LLGL1
protein-codingLLGL scribble cell polarity complex component 1, the group of WD repeat domain containing|Scribble complex
Gene summary
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]
- DLG4
- LLGL
- HUGL
- HUGL-1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to LLGL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004140.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 2 | 6 | 9 | ||
| missense | 156 | 10 | 3 | 169 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 161 | 12 | 9 | 182 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004131.4 | 22 | MANE Select | |
| Ensembl | ENSP00000321537.4 | 22 | MANE Select | |
| Ensembl | ENSP00000518781.1 | 13 | Standard | |
| Ensembl | ENSP00000525664.1 | 22 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| llgl1 | Danio rerio | Structure: peridermal cell Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Tight junction - Homo sapiens (human)
- Hippo signaling pathway - Homo sapiens (human)
- Human papillomavirus infection - Homo sapiens (human)
Biological Process
- exocytosis
- Golgi to plasma membrane transport
- axonogenesis
- regulation of Notch signaling pathway
- cortical actin cytoskeleton organization
Molecular Function
- GTPase activator activity
- structural molecule activity
- protein binding
- Rab GTPase binding
- protein kinase binding
Cellular Component
- Golgi cis cisterna
- cytoplasm
- cytoskeleton
- plasma membrane
- axon
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000316843
- Coding exons
- 22
- Length
- 19289
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125747
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.45 | 575 | 682 | 0.843 | 0.0000464 | 6823 |
| Missense (PolyPhen) | 188 | 267.13 | 0.70377 | 2671 | ||
| Synonymous | -2.16 | 341 | 294 | 1.16 | 0.0000212 | 2261 |
| Loss of Function | 4.16 | 17 | 48.1 | 0.353 | 0.00000247 | 508 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0.00015 | 0.00014 | rare |
| European (Non-Finnish) | 0.00011 | 0.00011 | rare |
| South Asian | 0.000099 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cortical cytoskeleton protein found in a complex involved in maintaining cell polarity and epithelial integrity. Involved in the regulation of mitotic spindle orientation, proliferation, differentiation and tissue organization of neuroepithelial cells. Involved in axonogenesis through RAB10 activation thereby regulating vesicular membrane trafficking toward the axonal plasma membrane. {ECO:0000269|PubMed:15735678, ECO:0000269|PubMed:16170365}.;
Recessive Scores
- pRec
- 0.133
Intolerance Scores
- LoFtool
- 0.326
- RVIS EVS
- -1.74
- RVIS percentile EVS
- 2.43
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.817
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |