LSM8

Chr 7

LSM8 homolog, U6 small nuclear RNA associated

NCBI Gene: 51691ENSG00000128534UniProt: O95777

This gene encodes a member of the like-Sm family of proteins. The encoded protein consists of a closed barrel shape, made up of five anti-parallel beta strands and an alpha helix. This protein partners with six paralogs to form a heteroheptameric ring which transiently binds U6 small nuclear RNAs and is involved in the general maturation of RNA in the nucleus. [provided by RefSeq, Jan 2010]

27
ClinVar variants
22
Pathogenic / LP
0.01
pLI score
0
Active trials
Clinical Summary— LSM8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.01) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 3 VUS of 27 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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.
1.49LOEUF
pLI 0.005
Z-score 0.75
OE 0.67 (0.33–1.49)
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.
1.09Z-score
OE missense 0.57 (0.42–0.78)
29 obs / 50.8 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.0.67 (0.33–1.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.57 (0.42–0.78)
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.1.13
0≤1.21.6
LoF obs/exp: 4 / 6.0Missense obs/exp: 29 / 50.8Syn Z: -0.46

ClinVar Variant Classifications

27 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic2
VUS3
Likely Benign1
Benign1
20
Pathogenic
2
Likely Pathogenic
3
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
————20
Likely Pathogenic
————2
VUS
————3
Likely Benign
————1
Benign
————1
Total—27

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

LSM8 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Nuclear LSm8 affects number of cytoplasmic processing bodies via controlling cellular distribution of Like-Sm proteins.
Novotny I et al.·Mol Biol Cell
2012
Analysis of Lsm1p and Lsm8p domains in the cellular localization of Lsm complexes in budding yeast.
Reijns MA et al.·FEBS J
2009
Genome-wide association analysis suggests novel loci underlying thyroid antibodies in Hashimoto's thyroiditis.
Brčić L et al.·Sci Rep
2019
3' processing of eukaryotic precursor tRNAs.
Maraia RJ et al.·Wiley Interdiscip Rev RNA
2011Review
Acquired Tertiary MET Resistance (MET D1228N and a Novel LSM8-MET Fusion) to Selpercatinib and Capmatinib in a Patient With KIF5B-RET-positive NSCLC With Secondary MET Amplification as Initial Resistance to Selpercatinib.
Zhu VW et al.·J Thorac Oncol
2021Case report
Genome-wide association study identifies novel recessive genetic variants for high TGs in an Arab population.
Hebbar P et al.·J Lipid Res
2018
Hypoxia-regulated components of the U4/U6.U5 tri-small nuclear riboprotein complex: possible role in autosomal dominant retinitis pigmentosa.
Schmidt-Kastner R et al.·Mol Vis
2008
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools