LSM7

protein-coding

LSM7 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_016199.3

Inheritance

ClinVar variants

P:2U:12

Top phenotype

In utero death

gnomAD constraint

pLI —, LoF o/e 0.18

Max pathogenic AF

—

Genomic locus

chr19:2,321,520-2,328,611

External References & Databases

Ensembl (ENSG00000130332)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

leukodystrophyMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0019046

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LSM7 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 9

In utero deathTotal: 1

LeukodystrophyTotal: 1

Joubert syndrome 36Total: 1

LSM7-related leukodystrophy and cerebellar atrophyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016199.3. 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	1 clinvar	1 clinvar	9 clinvar			11
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	1	12	0	0	14

Highest pathogenic variant AF is 0.000025916266

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016199.3	RefSeq	NP_057283.1	4	MANE Select
ENST00000252622.15	Ensembl	ENSP00000252622.8	4	MANE Select
ENST00000585395.6	Ensembl	ENSP00000466556.2	2	Standard
ENST00000585409.2	Ensembl	ENSP00000467145.1	3	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)
mRNA Processing
Metabolism of RNA
mRNA Splicing - Major Pathway

Biological Process

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

Molecular Function

protein binding
U6 snRNA binding

Cellular Component

nucleus
nucleoplasm
U6 snRNP
U12-type spliceosomal complex
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252622
Coding exons: 4
Length: 7104
Individuals with no LoFs: 0
Homozygous LoFs: 0
Heterozygous LoFs: 0
Defined: 0
p: 0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.43	24	53.5	0.449	0.00000282	658
Missense (PolyPhen)		6	19.029	0.31532		250
Synonymous	-0.710	27	22.7	1.19	0.00000151	180
Loss of Function	1.82	1	5.67	0.176	3.22e-7	68

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0	0.0	absent
South Asian	0	0.0	absent
Other	0	0.0	absent

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}.;

Intolerance Scores

RVIS EVS: -0.03
RVIS percentile EVS: 51.04

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): K
Indispensability pred.: E
Indispensability score: 0.973