CUL7 Gene - Cullin 7
CUL7: A Key Component of the E3 Ubiquitin-Protein Ligase Complex and Its Role in Growth Regulation and Disease
Gene Information Card
| Symbol | CUL7 |
|---|---|
| Full Name | cullin 7 |
| Gene Type | protein-coding |
| Chromosomal Location | 6p21.1 |
| NCBI Gene ID | 9820 ncbi.nlm.nih.gov/gene/9820 |
| Ensembl ID | ENSG00000144040 |
| UniProt ID | Q14999 |
| OMIM ID | 609577 |
| HGNC ID | 21024 |
| Aliases | CUL-7, dJ20C7.5, KIAA0076, p185 |
Description
CUL7 (cullin 7) encodes a member of the cullin protein family, which serves as a scaffold for the multisubunit E3 ubiquitin-protein ligase complex (CUL7-RING ubiquitin ligase). This complex targets specific substrates for ubiquitination and proteasomal degradation, regulating cell cycle progression, growth, and development. CUL7 is essential for normal embryonic and postnatal growth. Mutations in CUL7 cause 3-M syndrome (OMIM #273750) and Yakut short stature syndrome (OMIM #601718), both characterized by severe pre- and postnatal growth retardation, facial dysmorphism, and skeletal abnormalities. CUL7 also interacts with p53 and may influence tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| 3-M syndrome | Loss-of-function mutations in CUL7 impair the assembly or activity of the CUL7-RING E3 ubiquitin ligase complex, disrupting ubiquitination of growth-regulatory substrates (e.g., p53, cyclin D1). This leads to reduced cell proliferation and severe growth retardation. | OMIM #273750; ClinVar; PMID: 15805161 |
| Yakut short stature syndrome | Homozygous missense or nonsense mutations in CUL7 (e.g., p.Arg1445Ter) cause a phenotype overlapping with 3-M syndrome, including short stature, facial dysmorphism, and skeletal anomalies. The mechanism involves loss of CUL7 function in the ubiquitin-proteasome pathway. | OMIM #601718; PMID: 21539574 |
| 3-M syndrome (variant) | Compound heterozygous or homozygous CUL7 mutations (e.g., c.2781_2782delCT, p.Cys928Ter) result in truncated protein lacking the C-terminal domain required for complex formation, leading to defective ubiquitination and growth impairment. | ClinVar; PMID: 15805161 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adipose tissue | 5.2 | Low |
| Adrenal gland | 7.8 | Low |
| Brain | 6.1 | Low |
| Breast | 8.3 | Low |
| Colon | 9.5 | Low |
| Esophagus | 7.1 | Low |
| Heart | 6.8 | Low |
| Kidney | 10.2 | Medium |
| Liver | 11.4 | Medium |
| Lung | 9.9 | Low |
| Muscle | 5.6 | Low |
| Ovary | 8.7 | Low |
| Pancreas | 7.3 | Low |
| Placenta | 12.1 | Medium |
| Prostate | 9.0 | Low |
| Salivary gland | 6.4 | Low |
| Skin | 7.5 | Low |
| Small intestine | 8.1 | Low |
| Spleen | 7.9 | Low |
| Stomach | 8.6 | Low |
| Testis | 10.8 | Medium |
| Thyroid | 8.0 | Low |
| Urinary bladder | 7.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 10.5 | Embryonic kidney; moderate expression |
| HeLa | 9.8 | Cervical carcinoma; moderate expression |
| HepG2 | 11.2 | Hepatocellular carcinoma; moderate expression |
| K562 | 7.4 | Leukemia; low expression |
| MCF7 | 8.9 | Breast carcinoma; low expression |
| SH-SY5Y | 6.3 | Neuroblastoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2781_2782delCT (p.Cys928Ter) | Frameshift / nonsense | Rare | Loss of function; truncation of C-terminal domain; associated with 3-M syndrome |
| c.4333C>T (p.Arg1445Ter) | Nonsense | Rare | Loss of function; premature stop; associated with Yakut short stature syndrome |
| c.1945C>T (p.Arg649Trp) | Missense | Rare | Likely loss of function; disrupts protein folding; reported in 3-M syndrome |
| c.4348C>T (p.Arg1450Ter) | Nonsense | Rare | Loss of function; associated with 3-M syndrome |
Mutation functional classification
Loss of Function (LOF)
Most CUL7 mutations (nonsense, frameshift, missense) result in loss of E3 ubiquitin ligase activity, leading to impaired ubiquitination of substrates such as p53 and cyclin D1, causing growth retardation syndromes (3-M syndrome, Yakut short stature).
Gain of Function (GOF)
No gain-of-function mutations have been reported for CUL7 in the curated databases.
Dominant Negative (DN)
No dominant-negative mutations have been described for CUL7; all disease-associated mutations are recessive (homozygous or compound heterozygous).
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• p53 signaling pathway (KEGG: hsa04115) - via interaction with p53
• Cell cycle (KEGG: hsa04110) - via cyclin D1 regulation
• Protein ubiquitination (Reactome: R-HSA-983168)
Protein Summary
Cullin-7 (UniProt Q14999) is a 1698-amino acid protein (185 kDa) that functions as a scaffold in the CUL7-RING E3 ubiquitin ligase complex. It contains a cullin domain (residues 1-400) and a C-terminal domain that interacts with RBX1 and SKP1 to form the active ligase. CUL7 targets key regulators of cell growth (e.g., p53, cyclin D1) for ubiquitination and degradation. Loss of CUL7 function leads to accumulation of these substrates, resulting in cell cycle arrest and growth retardation. The protein is widely expressed, with highest levels in placenta, kidney, liver, and testis. CUL7 is not a known oncogene but may modulate tumor suppressor pathways.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CUL7 Knockout HEK293 Cell Line | EDJ-KQ1883 | Human | 9820 | Details Get a Quote |
| CUL7 Knockout A-549 Cell Line | EDJ-KQ23137 | Human | 9820 | Details Get a Quote |
| CUL7 Knockout HCT 116 Cell Line | EDJ-KQ23138 | Human | 9820 | Details Get a Quote |
| CUL7 Knockout HeLa Cell Line | EDJ-KQ23139 | Human | 9820 | Details Get a Quote |
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