GeneBe

KANK1

protein-coding

KN motif and ankyrin repeat domains 1, the group of KN motif and ankyrin repeat domain containing

Gene summary

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]

Previous symbols:
  • ANKRD15

MANE transcript

NM_015158.5

Inheritance

AD, AR

ClinVar variants

P:1U:627B:344

Top phenotype

Cerebral palsy, spastic quadriplegic, 2

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr9:470,291-746,105

External References & Databases

Ensembl (ENSG00000107104)NCBI Gene (23189)OMIM (607704)HGNC:19309GenCCUniProt (Q14678)AlphaFoldClinVar (KANK1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~275.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cerebral palsy, spastic quadriplegic, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013033

Submitter: G2P

cerebral palsy, spastic quadriplegic, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013033

Submitter: PanelApp Australia

nephrotic syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0005377

Submitter: PanelApp Australia

spastic quadriplegic cerebral palsySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016215

Submitter: Orphanet

cerebral palsy, spastic quadriplegic, 2LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0013033

Submitter: Ambry Genetics

cerebral palsy, spastic quadriplegic, 2LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0013033

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Cerebral palsy, spastic quadriplegic, 2AD

Manifestation: Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 16301218Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to KANK1 variants in ClinVar

10 Conditions Cataloged
not providedTotal: 817
not specifiedTotal: 419
Cerebral palsy, spastic quadriplegic, 2Total: 112
KANK1-related disorderTotal: 83
Rare genetic intellectual disabilityTotal: 2
Abnormality of neuronal migrationTotal: 2
SchizophreniaTotal: 1
Intellectual disabilityTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015158.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
7
clinvar
223
clinvar
 230
missense
1
clinvar
569
clinvar
118
clinvar
2
clinvar
 690
nonsense
17
clinvar
 17
start loss
2
clinvar
 2
frameshift
20
clinvar
1
clinvar
 21
splice donor/acceptor (+/-2bp)
12
clinvar
 12
Total016273413972

Highest pathogenic variant AF is 0.0000027366818

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 227 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_015158.5RefSeqNP_055973.211MANE Select
ENST00000382297.7EnsemblENSP00000371734.211MANE Select
NM_001256876.3RefSeqNP_001243805.111Standard
NM_001256877.3RefSeqNP_001243806.111Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

  • cell population proliferation
  • negative regulation of neuron projection development
  • actin cytoskeleton organization
  • positive regulation of Wnt signaling pathway
  • negative regulation of cell migration

Molecular Function

  • protein binding
  • beta-catenin binding

Cellular Component

  • nucleus
  • cytoplasm
  • plasma membrane
  • ruffle membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000382303
Coding exons
11
Length
275815
Individuals with no LoFs
125621
Homozygous LoFs
0
Heterozygous LoFs
127
Defined
125748
p
0.000505
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-4.8111657861.480.00004468877
Missense (PolyPhen)343247.941.38342814
Synonymous-5.274333141.380.00001932711
Loss of Function1.843447.70.7120.00000245581

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000370.00037rare
Latino/Admixed American0.000780.00078rare
Ashkenazi Jewish00.0absent
East Asian0.00100.0010notable
Finnish0.000650.00065rare
European (Non-Finnish)0.000440.00043rare
South Asian0.000390.00039rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Involved in the control of cytoskeleton formation by regulating actin polymerization. Inhibits actin fiber formation and cell migration. Inhibits RhoA activity; the function involves phosphorylation through PI3K/Akt signaling and may depend on the competetive interaction with 14-3-3 adapter proteins to sequester them from active complexes. Inhibits the formation of lamellipodia but not of filopodia; the function may depend on the competetive interaction with BAIAP2 to block its association with activated RAC1. Inhibits fibronectin-mediated cell spreading; the function is partially mediated by BAIAP2. Inhibits neurite outgrowth. Involved in the establishment and persistence of cell polarity during directed cell movement in wound healing. In the nucleus, is involved in beta-catenin-dependent activation of transcription. Potential tumor suppressor for renal cell carcinoma. {ECO:0000269|PubMed:16968744, ECO:0000269|PubMed:18458160, ECO:0000269|PubMed:19171758, ECO:0000269|PubMed:22084092}.;

Recessive Scores

pRec
0.0989

Intolerance Scores

LoFtool
0.810
RVIS EVS
-0.92
RVIS percentile EVS
9.78

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
N
Indispensability score
0.205

Gene Damage Prediction

AllRecessiveDominant
MendelianHighHighHigh
Primary ImmunodeficiencyHighHighHigh
CancerHighHighHigh
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