GENE REFERENCE / HGNC:2553

CUL3

cullin 3

protein-coding gene2q36.2Gene information

What does this gene do?

The CUL3 gene provides instructions for making a protein called cullin-3. This protein plays a role in the ubiquitin-proteasome system, which breaks down (degrades) unwanted proteins inside cells.

The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. Cullin-3 is a core piece of a complex known as an E3 ubiquitin ligase. E3 ubiquitin ligases tag proteins with molecules called ubiquitin. Ubiquitin signals specialized cell structures known as proteasomes to attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system also regulates several critical cell activities by controlling the amounts of proteins involved in them.

E3 ubiquitin ligases that contain cullin-3 tag many proteins that perform a variety of functions, such as cell growth and division. These ligases also tag blood pressure-related proteins called WNK1 and WNK4, which are produced from the WNK1 and WNK4 genes. By regulating the amount of WNK1 and WNK4 available, cullin-3 plays a role in blood pressure control.

Source: MedlinePlus, National Library of Medicine. Source publication: 2023-09-12. Source review: 2023-09.

ClinGen reviews

ClinGen reviews the evidence linking a particular gene to a condition. Each rating below describes the strength of that link. It does not classify a variant in your DNA file.

Condition	Inheritance	Evidence
pseudohypoaldosteronism type 2EMONDO:0013782 · Evaluated 2021-12-01	Autosomal dominant	DefinitiveTubulopathy Gene Curation Expert Panel
complex neurodevelopmental disorderMONDO:0100038 · Evaluated 2021-01-16	Autosomal dominant	DefinitiveIntellectual Disability and Autism Gene Curation Expert Panel

ClinVar records

These numbers show what has been submitted to ClinVar. They cannot tell you how likely you are to have a condition.

Submitted alleles: 751
Submissions for variants in or overlapping this gene: 977
Submissions explicitly reporting this gene: 925
Alleles reported pathogenic / likely pathogenic: 133
VariationIDs with uncertain significance: 314
VariationIDs with conflicting classifications: 24

The rows count different things: alleles, submissions or VariationIDs. Their categories can overlap, so do not add them together. Pathogenic/likely pathogenic counts exclude structural variants that merely overlap a gene. A dash in the source means “not reported,” not zero.

NCBI produces the gene-summary file each week using counts recorded at the start of the month. The numbers may differ from those on the live ClinVar website. Read the field definitions ↗

View this gene in ClinVar ↗

YOUR DNA FILE

Can your DNA file tell you about CUL3?

From a DNA test kit (such as 23andMe, AncestryDNA or MyHeritage). These kits check a fixed list of about 600,000 to 700,000 positions across your whole genome. ClinVar lists 133 alleles in CUL3 reported as pathogenic or likely pathogenic. A kit checks only some of these positions, and often none of them.

From whole genome sequencing (a VCF file). Sequencing reads most of your genome. Your file lists the places where your DNA differs from the reference genome. Some regions are hard to sequence, including parts of some genes that have near-identical copies elsewhere, and a VCF file does not record which positions were read well.

If a variant is not in your file, that does not mean you don’t have it.

What BioDecode checks

BioDecode compares every variant in your file with ClinVar, on your own computer. For each match, it shows the ClinVar classification, the review status and the condition it was reported for. Your file is not uploaded.

A ClinVar classification applies to one particular variant and the condition it was reported for. It does not tell you about other variants in CUL3.

BioDecode cannot fill gaps in your test, diagnose a condition or replace clinical testing.

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