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BRSK1

gene
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Also known as KIAA1811SAD-B

Summary

BRSK1 (BR serine/threonine kinase 1, HGNC:18994) is a protein-coding gene on chromosome 19q13.42, encoding Serine/threonine-protein kinase BRSK1 (Q8TDC3). Serine/threonine-protein kinase that plays a key role in polarization of neurons and centrosome duplication.

Enables magnesium ion binding activity and protein serine/threonine 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 cell junction; cytoplasm; and nucleoplasm.

Source: NCBI Gene 84446 — RefSeq curated summary.

At a glance

  • GWAS associations: 6
  • Clinical variants (ClinVar): 98 total — 1 pathogenic, 1 likely-pathogenic
  • Druggable target: yes — 21 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_032430

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:18994
Approved symbolBRSK1
NameBR serine/threonine kinase 1
Location19q13.42
Locus typegene with protein product
StatusApproved
AliasesKIAA1811, SAD-B
Ensembl geneENSG00000160469
Ensembl biotypeprotein_coding
OMIM609235
Entrez84446

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000309383, ENST00000326848, ENST00000585418, ENST00000586626, ENST00000588584, ENST00000590333, ENST00000591774, ENST00000592539

RefSeq mRNA: 1 — MANE Select: NM_032430 NM_032430

CCDS: CCDS12921

Canonical transcript exons

ENST00000309383 — 19 exons

ExonStartEnd
ENSE000010525725530546355305586
ENSE000010525775529432955294397
ENSE000010525805529421455294247
ENSE000010525815530625255306450
ENSE000010525885530863955308728
ENSE000010525895530331155303408
ENSE000010525915530151255301658
ENSE000010525955530405055304110
ENSE000010525975530213755302168
ENSE000013559065528399755284578
ENSE000016465625528700755287101
ENSE000017667775528721455287299
ENSE000035313105530366755303826
ENSE000036160965529401755294133
ENSE000036386595530269755302867
ENSE000036523405528948055289620
ENSE000036662365530455155304920
ENSE000036678755530532155305369
ENSE000038950785531191155312562

Expression profiles

Bgee: expression breadth ubiquitous, 184 present calls, max score 98.87.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3640 / max 129.1825, expressed in 770 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter IDTPM avgSamples expressed
1775982.1858598
1776000.7076256
1775970.231871
1776010.121260
1775990.086945
2089380.030717

Top tissues by expression

235 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right frontal lobeUBERON:000281098.87gold quality
cortical plateUBERON:000534398.62gold quality
Brodmann (1909) area 9UBERON:001354098.50gold quality
right hemisphere of cerebellumUBERON:001489098.35gold quality
prefrontal cortexUBERON:000045198.27gold quality
anterior cingulate cortexUBERON:000983598.24gold quality
cerebellar hemisphereUBERON:000224598.02gold quality
cerebellar cortexUBERON:000212997.97gold quality
ganglionic eminenceUBERON:000402397.70gold quality
dorsolateral prefrontal cortexUBERON:000983496.68gold quality
amygdalaUBERON:000187696.62gold quality
cerebellumUBERON:000203796.62gold quality
hypothalamusUBERON:000189896.34gold quality
frontal cortexUBERON:000187096.31gold quality
neocortexUBERON:000195096.26gold quality
putamenUBERON:000187496.10gold quality
nucleus accumbensUBERON:000188296.03gold quality
caudate nucleusUBERON:000187395.98gold quality
adenohypophysisUBERON:000219695.91gold quality
C1 segment of cervical spinal cordUBERON:000646994.87gold quality
cerebral cortexUBERON:000095694.77gold quality
forebrainUBERON:000189094.55gold quality
brainUBERON:000095594.45gold quality
pituitary glandUBERON:000000794.36gold quality
ventricular zoneUBERON:000305393.96gold quality
substantia nigraUBERON:000203893.59gold quality
Ammon’s hornUBERON:000195493.25gold quality
spinal cordUBERON:000224092.88gold quality
midbrainUBERON:000189191.84gold quality
temporal lobeUBERON:000187191.82gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

ExperimentMarker?Max mean expression
E-ANND-3yes2.93

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting BRSK1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-5692A100.0074.406850
HSA-MIR-3163100.0077.238605
HSA-MIR-27A-3P99.9872.132955
HSA-MIR-27B-3P99.9872.132955
HSA-MIR-998599.9872.112939
HSA-MIR-95-5P99.8972.173973
HSA-MIR-6887-3P99.6667.831778
HSA-MIR-613299.6065.831554
HSA-MIR-6836-5P99.6065.621538
HSA-MIR-3191-3P99.4563.94356
HSA-MIR-7109-5P99.1866.131057
HSA-MIR-328-5P99.0864.651000
HSA-MIR-10B-3P99.0466.98988
HSA-MIR-6885-5P98.7164.33902
HSA-MIR-6887-5P98.5668.491295
HSA-MIR-6795-5P98.5268.511277
HSA-MIR-3189-3P96.8066.34896
HSA-MIR-3678-5P96.6474.0293
HSA-MIR-56495.8565.01163
HSA-MIR-518694.6366.76627

Literature-anchored findings (GeneRIF, showing 9)

  • acts as checkpoint kinase upon DNA damage induced by UV (PMID:15150265)
  • protein phosphatase 2C is a likely candidate for catalyzing the dephosphorylation and inactivation of BRSK1/2. (PMID:18339622)
  • STRADalpha.MO25alpha complexes containing LKB1 variants were equally effective at phosphorylating and activating AMPK, BRSK1, and BRSK2 (PMID:18854318)
  • SADB kinase activity controls centrosome homeostasis by regulating phosphorylation of gamma-tubulin. (PMID:19648910)
  • Single nucleotide polymorphism in BRSK1 is associated with the length of reproductive lifespan. (PMID:22131368)
  • BRSK1 is a novel tumor suppressor in breast cancer which inversely correlated with Jab1 expression. (PMID:25036402)
  • These results suggest that frameshift mutations of EGR1 and BRSK1 might play a role in tumorigenesis through tumor suppressor gene inactivation in colorectal cancer and gastric cancer. (PMID:27677186)
  • Relationship between BRSK1 rs12611091 variant and age at natural menopause based on physical activity. (PMID:31895179)
  • BRSK1 confers cisplatin resistance in cervical cancer cells via regulation of mitochondrial respiration. (PMID:37140697)

Cross-species orthologs

8 orthologs

OrganismSymbolGene ID
mus_musculusBrsk1ENSMUSG00000035390
rattus_norvegicusBrsk1ENSRNOG00000017673
drosophila_melanogasterSnrkFBGN0033915
drosophila_melanogasterNuakFBGN0262617
caenorhabditis_elegansWBGENE00012638
caenorhabditis_elegansZK524.4WBGENE00013994
caenorhabditis_eleganstag-344WBGENE00015230
caenorhabditis_elegansWBGENE00044388

Paralogs (17): NUAK1 (ENSG00000074590), PRKAA1 (ENSG00000132356), TSSK4 (ENSG00000139908), HUNK (ENSG00000142149), SIK1 (ENSG00000142178), SIK3 (ENSG00000160584), PRKAA2 (ENSG00000162409), TSSK3 (ENSG00000162526), NUAK2 (ENSG00000163545), SNRK (ENSG00000163788), MELK (ENSG00000165304), SIK2 (ENSG00000170145), BRSK2 (ENSG00000174672), NIM1K (ENSG00000177453), TSSK6 (ENSG00000178093), TSSK2 (ENSG00000206203), TSSK1B (ENSG00000212122)

Protein

Protein identifiers

Serine/threonine-protein kinase BRSK1 — Q8TDC3 (reviewed: Q8TDC3)

Alternative names: Brain-selective kinase 1, Brain-specific serine/threonine-protein kinase 1, Serine/threonine-protein kinase SAD-B, Synapses of Amphids Defective homolog 1

All UniProt accessions (4): Q8TDC3, J3KNK0, K7EM68, K7EN26

UniProt curated annotations — full annotation on UniProt →

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 postmitotic 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.

Subcellular location. Cytoplasm. Nucleus. Cytoskeleton. Microtubule organizing center. Centrosome. Synapse. Presynaptic active zone. Cytoplasmic vesicle. Secretory vesicle. Synaptic vesicle.

Tissue specificity. Widely expressed, with highest levels in brain and testis. Protein levels remain constant throughout the cell cycle.

Post-translational modifications. Phosphorylated at Thr-189 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Not phosphorylated at Thr-189 by CaMKK2. In contrast, it is phosphorylated and activated by CaMKK1. May be inactivated via dephosphorylation of Thr-189 by PP2C.

Activity regulation. Activated by phosphorylation on Thr-189 by STK11/LKB1.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Isoforms (3)

UniProt IDNamesCanonical?
Q8TDC3-11, SADB-Long, Lyes
Q8TDC3-22
Q8TDC3-33, SADB-short, S

RefSeq proteins (1): NP_115806* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000719Prot_kinase_domDomain
IPR008271Ser/Thr_kinase_ASActive_site
IPR011009Kinase-like_dom_sfHomologous_superfamily
IPR015940UBADomain
IPR017441Protein_kinase_ATP_BSBinding_site
IPR048622BRSK1_2-like_UBADomain

Pfam: PF00069, PF21115, PF21122

Catalyzed reactions (Rhea), 4 shown:

  • L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H(+) (RHEA:12801)
  • L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
  • L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)
  • L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H(+) (RHEA:53904)

UniProt features (44 total): modified residue 18, sequence variant 6, compositionally biased region 5, region of interest 3, mutagenesis site 3, domain 2, binding site 2, splice variant 2, chain 1, active site 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TDC3-F167.440.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 156 (proton acceptor)

Ligand- & substrate-binding residues (2): 40–48; 63

Post-translational modifications (18): 189, 399, 443, 447, 450, 466, 481, 484, 498, 508, 525, 529, 535, 550, 583, 586, 587, 601

Mutagenesis-validated functional residues (3):

PositionPhenotype
59loss of kinase activity.
189prevents phosphorylation and activation by stk11/lkb1 complex.
327abolishes activation of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 185 (showing top): AHRARNT_01, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_SYNAPTIC_VESICLE_LOCALIZATION, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_VESICLE_LOCALIZATION, SP3_Q3, GOBP_ASSOCIATIVE_LEARNING, AREB6_03, GOBP_PEPTIDYL_SERINE_MODIFICATION, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_NEUROTRANSMITTER_TRANSPORT

GO Biological Process (22): G2/M transition of mitotic cell cycle (GO:0000086), protein phosphorylation (GO:0006468), DNA damage response (GO:0006974), mitotic G2 DNA damage checkpoint signaling (GO:0007095), neurotransmitter secretion (GO:0007269), axonogenesis (GO:0007409), associative learning (GO:0008306), response to UV (GO:0009411), regulation of synaptic vesicle priming (GO:0010807), regulation of neuron projection development (GO:0010975), peptidyl-serine phosphorylation (GO:0018105), central nervous system neuron differentiation (GO:0021953), establishment of cell polarity (GO:0030010), neuron differentiation (GO:0030182), regulation of synaptic plasticity (GO:0048167), regulation of axonogenesis (GO:0050770), centrosome duplication (GO:0051298), microtubule cytoskeleton organization involved in establishment of planar polarity (GO:0090176), synaptic vesicle cycle (GO:0099504), regulation of synaptic vesicle clustering (GO:2000807), nervous system development (GO:0007399), neuron projection morphogenesis (GO:0048812)

GO Molecular Function (13): magnesium ion binding (GO:0000287), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein kinase binding (GO:0019901), gamma-tubulin binding (GO:0043015), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (14): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), centrosome (GO:0005813), synaptic vesicle (GO:0008021), postsynaptic density (GO:0014069), cell junction (GO:0030054), presynaptic active zone (GO:0048786), cholinergic synapse (GO:0098981), distal axon (GO:0150034), cytoskeleton (GO:0005856), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995), synapse (GO:0045202)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure6
presynapse4
establishment of localization in cell2
protein kinase activity2
mitotic cell cycle1
mitotic cell cycle phase transition1
cell cycle G2/M phase transition1
phosphorylation1
protein modification process1
cellular response to stress1
mitotic G2 phase1
mitotic DNA damage checkpoint signaling1
mitotic G2/M transition checkpoint1
neurotransmitter transport1
chemical synaptic transmission1
signal release from synapse1
cell morphogenesis involved in neuron differentiation1
neuron projection morphogenesis1
axon development1
learning1
response to light stimulus1
synaptic vesicle priming1
regulation of protein-containing complex assembly1
neuron projection development1
regulation of plasma membrane bounded cell projection organization1
protein phosphorylation1
peptidyl-serine modification1
central nervous system development1
neuron differentiation1
establishment or maintenance of cell polarity1
cell differentiation1
generation of neurons1
modulation of chemical synaptic transmission1
regulation of biological quality1
axonogenesis1
regulation of neuron projection development1
regulation of anatomical structure morphogenesis1
centrosome cycle1
cell cycle process1
microtubule cytoskeleton organization1

Protein interactions and networks

STRING

1854 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
BRSK1CDR2Q01850778
BRSK1KMT5CQ86Y97775
BRSK1HSPBP1Q9NZL4760
BRSK1TMEM150BA6NC51631
BRSK1MCM8Q9UJA3556
BRSK1PPP1R9BQ96SB3554
BRSK1A0A494C100A0A494C100522
BRSK1CAB39Q9Y376512
BRSK1CDC25BP30305507
BRSK1SYCP2LQ5T4T6506
BRSK1UIMC1Q96RL1473
BRSK1LCN8Q6JVE9448
BRSK1ATP1A1P05023403
BRSK1ATP1A4Q13733403
BRSK1ATP1A3P13637398
BRSK1C12orf60Q5U649398

IntAct

13 interactions, top by confidence:

ABTypeScore
BRSK1PKMpsi-mi:“MI:0217”(phosphorylation reaction)0.440
BRSK1H2BC20Ppsi-mi:“MI:0915”(physical association)0.400
HSD17B7BRSK1psi-mi:“MI:0915”(physical association)0.370
AKAP10HAX1psi-mi:“MI:0914”(association)0.350
BRSK1ANKRD28psi-mi:“MI:0914”(association)0.350
MAPTSHTN1psi-mi:“MI:0914”(association)0.350
SYNGAP1POTEFpsi-mi:“MI:0914”(association)0.350
HCN1POTEFpsi-mi:“MI:0914”(association)0.350
SYNGAP1IGLON5psi-mi:“MI:0914”(association)0.350
ATG16L1ESYT2psi-mi:“MI:0914”(association)0.350
S100A2PLEKHG3psi-mi:“MI:0914”(association)0.350

BioGRID (40): BRCA1 (Two-hybrid), PAK1 (Affinity Capture-Western), BRSK1 (Affinity Capture-Western), BRSK1 (Reconstituted Complex), PAK1 (Biochemical Activity), BRSK1 (Affinity Capture-MS), BRSK1 (Affinity Capture-MS), MAPT (Biochemical Activity), BRSK1 (Proximity Label-MS), BRSK1 (Affinity Capture-MS), BRSK1 (Affinity Capture-MS), ANKRD28 (Affinity Capture-MS), IMPDH2 (Affinity Capture-MS), IDE (Affinity Capture-MS), ACO1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2JUG7, A1YER5, A1YFY1, A2T6X5, B2DD29, C0HBT3, O08629, O15156, O15169, O35730, O60307, O95343, P0C0T2, P28702, P28704, P29353, P50241, P98083, Q06587, Q0IHB0, Q13263, Q2V2M9, Q2YDU3, Q3U1V8, Q3U2S4, Q4KMP7, Q5DU25, Q5JU85, Q5PRF9, Q5R7W7, Q5RBI7, Q5RJI5, Q5TJF3, Q5TJF7, Q62233, Q62318, Q66J69, Q68DC2, Q6MGB6, Q6ZRS2

Diamond homologs: A0AUV4, A1A5Q6, A2KF29, A2XFF4, A8WYE4, B2DD29, B7XHR6, B8BBT7, C0HKC8, C0HKC9, F1QGZ6, O08678, O08679, O22932, O22971, O65554, O74536, O94168, P27448, P52497, P54645, P54646, P57059, P92958, Q00372, Q02723, Q03141, Q05512, Q09137, Q0D4B2, Q0JI49, Q13131, Q19469, Q28948, Q2QY53, Q2RAX3, Q2V452, Q38997, Q54DF2, Q54TA3

SIGNOR signaling

9 interactions.

AEffectBMechanism
BRSK1“down-regulates activity”CDC25Bphosphorylation
BRSK1“down-regulates activity”CDC25Cphosphorylation
STK11up-regulatesBRSK1phosphorylation
BRSK1down-regulatesCDC25Bphosphorylation
BRSK1up-regulatesTUBG1phosphorylation
CAMKK1“up-regulates activity”BRSK1phosphorylation
BRSK1down-regulatesCDC25Cphosphorylation
BRSK1“up-regulates activity”CASTphosphorylation
BRSK1unknownWEE1phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

98 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic1
Likely pathogenic1
Uncertain significance72
Likely benign0
Benign1

Top pathogenic / likely-pathogenic (2)

Variant IDHGVSClassification
4819172NM_032430.2(BRSK1):c.1450_1483del (p.Arg484fs)Pathogenic
1341017GRCh37/hg19 19q13.42-13.43(chr19:55247893-56503347)x1Likely pathogenic

SpliceAI

3169 predictions. Top by Δscore:

VariantEffectΔscore
19:55287002:TGCA:Tacceptor_loss1.0000
19:55287004:CAGG:Cacceptor_loss1.0000
19:55287005:A:AGacceptor_gain1.0000
19:55287005:AG:Aacceptor_gain1.0000
19:55287005:AGGG:Aacceptor_loss1.0000
19:55287006:G:GGacceptor_gain1.0000
19:55287006:GG:Gacceptor_gain1.0000
19:55287006:GGGCT:Gacceptor_gain1.0000
19:55287101:GGTG:Gdonor_loss1.0000
19:55287197:C:Gacceptor_gain1.0000
19:55287204:T:TAacceptor_gain1.0000
19:55287210:TCAG:Tacceptor_loss1.0000
19:55287211:CA:Cacceptor_loss1.0000
19:55287212:A:AGacceptor_gain1.0000
19:55287212:AG:Aacceptor_gain1.0000
19:55287212:AGGT:Aacceptor_gain1.0000
19:55287212:AGGTG:Aacceptor_gain1.0000
19:55287213:G:GAacceptor_gain1.0000
19:55287213:GG:Gacceptor_gain1.0000
19:55287213:GGT:Gacceptor_gain1.0000
19:55287213:GGTG:Gacceptor_gain1.0000
19:55287213:GGTGG:Gacceptor_gain1.0000
19:55287295:TATTT:Tdonor_gain1.0000
19:55287296:ATTT:Adonor_gain1.0000
19:55287297:TTT:Tdonor_gain1.0000
19:55287300:G:GGdonor_gain1.0000
19:55289617:TCTG:Tdonor_gain1.0000
19:55289619:TG:Tdonor_gain1.0000
19:55289620:GG:Gdonor_gain1.0000
19:55289621:G:GGdonor_gain1.0000

AlphaMissense

5035 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
19:55284536:G:CG32R1.000
19:55284537:G:AG32D1.000
19:55284542:T:GY34D1.000
19:55284561:T:CL40P1.000
19:55284563:G:AG41S1.000
19:55284563:G:CG41R1.000
19:55284563:G:TG41C1.000
19:55284564:G:AG41D1.000
19:55284564:G:TG41V1.000
19:55284569:G:AG43R1.000
19:55284569:G:CG43R1.000
19:55284570:G:AG43E1.000
19:55284570:G:CG43A1.000
19:55284570:G:TG43V1.000
19:55284576:C:TT45I1.000
19:55284578:G:AG46R1.000
19:55284578:G:CG46R1.000
19:55284578:G:TG46W1.000
19:55287007:G:AG46E1.000
19:55287007:G:TG46V1.000
19:55287010:T:CL47P1.000
19:55287013:T:AV48D1.000
19:55287013:T:CV48A1.000
19:55287015:A:GK49E1.000
19:55287017:A:CK49N1.000
19:55287017:A:TK49N1.000
19:55287021:G:AG51R1.000
19:55287021:G:CG51R1.000
19:55287021:G:TG51W1.000
19:55287022:G:AG51E1.000

dbSNP variants (sampled 300 via entrez): RS1000039644 (19:55290791 G>A), RS1000166595 (19:55304602 G>A,T), RS1000172205 (19:55312723 G>A), RS1000207068 (19:55301956 C>G,T), RS1000404439 (19:55307937 G>A), RS1000434213 (19:55308280 A>G), RS1000442087 (19:55300738 T>C), RS1000680060 (19:55296711 G>A), RS1000832774 (19:55307186 C>T), RS1000914655 (19:55291685 G>A), RS1001051751 (19:55285881 A>G), RS1001239713 (19:55296515 T>C), RS1001326330 (19:55288345 A>G), RS1001374531 (19:55286275 C>G,T), RS1001549276 (19:55307395 C>A)

Disease associations

OMIM: gene MIM:609235 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

StudyTraitp-value
GCST000401_6Menopause (age at onset)6.000000e-11
GCST000403_5Menarche and menopause (age at onset)2.000000e-19
GCST005312_14Menopause (age at onset)6.000000e-85
GCST005312_15Menopause (age at onset)3.000000e-13
GCST005312_16Menopause (age at onset)8.000000e-16
GCST90007526_14Low hand grip strength (60 years and older) (EWGSOP)1.000000e-08

EFO canonical traits (2, from GWAS)

EFO IDTrait name
EFO:0004704age at menopause
EFO:0006941grip strength measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5650 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

21 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 231,133 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL3545311BRIGATINIB45,634
CHEMBL535SUNITINIB479,020
CHEMBL608533MIDOSTAURIN47,259
CHEMBL939GEFITINIB4117,814
CHEMBL223360LINIFANIB33,925
CHEMBL483158ALISERTIB32,305
CHEMBL522892DOVITINIB34,944
CHEMBL603469LESTAURTINIB3
CHEMBL1721885SU-0148132363
CHEMBL1967878CENISERTIB2358
CHEMBL1980297ILORASERTIB2581
CHEMBL230011TG100-11521,504
CHEMBL253969OSI-63221,150
CHEMBL565612SOTRASTAURIN21,355
CHEMBL572878TOZASERTIB22,998
CHEMBL1084546PF-005622711399
CHEMBL1908397KW-24491622
CHEMBL1980391RG-1530137
CHEMBL4169078SRA-7371529
CHEMBL482767SNS-3141336
CHEMBL482967CYC-1161

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — BRSK subfamily

Binding affinities (BindingDB)

5 measured of 6 human assays (6 total across all organisms); most potent 5 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
StaurosporineKD1.7 nM
PKC-412KD190 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamideKD2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3bKD3100 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamideKD3500 nM

ChEMBL bioactivities

255 potent at pChembl≥5 of 255 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.30IC500.498nMSTAUROSPORINE
9.07IC500.856nMSTAUROSPORINE
8.93IC501.17nMSTAUROSPORINE
8.70IC502nMCHEMBL3780091
7.90Ki12.59nMCHEMBL1973540
7.85Kd14nMCHEMBL1241674
7.80Ki15.85nMCENISERTIB
7.60Kd25nMLESTAURTINIB
7.60Ki25.12nMCHEMBL1990482
7.58Kd26nMSTAUROSPORINE
7.50Ki31.62nMCHEMBL1965507
7.40Ki39.81nMCHEMBL1997129
7.40Ki39.81nMCHEMBL1993661
7.37IC5043nMCHEMBL5407732
7.30Ki50.12nMTAE-684
7.30Ki50.12nMCHEMBL1972576
7.10Ki79.43nMCYC-116
7.10Ki79.43nMCHEMBL1983111
7.10Ki79.43nMCHEMBL1969502
7.10Ki79.43nMCHEMBL592030
7.10Ki79.43nMCHEMBL1082440
7.10Ki79.43nMCHEMBL1988594
6.96Kd109nMCHEMBL4465866
6.90Ki125.9nMCHEMBL248757
6.80Ki158.5nMCHEMBL1982711
6.80Ki158.5nMALSTERPAULLONE
6.80Ki158.5nMCHEMBL2001751
6.80Ki158.5nMCHEMBL1990885
6.80Ki158.5nMCHEMBL1980144
6.73IC50187nMCHEMBL1231206
6.71Kd194nMCHEMBL4576489
6.70Ki199.5nMCHEMBL1988163
6.70Ki199.5nMCHEMBL1978448
6.70Ki199.5nMCHEMBL1987007
6.60Ki251.2nMCHEMBL474432
6.60Ki251.2nMCHEMBL1988437
6.60Ki251.2nMGW843682X
6.51Kd310nMTAE-684
6.50Ki316.2nMCHEMBL1969523
6.47IC50338nMBRIGATINIB
6.40Ki398.1nMCHEMBL1993424
6.40Ki398.1nMDOVITINIB
6.40Ki398.1nMCHEMBL223460
6.40Ki398.1nMCHEMBL1990254
6.40Ki398.1nMCHEMBL1998121
6.40Ki398.1nMCHEMBL1981047
6.30Ki501.2nMCHEMBL1986263
6.30Ki501.2nMCHEMBL1989646
6.30Ki501.2nMCHEMBL223367
6.30Ki501.2nMCHEMBL1970203

PubChem BioAssay actives

30 with measured affinity, of 1312 total; 20 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one1715439: Inhibition of human BRSK1 using KKKVSRSGLYRSPSMPENLNRPR as substrate by [gamma-33P]-ATP assayic500.0005uM
4-[(4-aminocyclohexyl)amino]-3-(1H-benzimidazol-2-yl)-1H-pyridin-2-one1287936: Inhibition of BRSK1 (unknown origin)ic500.0020uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol624702: Binding constant for BRSK1 kinase domainkd0.0140uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one507849: Binding affinity to BRSK1kd0.0250uM
N-[7-chloro-6-[1-[(3R,4R)-4-hydroxy-3-methyloxolan-3-yl]piperidin-4-yl]isoquinolin-3-yl]cyclopropanecarboxamide2020507: Inhibition of BRSK1 (unknown origin)ic500.0430uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526173: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged BRSK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.1090uM
(15R)-15-methyl-5-(6-methyl-3-pyridinyl)-11-thia-6,14,17-triazatetracyclo[8.8.0.02,7.012,18]octadeca-1(10),2(7),3,5,8,12(18)-hexaen-13-one2167725: Inhibition of BrSK1 (unknown origin)ic500.1870uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide1526173: Binding affinity to recombinant full-length N-terminal His-FLAG-GST-tagged BRSK1 (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assaykd0.1940uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine624702: Binding constant for BRSK1 kinase domainkd0.3100uM
Brigatinib2182855: Inhibition of human BRSK1 using KKKVSRSGLYRSPSMPENLNRPR as substrate in presence of [gamma33P]-ATP by HotSpot assayic500.3380uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol624702: Binding constant for BRSK1 kinase domainkd0.7300uM
Momelotinib2183887: Inhibition of BRSK1 (unknown origin)ic501.0000uM
Midostaurin435782: Binding constant for BRSK1 kinase domainkd1.2000uM
5-[[4-[[(2R)-morpholin-2-yl]methylamino]-5-(trifluoromethyl)-2-pyridinyl]amino]pyrazine-2-carbonitrile2154708: Inhibition of human BRSK1 by FRET based Z-LYTE kinase assayic501.6600uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone624702: Binding constant for BRSK1 kinase domainkd1.9000uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one624702: Binding constant for BRSK1 kinase domainkd3.4000uM
Sunitinib435782: Binding constant for BRSK1 kinase domainkd3.5000uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide435782: Binding constant for BRSK1 kinase domainkd5.0000uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide435782: Binding constant for BRSK1 kinase domainkd6.5000uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide624702: Binding constant for BRSK1 kinase domainkd8.4000uM

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

ChemicalActions (top 5)PubMed papers
aristolochic acid Iincreases expression1
GSK-J4decreases expression1
kojic aciddecreases expression1
tris(1,3-dichloro-2-propyl)phosphateincreases expression1
diallyl trisulfideincreases expression1
abrineincreases expression1
bisphenol Sincreases methylation1
Rosiglitazonedecreases expression1
Temozolomidedecreases expression1
Sunitinibdecreases expression1
Arbutindecreases expression1
Atrazineincreases expression1
Bleomycinincreases expression1
Doxorubicindecreases expression1
Estradiolaffects cotreatment, increases expression1
Smokedecreases expression1
Tobacco Smoke Pollutionincreases expression1
Valproic Acidincreases methylation1
Aflatoxin B1increases methylation1
Gold Compoundsincreases expression1
Cadmium Chlorideincreases expression1
Thapsigarginincreases expression1
Permethrinincreases expression1

ChEMBL screening assays

250 unique, capped per target: 249 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1032266BindingInhibition of BRSK1 at 3 uMDiscovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL1964105FunctionalPUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: KIAA1811PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B1LJAbcam HeLa BRSK1 KOCancer cell lineFemale
CVCL_SF80HAP1 BRSK1 (-) 1Cancer cell lineMale
CVCL_SF81HAP1 BRSK1 (-) 2Cancer cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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BioBTree
v2.0.2

Sources 79

This page pulls from 79 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot