BRSK2

protein-coding

BR serine/threonine kinase 2, the group of BR serine/threonine kinases

Gene summary

Enables several functions, including ATP binding activity; ATPase binding activity; and magnesium ion binding activity. Involved in several processes, including G2/M transition of mitotic cell cycle; intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; and regulation of insulin secretion involved in cellular response to glucose stimulus. Located in centrosome and endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C11orf7
STK29

MANE transcript

NM_001256627.2

Inheritance

ClinVar variants

P:39U:168B:92

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr11:1,389,899-1,462,689

External References & Databases

Ensembl (ENSG00000174672)

Transcript & Mutation Effects

hg38 • Region Span ~72.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: ClinGen

Variants in BRSK2 were first reported in relation to complex neurodevelopmental disorder as early as 2012 (O’Roak et al., PMID: 22495309), and later reported in at least another 18 probands in 6 publications (PMIDs: 25363760, 28135719, 30879638, 31452935, 31981491, 33057194). Affected individuals have speech delay, intellectual disability, motor delay, behavioral issues including autism, and facial dysmorphism. Variant types include frameshift, nonsense, splice site, in-frame deletions, and missense variants, with most variants occurring de novo. Because functional studies were not performed, missense and in-frame deletions were only scored 0.1 points. The mechanism for disease is haploinsufficiency. More evidence is available in the literature, but the maximum score for genetic evidence (12 points) has been reached. This gene-disease association is also supported by phenotype characterization in a knockout mouse model (1.5 points). In summary, BRSK2 is definitely associated with autosomal dominant complex neurodevelopmental disorder. This classification was approved by the ClinGen Intellectual Disability and Autism Gene Curation Expert Panel on 02/03/2021 (SOP Version 8).

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

neurodevelopmental disorderSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0700092

Submitter: G2P

autosomal dominant non-syndromic intellectual disabilitySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015802

Submitter: Orphanet

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BRSK2 variants in ClinVar

13 Conditions Cataloged

not providedTotal: 170

Inborn genetic diseasesTotal: 97

BRSK2-related disorderTotal: 69

not specifiedTotal: 37

Autosomal dominant non-syndromic intellectual disabilityTotal: 34

BRSK2-related neurodevelopmental disorderTotal: 2

Complex neurodevelopmental disorderTotal: 2

BRSK2-associated neurodevelopmental disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001256627.2. 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		1 clinvar	4 clinvar	68 clinvar	3 clinvar	76
missense		6 clinvar	149 clinvar	21 clinvar		176
nonsense	5 clinvar	1 clinvar	3 clinvar			9
start loss						0
frameshift	6 clinvar	11 clinvar	8 clinvar			25
splice donor/acceptor (+/-2bp)	4 clinvar	5 clinvar	4 clinvar			13
Total	15	24	168	89	3	299

Highest pathogenic variant AF is 0.000006938884

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 64 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001256627.2	RefSeq	NP_001243556.1	20	MANE Select
ENST00000528841.6	Ensembl	ENSP00000432000.1	20	MANE Select
NM_001256629.2	RefSeq	NP_001243558.1	19	Standard
NM_001256630.1	RefSeq	NP_001243559.1	20	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

LKB1 signaling events

Biological Process

G2/M transition of mitotic cell cycle
protein phosphorylation
exocytosis
axonogenesis
regulation of neuron projection development

Molecular Function

magnesium ion binding
protein serine/threonine kinase activity
ATP binding
protein kinase binding
tau protein binding

Cellular Component

nucleus
cytoplasm
endoplasmic reticulum
centrosome
perinuclear region of cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000382179
Coding exons: 20
Length: 72791
Individuals with no LoFs: 124886
Homozygous LoFs: 0
Heterozygous LoFs: 6
Defined: 124892
p: 0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.95	310	494	0.627	0.0000342	4916
Missense (PolyPhen)		74	171.71	0.43097		1618
Synonymous	-2.31	260	217	1.20	0.0000168	1533
Loss of Function	4.63	6	36.0	0.167	0.00000176	426

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.00010	0.000093	rare
European (Non-Finnish)	0.0000094	0.0000088	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 plays a key role in polarization of neurons and axonogenesis, cell cycle progress and insulin secretion. Phosphorylates CDK16, CDC25C, MAPT/TAU, PAK1 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 postmitotic neurons, leading to down-regulate WEE1 activity in polarized neurons. Plays a role in the regulation of the mitotic cell cycle progress and the onset of mitosis. Plays a role in the regulation of insulin secretion in response to elevated glucose levels, probably via phosphorylation of CDK16 and PAK1. While BRSK2 phosphorylated at Thr-174 can inhibit insulin secretion (PubMed:22798068), BRSK2 phosphorylated at Thr-260 can promote insulin secretion (PubMed:22669945). Regulates reorganization of the actin cytoskeleton. May play a role in the apoptotic response triggered by endoplasmic reticulum (ER) stress. {ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:20026642, ECO:0000269|PubMed:21985311, ECO:0000269|PubMed:22669945, ECO:0000269|PubMed:22798068, ECO:0000269|PubMed:23029325}.;

Recessive Scores

pRec: 0.107

Intolerance Scores

LoFtool: 0.286
RVIS EVS: -1.51
RVIS percentile EVS: 3.54

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.824

Gene Damage Prediction

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