BRSK2

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

Basic information

Region (hg38): 11:1389899-1462689

Previous symbols: [ "C11orf7", "STK29" ]

Links

ENSG00000174672 ∙ NCBI:9024 ∙ OMIM:609236 ∙ HGNC:11405 ∙ Uniprot:Q8IWQ3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant non-syndromic intellectual disability (Supportive), mode of inheritance: AD
• complex neurodevelopmental disorder (Moderate), mode of inheritance: AD
• complex neurodevelopmental disorder (Definitive), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRSK2 gene.

• Inborn genetic diseases (4 variants)
• not specified (1 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRSK2 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			1	49	2	52
missense		2	62	7	1	72
nonsense	1	1	2			4
start loss			1			1
frameshift	3	2	6	1		12
inframe indel			6			6
splice donor/acceptor (+/-2bp)	2	2				4
splice region		1	2	7	1	11
non coding			6	13	9	28
Total	6	7	84	70	12

Variants in BRSK2

This is a list of pathogenic ClinVar variants found in the BRSK2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-1390271-C-T			Benign (Jun 16, 2021)
11-1390303-G-A		Inborn genetic diseases • BRSK2-related disorder	Uncertain significance (Feb 28, 2023)
11-1390309-G-A		Inborn genetic diseases	Uncertain significance (Feb 21, 2024)
11-1390366-G-C			Uncertain significance (Dec 14, 2022)
11-1411395-G-A		BRSK2-related disorder	Likely benign (Apr 11, 2019)
11-1411423-C-T		BRSK2-related disorder	Uncertain significance (Mar 14, 2023)
11-1411445-G-A		BRSK2-related disorder	Uncertain significance (Dec 31, 2023)
11-1411461-T-C		BRSK2-related disorder	Benign (Oct 18, 2019)
11-1411479-C-G		BRSK2-related disorder	Likely benign (Mar 29, 2019)
11-1411524-C-T			Likely benign (Feb 01, 2024)
11-1411572-C-T		BRSK2-related disorder	Likely benign (Jul 01, 2024)
11-1411585-C-T		BRSK2-related disorder	Uncertain significance (Jun 22, 2023)
11-1411617-G-GCAGCC			Uncertain significance (Apr 19, 2023)
11-1436036-G-A		BRSK2-related disorder	Likely benign (Oct 06, 2023)
11-1436037-C-T		BRSK2-related disorder	Benign/Likely benign (Aug 01, 2024)
11-1436045-G-A			Uncertain significance (Sep 21, 2022)
11-1436068-C-T			Likely benign (Mar 01, 2024)
11-1436082-T-C			Uncertain significance (Dec 04, 2023)
11-1436103-G-A			Uncertain significance (Mar 12, 2023)
11-1436103-G-C			Uncertain significance (Aug 19, 2019)
11-1436121-C-T		Inborn genetic diseases	Uncertain significance (Jun 23, 2023)
11-1436130-T-C		BRSK2-related Intellectual Disability and Autism	Uncertain significance (Aug 12, 2021)
11-1436130-TGAA-T			Uncertain significance (May 24, 2022)
11-1438313-G-A		Inborn genetic diseases	Uncertain significance (Oct 09, 2022)
11-1438321-G-T			Uncertain significance (Dec 29, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRSK2	protein_coding	protein_coding	ENST00000382179	20	72791

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.951	0.0486	124886	0	6	124892	0.0000240

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.95	310	494	0.627	0.0000342	4916
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000100	0.0000928
European (Non-Finnish)	0.00000943	0.00000883
Middle Eastern	0.00	0.00
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

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}.
• Pathway: LKB1 signaling events (Consensus)

Recessive Scores

• pRec: 0.107

Intolerance Scores

• loftool: 0.286
• rvis_EVS: -1.51
• rvis_percentile_EVS: 3.54

Haploinsufficiency Scores

• pHI: 0.167
• hipred: Y
• hipred_score: 0.850
• ghis: 0.588

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.824

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brsk2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype

Gene ontology

• Biological process: G2/M transition of mitotic cell cycle;protein phosphorylation;exocytosis;axonogenesis;regulation of neuron projection development;peptidyl-serine phosphorylation;establishment of cell polarity;neuron differentiation;actin cytoskeleton reorganization;intracellular signal transduction;ERAD pathway;regulation of ATPase activity;regulation of axonogenesis;cell division;regulation of insulin secretion involved in cellular response to glucose stimulus;intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress;microtubule cytoskeleton organization involved in establishment of planar polarity;regulation of retrograde protein transport, ER to cytosol;regulation of synaptic vesicle clustering
• Cellular component: nucleus;cytoplasm;endoplasmic reticulum;centrosome;perinuclear region of cytoplasm;distal axon
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;ATP binding;protein kinase binding;tau protein binding;tau-protein kinase activity;ATPase binding;ATPase regulator activity