LSG1

Chr 3

large 60S subunit nuclear export GTPase 1

NCBI Gene: 55341 ENSG00000041802 UniProt: Q9H089 OMIM: 610780

This gene encodes a protein related to the yeast large subunit GTPase 1. The encoded protein is necessary for cell viability and may localize in the endoplasmic reticulum, nucleus and cytoplasm.[provided by RefSeq, Feb 2009]

OMIM Research

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.89

Clinical Summary— LSG1

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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

119 VUS of 154 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?

0.89LOEUF

pLI 0.000

Z-score 2.07

OE 0.64 (0.46–0.89)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.33Z-score

OE missense 0.95 (0.87–1.04)

351 obs / 369.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.64 (0.46–0.89)

0≤0.351.4

Missense OE?0.95 (0.87–1.04)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 24 / 37.7Missense obs/exp: 351 / 369.1Syn Z: -0.09

This gene — mechanism propensity

0.6939th %ile

GOF

0.5269th %ile

LOF

0.2871th %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

154 submitted variants in ClinVar

ClinVar

Classification Summary

VUS119

Likely Benign7

Benign2

119

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	119	0	0	119
Likely Benign	5	0	2	7
Benign	0	1	1	2
Total	124	1	3	128

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

View in ClinVar →

38 pathogenic / likely-pathogenic (of 47) ClinVar copy-number / structural variants overlap LSG1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →