BRSK2

Chr 11

BR serine/threonine kinase 2

This serine/threonine protein kinase regulates neuronal polarization and axon formation by phosphorylating microtubule-associated proteins, and also controls cell cycle progression and insulin secretion. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and seizures. The gene is highly constrained against loss-of-function variants (pLI = 0.95), indicating that heterozygous mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.33
Clinical SummaryBRSK2
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Gene-Disease Validity (ClinGen)
complex neurodevelopmental disorder · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.95). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.33LOEUF
pLI 0.951
Z-score 4.63
OE 0.17 (0.090.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.95Z-score
OE missense 0.63 (0.570.69)
310 obs / 494.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.17 (0.090.33)
00.351.4
Missense OE0.63 (0.570.69)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 6 / 36.0Missense obs/exp: 310 / 494.4Syn Z: -2.31
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongBRSK2-related neurodevelopmental disorderLOFAD
DN
0.4884th %ile
GOF
0.5169th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.33

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

BRSK2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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