LSM5

protein-coding

LSM5 homolog, U6 small nuclear RNA and mRNA degradation associated, the group of LSm proteins

Gene summary

Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; MIM 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.[supplied by OMIM, Apr 2004]

MANE transcript

NM_012322.3

Inheritance

—

ClinVar variants

U:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr7:32,485,338-32,495,283

External References & Databases

Ensembl (ENSG00000106355)

Transcript & Mutation Effects

hg38 • Region Span ~9.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LSM5 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012322.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			5 clinvar			5
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	5	0	0	5

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012322.3	RefSeq	NP_036454.1	5	MANE Select
ENST00000450169.7	Ensembl	ENSP00000410758.2	5	MANE Select
NM_001130710.2	RefSeq	NP_001124182.1	4	Standard
NM_001139499.2	RefSeq	NP_001132971.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

RNA degradation - Homo sapiens (human)
Spliceosome - Homo sapiens (human)
Metabolism of RNA
mRNA Splicing - Major Pathway
mRNA decay by 5, to 3, exoribonuclease

Biological Process

mRNA splicing, via spliceosome
mRNA processing
response to bacterium
exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay

Molecular Function

RNA binding
protein binding

Cellular Component

nucleus
nucleoplasm
U6 snRNP
cytosol
U4/U6 x U5 tri-snRNP complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000450169
Coding exons: 5
Length: 9945
Individuals with no LoFs: 125678
Homozygous LoFs: 0
Heterozygous LoFs: 10
Defined: 125688
p: 0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.827	32	48.2	0.665	0.00000215	589
Missense (PolyPhen)		8	13.491	0.59301		187
Synonymous	-0.900	22	17.2	1.28	8.26e-7	176
Loss of Function	1.03	3	5.64	0.532	2.36e-7	75

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.000036	0.000033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320). {ECO:0000269|PubMed:10523320, ECO:0000269|PubMed:28781166}.;

Recessive Scores

pRec: 0.114

Intolerance Scores

LoFtool: 0.451
RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.934

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium