LGALS9

Chr 17

galectin 9

Also known as: HUAT, LGALS9A

NCBI Gene: 3965ENSG00000168961UniProt: O00182

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]

0
Active trials
6
Pathogenic / LP
88
ClinVar variants
5
Pubs (1 yr)
0.9
Missense Z
0.99
LOEUF
Clinical Summary— LGALS9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 Pathogenic / Likely Pathogenic· 72 VUS of 88 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.60 (0.38–0.99)
Tolerant

Typical tolerance to LoF variation

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.
0.91Z-score
OE missense 0.82 (0.73–0.93)
175 obs / 212.4 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.0.60 (0.38–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.82 (0.73–0.93)
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.0.99
0≤1.21.6
LoF obs/exp: 11 / 18.4Missense obs/exp: 175 / 212.4Syn Z: 0.11
DN
0.80top 10%
GOF
0.5563th %ile
LOF
0.2484th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS72
Likely Benign9
Benign1
5
Pathogenic
1
Likely Pathogenic
72
VUS
9
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
64
8
0
72
Likely Benign
0
6
3
0
9
Benign
0
1
0
0
1
Total07117088

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

View in ClinVar →

Protein Context — Lollipop Plot

LGALS9 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Single-cell profiling of response to neoadjuvant chemo-immunotherapy in surgically resectable esophageal squamous cell carcinoma.
Ji G et al.·Genome Med
2024
Integration of Pan-Cancer Single-Cell and Spatial Transcriptomics Reveals Stromal Cell Features and Therapeutic Targets in Tumor Microenvironment.
Du Y et al.·Cancer Res
2024
Single-cell characterization of differentiation trajectories and drug resistance features in gastric cancer with peritoneal metastasis.
Peng H et al.·Clin Transl Med
2024
Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma.
Yan ZX et al.·Nat Commun
2024Clinical trial
Gene polymorphisms of LGALS2, LGALS3 and LGALS9 in patients with rheumatoid arthritis.
Xu WD et al.·Cell Immunol
2021Cohort
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
The LGALS9/miR-491-5p Axis Regulates CD8+ T Cell Function and Inhibits the Progression of Gastric Cancer.
Huang W et al.·Cancer Sci
2026Open Access
MFSD12 promotes proliferation, metastasis and invasion of hepatocellular carcinoma cells and its potential correlation with HAVCR2/LGALS9 immune checkpoint axis.
Sun K et al.·Front Immunol
2025Open Access
Single-cell RNA sequencing reveals LGALS9+ epithelial and COMP+ stromal cell crosstalk driving keratoconus pathogenesis.
Han T et al.·Int J Biol Macromol
2025
Autophagy inhibition in LGALS9-overexpressing nasopharyngeal carcinoma unleashes immune response.
Pascual C et al.·Autophagy
2025Open Access
Rhamnose alleviates the proinflammatory response during endotoxemia via the CEACAM1/LGALS9-p38 axis.
Wei R et al.·Acta Biochim Biophys Sin (Shanghai)
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients