CUL4B

Chr Xq24

cullin 4B

MANE:: ENST00000371322.11

OMIM: 300304 ↗NCBI: 8450 ↗Ensembl ↗

Annotations refreshed 10 hours ago.

Predicted protein structure

AlphaFold predicted structure

CUL4B · Q13620

v62025-08-01

Predicted Aligned Error matrix for CUL4B — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

78.5/ 100

Confident

913 residues

Confidence breakdown

Very high(≥ 90)59%
Confident(70–90)16%
Low(50–70)3%
Very low(< 50)21%

Open interactive 3D viewer

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

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

DDG2P
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Differences in sex development
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Early onset or syndromic epilepsy
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hypogonadotropic hypogonadism
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Hypogonadotropic hypogonadism (GMS)
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Intellectual disability
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Arthrogryposis

Disease associations (Open Targets)

X-linked intellectual disability, Cabezas type
0.81
X-linked intellectual disability, Vitale type
0.69
hereditary disease
0.50
Intellectual disability
0.47
Seizure
0.46
X-linked syndromic intellectual disability
0.37
Global developmental delay
0.34
Abnormal facial shape
0.34
Short stature
0.34
X-linked intellectual disability - Dandy-Walker malformation - basal ganglia disease - Seizures
0.27

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

Protein function (UniProt)

Cullin-4B

Core component of multiple cullin-RING-based E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14578910, PubMed:16322693, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948, PubMed:30166453, PubMed:33854232, PubMed:33854239, PubMed:25970626). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460, PubMed:29779948). CUL4B may act within the complex as a scaffold protein, contributing to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme (PubMed:14578910, PubMed:16678110, PubMed:18593899, PubMed:22118460). Plays a role as part of the E3 ubiquitin-protein ligase complex in polyubiquitination of CDT1, histone H2A, histone H3 and histone H4 in response to radiation-induced DNA damage (PubMed:14578910, PubMed:16678110, PubMed:18593899). Targeted to UV damaged chromatin by DDB2 and may be important for DNA repair and DNA replication (PubMed:16678110). A number of DCX complexes (containing either TRPC4AP or DCAF12 as substrate-recognition component) are part of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948). The DCX(AMBRA1) complex is a master regulator of the transition from G1 to S cell phase by mediating ubiquitination of phosphorylated cyclin-D (CCND1, CCND2 and CCND3) (PubMed:33854232, PubMed:33854239). The DCX(AMBRA1) complex also acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:30166453). Required for ubiquitination of cyclin E (CCNE1 or CCNE2), and consequently, normal G1 cell cycle progression (PubMed:16322693, PubMed:19801544). Regulates the mammalian target-of-rapamycin (mTOR) pathway involved in control of cell growth, size and metabolism (PubMed:18235224). Specific CUL4B regulation of the mTORC1-mediated pathway is dependent upon 26S proteasome function and requires interaction between CUL4B and MLST8 (PubMed:18235224). With CUL4A, contributes to ribosome biogenesis (PubMed:26711351)