ULK3

protein-coding

unc-51 like kinase 3, the group of MicroRNA protein coding host genes

Gene summary

Enables protein serine/threonine kinase activity. Involved in several processes, including fibroblast activation; protein autophosphorylation; and regulation of smoothened signaling pathway. Located in cytoplasm. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001099436.4

Inheritance

—

ClinVar variants

U:94B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.34

Max pathogenic AF

—

Genomic locus

chr15:74,836,118-74,843,346

External References & Databases

Ensembl (ENSG00000140474)

Transcript & Mutation Effects

hg38 • Region Span ~7.2 kb

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GenCC 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 ULK3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 81

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001099436.4. 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 clinvar	4 clinvar	2 clinvar	7
missense			84 clinvar	2 clinvar	1 clinvar	87
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			9 clinvar			9
Total	0	0	94	6	3	103

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 111 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001099436.4	RefSeq	NP_001092906.3	16	MANE Select
ENST00000440863.7	Ensembl	ENSP00000400312.2	16	MANE Select
NM_001284364.3	RefSeq	NP_001271293.2	16	Standard
NM_001284365.3	RefSeq	NP_001271294.1	14	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Target Of Rapamycin (TOR) Signaling
Signal Transduction
Hedgehog ,on, state
Signaling by Hedgehog

Biological Process

autophagosome assembly
autophagy
regulation of autophagy
negative regulation of smoothened signaling pathway
positive regulation of smoothened signaling pathway

Molecular Function

protein serine/threonine kinase activity
protein binding
ATP binding

Cellular Component

phagophore assembly site
cytoplasm
cytosol
membrane
ciliary tip

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000440863
Coding exons: 16
Length: 7231
Individuals with no LoFs: 124644
Homozygous LoFs: 0
Heterozygous LoFs: 16
Defined: 124660
p: 0.0000642

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	215	273	0.789	0.0000171	2955
Missense (PolyPhen)		71	98.613	0.71999		1145
Synonymous	1.22	96	112	0.854	0.00000684	927
Loss of Function	3.28	10	29.1	0.344	0.00000155	316

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000065	0.000065	rare
Latino/Admixed American	0.000092	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.00010	0.000097	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy. {ECO:0000269|PubMed:19279323, ECO:0000269|PubMed:19878745, ECO:0000269|PubMed:20643644}.;

Recessive Scores

pRec: 0.150

Intolerance Scores

LoFtool: 0.839
RVIS EVS: -0.49
RVIS percentile EVS: 22.51

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.726

Gene Damage Prediction

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