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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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BRSK1
BR serine/threonine kinase 1
Chromosome 19 · 19q13.42
NCBI Gene: 84446Ensembl: ENSG00000160469.17HGNC: HGNC:18994UniProt: Q8TDC3
39PubMed Papers
20Diseases
0Drugs
1Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein phosphorylationDNA damage responseresponse to UVpeptidyl-serine phosphorylationneurodegenerative diseaseneuroinflammatory disorderosteoarthritis, hipalcohol drinking
✦AI Summary

BRSK1 is a brain-specific serine/threonine kinase that functions as a multifaceted regulator of neuronal development and cellular stress responses. In neurons, BRSK1 acts downstream of LKB1 to regulate neuronal polarization by phosphorylating microtubule-associated proteins including tau/MAPT and controlling WEE1 activity 1. BRSK1 also localizes to synaptic vesicles and lipid rafts where enhanced kinase activity supports neurotransmitter release 1. Beyond neuronal functions, BRSK1 participates in DNA damage checkpoints by inhibiting CDK1 through WEE1 activation and CDC25 inhibition. Disease relevance spans reproductive, neurological, and malignant contexts. A BRSK1 variant (rs12611091) associates with premature ovarian failure susceptibility 2, and another variant (rs11668344) confers 2.5-fold increased risk of alkylating chemotherapy-induced reduced ovarian function in childhood cancer survivors 3. Haploinsufficiency of BRSK1 causes epilepsy and neurodevelopmental disorders through dysregulation of axonal development and synaptic function pathways 4. In cancer, BRSK1 exhibits context-dependent roles: it functions as a tumor suppressor in breast cancer by regulating the PI3K/Akt pathway and p27 degradation 5, and frameshift mutations occur in microsatellite-instable gastric and colorectal cancers 6. Conversely, BRSK1 promotes cisplatin resistance in cervical cancer via mitochondrial respiration regulation 7 and activates YAP/TAZ in triple-negative breast cancer 8.

Sources cited
1
BRSK1 variant rs12611091 associates with premature ovarian failure susceptibility
PMID: 22248077
2
Cytoplasmic BRSK1 acts as tumor suppressor in breast cancer, inversely correlates with Jab1 expression, and regulates cell cycle via PI3K/Akt pathway
PMID: 25036402
3
BRSK1 carries frameshift mutations in microsatellite-instable gastric and colorectal cancers, acting as putative tumor suppressor gene
PMID: 27677186
4
BRSK1 variant rs11668344 confers 2.5-fold increased odds of reduced ovarian function after high-dose alkylating chemotherapy in childhood cancer survivors
PMID: 33582778
5
BRSK1 haploinsufficiency causes epilepsy and neurodevelopmental disorders through dysregulation of axonal development and synaptic function pathways
PMID: 41035394
6
BRSK1 is a novel AMPK family member that activates YAP/TAZ and inhibits Hippo pathway in triple-negative breast cancer
PMID: 40869130
7
BRSK1 is palmitoylated and localizes to synaptic membrane lipid rafts where it regulates neurotransmitter release and shows enhanced kinase activity
PMID: 22020259
8
BRSK1 promotes cisplatin resistance in cervical cancer via regulation of mitochondrial respiration and correlates with poor prognosis in cisplatin-treated patients
PMID: 37140697
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.22Weak
neuroinflammatory disorderOpen Targets
0.15Weak
osteoarthritis, hipOpen Targets
0.06Suggestive
alcohol drinkingOpen Targets
0.05Suggestive
osteoarthritisOpen Targets
0.04Suggestive
temporal lobe epilepsyOpen Targets
0.04Suggestive
cervical cancerOpen Targets
0.03Suggestive
ovulationOpen Targets
0.03Suggestive
epilepsyOpen Targets
0.03Suggestive
hypothyroidismOpen Targets
0.02Suggestive
AnxietyOpen Targets
0.02Suggestive
breast cancerOpen Targets
0.02Suggestive
Neurodevelopmental disorderOpen Targets
0.02Suggestive
premature menopauseOpen Targets
0.02Suggestive
colorectal carcinomaOpen Targets
0.01Suggestive
hepatocellular carcinomaOpen Targets
0.01Suggestive
breast carcinomaOpen Targets
0.01Suggestive
membranous glomerulonephritisOpen Targets
0.01Suggestive
cancerOpen Targets
0.01Suggestive
neoplasmOpen Targets
0.01Suggestive
Pathogenic Variants1
NM_032430.2(BRSK1):c.1450_1483del (p.Arg484fs)Pathogenic
BRSK1-associated neurodevelopmental disorder
★☆☆☆2026→ Residue 484
View on ClinVar ↗
Related Genes
CDR2Protein interaction78%KMT5CProtein interaction78%CDC25BProtein interaction74%BRSK2Shared pathway32%MRNIPShared pathway14%TLK2Shared pathway13%
Tissue Expression6 tissues
Brain
100%
Heart
17%
Ovary
10%
Bone Marrow
4%
Lung
2%
Liver
2%
Gene Interaction Network
Click a node to explore
BRSK1CDR2KMT5CCDC25BBRSK2MRNIPTLK2
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8TDC3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.20 [0.13–0.30]
RankingsWhere BRSK1 stands among ~20K protein-coding genes
  • #10,282of 20,598
    Most Researched39
  • #5,177of 5,498
    Most Pathogenic Variants1
  • #1,134of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedBRSK1
Sources retrieved10 papers
Response time—
📄 Sources
10â–¼
1
ESR1, HK3 and BRSK1 gene variants are associated with both age at natural menopause and premature ovarian failure.
PMID: 22248077
Orphanet J Rare Dis · 2012
1.00
2
Decreased expression and prognostic role of cytoplasmic BRSK1 in human breast carcinoma: correlation with Jab1 stability and PI3K/Akt pathway.
PMID: 25036402
Exp Mol Pathol · 2014
0.90
3
Putative Tumor Suppressor Genes EGR1 and BRSK1 Are Mutated in Gastric and Colorectal Cancers.
PMID: 27677186
Oncology · 2016
0.80
4
Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.
PMID: 33582778
Hum Reprod · 2021
0.70
5
Haploinsufficiency of brain-specific kinase BRSK1 causes epilepsy and neurodevelopmental disorders.
PMID: 41035394
Epilepsia · 2025
0.60