WDR48

WD repeat domain 48, the group of WD repeat domain containing

Basic information

Region (hg38): 3:39052013-39096671

Links

ENSG00000114742 ∙ NCBI:57599 ∙ OMIM:612167 ∙ HGNC:30914 ∙ Uniprot:Q8TAF3 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive spastic paraplegia type 60 (Supportive), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WDR48 gene.

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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	2	5
missense			11		1	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding				2		2
Total	0	0	11	5	3

Variants in WDR48

This is a list of pathogenic ClinVar variants found in the WDR48 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-39052082-G-C			Likely benign (Jan 01, 2023)
3-39063106-T-C			Benign (Dec 31, 2019)
3-39063113-C-G		not specified	Uncertain significance (Jan 17, 2023)
3-39063129-A-G		not specified	Uncertain significance (Feb 15, 2023)
3-39065842-A-T		not specified	Uncertain significance (Jun 22, 2024)
3-39065870-C-G		WDR48-related disorder	Benign (Jun 18, 2019)
3-39066540-T-G		WDR48-related disorder	Likely benign (Jul 01, 2019)
3-39066559-T-G		Hereditary spastic paraplegia • WDR48-related disorder	Uncertain significance (Jul 01, 2018)
3-39066855-C-T		not specified	Uncertain significance (Jul 27, 2022)
3-39067051-C-T		WDR48-related disorder	Likely benign (Apr 16, 2019)
3-39068773-T-G		not specified	Uncertain significance (Jun 07, 2024)
3-39068800-A-G		WDR48-related disorder	Uncertain significance (Mar 08, 2023)
3-39068813-C-T		not specified	Uncertain significance (May 30, 2024)
3-39069740-C-T		not specified	Uncertain significance (Dec 13, 2022)
3-39074783-T-A		not specified	Uncertain significance (Jan 31, 2024)
3-39077164-C-T		not specified	Uncertain significance (Mar 06, 2023)
3-39078176-T-A		not specified	Uncertain significance (Oct 05, 2023)
3-39078192-C-G		not specified	Uncertain significance (Dec 06, 2022)
3-39078213-G-C		not specified	Uncertain significance (Jul 05, 2022)
3-39079705-C-T		WDR48-related disorder	Likely benign (Feb 20, 2024)
3-39084654-A-G		not specified	Uncertain significance (May 30, 2024)
3-39088204-T-C		WDR48-related disorder	Likely benign (Sep 18, 2019)
3-39089294-A-G		WDR48-related disorder	Likely benign (Dec 29, 2022)
3-39091638-A-G		WDR48-related disorder	Benign (Jul 26, 2019)
3-39094012-A-G		WDR48-related disorder	Likely benign (Sep 18, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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