LSM1

Chr 8AR

LSM1 homolog, mRNA degradation associated

Also known as: CASM, FICUS, YJL124C

NCBI Gene: 27257 ENSG00000175324 UniProt: O15116 OMIM: 607281

This gene encodes a member of the LSm family of RNA-binding proteins. LSm proteins form stable heteromers that bind specifically to the 3'-terminal oligo(U) tract of U6 snRNA and may play a role in pre-mRNA splicing by mediating U4/U6 snRNP formation. Increased expression of this gene may play a role in cellular transformation and the progression of several malignancies including lung cancer, mesothelioma and breast cancer. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9. [provided by RefSeq, Nov 2011]

OMIM Research

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

FICUS syndromeMIM #621193

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists FICUS syndrome; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.21

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.011

Z-score 1.20

OE 0.53 (0.26–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

1.00Z-score

OE missense 0.67 (0.53–0.85)

48 obs / 71.9 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.53 (0.26–1.21)

0≤0.351.4

Missense OE?0.67 (0.53–0.85)

0≤0.61.4

Synonymous OE?0.86

0≤1.21.6

LoF obs/exp: 4 / 7.6Missense obs/exp: 48 / 71.9Syn Z: 0.55

Background carrier burden — how many people carry a rare variant somewhere in LSM1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 740

165 rare PASS variants

Rare truncating (LoF)

1 in 6,600

29 rare PASS variants

Rare synonymous (reference)

1 in 1,500

47 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for LSM1. 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 880	1 in 7,200
South Asian	~43k	1 in 310	1 in 8,600
Remaining (unassigned)	~30k	1 in 470	≈ 1 in 30,000
European (Finnish)	~27k	1 in 3,800	≈ 1 in 27,000
Admixed American	~22k	1 in 1,300	≈ 1 in 5,700
African / African American	~21k	1 in 690	≈ 1 in 5,600
East Asian	~20k	1 in 450	1 in 1,200
Ashkenazi Jewish	~13k	1 in 1,900	none seen
Middle Eastern	~2,884	≈ 1 in 720	none seen

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.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓