ULK2
protein-codingunc-51 like autophagy activating kinase 2, the group of Autophagy related
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~97.1 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 ULK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014683.4. 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 | 1 | 3 | 4 | 8 | ||
| missense | 1 | 137 | 5 | 1 | 144 | |
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 1 | 145 | 8 | 5 | 159 |
Highest pathogenic variant AF is 6.841012e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055498.3 | 27 | MANE Select | |
| Ensembl | ENSP00000378914.4 | 27 | MANE Select | |
| RefSeq | NP_001136082.1 | 27 | Standard | |
| Ensembl | ENSP00000354877.2 | 27 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| ulk2 | Danio rerio | Structure: ventral habenular nucleus Quality: decreased volume abnormal |
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)
- Autophagy - other - Homo sapiens (human)
- Target Of Rapamycin (TOR) Signaling
- Nanoparticle triggered autophagic cell death
Biological Process
- autophagosome assembly
- autophagy
- signal transduction
- regulation of autophagy
- response to starvation
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
Cellular Component
- phagophore assembly site
- cytosol
- membrane
- cytoplasmic vesicle membrane
- phagophore assembly site membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395544
- Coding exons
- 27
- Length
- 97108
- Individuals with no LoFs
- 125703
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 45
- Defined
- 125748
- p
- 0.000179
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.62 | 451 | 559 | 0.807 | 0.0000298 | 6705 |
| Missense (PolyPhen) | 119 | 158.13 | 0.75256 | 1984 | ||
| Synonymous | 0.0850 | 201 | 203 | 0.992 | 0.0000110 | 2040 |
| Loss of Function | 4.03 | 23 | 55.4 | 0.415 | 0.00000302 | 661 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00038 | 0.00038 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00016 | 0.00016 | rare |
| South Asian | 0.00022 | 0.00020 | rare |
| Other | 0.00052 | 0.00049 | rare |
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 a negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK, also acts as a negative regulator of AMPK through phosphorylation of the AMPK subunits PRKAA1, PRKAB2 and PRKAG1. May phosphorylate ATG13/KIAA0652, FRS2, FRS3 and RPTOR; however such data need additional evidences. Not involved in ammonia-induced autophagy or in autophagic response of cerebellar granule neurons (CGN) to low potassium concentration. Plays a role early in neuronal differentiation and is required for granule cell axon formation: may govern axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons. {ECO:0000269|PubMed:18936157, ECO:0000269|PubMed:21460634, ECO:0000269|PubMed:21460635, ECO:0000269|PubMed:21690395, ECO:0000269|PubMed:21795849}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.822
- RVIS EVS
- -1.01
- RVIS percentile EVS
- 8.16
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.933
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |