ULK4

protein-coding

unc-51 like kinase 4, the group of Armadillo like helical domain containing

Gene summary

This gene encodes a member of the unc-51-like serine/threonine kinase (STK) family. Members of this protein family play a role in neuronal growth and endocytosis. The encoded protein is likely involved in neurite branching, neurite elongation and neuronal migration. Genome-wide association studies (GWAS) indicate an association of variations in this gene with blood pressure and hypertension. Sequence variations in this gene may also be be associated with psychiatric disorders, including schizophrenia and bipolar disorder. Pseudogenes associated with this gene have been identified and are located on chromosome 15. [provided by RefSeq, Jul 2016]

MANE transcript

NM_017886.4

Inheritance

ClinVar variants

U:196B:33

Top phenotype

ULK4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr3:41,246,599-41,962,130

External References & Databases

Ensembl (ENSG00000168038)

Transcript & Mutation Effects

hg38 • Region Span ~715.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

prostate cancerLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0008315

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ULK4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 189

ULK4-related disorderTotal: 19

not providedTotal: 14

Moderate intellectual disabilityTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017886.4. 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			3 clinvar	13 clinvar	2 clinvar	18
missense			185 clinvar	16 clinvar	1 clinvar	202
nonsense			1 clinvar	1 clinvar		2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			7 clinvar			7
Total	0	0	196	30	3	229

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017886.4	RefSeq	NP_060356.2	36	MANE Select
ENST00000301831.9	Ensembl	ENSP00000301831.4	36	MANE Select
NM_001322500.2	RefSeq	NP_001309429.1	35	Standard
NM_001322501.2	RefSeq	NP_001309430.1	28	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

microtubule cytoskeleton organization
protein phosphorylation
regulation of neuron projection development
regulation of MAPK cascade
regulation of JNK cascade

Molecular Function

protein serine/threonine kinase activity
ATP binding

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000301831
Coding exons: 36
Length: 715833
Individuals with no LoFs: 124190
Homozygous LoFs: 6
Heterozygous LoFs: 1112
Defined: 125308
p: 0.00447

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.906	722	657	1.10	0.0000336	8260
Missense (PolyPhen)		167	157.83	1.0581		2081
Synonymous	-0.413	251	243	1.03	0.0000123	2465
Loss of Function	0.882	62	70.0	0.886	0.00000332	894

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0030	0.0029	notable
Latino/Admixed American	0.0020	0.0019	notable
Ashkenazi Jewish	0.0028	0.0028	notable
East Asian	0.0041	0.0040	notable
Finnish	0.0065	0.0064	notable
European (Non-Finnish)	0.0057	0.0056	notable
South Asian	0.0038	0.0037	notable
Other	0.0037	0.0036	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May be involved in the remodeling of cytoskeletal components, such as alpha-tubulin, and in this way regulates neurite branching and elongation, as well as cell motility. {ECO:0000269|PubMed:24284070}.;
Disease: DISEASE: Note=Various anomalies in ULK4 gene have been reported for several cases of schizophrenia, schizophrenia plus bipolar disorder and autism. ULK4 gene has been proposed to be a rare susceptibility risk factor for a range of psychiatric diseases including schizophrenia. {ECO:0000269|PubMed:24284070}.;

Intolerance Scores

LoFtool: 0.979
RVIS EVS: 1.71
RVIS percentile EVS: 96.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.923

Gene Damage Prediction

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