CASKIN2

Chr 17

CASK interacting protein 2

Also known as: ANKS5B

The protein contains six ankyrin repeats, an SH3 domain, and two SAM domains that mediate protein-protein interactions, and interacts with calcium/calmodulin-dependent serine protein kinase (CASK). Loss-of-function mutations cause autosomal dominant neurodevelopmental disorders due to haploinsufficiency. The gene is highly intolerant to loss-of-function variation, indicating that reduced protein dosage disrupts normal neurological function.

Summary from RefSeq, Mechanism
0
Active trials
3
Pubs (1 yr)
13
P/LP submissions
0%
P/LP missense
0.23
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryCASKIN2
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.
📋
ClinVar Variants
13 unique Pathogenic / Likely Pathogenic· 257 VUS of 296 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.23LOEUF
pLI 1.000
Z-score 5.55
OE 0.11 (0.060.23)
Highly constrained

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

Missense Constraint
0.74Z-score
OE missense 0.92 (0.870.98)
682 obs / 738.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.11 (0.060.23)
00.351.4
Missense OE0.92 (0.870.98)
00.61.4
Synonymous OE1.07
01.21.6
LoF obs/exp: 5 / 45.4Missense obs/exp: 682 / 738.4Syn Z: -0.97
DN
0.3793th %ile
GOF
0.5856th %ile
LOF
0.71top 10%

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

LOFprediction above median · LOEUF 0.23

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

296 submitted variants in ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS257
Likely Benign4
Benign1
12
Pathogenic
1
Likely Pathogenic
257
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
12
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
249
8
0
257
Likely Benign
0
3
1
0
4
Benign
0
0
1
0
1
Total0252230275

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

View in ClinVar →

Protein Context — Lollipop Plot

CASKIN2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗