KLHL13
protein-codingkelch like family member 13, the group of BTB domain containing|Kelch like
Gene summary
This gene encodes a BTB and kelch domain containing protein and belongs to the kelch repeat domain containing superfamily of proteins. The encoded protein functions as an adaptor protein that complexes with Cullin 3 and other proteins to form the Cullin 3-based E3 ubiquitin-protein ligase complex. This complex is necessary for proper chromosome segregation and completion of cytokinesis. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
- BKLHD2
- KIAA1309
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~219.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: XL
Disease ID:MONDO:0700092
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLHL13 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001168302.2. 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 | 17 | 6 | 3 | 26 | ||
| missense | 92 | 1 | 93 | |||
| nonsense | 11 | 11 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 12 | 12 | ||||
| Total | 0 | 0 | 132 | 7 | 3 | 142 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001161774.1 | 7 | MANE Select | |
| Ensembl | ENSP00000441029.1 | 7 | MANE Select | |
| RefSeq | NP_001161771.1 | 8 | Standard | |
| RefSeq | NP_001161772.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Ubiquitin mediated proteolysis - Homo sapiens (human)
- Post-translational protein modification
- Metabolism of proteins
- Immune System
- Adaptive Immune System
Biological Process
- cell cycle
- protein ubiquitination
- regulation of cytokinesis
- post-translational protein modification
- cell division
Molecular Function
- ubiquitin-protein transferase activity
Cellular Component
- cytosol
- midbody
- Cul3-RING ubiquitin ligase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000539496
- Coding exons
- 8
- Length
- 219528
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 4
- Heterozygous LoFs
- 6
- Defined
- 125735
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.20 | 157 | 256 | 0.612 | 0.0000195 | 4356 |
| Missense (PolyPhen) | 46 | 96.313 | 0.47761 | 1544 | ||
| Synonymous | 0.733 | 83 | 91.9 | 0.903 | 0.00000710 | 1237 |
| Loss of Function | 2.78 | 6 | 19.1 | 0.313 | 0.00000147 | 346 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00030 | 0.00025 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000062 | 0.000044 | rare |
| South Asian | 0.000052 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis. {ECO:0000269|PubMed:14528312, ECO:0000269|PubMed:17543862, ECO:0000269|PubMed:19995937}.;
Recessive Scores
- pRec
- 0.0909
Intolerance Scores
- LoFtool
- 0.514
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 37.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.968
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |