KLHDC3
protein-codingkelch domain containing 3
Gene summary
The protein encoded by this gene contains six repeated kelch motifs that are structurally similar to recombination activating gene 2, a protein involved in the activation of the V(D)J recombination. In mouse, this gene is found to be expressed specifically in testis. Its expression in pachytene spermatocytes is localized to cytoplasma and meiotic chromatin, suggesting that this gene may be involved in meiotic recombination. [provided by RefSeq, Jun 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.2 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 KLHDC3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_057161.4. 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 | 1 | 2 | |||
| missense | 32 | 32 | ||||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 37 | 1 | 0 | 38 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_476502.1 | 10 | MANE Select | |
| Ensembl | ENSP00000313995.4 | 10 | MANE Select | |
| Ensembl | ENSP00000244670.8 | 8 | Standard | |
| Ensembl | ENSP00000244670.8 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- XBP1(S) activates chaperone genes
Biological Process
- reciprocal meiotic recombination
- IRE1-mediated unfolded protein response
Molecular Function
- chromatin binding
- protein binding
Cellular Component
- nuclear chromatin
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326974
- Coding exons
- 10
- Length
- 7086
- Individuals with no LoFs
- 125746
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125748
- p
- 0.00000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 3.45 | 93 | 245 | 0.380 | 0.0000160 | 2510 |
| Missense (PolyPhen) | 18 | 110.12 | 0.16346 | 1057 | ||
| Synonymous | 0.637 | 83 | 90.7 | 0.915 | 0.00000549 | 751 |
| Loss of Function | 4.17 | 0 | 20.2 | 0.00 | 0.00000102 | 225 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May be involved in meiotic recombination process.;
Recessive Scores
- pRec
- 0.273
Intolerance Scores
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.900
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |