BRSK1

protein-coding

BR serine/threonine kinase 1, the group of BR serine/threonine kinases

Gene summary

Enables magnesium ion binding activity and tau-protein kinase activity. Involved in mitotic G2 DNA damage checkpoint signaling and protein phosphorylation. Acts upstream of or within G2/M transition of mitotic cell cycle; peptidyl-serine phosphorylation; and response to UV. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_032430.2

Inheritance

—

ClinVar variants

P:1U:83B:1

Top phenotype

BRSK1-associated neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.08

Max pathogenic AF

—

Genomic locus

chr19:55,282,072-55,312,562

External References & Databases

Ensembl (ENSG00000160469)

Transcript & Mutation Effects

hg38 • Region Span ~30.5 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 BRSK1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 6

BRSK1-associated neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032430.2. 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			5 clinvar		1 clinvar	6
missense			72 clinvar			72
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar		1 clinvar			2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	1	0	83	0	1	85

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 10 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032430.2	RefSeq	NP_115806.1	19	MANE Select
ENST00000309383.6	Ensembl	ENSP00000310649.1	19	MANE Select
ENST00000326848.7	Ensembl	ENSP00000320853.7	10	Standard
ENST00000326848.8	Ensembl	ENSP00000320853.7	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

LKB1 signaling events

Biological Process

protein phosphorylation
cellular response to DNA damage stimulus
mitotic G2 DNA damage checkpoint
neurotransmitter secretion
axonogenesis

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
ATP binding
protein kinase binding
gamma-tubulin binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
centrosome
synaptic vesicle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000309383
Coding exons: 19
Length: 30462
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125744
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	3.94	240	484	0.496	0.0000336	4964
Missense (PolyPhen)		36	95.257	0.37792		913
Synonymous	-0.267	208	203	1.02	0.0000147	1629
Loss of Function	5.24	3	37.8	0.0794	0.00000209	421

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication. Phosphorylates CDC25B, CDC25C, MAPT/TAU, RIMS1, TUBG1, TUBG2 and WEE1. Following phosphorylation and activation by STK11/LKB1, acts as a key regulator of polarization of cortical neurons, probably by mediating phosphorylation of microtubule-associated proteins such as MAPT/TAU at 'Thr-529' and 'Ser-579'. Also regulates neuron polarization by mediating phosphorylation of WEE1 at 'Ser-642' in post-mitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. In neurons, localizes to synaptic vesicles and plays a role in neurotransmitter release, possibly by phosphorylating RIMS1. Also acts as a positive regulator of centrosome duplication by mediating phosphorylation of gamma- tubulin (TUBG1 and TUBG2) at 'Ser-131', leading to translocation of gamma-tubulin and its associated proteins to the centrosome. Involved in the UV-induced DNA damage checkpoint response, probably by inhibiting CDK1 activity through phosphorylation and activation of WEE1, and inhibition of CDC25B and CDC25C. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:15150265, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311}.;

Recessive Scores

pRec: 0.113

Intolerance Scores

LoFtool: 0.409
RVIS EVS: -0.8
RVIS percentile EVS: 12.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.826

Gene Damage Prediction

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