CNKSR1

Chr 1

connector enhancer of kinase suppressor of Ras 1

Also known as: CNK, CNK1

The protein functions as a scaffold component for receptor tyrosine kinase signaling and contains multiple protein-protein interaction domains including PDZ, PH, and SAM domains. Mutations cause X-linked intellectual disability with seizures and behavioral abnormalities. The gene shows X-linked inheritance and is not highly constrained against loss-of-function variants.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 1.28
Clinical SummaryCNKSR1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
5 unique Pathogenic / Likely Pathogenic· 87 VUS of 139 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.28LOEUF
pLI 0.000
Z-score 0.00
OE 1.00 (0.791.28)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.57Z-score
OE missense 0.92 (0.841.00)
376 obs / 408.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.00 (0.791.28)
00.351.4
Missense OE0.92 (0.841.00)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 45 / 45.0Missense obs/exp: 376 / 408.4Syn Z: 0.03
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedCNKSR1-related intellectual developmental disorderLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.5869th %ile
GOF
0.6833th %ile
LOF
0.4331th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

139 submitted variants in ClinVar

Classification Summary

Pathogenic5
VUS87
Likely Benign13
Benign14
Conflicting1
5
Pathogenic
87
VUS
13
Likely Benign
14
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
0
0
0
VUS
2
81
4
0
87
Likely Benign
1
8
0
4
13
Benign
2
6
2
4
14
Conflicting
1
Total595118120

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

View in ClinVar →

Protein Context — Lollipop Plot

CNKSR1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →