ULK2

Chr 17

unc-51 like autophagy activating kinase 2

Also known as: ATG1B, Unc51.2

The protein is a serine/threonine kinase that regulates autophagy in response to starvation and plays a critical role in early neuronal differentiation and granule cell axon formation. Mutations cause autosomal recessive developmental and epileptic encephalopathy with movement abnormalities, typically presenting in early childhood with seizures, developmental delays, and neurological dysfunction. This gene is highly constrained against loss-of-function variants in the population, indicating that complete loss of function is likely not tolerated.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.59
Clinical SummaryULK2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.59LOEUF
pLI 0.000
Z-score 4.03
OE 0.42 (0.300.59)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.62Z-score
OE missense 0.81 (0.750.87)
451 obs / 559.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.42 (0.300.59)
00.351.4
Missense OE0.81 (0.750.87)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 23 / 55.4Missense obs/exp: 451 / 559.1Syn Z: 0.09
DN
0.7035th %ile
GOF
0.5661th %ile
LOF
0.4431th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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