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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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LLGL1
LLGL scribble cell polarity complex component 1
Chromosome 17 · 17p11.2
NCBI Gene: 3996Ensembl: ENSG00000131899.14HGNC: HGNC:6628UniProt: Q15334
116PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cortical actin cytoskeletoncortical actin cytoskeleton organizationprotein bindingcytoplasmAbnormality of the skeletal systemurethral syndromegliomainfection
✦AI Summary

LLGL1 (LLGL scribble cell polarity complex component 1) functions as a scaffolding protein that regulates apical-basal polarity establishment in epithelial cells 1. The protein operates through a sophisticated capture-and-release mechanism with aPKC-Par6, where LLGL1 forms a stable complex that mutually inhibits both kinase and substrate activities until released by active Cdc42 and Crumbs signaling 2. LLGL1 demonstrates context-dependent functions across different cell types. In hematopoietic stem cells (HSCs), loss of LLGL1 paradoxically increases HSC fitness and self-renewal capacity, unlike its complex partner Scrib which impairs HSC function 3. However, in acute myeloid leukemia (AML), LLGL1 is required for leukemia propagation, maintaining stemness-associated gene expression including HoxA genes, and its inactivation induces differentiation toward a GMP-like phenotype 4. In solid tumors, LLGL1 loss correlates with cancer progression - it is associated with diffuse gastric cancer and peritoneal metastases, co-expressing with E-cadherin and promoting cellular adhesion 5. LLGL1 is also regulated by microRNA-652-3p, which targets it to modulate cell polarity mechanisms affecting cancer metastasis 6. These findings establish LLGL1 as having diverse, cell-type-specific roles in polarity regulation and cancer biology.

Sources cited
1
LLGL1 functions as a scaffolding protein regulating apical-basal polarity in epithelial cells
PMID: 30996345
2
LLGL1 operates through capture-and-release mechanism with aPKC-Par6 complex
PMID: 39762628
3
Loss of LLGL1 increases HSC fitness and self-renewal capacity
PMID: 30083817
4
LLGL1 is required for AML propagation and maintains stemness genes
PMID: 37587260
5
LLGL1 loss correlates with diffuse gastric cancer and peritoneal metastases
PMID: 31058107
6
LLGL1 is targeted by microRNA-652-3p affecting cell polarity and cancer metastasis
PMID: 33712860
Disease Associationsⓘ20
Abnormality of the skeletal systemOpen Targets
0.33Weak
urethral syndromeOpen Targets
0.23Weak
gliomaOpen Targets
0.09Suggestive
infectionOpen Targets
0.08Suggestive
hepatocellular carcinomaOpen Targets
0.08Suggestive
response to xenobiotic stimulusOpen Targets
0.08Suggestive
acute myeloid leukemiaOpen Targets
0.07Suggestive
attention deficit hyperactivity disorderOpen Targets
0.07Suggestive
substance abuseOpen Targets
0.07Suggestive
neoplasmOpen Targets
0.07Suggestive
hair colorOpen Targets
0.06Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
glioblastomaOpen Targets
0.04Suggestive
endometrial cancerOpen Targets
0.04Suggestive
melanomaOpen Targets
0.04Suggestive
subcortical band heterotopiaOpen Targets
0.04Suggestive
breast cancerOpen Targets
0.04Suggestive
Chudley-McCullough syndromeOpen Targets
0.03Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.03Suggestive
gastric cancerOpen Targets
0.03Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PRKCZProtein interaction100%PRKCIProtein interaction100%DLG4Protein interaction98%DLG1Protein interaction98%SCRIBProtein interaction96%DLG3Protein interaction94%
Tissue Expression6 tissues
Brain
100%
Ovary
65%
Bone Marrow
38%
Heart
30%
Lung
24%
Liver
12%
Gene Interaction Network
Click a node to explore
LLGL1PRKCZPRKCIDLG4DLG1SCRIBDLG3
PROTEIN STRUCTURE
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PDB8R3Y · 3.68 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.67LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.54 [0.43–0.67]
RankingsWhere LLGL1 stands among ~20K protein-coding genes
  • #4,087of 20,598
    Most Researched116 · top quartile
  • #4,908of 17,882
    Most Constrained (LOEUF)0.67
Genes detectedLLGL1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
LLGL2 rescues nutrient stress by promoting leucine uptake in ER
PMID: 30996345
Nature · 2019
1.00
2
Capture, mutual inhibition and release mechanism for aPKC-Par6 and its multisite polarity substrate Lgl.
PMID: 39762628
Nat Struct Mol Biol · 2025
0.90
3
Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.
PMID: 37587260
Leukemia · 2023
0.80
4
Wnt Signalling in Acute Myeloid Leukaemia.
PMID: 31703382
Cells · 2019
0.70
5
Targets and regulation of microRNA-652-3p in homoeostasis and disease.
PMID: 33712860
J Mol Med (Berl) · 2021
0.60