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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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CUL7
cullin 7
Chromosome 6 Β· 6p21.1
NCBI Gene: 9820Ensembl: ENSG00000044090.13HGNC: HGNC:21024UniProt: A0A669KBH4
130PubMed Papers
21Diseases
0Drugs
126Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
plasma membraneperinuclear region of cytoplasmmicrotubule cytoskeleton organizationCul7-RING ubiquitin ligase complex3M syndrome3-M syndromegenetic disorderyakut short stature syndrome
✦AI Summary

CUL7 (cullin 7) is a core component of two distinct E3 ubiquitin ligase complexes: the 3M complex and the Cul7-RING(FBXW8) complex, both involved in protein ubiquitination and degradation pathways 1. The protein functions as a molecular scaffold that positions substrates near RING-bound E2 ubiquitin-conjugating enzymes to facilitate ubiquitin transfer 1. CUL7-containing complexes target various proteins for degradation, including IRS1 in insulin signaling, ATGL in lipolysis regulation, and TET2 in cancer drug resistance 234. The 3M complex regulates microtubule dynamics and genome integrity, though the precise mechanism remains unclear 1. Disease associations include 3M syndrome 1, caused by CUL7 mutations leading to growth defects 5. In cancer, CUL7 expression is often upregulated and associated with poor prognosis in colon adenocarcinoma 6. Additionally, CUL7 contributes to photoreceptor ferroptosis in retinal degeneration by promoting GPX4 ubiquitination and degradation 7. The gene shows potential involvement in autism spectrum disorders through inherited truncating mutations 8, highlighting its broad physiological importance in development, metabolism, and disease pathogenesis.

Sources cited
1
CUL7 is part of Cullin-RING E3 ubiquitin ligase complexes that function as molecular scaffolds
PMID: 21554755
2
CUL7FBXW8 complex regulates ATGL-driven lipolysis through glucose sensing mechanism
PMID: 38561547
3
CUL7FBXW11 complex degrades TET2 in EGFR-TKI resistant lung cancer
PMID: 38461173
4
CUL7-FBXW8 E3 ligase promotes YTHDF1 degradation in cancer immune surveillance
PMID: 39900921
5
CUL7 mutations cause 3M syndrome with growth hormone insensitivity features
PMID: 34136918
6
CUL7 is upregulated in colon adenocarcinoma and associated with poor prognosis
PMID: 36304472
7
CUL7 promotes photoreceptor ferroptosis by mediating GPX4 ubiquitination in retinal degeneration
PMID: 39267786
8
CUL7 shows excess inherited truncating mutations in autism spectrum disorders
PMID: 25961944
Disease Associationsβ“˜21
3M syndromeOpen Targets
0.82Strong
3-M syndromeOpen Targets
0.67Moderate
genetic disorderOpen Targets
0.49Moderate
yakut short stature syndromeOpen Targets
0.33Weak
bilirubin metabolism diseaseOpen Targets
0.18Weak
Growth delayOpen Targets
0.12Weak
Short statureOpen Targets
0.12Weak
gliomaOpen Targets
0.08Suggestive
cancerOpen Targets
0.07Suggestive
lung adenocarcinomaOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
hypertriglyceridemia 2Open Targets
0.06Suggestive
familial hypercholesterolemiaOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.05Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.05Suggestive
Combined hyperlipidemiaOpen Targets
0.04Suggestive
thyroid hormone metabolism, abnormal, 2Open Targets
0.04Suggestive
sitosterolemia 2Open Targets
0.04Suggestive
homozygous familial hypercholesterolemiaOpen Targets
0.04Suggestive
pancreatic triacylglycerol lipase deficiencyOpen Targets
0.04Suggestive
3M syndrome 1UniProt
Pathogenic Variants126
NM_014780.5(CUL7):c.3356-2A>CLikely pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2026
NM_014780.5(CUL7):c.2112G>A (p.Trp704Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 704
NM_014780.5(CUL7):c.4333C>T (p.Arg1445Ter)Pathogenic
3M syndrome 1|not provided|3-M syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 1445
NM_014780.5(CUL7):c.3041T>G (p.Leu1014Arg)Pathogenic
Inborn genetic diseases|not provided|3M syndrome 1|3-M syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 1014
NM_014780.5(CUL7):c.3136del (p.Leu1046fs)Pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 1046
NM_014780.5(CUL7):c.1392G>A (p.Trp464Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 464
NM_014780.5(CUL7):c.3907C>T (p.Gln1303Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1303
NM_014780.5(CUL7):c.1648C>T (p.Arg550Ter)Pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 550
NM_014780.5(CUL7):c.2164C>T (p.Arg722Ter)Pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 722
NM_014780.5(CUL7):c.4318C>T (p.Arg1440Ter)Pathogenic
not provided|3-M syndrome|3M syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 1440
NM_014780.5(CUL7):c.3924_3931del (p.Leu1308_Ser1309insTer)Pathogenic
3M syndrome 1|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 1308
NM_014780.5(CUL7):c.3129G>A (p.Trp1043Ter)Pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2025β†’ Residue 1043
NM_014780.5(CUL7):c.4451_4452del (p.Val1484fs)Pathogenic
3M syndrome 1|CUL7-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 1484
NM_014780.5(CUL7):c.4717C>T (p.Arg1573Ter)Pathogenic
not provided|Inborn genetic diseases|3M syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 1573
NM_014780.5(CUL7):c.2398-2A>GLikely pathogenic
3-M syndrome|not provided
β˜…β˜…β˜†β˜†2024
NM_014780.5(CUL7):c.2787del (p.Ser930fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 930
NM_014780.5(CUL7):c.2710C>T (p.Arg904Ter)Pathogenic
not provided|3-M syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 904
NM_014780.5(CUL7):c.263del (p.Val88fs)Pathogenic
not provided|3M syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 88
NM_014780.5(CUL7):c.4763T>C (p.Leu1588Pro)Pathogenic
3M syndrome 1|not provided|3-M syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 1588
NM_014780.5(CUL7):c.2130_2131delinsTGCCTG (p.Cys711fs)Pathogenic
not provided|3-M syndrome|3M syndrome 1
β˜…β˜…β˜†β˜†2024β†’ Residue 711
View on ClinVar β†—
Related Genes
NEDD8Protein interaction100%SKP1Protein interaction100%CUL5Protein interaction100%CUL4BProtein interaction100%CUL4AProtein interaction100%CUL3Protein interaction100%
Tissue Expression6 tissues
Ovary
100%
Liver
54%
Lung
52%
Brain
46%
Heart
39%
Bone Marrow
25%
Gene Interaction Network
Click a node to explore
CUL7NEDD8SKP1CUL5CUL4BCUL4ACUL3
PROTEIN STRUCTURE
Preparing viewer…
PDB7Z8B Β· 2.80 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.62LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.52 [0.44–0.62]
RankingsWhere CUL7 stands among ~20K protein-coding genes
  • #3,586of 20,598
    Most Researched130 Β· top quartile
  • #617of 5,498
    Most Pathogenic Variants126 Β· top quartile
  • #4,341of 17,882
    Most Constrained (LOEUF)0.62 Β· top quartile
Genes detectedCUL7
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Excess of rare, inherited truncating mutations in autism.
PMID: 25961944
Nat Genet Β· 2015
1.00
2
Glucose controls lipolysis through Golgi PtdIns4P-mediated regulation of ATGL.
PMID: 38561547
Nat Cell Biol Β· 2024
0.90
3
Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.
PMID: 38461173
Signal Transduct Target Ther Β· 2024
0.80
4
Photoreceptor-targeted extracellular vesicles-mediated delivery of Cul7 siRNA for retinal degeneration therapy.
PMID: 39267786
Theranostics Β· 2024
0.70
5
USP5 stabilizes YTHDF1 to control cancer immune surveillance through mTORC1-mediated phosphorylation.
PMID: 39900921
Nat Commun Β· 2025
0.60