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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KANK1
KN motif and ankyrin repeat domains 1
Chromosome 9 · 9p24.3
NCBI Gene: 23189Ensembl: ENSG00000107104.21HGNC: HGNC:19309UniProt: A0A8I5KRP2
82PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Transcription FactorTumor Suppressor
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
negative regulation of actin filament polymerizationprotein bindingbeta-catenin bindingprotein-macromolecule adaptor activitybasal cell carcinomauterine fibroidInherited congenital spastic tetraplegiaUterine leiomyoma
✦AI Summary

KANK1 is an adapter protein that organizes cortical microtubule-stabilizing complexes at focal adhesions and regulates cytoskeleton dynamics 1. It links microtubule and actin networks by interacting with talin and recruiting KIF21A, thereby controlling microtubule-actin crosstalk at cell edges and guiding axon growth 1. KANK1 inhibits RhoA activation and lamellipodium formation through PI3K/Akt signaling and 14-3-3 protein sequestration, thereby suppressing cell migration 2. Optogenetic activation of KANK1-mediated microtubule/talin linkage promotes focal adhesion disassembly via GEF-H1/RhoA/ROCK-dependent contractility 3. KANK1 participates in Wnt/β-catenin-dependent transcription in the nucleus 4. Mutations in KANK1 cause spastic cerebral palsy through axonal dysfunction and TDP-43 mislocalization in motor neurons, highlighting its ALS disease relevance 5. The clinical significance of KANK1 is paradoxical: while upregulation suppresses lung, gastric, and brain glioma cancer progression through apoptosis and cell-cycle arrest 678, high KANK1 expression associates with poor breast cancer prognosis by competing with Scribble for Hippo pathway inhibition 9. Low KANK1 expression correlates with poor pulmonary adenocarcinoma prognosis 10, suggesting tissue-specific tumor suppressor or oncogenic roles.

Sources cited
1
KANK1 organizes cortical microtubule-stabilizing complexes at focal adhesion rims and recruits KIF21A for axon guidance
PMID: 24120883
2
KANK1 inhibits RhoA activation and cell migration through PI3K/Akt signaling and 14-3-3 protein interactions
PMID: 25961457
3
KANK1-mediated microtubule/talin linkage activation promotes focal adhesion disassembly via GEF-H1/RhoA/ROCK contractility
PMID: 38769437
4
KANK1 is involved in beta-catenin-dependent transcriptional activation in the nucleus
PMID: 16968744
5
KANK1 mutations cause ALS through axonal dysfunction and TDP-43 mislocalization in motor neurons
PMID: 35045337
6
KANK1 upregulation inhibits lung cancer progression through apoptosis and cell-cycle arrest
PMID: 29956815
7
KANK1 upregulation inhibits gastric cancer progression through apoptosis and reduced invasion/metastasis
PMID: 28731169
8
KANK1 upregulation induces brain glioma apoptosis via mitochondrial pathway and G0/G1 cell-cycle arrest
PMID: 24399197
9
High KANK1 expression promotes breast cancer by competing with Scribble to inhibit Hippo pathway activation
PMID: 39613731
10
Low KANK1 expression is associated with poor prognosis in pulmonary adenocarcinoma
PMID: 33042336
Disease Associationsⓘ21
basal cell carcinomaOpen Targets
0.52Moderate
uterine fibroidOpen Targets
0.52Moderate
Inherited congenital spastic tetraplegiaOpen Targets
0.48Moderate
Uterine leiomyomaOpen Targets
0.48Moderate
cancerOpen Targets
0.47Moderate
skin cancerOpen Targets
0.40Moderate
uterine benign neoplasmOpen Targets
0.34Weak
Peyronie diseaseOpen Targets
0.32Weak
non-melanoma skin carcinomaOpen Targets
0.32Weak
alcohol drinkingOpen Targets
0.32Weak
sialolithiasisOpen Targets
0.31Weak
skin neoplasmOpen Targets
0.30Weak
ovarian dysfunctionOpen Targets
0.30Weak
thyroiditisOpen Targets
0.29Weak
Abruptio PlacentaeOpen Targets
0.29Weak
disorder of uterine broad ligamentOpen Targets
0.27Weak
fallopian tube diseaseOpen Targets
0.27Weak
ovarian diseaseOpen Targets
0.27Weak
Abnormal brain morphologyOpen Targets
0.27Weak
response to antihypertensive drugOpen Targets
0.18Weak
Cerebral palsy, spastic quadriplegic 2UniProt
Pathogenic Variants2
NM_015158.5(KANK1):c.3237C>G (p.Ile1079Met)Likely pathogenic
Abnormal brain morphology
★☆☆☆→ Residue 1079
NC_000009.12:g.(606181_654801)_831563delPathogenic
Cerebral palsy, spastic quadriplegic, 2
☆☆☆☆2005
View on ClinVar ↗
Related Genes
KIF21AProtein interaction100%PHLDB2Protein interaction99%TLN1Protein interaction98%TLN2Protein interaction97%DMRT1Protein interaction92%DOCK8Protein interaction85%
Tissue Expression6 tissues
Heart
100%
Liver
72%
Ovary
19%
Brain
16%
Lung
12%
Bone Marrow
5%
Gene Interaction Network
Click a node to explore
KANK1KIF21APHLDB2TLN1TLN2DMRT1DOCK8
PROTEIN STRUCTURE
Preparing viewer…
PDB5YBU · 1.89 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.97 [0.83–1.15]
RankingsWhere KANK1 stands among ~20K protein-coding genes
  • #5,800of 20,598
    Most Researched82
  • #4,352of 5,498
    Most Pathogenic Variants2
  • #11,964of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedKANK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Genome-wide identification of the genetic basis of amyotrophic lateral sclerosis.
PMID: 35045337
Neuron · 2022
1.00
2
Cerebral Palsy: Diagnosis, Epidemiology, Genetics, and Clinical Update.
PMID: 31230694
Adv Pediatr · 2019
0.90
3
KANK1 promotes breast cancer development by compromising Scribble-mediated Hippo activation.
PMID: 39613731
Nat Commun · 2024
0.80
4
Kank1 and Ki67 expression are associated with poor prognosis in human pulmonary adenocarcinoma.
PMID: 33042336
Int J Clin Exp Pathol · 2020
0.70
5
Upregulation of the Kank1 gene inhibits human lung cancer progression in vitro and in vivo.
PMID: 29956815
Oncol Rep · 2018
0.60