LAGE3

Chr XXLR

L antigen family member 3

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

NCBI Gene: 8270 ENSG00000196976 UniProt: Q14657 OMIM: 300060

LAGE3 encodes a component of the EKC/KEOPS complex that functions as a dimerization module and is required for threonylcarbamoyl modification of specific tRNAs. Mutations cause Galloway-Mowat syndrome 2, a disorder affecting the kidneys and nervous system with X-linked recessive inheritance. The gene shows relatively low constraint scores, consistent with recessive disease mechanisms.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

XLRLOEUF 1.811 OMIM phenotype

Clinical Summary— LAGE3

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Population Constraint (gnomAD)

Low constraint (pLI 0.13) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

2 unique Pathogenic / Likely Pathogenic· 56 VUS of 107 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

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?

0.41Z-score

OE missense 0.84 (0.67–1.08)

46 obs / 54.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.60 (0.19–1.81)

0≤0.351.4

Missense OE?0.84 (0.67–1.08)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 1 / 1.7Missense obs/exp: 46 / 54.5Syn Z: 0.57

ClinVar Variant Classifications

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

VUS56

Likely Benign19

Benign10

Conflicting5

Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	1	0	0	2
Likely Pathogenic	0	0	0	0	0
VUS	4	49	3	0	56
Likely Benign	0	2	1	16	19
Benign	0	5	4	1	10
Conflicting	—				5
Total	5	57	8	17	92

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

View in ClinVar →

125 pathogenic / likely-pathogenic (of 141) ClinVar copy-number / structural variants overlap LAGE3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →