BRSK1

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

Basic information

Region (hg38): 19:55282071-55312562

Links

ENSG00000160469 ∙ NCBI:84446 ∙ OMIM:609235 ∙ HGNC:18994 ∙ Uniprot:Q8TDC3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the BRSK1 gene.

• Inborn genetic diseases (23 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the BRSK1 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	1
missense			23			23
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	23	0	1

Variants in BRSK1

This is a list of pathogenic ClinVar variants found in the BRSK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
19-55287033-A-G		not specified	Uncertain significance (Mar 06, 2023)
19-55289548-C-T		not specified	Uncertain significance (May 22, 2023)
19-55289583-G-T		not specified	Uncertain significance (Oct 18, 2021)
19-55302809-G-A		not specified	Uncertain significance (Aug 10, 2021)
19-55303314-G-C		not specified	Uncertain significance (Sep 22, 2023)
19-55303704-C-T			Benign (Apr 30, 2018)
19-55303705-C-T		not specified	Uncertain significance (Oct 29, 2021)
19-55303711-G-A		not specified	Uncertain significance (May 17, 2023)
19-55303723-C-T		not specified	Uncertain significance (Jan 02, 2024)
19-55303759-G-C		not specified	Uncertain significance (Oct 29, 2021)
19-55303795-C-T		not specified	Uncertain significance (Nov 18, 2022)
19-55303796-G-A		not specified	Uncertain significance (Apr 07, 2022)
19-55304584-G-T		not specified	Uncertain significance (Aug 09, 2021)
19-55304695-C-A		not specified	Uncertain significance (Jul 20, 2022)
19-55304833-G-A		not specified	Uncertain significance (Dec 21, 2022)
19-55304842-G-A		not specified	Uncertain significance (May 22, 2023)
19-55304864-A-G		not specified	Uncertain significance (Jul 25, 2023)
19-55305326-A-G		not specified	Uncertain significance (Dec 17, 2023)
19-55305518-A-C		not specified	Uncertain significance (Nov 21, 2022)
19-55305527-G-A		not specified	Uncertain significance (Sep 27, 2021)
19-55306276-C-G		not specified	Uncertain significance (Feb 09, 2023)
19-55306318-G-A		not specified	Uncertain significance (Aug 21, 2023)
19-55306391-C-T		not specified	Uncertain significance (Jun 18, 2021)
19-55306397-G-A		not specified	Uncertain significance (Feb 15, 2023)
19-55308657-A-G		not specified	Uncertain significance (Dec 21, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
BRSK1	protein_coding	protein_coding	ENST00000309383	19	30462

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000185	125736	0	8	125744	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.94	240	484	0.496	0.0000336	4964
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000625	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000219	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000270	0.0000264
Middle Eastern	0.000219	0.000217
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

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}.
• Pathway: LKB1 signaling events (Consensus)

Recessive Scores

• pRec: 0.113

Intolerance Scores

• loftool: 0.409
• rvis_EVS: -0.8
• rvis_percentile_EVS: 12.24

Haploinsufficiency Scores

• pHI: 0.385
• hipred: Y
• hipred_score: 0.572
• ghis: 0.586

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.826

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Brsk1
• Phenotype: 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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; 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)

Gene ontology

• Biological process: protein phosphorylation;cellular response to DNA damage stimulus;mitotic G2 DNA damage checkpoint;neurotransmitter secretion;axonogenesis;associative learning;response to UV;response to ionizing radiation;regulation of neuron projection development;establishment of cell polarity;neuron differentiation;intracellular signal transduction;regulation of synaptic plasticity;regulation of axonogenesis;centrosome duplication;microtubule cytoskeleton organization involved in establishment of planar polarity;synaptic vesicle cycle;regulation of synaptic vesicle clustering
• Cellular component: nucleus;nucleoplasm;cytoplasm;centrosome;synaptic vesicle;cell junction;presynaptic active zone;distal axon
• Molecular function: magnesium ion binding;protein serine/threonine kinase activity;ATP binding;protein kinase binding;gamma-tubulin binding;tau protein binding;tau-protein kinase activity