LAGE3

Chr XXLR

L antigen family member 3

Also known as: CVG5, DXS9879E, DXS9951E, ESO3, GAMOS2, ITBA2, Pcc1

NCBI Gene: 8270ENSG00000196976UniProt: Q14657

This gene belongs to the ESO/LAGE gene family, members of which are clustered together on chromosome Xq28, and have similar exon-intron structures. Unlike the other family members which are normally expressed only in testis and activated in a wide range of human tumors, this gene is ubiquitously expressed in somatic tissues. The latter, combined with the finding that it is highly conserved in mouse and rat, suggests that the encoded protein is functionally important. An intronless pseudogene with high sequence similarity to this gene is located on chromosome 9. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Galloway-Mowat syndrome 2, X-linkedMIM #301006
XLR
0
Active trials
123
Pathogenic / LP
225
ClinVar variants
2
Pubs (1 yr)
0.4
Missense Z
1.81
LOEUF
Clinical Summary— LAGE3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.13) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
123 Pathogenic / Likely Pathogenic· 68 VUS of 225 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.
1.81LOEUF
pLI 0.127
Z-score 0.49
OE 0.60 (0.19–1.81)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.41Z-score
OE missense 0.84 (0.67–1.08)
46 obs / 54.5 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 (0.19–1.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.84 (0.67–1.08)
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.0.85
0≤1.21.6
LoF obs/exp: 1 / 1.7Missense obs/exp: 46 / 54.5Syn Z: 0.57

ClinVar Variant Classifications

225 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic120
Likely Pathogenic3
VUS68
Likely Benign19
Benign10
Conflicting5
120
Pathogenic
3
Likely Pathogenic
68
VUS
19
Likely Benign
10
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
117
0
120
Likely Pathogenic
0
0
3
0
3
VUS
3
47
18
0
68
Likely Benign
0
2
1
16
19
Benign
0
5
4
1
10
Conflicting
—5
Total45614317225

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

View in ClinVar →

Protein Context — Lollipop Plot

LAGE3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

LAGE3-related Galloway-Mowat syndrome

limited
Monoallelic X HemizygousUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

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 4 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
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