ULK1
protein-codingunc-51 like autophagy activating kinase 1, the group of Autophagy related
Gene summary
Enables identical protein binding activity; protein serine/threonine kinase activity; and small GTPase binding activity. Involved in several processes, including protein phosphorylation; regulation of autophagy; and regulation of protein lipidation. Located in bounding membrane of organelle; cytosol; and phagophore assembly site membrane. Part of Atg1/ULK1 kinase complex. Is active in cytoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~28.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ULK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003565.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 6 | 6 | 16 | ||
| missense | 184 | 8 | 2 | 194 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 193 | 14 | 8 | 215 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003556.2 | 28 | MANE Select | |
| Ensembl | ENSP00000324560.3 | 28 | MANE Select | |
| Ensembl | ENSP00000551624.1 | 28 | Standard | |
| Ensembl | ENSP00000551624.1 | 28 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- mTOR signaling pathway - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- Mitophagy - animal - Homo sapiens (human)
- AMPK signaling pathway - Homo sapiens (human)
- Longevity regulating pathway - Homo sapiens (human)
Biological Process
- autophagosome assembly
- protein phosphorylation
- autophagy
- signal transduction
- protein localization
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- kinase activity
- Rab GTPase binding
Cellular Component
- phagophore assembly site
- cytoplasm
- mitochondrial outer membrane
- autophagosome
- endoplasmic reticulum membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000321867
- Coding exons
- 28
- Length
- 28517
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 18
- Defined
- 125722
- p
- 0.0000716
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.07 | 585 | 663 | 0.883 | 0.0000447 | 6675 |
| Missense (PolyPhen) | 251 | 319.9 | 0.78462 | 3071 | ||
| Synonymous | -3.57 | 379 | 300 | 1.26 | 0.0000218 | 2205 |
| Loss of Function | 5.51 | 8 | 50.1 | 0.160 | 0.00000248 | 554 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3- kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2 and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. May also phosphorylate SESN2 and SQSTM1 to regulate autophagy (PubMed:25040165). {ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21795849, ECO:0000269|PubMed:25040165}.;
Recessive Scores
- pRec
- 0.143
Intolerance Scores
- LoFtool
- 0.315
- RVIS EVS
- -1.22
- RVIS percentile EVS
- 5.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.617
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |