KLHL17
protein-codingkelch like family member 17, the group of Kelch like|BTB domain containing
Gene summary
The protein encoded by this gene is expressed in neurons of most regions of the brain. It contains an N-terminal BTB domain, which mediates dimerization of the protein, and a C-terminal Kelch domain, which mediates binding to F-actin. This protein may play a key role in the regulation of actin-based neuronal function. [provided by RefSeq, Aug 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.1 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLHL17 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_198317.3. 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 | 1 | 5 | 4 | 10 | ||
| missense | 1 | 183 | 4 | 188 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 1 | 1 | 5 | ||
| Total | 0 | 1 | 188 | 10 | 5 | 204 |
Highest pathogenic variant AF is 6.6140893e-7
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_938073.1 | 12 | MANE Select | |
| Ensembl | ENSP00000343930.3 | 12 | MANE Select | |
| Ensembl | ENSP00000463694.1 | 3 | Standard | |
| Ensembl | ENSP00000557575.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- brain development
- protein ubiquitination
- actin cytoskeleton organization
Molecular Function
- POZ domain binding
- protein-containing complex scaffold activity
- actin filament binding
Cellular Component
- extracellular space
- postsynaptic density
- actin cytoskeleton
- cell junction
- dendrite cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000338591
- Coding exons
- 12
- Length
- 5129
- Individuals with no LoFs
- 125310
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 60
- Defined
- 125370
- p
- 0.000239
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.571 | 467 | 434 | 1.08 | 0.0000313 | 4083 |
| Missense (PolyPhen) | 167 | 175.58 | 0.95114 | 1558 | ||
| Synonymous | -8.81 | 360 | 201 | 1.79 | 0.0000163 | 1359 |
| Loss of Function | 0.459 | 26 | 28.6 | 0.907 | 0.00000165 | 292 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00038 | 0.00037 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-recognition component of some cullin-RING- based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. The BCR(KLHL17) mediates the ubiquitination and subsequenct degradation of GLUR6. May play a role in the actin-based neuronal function (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0991
Intolerance Scores
- LoFtool
- 0.386
- RVIS EVS
- -2.65
- RVIS percentile EVS
- 0.75
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.323
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |