KANK2
protein-codingKN motif and ankyrin repeat domains 2, the group of KN motif and ankyrin repeat domain containing
Gene summary
This gene encodes a member of the KN motif and ankyrin repeat domains (KANK) family of proteins, which play a role in cytoskeletal formation by regulating actin polymerization. The encoded protein functions in the sequestration of steroid receptor coactivators and possibly other proteins. Mutations in this gene are associated with impaired kidney podocyte function and nephrotic syndrome, and keratoderma and woolly hair. [provided by RefSeq, Jul 2016]
- MXRA3
- ANKRD25
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014492
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0014492
Submitter: G2P
Inheritance Pattern: Unknown
Disease ID:MONDO:0014492
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0033280
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0014492
Submitter: PanelApp Australia
Inheritance Pattern: Unknown
Disease ID:MONDO:0033280
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Dermatologic; Musculoskeletal; Renal
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
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KANK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001136191.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 7 | 122 | 3 | 132 | ||
| missense | 2 | 288 | 33 | 2 | 325 | |
| nonsense | 2 | 2 | ||||
| start loss | 1 | 1 | ||||
| frameshift | 1 | 1 | 2 | |||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 2 | 1 | 305 | 155 | 5 | 468 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001129663.1 | 11 | MANE Select | |
| Ensembl | ENSP00000465650.1 | 11 | MANE Select | |
| RefSeq | NP_001316380.1 | 11 | Standard | |
| RefSeq | NP_001366477.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| kank2 | Danio rerio | Structure: podocyte Quality: disorganized abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- apoptotic process
- negative regulation of cell population proliferation
- negative regulation of intracellular estrogen receptor signaling pathway
- regulation of Rho protein signal transduction
Molecular Function
- protein binding
Cellular Component
- cytoplasm
- mitochondrion
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000432929
- Coding exons
- 11
- Length
- 33525
- Individuals with no LoFs
- 125645
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 103
- Defined
- 125748
- p
- 0.000410
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.484 | 549 | 582 | 0.944 | 0.0000413 | 5423 |
| Missense (PolyPhen) | 299 | 326.22 | 0.91656 | 2949 | ||
| Synonymous | -1.25 | 284 | 258 | 1.10 | 0.0000193 | 1890 |
| Loss of Function | 3.88 | 9 | 33.1 | 0.272 | 0.00000182 | 337 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0043 | 0.0039 | notable |
| Finnish | 0.000047 | 0.000046 | rare |
| European (Non-Finnish) | 0.00022 | 0.00021 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00018 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in transcription regulation by sequestering nuclear receptor coactivators, such as NCOA1, NCOA2 and NCOA3, in the cytoplasm; the function is deregulated by phosphorylation. Involved in the negative control of vitamin D receptor signaling pathway (PubMed:24671081). May be involved in the control of cytoskeleton formation by regulating actin polymerization. Involved in regulation of caspase-independent apoptosis; proposed to sequester AIFM1 in mitochondria and apoptotic stimuli lead to its proteasomal degradation allowing the release of AIFM1 to the nucleus (PubMed:22371500). May be involved in promotion of cell proliferation (By similarity). {ECO:0000250|UniProtKB:Q8BX02, ECO:0000269|PubMed:17476305, ECO:0000269|PubMed:22371500, ECO:0000269|PubMed:24671081}.;
- Disease
- DISEASE: Palmoplantar keratoderma and woolly hair (PPKWH) [MIM:616099]: A disorder characterized by abnormal thickening of the skin on the palms and soles, in association with woolly scalp hair. Affected individuals manifest a variable degree of striate palmoplantar keratoderma, generally more severe on the soles. Leukonychia is more pronounced on the fingernails than toenails. Scalp hair, body hair, eyebrows, and eyelashes are sparse. The fifth toes show variable degrees of pseudoainhum, ranging from external rotation to a deep sulcus at the digitoplantar fold, accompanied by a bulbous appearance of the distal toe. {ECO:0000269|PubMed:24671081}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.357
- RVIS EVS
- 0.59
- RVIS percentile EVS
- 82.38
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.237
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |