CASKIN1

Chr 16

CASK interacting protein 1

Also known as: ANKS5A

NCBI Gene: 57524 ENSG00000167971 UniProt: Q8WXD9

The CASKIN1 protein links the scaffolding protein CASK to downstream intracellular effectors at glutamatergic synapses. Mutations cause autosomal recessive neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely incompatible with normal development.

ResearchSummary from RefSeq, UniProt

Enables identical protein binding activity. Predicted to be involved in signal transduction. Predicted to be active in cytoplasm; glutamatergic synapse; and postsynapse. [provided by Alliance of Genome Resources, Apr 2025]

ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.16

Clinical Summary— CASKIN1

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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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ClinVar Variants

288 VUS of 311 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.16LOEUF

pLI 1.000

Z-score 5.98

OE 0.06 (0.03–0.16)

Highly constrained

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

Missense Constraint?

1.79Z-score

OE missense 0.82 (0.77–0.88)

665 obs / 808.0 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.06 (0.03–0.16)

0≤0.351.4

Missense OE?0.82 (0.77–0.88)

0≤0.61.4

Synonymous OE?1.16

0≤1.21.6

LoF obs/exp: 3 / 47.4Missense obs/exp: 665 / 808.0Syn Z: -2.53

This gene — mechanism propensity

0.3594th %ile

GOF

0.4874th %ile

LOF

0.79top 5%

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

LOFprediction above median · LOEUF 0.16

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

311 submitted variants in ClinVar

ClinVar

Classification Summary

VUS288

Likely Benign14

288

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	288	0	0	288
Likely Benign	8	1	5	14
Benign	0	0	0	0
Total	296	1	5	302

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

View in ClinVar →

37 pathogenic / likely-pathogenic (of 54) ClinVar copy-number / structural variants overlap CASKIN1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →