ULK1

unc-51 like autophagy activating kinase 1, the group of Autophagy related

Basic information

Region (hg38): 12:131894622-131923150

Links

ENSG00000177169 ∙ NCBI:8408 ∙ OMIM:603168 ∙ HGNC:12558 ∙ Uniprot:O75385 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the ULK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ULK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5	6	11
missense			70	4	2	76
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding				1		1
Total	0	0	70	10	8

Variants in ULK1

This is a list of pathogenic ClinVar variants found in the ULK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-131895053-C-T		not specified	Uncertain significance (Jan 24, 2023)
12-131895067-C-G		not specified	Uncertain significance (Apr 23, 2024)
12-131895101-C-T		not specified	Uncertain significance (Jan 16, 2024)
12-131895624-C-T			Likely benign (Jul 01, 2022)
12-131908644-C-A		not specified	Uncertain significance (Mar 20, 2023)
12-131908797-A-G		not specified	Uncertain significance (Jun 18, 2024)
12-131908934-T-C		not specified	Uncertain significance (Aug 20, 2023)
12-131909219-G-A			Benign (May 31, 2018)
12-131909833-C-T		ULK1-related disorder	Likely benign (Feb 01, 2022)
12-131909981-A-G		not specified	Uncertain significance (Apr 01, 2024)
12-131910266-A-G		not specified	Uncertain significance (Apr 06, 2022)
12-131910753-G-A		not specified	Uncertain significance (Jun 18, 2021)
12-131910799-C-T		not specified	Uncertain significance (Dec 05, 2022)
12-131911951-G-A		not specified	Uncertain significance (Dec 13, 2022)
12-131912018-G-A		not specified	Uncertain significance (Feb 14, 2024)
12-131912020-G-A		not specified	Uncertain significance (Aug 02, 2021)
12-131912030-G-C		not specified	Uncertain significance (Jun 10, 2024)
12-131912071-G-A		not specified	Uncertain significance (May 25, 2022)
12-131913767-C-T		not specified	Uncertain significance (Nov 01, 2022)
12-131913768-G-T			Likely benign (Mar 01, 2022)
12-131914356-G-A		not specified	Uncertain significance (Mar 31, 2023)
12-131914363-C-T		not specified	Uncertain significance (Jan 11, 2023)
12-131914383-G-A		not specified	Uncertain significance (Feb 06, 2024)
12-131914414-A-C		not specified	Uncertain significance (Jan 26, 2022)
12-131914428-C-G		not specified	Uncertain significance (Jun 22, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ULK1	protein_coding	protein_coding	ENST00000321867	28	28517

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.993	0.00682	125704	0	18	125722	0.0000716

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.07	585	663	0.883	0.0000447	6675
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000117	0.000114
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000654	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: 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);Target Of Rapamycin (TOR) Signaling;Nanoparticle triggered autophagic cell death;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Senescence and Autophagy in Cancer;Vesicle-mediated transport;TBC/RABGAPs;Membrane Trafficking;Receptor Mediated Mitophagy;Mitophagy;Macroautophagy;Cellular responses to external stimuli;Rab regulation of trafficking;RAB GEFs exchange GTP for GDP on RABs;mTOR signaling pathway (Consensus)

Recessive Scores

• pRec: 0.143

Intolerance Scores

• loftool: 0.315
• rvis_EVS: -1.22
• rvis_percentile_EVS: 5.56

Haploinsufficiency Scores

• pHI: 0.395
• hipred: Y
• hipred_score: 0.663
• ghis: 0.471

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.617

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Ulk1
• Phenotype: cellular phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; immune system phenotype

Gene ontology

• Biological process: autophagosome assembly;protein phosphorylation;autophagy;signal transduction;protein localization;regulation of autophagy;macroautophagy;regulation of macroautophagy;peptidyl-serine phosphorylation;peptidyl-threonine phosphorylation;neuron projection regeneration;neuron projection development;negative regulation of protein complex assembly;cellular response to nutrient levels;response to starvation;protein autophosphorylation;axon extension;autophagy of host cells involved in interaction with symbiont;positive regulation of autophagosome assembly
• Cellular component: phagophore assembly site;cytoplasm;mitochondrial outer membrane;autophagosome;endoplasmic reticulum membrane;cytosol;membrane;axon;guanyl-nucleotide exchange factor complex;phagophore assembly site membrane;recycling endosome;extrinsic component of omegasome membrane;extrinsic component of phagophore assembly site membrane;extrinsic component of autophagosome membrane;Atg1/ULK1 kinase complex
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;kinase activity;Rab GTPase binding;identical protein binding;protein-containing complex binding;GTPase binding