KLHDC8B
protein-codingkelch domain containing 8B
Gene summary
This gene encodes a protein which forms a distinct beta-propeller protein structure of kelch domains allowing for protein-protein interactions. Mutations in this gene have been associated with Hodgkin lymphoma. [provided by RefSeq, Sep 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.9 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0009348
Submitter: Ambry Genetics
Inheritance Pattern: Unknown
Disease ID:MONDO:0009348
Submitter: Labcorp Genetics (formerly Invitae)
Clinical Genomic Database (CGD)
Manifestation: Oncologic
Intervention: Oncologic
Rationale: Surveillance and/or awareness of cancer risk may allow early diagnosis, which could potentially be beneficial
Comments: One family with a gene disruption has been described
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLHDC8B variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_173546.3. 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 | 37 | 2 | 39 | |||
| missense | 106 | 2 | 108 | |||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 113 | 39 | 2 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_775817.1 | 5 | MANE Select | |
| Ensembl | ENSP00000327468.2 | 5 | MANE Select | |
| Ensembl | ENSP00000574880.1 | 5 | Standard | |
| Ensembl | ENSP00000574880.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- nuclear chromosome segregation
- mitotic nuclear division
- mitotic cytokinetic process
Cellular Component
- cytoplasm
- cytosol
- midbody
- intercellular bridge
- cellularization cleavage furrow
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000332780
- Coding exons
- 5
- Length
- 4874
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 13
- Defined
- 125742
- p
- 0.0000517
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.59 | 165 | 234 | 0.706 | 0.0000146 | 2246 |
| Missense (PolyPhen) | 63 | 99.015 | 0.63627 | 947 | ||
| Synonymous | 0.509 | 81 | 87.0 | 0.931 | 0.00000453 | 809 |
| Loss of Function | 1.47 | 6 | 11.4 | 0.528 | 4.87e-7 | 125 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00011 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000045 | 0.000044 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in pinching off the separated nuclei at the cleavage furrow and in cytokinesis (PubMed:20107318). Required for mitotic integrity and maintenance of chromosomal stability. Protects cells against mitotic errors, centrosomal amplification, micronucleus formation and aneuploidy. Plays a key role of midbody function involving abscission of the daughter cells during cytokinesis and appropriate chromosomal and nuclear segregation into the daughter cells (PubMed:22988245, PubMed:23713010). {ECO:0000269|PubMed:20107318, ECO:0000269|PubMed:22988245, ECO:0000269|PubMed:23713010}.;
- Disease
- DISEASE: Lymphoma, Hodgkin, classic (CHL) [MIM:236000]: A malignant disease characterized by progressive enlargement of the lymph nodes, spleen and general lymphoid tissue, and the presence of large, usually multinucleate, cells (Reed-Sternberg cells). Reed-Sternberg cells compose only 1-2% of the total tumor cell mass. The remainder is composed of a variety of reactive, mixed inflammatory cells consisting of lymphocytes, plasma cells, neutrophils, eosinophils and histiocytes. {ECO:0000269|PubMed:19706467}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. A variant in the 5'-UTR of KLHDC8B, responsible for decreasing its expression, is associated with classic Hodgkin lymphoma and segregates with the disease in some families (PubMed:19706467). {ECO:0000269|PubMed:19706467}.; DISEASE: Note=A chromosomal aberration disrupting KLHDC8B has been found in a family with the nodular sclerosis type of Hodgkin lymphoma. Translocation t(2,3)(q11.2;p21.31).;
Recessive Scores
- pRec
- 0.109
Intolerance Scores
- LoFtool
- 0.476
- RVIS EVS
- -0.63
- RVIS percentile EVS
- 17.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.216
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |