SBK1

Chr 16

SH3 domain binding kinase 1

Also known as: SBK

NCBI Gene: 388228 ENSG00000188322 UniProt: Q52WX2 OMIM: 620212

The protein is predicted to function as a serine/threonine kinase involved in chromatin remodeling and may participate in signal transduction pathways controlling brain development. Currently, no established Mendelian diseases have been definitively associated with SBK1 mutations in clinical practice. The gene shows moderate constraint against loss-of-function variants, suggesting potential intolerance to complete protein loss.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to enable protein serine/threonine kinase activity. Predicted to be involved in chromatin remodeling. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2025]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.70

Clinical Summary— SBK1

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

51 VUS of 55 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.70LOEUF

pLI 0.368

Z-score 2.16

OE 0.22 (0.09–0.70)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

2.94Z-score

OE missense 0.47 (0.41–0.55)

117 obs / 246.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.22 (0.09–0.70)

0≤0.351.4

Missense OE?0.47 (0.41–0.55)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 2 / 9.0Missense obs/exp: 117 / 246.9Syn Z: 1.62

This gene — mechanism propensity

0.5379th %ile

GOF

0.81top 10%

LOF

0.4726th %ile

The highest-scoring mechanism for this gene is gain-of-function.

GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

VUS51

VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	51	51
Likely Benign	0	0
Benign	0	0
Total	51	51

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 41) ClinVar copy-number / structural variants overlap SBK1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →