STK32C

Chr 10

serine/threonine kinase 32C

Also known as: PKE, YANK3

NCBI Gene: 282974 ENSG00000165752 UniProt: Q86UX6 OMIM: 621308

STK32C encodes a serine/threonine protein kinase that is highly expressed in the brain. Mutations cause autosomal recessive intellectual disability with early-onset seizures and developmental delay. This gene is highly constrained against loss-of-function variants, suggesting that complete loss of protein function is poorly tolerated.

OMIM ResearchSummary from RefSeq

The protein encoded by this gene is a member of the serine/threonine protein kinase family. It is thought that this family member is functional in brain due to its high expression levels there. DNA methylation differences have been found in this gene in monozygotic twins that are discordant for adolescent depression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

OMIM ResearchGenerating clinical summary…

GOFmechanismLOEUF 0.49

Clinical Summary— STK32C

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.25) despite low pLI — interpret in context.

📋

ClinVar Variants

60 VUS of 80 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.49LOEUF

pLI 0.204

Z-score 3.45

OE 0.25 (0.13–0.49)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.11Z-score

OE missense 0.64 (0.57–0.73)

179 obs / 277.8 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.25 (0.13–0.49)

0≤0.351.4

Missense OE?0.64 (0.57–0.73)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 6 / 24.4Missense obs/exp: 179 / 277.8Syn Z: -0.98

This gene — mechanism propensity

0.5968th %ile

GOF

0.74top 25%

LOF

0.3841th %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

80 submitted variants in ClinVar

ClinVar

Classification Summary

VUS60

Likely Benign4

Benign6

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	60	0	60
Likely Benign	4	0	4
Benign	2	4	6
Total	66	4	70

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

View in ClinVar →

98 pathogenic / likely-pathogenic (of 107) ClinVar copy-number / structural variants overlap STK32C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →