WDR48
WD repeat domain 48, the group of WD repeat domain containing
Basic information
Region (hg38): 3:39052013-39096671
Links
Phenotypes
GenCC
Source:
- autosomal recessive spastic paraplegia type 60 (Supportive), mode of inheritance: AR
ClinVar
This is a list of variants' phenotypes submitted to
- not_specified (30 variants)
- WDR48-related_disorder (10 variants)
- not_provided (3 variants)
- Hereditary_spastic_paraplegia (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the WDR48 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000020839.4. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 6 | |||||
| missense | 31 | 32 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 31 | 3 | 4 |
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| WDR48 | protein_coding | protein_coding | ENST00000302313 | 19 | 44667 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000154 | 125704 | 0 | 15 | 125719 | 0.0000597 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.80 | 211 | 361 | 0.585 | 0.0000175 | 4461 |
| Missense in Polyphen | 41 | 115.65 | 0.35452 | 1381 | ||
| Synonymous | -0.791 | 140 | 129 | 1.09 | 0.00000653 | 1267 |
| Loss of Function | 5.49 | 4 | 42.7 | 0.0937 | 0.00000243 | 477 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000585 | 0.0000585 |
| Ashkenazi Jewish | 0.0000995 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000973 | 0.0000967 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000164 | 0.000163 |
dbNSFP
Source:
- Function
- FUNCTION: Regulator of deubiquitinating complexes. Acts as a strong activator of USP1 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:26388029). Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself (PubMed:18082604). Also activates deubiquitinating activity of complexes containing USP12 (PubMed:19075014, PubMed:27650958, PubMed:27373336). Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme (PubMed:27650958, PubMed:27373336). Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate (PubMed:19075014, PubMed:27373336). In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). In case of infection by Herpesvirus saimiri, may play a role in vesicular transport or membrane fusion events necessary for transport to lysosomes. Induces lysosomal vesicle formation via interaction with Herpesvirus saimiri tyrosine kinase-interacting protein (TIP). Subsequently, TIP recruits tyrosine-protein kinase LCK, resulting in down-regulation of T-cell antigen receptor TCR. May play a role in generation of enlarged endosomal vesicles via interaction with TIP (PubMed:12196293). In case of infection by papillomavirus HPV11, promotes the maintenance of the viral genome via its interaction with HPV11 helicase E1 (PubMed:18032488). {ECO:0000269|PubMed:12196293, ECO:0000269|PubMed:18032488, ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:19075014, ECO:0000269|PubMed:24145035, ECO:0000269|PubMed:26388029, ECO:0000269|PubMed:27373336, ECO:0000269|PubMed:27650958}.;
- Pathway
- Fanconi anemia pathway - Homo sapiens (human);Fanconi Anemia Pathway;DNA Repair;Post-translational protein modification;Metabolism of proteins;Fanconi anemia pathway;Ub-specific processing proteases;Deubiquitination;Recognition of DNA damage by PCNA-containing replication complex;DNA Damage Bypass
(Consensus)
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- loftool
- 0.193
- rvis_EVS
- -0.47
- rvis_percentile_EVS
- 23.25
Haploinsufficiency Scores
- pHI
- 0.470
- hipred
- Y
- hipred_score
- 0.714
- ghis
- 0.664
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.898
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Wdr48
- Phenotype
- integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; skeleton phenotype; embryo phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- double-strand break repair via homologous recombination;spermatogenesis;single fertilization;viral process;protein deubiquitination;multicellular organism growth;DNA damage response, detection of DNA damage;skin development;embryonic organ development;skeletal system morphogenesis;homeostasis of number of cells;positive regulation of epithelial cell proliferation;seminiferous tubule development;regulation of protein monoubiquitination;positive regulation of protein deubiquitination
- Cellular component
- nucleus;nucleoplasm;lysosome;late endosome;intracellular membrane-bounded organelle
- Molecular function
- protein binding;thiol-dependent ubiquitinyl hydrolase activity;ubiquitin binding