LLGL1

Chr 17

LLGL scribble cell polarity complex component 1

Also known as: DLG4, HUGL, HUGL-1, HUGL1, LLGL, Lgl1, Mgl1

NCBI Gene: 3996ENSG00000131899UniProt: Q15334

This gene encodes a protein that is similar to a tumor suppressor in Drosophila. The protein is part of a cytoskeletal network and is associated with nonmuscle myosin II heavy chain and a kinase that specifically phosphorylates this protein at serine residues. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

294
ClinVar variants
116
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— LLGL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
116 Pathogenic / Likely Pathogenic· 155 VUS of 294 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.53LOEUF
pLI 0.000
Z-score 4.16
OE 0.35 (0.24–0.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.45Z-score
OE missense 0.84 (0.79–0.90)
575 obs / 681.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.35 (0.24–0.53)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.79–0.90)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.16
0≤1.21.6
LoF obs/exp: 17 / 48.1Missense obs/exp: 575 / 681.9Syn Z: -2.16

ClinVar Variant Classifications

294 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic116
VUS155
Likely Benign12
Benign11
116
Pathogenic
155
VUS
12
Likely Benign
11
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
116
0
116
Likely Pathogenic
0
0
0
0
0
VUS
0
151
4
0
155
Likely Benign
0
9
1
2
12
Benign
0
3
2
6
11
Total01631238294

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LLGL1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Wnt Signalling in Acute Myeloid Leukaemia.
Gruszka AM et al.·Cells
2019Review
Cell fate determinant Llgl1 is required for propagation of acute myeloid leukemia.
Eifert T et al.·Leukemia
2023
LLGL1 Regulates Gemcitabine Resistance by Modulating the ERK-SP1-OSMR Pathway in Pancreatic Ductal Adenocarcinoma.
Zhu YX et al.·Cell Mol Gastroenterol Hepatol
2020
Llgl1 prevents metaplastic survival driven by epidermal growth factor dependent migration.
Greenwood E et al.·Oncotarget
2016
Causal and Candidate Gene Variants in a Large Cohort of Women With Primary Ovarian Insufficiency.
Gorsi B et al.·J Clin Endocrinol Metab
2022Cohort
Scribble, Erbin, and Lano redundantly regulate epithelial polarity and apical adhesion complex.
Choi J et al.·J Cell Biol
2019
Identification of Rac guanine nucleotide exchange factors promoting Lgl1 phosphorylation in glioblastoma.
Lavictoire SJ et al.·J Biol Chem
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools