CASK

Chr XXLRX-linked

calcium/calmodulin dependent serine protein kinase

Also known as: CAGH39, CAMGUK, CMG, FGS4, LIN2, MICPCH, MRXSNA, TNRC8

This gene encodes a calcium/calmodulin-dependent serine protein kinase. The encoded protein is a MAGUK (membrane-associated guanylate kinase) protein family member. These proteins are scaffold proteins and the encoded protein is located at synapses in the brain. Mutations in this gene are associated with FG syndrome 4, intellectual disability and microcephaly with pontine and cerebellar hypoplasia, and a form of X-linked intellectual disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

OMIMResearchGenerating clinical summary…
LOFmechanismXLR/X-linkedLOEUF 0.073 OMIM phenotypes
Clinical SummaryCASK
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Gene-Disease Validity (ClinGen)
X-linked syndromic intellectual disability · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). 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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint?
0.07LOEUF
pLI 1.000
Z-score 5.93
OE 0.00 (0.000.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
4.25Z-score
OE missense 0.37 (0.320.43)
133 obs / 359.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.00 (0.000.07)
00.351.4
Missense OE?0.37 (0.320.43)
00.61.4
Synonymous OE?0.99
01.21.6
LoF obs/exp: 0 / 41.0Missense obs/exp: 133 / 359.9Syn Z: 0.08
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveCASK-related intellectual developmental disorder, with or without nystagmusOTHERXLR
definitiveCASK-related intellectual developmental disorderLOFmonoallelic_X_heterozygous

This gene — mechanism propensity

DN
0.3594th %ile
GOF
0.5563th %ile
LOF
0.73top 10%

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

LOFprediction above median · LOEUF 0.07

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

CASK · protein map & ClinVar variants

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