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…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.06

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in LGALS8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 130

450 rare PASS variants

Rare truncating (LoF)

1 in 640

127 rare PASS variants

Rare synonymous (reference)

1 in 480

171 rare PASS variants

Rare missense and truncating variants are carried at similar rates in LGALS8; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 140	1 in 580
South Asian	~43k	1 in 160	1 in 380
Remaining (unassigned)	~30k	1 in 140	1 in 640
European (Finnish)	~27k	1 in 310	1 in 5,300
Admixed American	~22k	1 in 95	1 in 1,200
African / African American	~21k	1 in 160	1 in 240
East Asian	~20k	1 in 160	1 in 920
Ashkenazi Jewish	~13k	1 in 1,100	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 91	≈ 1 in 670

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.