LGALS9B

Chr 17

galectin 9B

NCBI Gene: 284194 ENSG00000170298 UniProt: Q3B8N2

The protein binds galactosides and is structurally highly similar to galectin 9. This gene shows low constraint against loss-of-function variants (pLI < 0.1, LOEUF > 1), suggesting tolerance to protein loss. No established disease associations have been reported for mutations in this gene.

ResearchSummary from RefSeq, UniProt

This gene was initially thought to represent a pseudogene of galectin 9; however, this transcript has good exon-intron structure and encodes a predicted protein of the same size as and highly similar to galectin 9. This gene is one of two similar loci on chromosome 17p similar to galectin 9 and now thought to be protein-encoding. This gene is the more centromeric gene. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.17

Clinical Summary— LGALS9B

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

54 VUS of 61 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.17LOEUF

pLI 0.000

Z-score 1.15

OE 0.65 (0.38–1.17)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.54Z-score

OE missense 0.88 (0.78–1.01)

154 obs / 174.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.65 (0.38–1.17)

0≤0.351.4

Missense OE?0.88 (0.78–1.01)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 8 / 12.4Missense obs/exp: 154 / 174.1Syn Z: 0.44

This gene — mechanism propensity

0.76top 25%

GOF

0.4381th %ile

LOF

0.3065th %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

61 submitted variants in ClinVar

ClinVar

Classification Summary

VUS54

Likely Benign6

Benign1

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	54	0	54
Likely Benign	5	1	6
Benign	1	0	1
Total	60	1	61

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

View in ClinVar →

43 pathogenic / likely-pathogenic (of 49) ClinVar copy-number / structural variants overlap LGALS9B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →