• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
CUL4B (HGNC:2555) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
cullin 4B
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
No aliases found
%HI
8.31(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.09(Read more about gnomAD LOEUF score)
Cytoband
Xq24
Genomic Coordinates
GRCh37/hg19: chrX:119657713-119709387 NCBI Ensembl UCSC
GRCh38/hg38: chrX:120523858-120575532 NCBI Ensembl UCSC
MANE Select Transcript
NM_001079872.2 ENST00000371322.11 (Read more about MANE Select)
Function
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:29779948, PubMed:30166453, PubMed:33854232, PubMed:33854239, PubMed:22118460). The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition subunit (PubMed:14578910, PubMed:16678110, PubMed:1859... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-27615
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
02/09/2021

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • X-linked intellectual disability, Cabezas type Monarch
HI Evidence:
  • PUBMED: 17236139
    Tarpey (2007): A report of five families with intellectual disability in males who were found to have loss of function variants in CUL4B, including one frameshift, two nonsense, and two splice variants. Carrier females were unaffected.
  • PUBMED: 17273978
    Zou (2007) reported a large family with X-linked intellectual disability. They identified a nonsense variant in CUL4B (R388X) in seven affected males and six carrier females. All female carriers were phenotypically normal and had skewed X-inactivation.
  • PUBMED: 22182342
    Ravn (2011): A report of monozygotic male twins with intellectual disability, seizures, short stature, truncal obesity and dysmorphic features who had a 28 kb deletion involving only CUL4B. The deletion was inherited from a normal mother who had skewed X-inactivation.
  • PUBMED: 26350204
    In a cohort of 986 individuals with intellectual disability Grozeva et al (2015) identified 5 loss of function variants in CUL4B including 1 frameshift, 1 splice-site, and 3 nonsense variants.
HI Evidence Comments:
Loss of function mutations in CUL4B are now considered to be the cause of Cabezas syndrome, a form of syndromic X-linked intellectual disability. Additional features frequently include speech impairment, short stature, hypogonadism, central obesity and abnormal gait.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)