CUL4B

Chr X

cullin 4B

Also known as: CUL-4B, MRXHF2, MRXS15, MRXSC, SFM2

NCBI Gene: 8450 ENSG00000158290 UniProt: Q13620

The encoded protein forms an E3 ubiquitin ligase complex that catalyzes polyubiquitination of specific protein substrates and is required for proteolysis of DNA replication regulators including chromatin licensing and DNA replication factor 1 and cyclin E. Loss-of-function mutations cause X-linked syndromic intellectual developmental disorder, Cabezas type, with X-linked recessive inheritance. The gene is extremely intolerant to loss-of-function variation, consistent with its essential role in protein degradation pathways critical for DNA replication.

ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is a member of the cullin family. The encoded protein forms a complex that functions as an E3 ubiquitin ligase and catalyzes the polyubiquitination of specific protein substrates in the cell. The protein interacts with a ring finger protein, and is required for the proteolysis of several regulators of DNA replication including chromatin licensing and DNA replication factor 1 and cyclin E. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtIntellectual developmental disorder, X-linked, syndromic, Cabezas type

Clinical highlights

Gene-disease validity (ClinGen)

X-linked intellectual disability, Cabezas type · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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