LGSN
protein-codinglengsin, lens protein with glutamine synthetase domain
Gene summary
This gene encodes a protein with similarity to the GS I members of the glutamine synthetase superfamily. The encoded protein is referred to as a pseudo-glutamine synthetase because it has no glutamine synthesis activity and may function as a chaperone protein. This protein is localized to the lens and may be associated with cataract disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2009]
- GLULD1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~44.0 kbGenCC 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 LGSN variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016571.3. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 3 | 3 | ||||
| missense | 83 | 6 | 1 | 90 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 83 | 9 | 1 | 93 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057655.2 | 4 | MANE Select | |
| Ensembl | ENSP00000359691.4 | 4 | MANE Select | |
| RefSeq | NP_001137412.1 | 5 | Standard | |
| Ensembl | ENSP00000359692.5 | 5 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| lgsn | Danio rerio | Structure: retina Quality: decreased size abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- glutamine biosynthetic process
- nitrogen utilization
Molecular Function
- glutamate-ammonia ligase activity
Cellular Component
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370657
- Coding exons
- 4
- Length
- 44027
- Individuals with no LoFs
- 125676
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 72
- Defined
- 125748
- p
- 0.000286
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.555 | 297 | 271 | 1.09 | 0.0000133 | 3369 |
| Missense (PolyPhen) | 60 | 67.84 | 0.88443 | 829 | ||
| Synonymous | -2.28 | 129 | 100 | 1.29 | 0.00000513 | 974 |
| Loss of Function | -0.251 | 19 | 17.9 | 1.06 | 0.00000108 | 223 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00061 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00083 | 0.00082 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00024 | 0.00024 | rare |
| South Asian | 0.00036 | 0.00036 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens. Does not seem to have enzymatic activity (By similarity). {ECO:0000250}.;
Recessive Scores
- pRec
- 0.141
Intolerance Scores
- LoFtool
- 0.321
- RVIS EVS
- 0.62
- RVIS percentile EVS
- 83.47
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0939
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |