LGALS9
protein-codinggalectin 9, the group of Galectins|Receptor ligands
Gene summary
The galectins are a family of beta-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. The protein encoded by this gene is an S-type lectin. It is overexpressed in Hodgkin's disease tissue and might participate in the interaction between the H&RS cells with their surrounding cells and might thus play a role in the pathogenesis of this disease and/or its associated immunodeficiency. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.8 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 LGALS9 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_009587.3. 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 | 2 | 2 | ||||
| missense | 67 | 6 | 1 | 74 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 73 | 6 | 1 | 80 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_033665.1 | 11 | MANE Select | |
| Ensembl | ENSP00000378856.2 | 11 | MANE Select | |
| RefSeq | NP_001317092.1 | 9 | Standard | |
| RefSeq | NP_002299.2 | 10 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Uricosurics Pathway, Pharmacodynamics
- Vitamin D Receptor Pathway
- Signaling by Interleukins
- Cytokine Signaling in Immune system
- Immune System
Biological Process
- natural killer cell tolerance induction
- chemotaxis
- inflammatory response
- female pregnancy
- positive regulation of gene expression
Molecular Function
- galactose binding
- enzyme binding
- carbohydrate binding
- disaccharide binding
Cellular Component
- extracellular space
- nucleus
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395473
- Coding exons
- 11
- Length
- 19763
- Individuals with no LoFs
- 125661
- Homozygous LoFs
- 2
- Heterozygous LoFs
- 85
- Defined
- 125748
- p
- 0.000346
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.912 | 175 | 212 | 0.824 | 0.0000127 | 2329 |
| Missense (PolyPhen) | 52 | 64.037 | 0.81203 | 717 | ||
| Synonymous | 0.105 | 86 | 87.3 | 0.986 | 0.00000577 | 697 |
| Loss of Function | 1.60 | 11 | 18.4 | 0.598 | 9.57e-7 | 191 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.000088 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0040 | 0.0038 | notable |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00019 | 0.00018 | rare |
| European (Non-Finnish) | 0.00020 | 0.00020 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) death (PubMed:16286920). Also stimulates bactericidal activity in infected macrophages by causing macrophage activation and IL1B secretion which restricts intracellular bacterial growth (By similarity). Ligand for P4HB; the interaction retains P4HB at the cell surface of Th2 T-helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). Ligand for CD44; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up- regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (By similarity). Promotes ability of mesenchymal stromal cells to suppress T-cell proliferation (PubMed:23817958). Expands regulatory T-cells and induces cytotoxic T-cell apoptosis following virus infection (PubMed:20209097). Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) and chemokine (CCL2) production in mast and dendritic cells (PubMed:24465902, PubMed:16116184). Inhibits degranulation and induces apoptosis of mast cells (PubMed:24465902). Induces maturation and migration of dendritic cells (PubMed:25754930, PubMed:16116184). Inhibits natural killer (NK) cell function (PubMed:23408620). Can transform NK cell phenotype from peripheral to decidual during pregnancy (PubMed:25578313). Astrocyte derived galectin-9 enhances microglial TNF production (By similarity). May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. May provide the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion (By similarity). Highly selective to the anion urate (By similarity). {ECO:0000250|UniProtKB:O08573, ECO:0000250|UniProtKB:P97840, ECO:0000269|PubMed:16116184, ECO:0000269|PubMed:16286920, ECO:0000269|PubMed:18005988, ECO:0000269|PubMed:18977853, ECO:0000269|PubMed:20209097, ECO:0000269|PubMed:21670307, ECO:0000269|PubMed:23408620, ECO:0000269|PubMed:23817958, ECO:0000269|PubMed:24465902, ECO:0000269|PubMed:25578313, ECO:0000269|PubMed:25754930}.;
Recessive Scores
- pRec
- 0.220
Intolerance Scores
- LoFtool
- 0.890
- RVIS EVS
- 0.8
- RVIS percentile EVS
- 87.54
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.693
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |