KANK1

Chr 9

KN motif and ankyrin repeat domains 1

Also known as: ANKRD15, CPSQ2, KANK

NCBI Gene: 23189ENSG00000107104UniProt: Q14678

The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

Primary Disease Associations & Inheritance

Cerebral palsy, spastic quadriplegic, 2MIM #612900
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— KANK1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.95LOEUF
pLI 0.000
Z-score 1.84
OE 0.71 (0.54–0.95)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-4.81Z-score
OE missense 1.48 (1.41–1.56)
1165 obs / 785.9 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.71 (0.54–0.95)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.48 (1.41–1.56)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.38
0≤1.21.6
LoF obs/exp: 34 / 47.7Missense obs/exp: 1165 / 785.9Syn Z: -5.27

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

Gene2Phenotype Curations

KANK1-related cerebral palsy spastic quadriplegic

limited
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Cerebral palsy, spastic quadriplegic, 2

MIM #612900

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis.
Zhang S et al.·Neuron
2022
Duplication of 9p24.3 in three unrelated patients and their phenotypes, considering affected genes, and similar recurrent variants.
Capkova Z et al.·Mol Genet Genomic Med
2021Cohort
Update on genetics of amyotrophic lateral sclerosis.
Brenner D et al.·Curr Opin Neurol
2022Review
Aberrant Kank1 expression regulates YAP to promote apoptosis and inhibit proliferation in OSCC.
Fan H et al.·J Cell Physiol
2020
Clinical significance of copy number variants involving KANK1 in patients with neurodevelopmental disorders.
Vanzo RJ et al.·Eur J Med Genet
2019Cohort
Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.
Wang Y et al.·Genome Med
2025Cohort
KANK1 regulates paclitaxel resistance in lung adenocarcinoma A549 cells.
Pu J et al.·Artif Cells Nanomed Biotechnol
2020
Small interstitial 9p24.3 deletions principally involving KANK1 are likely benign copy number variants.
Wallis MJ et al.·Eur J Med Genet
2020
Molecular characterisation of pancreatic ductal adenocarcinoma with NTRK fusions and review of the literature.
Allen MJ et al.·J Clin Pathol
2023Review
Beyond Hybrid Morphology: A Large Series of Fusion-Driven Benign Peripheral Nerve Sheath Tumors Including 5 Tumors With Novel Fusions.
Dehner CA et al.·Mod Pathol
2025Cohort
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools