LGALS8

Chr 1

galectin 8

Also known as: Gal-8, PCTA-1, PCTA1, Po66-CBP

NCBI Gene: 3964 ENSG00000116977 UniProt: O00214 OMIM: 606099

The protein encoded by this gene is a beta-galactoside-binding lectin that functions as a cellular sensor of membrane damage, detecting pathogens by binding to exposed galactoside ligands and targeting them for autophagy to restrict bacterial and viral infections. This gene has very low constraint against loss-of-function variants (pLI near 0, LOEUF >1), and no established Mendelian diseases have been associated with LGALS8 mutations to date. The gene is widely expressed and involved in cell adhesion, growth regulation, and immune defense mechanisms.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.06

Clinical Summary— LGALS8

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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

39 VUS of 88 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?

1.06LOEUF

pLI 0.000

Z-score 1.39

OE 0.64 (0.40–1.06)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.03Z-score

OE missense 1.01 (0.90–1.13)

197 obs / 195.9 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.64 (0.40–1.06)

0≤0.351.4

Missense OE?1.01 (0.90–1.13)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 11 / 17.2Missense obs/exp: 197 / 195.9Syn Z: -0.73

This gene — mechanism propensity

0.79top 25%

GOF

0.5953th %ile

LOF

0.2582th %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

VUS39

Likely Benign6

Benign4

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	39	0	0	39
Likely Benign	5	0	1	6
Benign	1	2	1	4
Total	45	2	2	49

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

View in ClinVar →

47 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap LGALS8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →