146
Likely Benign
0
5
0
3
8
Benign
0
1
0
4
5
Total01371147258

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

View in ClinVar →

Protein Context — Lollipop Plot

ULK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Copper metabolism in cell death and autophagy.
Xue Q et al.·Autophagy
2023Review
Connecting copper and cancer: from transition metal signalling to metalloplasia.
Ge EJ et al.·Nat Rev Cancer
2022Review
Therapeutic targeting of the USP2-E2F4 axis inhibits autophagic machinery essential for zinc homeostasis in cancer progression.
Xiao W et al.·Autophagy
2022
ULK2 deficiency stratifies autophagy-driven molecular subtypes and exacerbates trophoblasts apoptosis in preeclampsia.
Gan J et al.·Placenta
2025
Methylation silencing of ULK2 via epithelial-mesenchymal transition causes transformation to poorly differentiated gastric cancers.
Motoo I et al.·Gastric Cancer
2022
Genome-wide pleiotropy analysis of longitudinal blood pressure and harmonized cognitive performance measures.
Kang M et al.·Alzheimers Dement
2025Natural history
A genome-wide search for pleiotropy in more than 100,000 harmonized longitudinal cognitive domain scores.
Kang M et al.·Mol Neurodegener
2023Meta-analysis
Plasma and CSF miRNA dysregulations in subarachnoid hemorrhage reveal clinical courses and underlying pathways.
Chan MTH et al.·J Clin Neurosci
2019
A Distinguishable Peripheral Blood and Conjunctival Transcriptome and Gut Microbiome in Sjögren's Disease: A Pilot Study.
Nguyen RD et al.·Eye Contact Lens
2025
Conservation of structure, function and inhibitor binding in UNC-51-like kinase 1 and 2 (ULK1/2).
Chaikuad A et al.·Biochem J
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools