WDR18
protein-codingWD repeat domain 18, the group of WD repeat domain containing|Large ribosomal subunit biogenesis complex
Gene summary
This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~14.1 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 WDR18 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_024100.4. 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 | 1 | 3 | ||
| missense | 86 | 5 | 91 | |||
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 90 | 6 | 1 | 97 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_077005.2 | 10 | MANE Select | |
| Ensembl | ENSP00000476117.3 | 10 | MANE Select | |
| RefSeq | NP_001359014.1 | 10 | Standard | |
| RefSeq | NP_001359015.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| wdr18 | Danio rerio | Structure: pancreas Quality: mislocalised abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- ribosomal large subunit assembly
- pre-replicative complex assembly involved in nuclear cell cycle DNA replication
- rRNA processing
- multicellular organism development
- regulation of DNA-dependent DNA replication initiation
Molecular Function
- protein binding
Cellular Component
- nucleoplasm
- nuclear pre-replicative complex
- nucleolus
- cytoplasm
- Rix1 complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000251289
- Coding exons
- 10
- Length
- 11396
- Individuals with no LoFs
- 125511
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125532
- p
- 0.0000836
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.479 | 232 | 253 | 0.915 | 0.0000161 | 2734 |
| Missense (PolyPhen) | 66 | 71.135 | 0.92781 | 749 | ||
| Synonymous | -1.52 | 138 | 117 | 1.18 | 0.00000846 | 879 |
| Loss of Function | 3.84 | 1 | 19.1 | 0.0524 | 8.88e-7 | 214 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00020 | 0.00020 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00038 | 0.00023 | rare |
| European (Non-Finnish) | 0.000055 | 0.000053 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211). {ECO:0000269|PubMed:21326211, ECO:0000269|PubMed:22872859}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.298
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.85
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.906
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |