GeneBe

CUL1

protein-coding

cullin 1, the group of Cullins|SCF complex core subunits

Gene summary

Enables ubiquitin protein ligase binding activity. Contributes to ubiquitin ligase complex scaffold activity. Involved in several processes, including SCF-dependent proteasomal ubiquitin-dependent protein catabolic process; positive regulation of canonical NF-kappaB signal transduction; and protein K48-linked ubiquitination. Located in plasma membrane. Part of Parkin-FBXW7-Cul1 ubiquitin ligase complex and SCF ubiquitin ligase complex. Is active in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_003592.3

Inheritance

—

ClinVar variants

U:38

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.06

Max pathogenic AF

—

Genomic locus

chr7:148,697,914-148,801,110

External References & Databases

Ensembl (ENSG00000055130)NCBI Gene (8454)OMIM (603134)HGNC:2551GenCCUniProt (Q13616)AlphaFoldClinVar (CUL1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~103.2 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CUL1 variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 20
not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003592.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
 2
missense
26
clinvar
 26
nonsense
2
clinvar
 2
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total00380038
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 108 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_003592.3RefSeqNP_003583.221MANE Select
ENST00000325222.9EnsemblENSP00000326804.321MANE Select
NM_001370660.1RefSeqNP_001357589.121Standard
NM_001370661.1RefSeqNP_001357590.121Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Circadian rhythm - Homo sapiens (human)
  • TGF-beta signaling pathway - Homo sapiens (human)
  • Cell cycle - Homo sapiens (human)
  • Oocyte meiosis - Homo sapiens (human)
  • Ubiquitin mediated proteolysis - Homo sapiens (human)

Biological Process

  • G1/S transition of mitotic cell cycle
  • G2/M transition of mitotic cell cycle
  • protein polyubiquitination
  • ubiquitin-dependent protein catabolic process
  • protein monoubiquitination

Molecular Function

  • ubiquitin-protein transferase activity
  • protein binding
  • ubiquitin protein ligase binding
  • ubiquitin protein ligase activity

Cellular Component

  • nucleoplasm
  • cytosol
  • SCF ubiquitin ligase complex
  • cullin-RING ubiquitin ligase complex
  • Parkin-FBXW7-Cul1 ubiquitin ligase complex

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000325222
Coding exons
21
Length
103123
Individuals with no LoFs
125744
Homozygous LoFs
0
Heterozygous LoFs
4
Defined
125748
p
0.0000159
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense5.70934230.2200.00002345118
Missense (PolyPhen)17142.990.118891942
Synonymous-0.2071671641.020.000009871380
Loss of Function6.43353.90.05560.00000313615

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish00.0absent
East Asian0.0000550.000054rare
Finnish00.0absent
European (Non-Finnish)0.0000270.000026rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Core component of multiple cullin-RING-based SCF (SKP1- CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin- protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25704143, PubMed:25503564). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2. {ECO:0000269|PubMed:15531760, ECO:0000269|PubMed:15640526, ECO:0000269|PubMed:18644861, ECO:0000269|PubMed:19679664, ECO:0000269|PubMed:22113614, ECO:0000269|PubMed:22405651, ECO:0000269|PubMed:23263282, ECO:0000269|PubMed:23431138, ECO:0000269|PubMed:25503564, ECO:0000269|PubMed:25704143, ECO:0000269|PubMed:27565346, ECO:0000269|PubMed:9663463}.;

Recessive Scores

pRec
0.256

Intolerance Scores

LoFtool
0.277
RVIS EVS
-0.52
RVIS percentile EVS
21.2

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.962

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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