WDR48

Chr 3p22.2

WD repeat domain 48

Aliases:: UAF1, KIAA1449, P80, SPG60, Bun62
MANE:: ENST00000302313.10

OMIM: 612167 ↗NCBI: 57599 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

WDR48 · Q8TAF3

v62025-08-01

Predicted Aligned Error matrix for WDR48 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

88.9/ 100

Confident

677 residues

Confidence breakdown

Very high(≥ 90)75%
Confident(70–90)13%
Low(50–70)5%
Very low(< 50)7%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Moderate Evidence (Amber)

Adult onset hereditary spastic paraplegia
BIALLELIC, autosomal or pseudoautosomal
Childhood onset hereditary spastic paraplegia
BIALLELIC, autosomal or pseudoautosomal
Adult onset neurodegenerative disorder
BIALLELIC, autosomal or pseudoautosomal
Hereditary spastic paraplegia
BIALLELIC, autosomal or pseudoautosomal

Disease associations (Open Targets)

neurodegenerative disease
0.52
cancer
0.47
autosomal recessive spastic paraplegia type 60
0.37
cornea transplantation
0.24
Spastic paraplegia
0.23
venous thromboembolism
0.17
Thromboembolism
0.13
hereditary spastic paraplegia
0.12
hepatocellular carcinoma
0.09
colitis
0.07

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

WD repeat-containing protein 48

Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46 (PubMed:18082604, PubMed:19075014, PubMed:26388029, PubMed:31253762). Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself (PubMed:18082604, PubMed:31253762). Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate (PubMed:19075014, PubMed:27373336). Also activates deubiquitinating activity of complexes containing USP12 (PubMed:19075014, PubMed:27373336, PubMed:27650958). In complex with USP12, acts as a potential tumor suppressor by positively regulating PHLPP1 stability (PubMed:24145035). 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:27373336, PubMed:27650958). Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination (PubMed:27239033, PubMed:27463890, PubMed:32350107). Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA) (PubMed:27239033, PubMed:31253762, PubMed:32350107). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes (PubMed:31253762, PubMed:32350107). Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:20147293). Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress (PubMed:31844045)