ULK2

unc-51 like autophagy activating kinase 2, the group of Autophagy related

Basic information

Region (hg38): 17:19770828-19867936

Links

ENSG00000083290 ∙ NCBI:9706 ∙ OMIM:608650 ∙ HGNC:13480 ∙ Uniprot:Q8IYT8 ∙ 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 ULK2 gene.

• Inborn genetic diseases (39 variants)
• not provided (7 variants)
• Abnormal brain morphology (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the ULK2 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				2	4	6
missense		1	37	2	1	41
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	1	37	4	5

Variants in ULK2

This is a list of pathogenic ClinVar variants found in the ULK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-19776360-C-T		not specified	Uncertain significance (Aug 28, 2023)
17-19776380-G-A		not specified	Uncertain significance (Dec 21, 2022)
17-19777680-T-C		not specified	Uncertain significance (Jun 16, 2023)
17-19777709-G-C		not specified	Uncertain significance (Jan 03, 2024)
17-19780500-T-C		not specified	Uncertain significance (Nov 10, 2022)
17-19780528-C-A		not specified	Uncertain significance (Jan 24, 2024)
17-19780548-G-A		not specified	Uncertain significance (Dec 13, 2023)
17-19781025-T-C		not specified	Uncertain significance (Oct 06, 2021)
17-19781034-C-T		not specified	Uncertain significance (Nov 20, 2023)
17-19781061-G-T		not specified	Uncertain significance (Feb 16, 2023)
17-19781102-C-T			Benign (Dec 31, 2019)
17-19781893-A-C		not specified	Uncertain significance (Dec 19, 2023)
17-19782016-C-T		not specified	Uncertain significance (Aug 12, 2021)
17-19783741-T-C		not specified	Uncertain significance (May 17, 2023)
17-19783758-G-A		not specified	Uncertain significance (Apr 28, 2022)
17-19783772-G-A			Benign (Dec 31, 2019)
17-19783817-G-A			Likely benign (Jan 01, 2023)
17-19783842-G-A		not specified	Uncertain significance (Jan 23, 2024)
17-19783858-C-T		not specified	Uncertain significance (Feb 03, 2022)
17-19786033-T-A		not specified	Uncertain significance (Jan 30, 2024)
17-19786069-C-T		not specified	Uncertain significance (Jul 14, 2021)
17-19795636-C-T		not specified	Uncertain significance (Jun 26, 2023)
17-19795642-G-C		not specified	Uncertain significance (Jun 03, 2022)
17-19795695-T-C			Likely benign (Jan 01, 2023)
17-19796123-C-T		not specified	Uncertain significance (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
ULK2	protein_coding	protein_coding	ENST00000395544	27	97108

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.88e-8	1.00	125703	0	45	125748	0.000179

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.62	451	559	0.807	0.0000298	6705
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000441	0.000441
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000111	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000163	0.000158
Middle Eastern	0.000111	0.000109
South Asian	0.000217	0.000196
Other	0.000525	0.000489

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 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}.
• Pathway: 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;mTOR signaling pathway (Consensus)

Recessive Scores

• pRec: 0.103

Intolerance Scores

• loftool: 0.822
• rvis_EVS: -1.01
• rvis_percentile_EVS: 8.16

Haploinsufficiency Scores

• pHI: 0.440
• hipred: Y
• hipred_score: 0.542
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.933

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ulk2
• 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: ulk2
• Affected structure: ventral habenular nucleus
• Phenotype tag: abnormal
• Phenotype quality: decreased volume

Gene ontology

• Biological process: autophagosome assembly;autophagy;signal transduction;regulation of autophagy;response to starvation;protein autophosphorylation;negative regulation of collateral sprouting;axon extension;autophagy of host cells involved in interaction with symbiont
• Cellular component: phagophore assembly site;cytosol;membrane;cytoplasmic vesicle membrane;phagophore assembly site membrane
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding