KANK1

Chr 9

KN motif and ankyrin repeat domains 1

Also known as: ANKRD15, CPSQ2, KANK

KANK1 encodes an adapter protein that regulates microtubule and actin cytoskeleton dynamics during cell morphogenesis, organizing complexes at focal adhesions and controlling microtubule-actin crosstalk at the cell edge. Mutations cause cerebral palsy spastic quadriplegic type 2, which involves severe motor impairment affecting all four limbs due to central nervous system developmental abnormalities. The gene shows extremely high constraint against loss-of-function variants (pLI approaching 1), indicating that complete loss of protein function is not well tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismLOEUF 0.951 OMIM phenotype
Clinical SummaryKANK1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 208 VUS of 300 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.95LOEUF
pLI 0.000
Z-score 1.84
OE 0.71 (0.540.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-4.81Z-score
OE missense 1.48 (1.411.56)
1165 obs / 785.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.71 (0.540.95)
00.351.4
Missense OE1.48 (1.411.56)
00.61.4
Synonymous OE1.38
01.21.6
LoF obs/exp: 34 / 47.7Missense obs/exp: 1165 / 785.9Syn Z: -5.27

ClinVar Variant Classifications

300 submitted variants in ClinVar

Classification Summary

Pathogenic3
Likely Pathogenic3
VUS208
Likely Benign80
Benign1
Conflicting5
3
Pathogenic
3
Likely Pathogenic
208
VUS
80
Likely Benign
1
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
3
0
3
Likely Pathogenic
0
0
3
0
3
VUS
9
177
19
3
208
Likely Benign
0
11
19
50
80
Benign
0
0
1
0
1
Conflicting
5
Total91884553300

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

View in ClinVar →

Protein Context — Lollipop Plot

KANK1 · 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.

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Clinical Literature
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