LMOD3

leiomodin 3, the group of Leiomodins

Basic information

Region (hg38): 3:69106065-69123032

Links

ENSG00000163380

∙ NCBI:56203 ∙ OMIM:616112 ∙ HGNC:6649 ∙ Uniprot:Q0VAK6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

nemaline myopathy 10 (Definitive), mode of inheritance: AR
nemaline myopathy 10 (Strong), mode of inheritance: AR
severe congenital nemaline myopathy (Supportive), mode of inheritance: AR
typical nemaline myopathy (Supportive), mode of inheritance: AD
nemaline myopathy 10 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Nemaline myopathy 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	25250574; 30291184

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LMOD3 gene.

Nemaline_myopathy_10 (381 variants)
Inborn_genetic_diseases (70 variants)
not_provided (64 variants)
LMOD3-related_disorder (14 variants)
not_specified (8 variants)
Joubert_syndrome_24 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LMOD3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198271.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				107 clinvar	2 clinvar	109
missense	3 clinvar	2 clinvar	209 clinvar	19 clinvar	4 clinvar	237
nonsense	12 clinvar	3 clinvar				15
start loss						0
frameshift	19 clinvar	4 clinvar	2 clinvar			25
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	34	9	212	126	6

Highest pathogenic variant AF is 0.0000273654

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LMOD3	protein_coding	protein_coding	ENST00000420581	3	16161

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.55e-7	0.637	124575	0	72	124647	0.000289

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.618	331	301	1.10	0.0000162	3761
Missense in Polyphen		132	126.93	1.0399		1587
Synonymous	-1.30	133	115	1.15	0.00000673	988
Loss of Function	1.12	13	18.2	0.716	9.42e-7	248

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000789	0.000789
Ashkenazi Jewish	0.00	0.00
East Asian	0.000167	0.000167
Finnish	0.0000523	0.0000464
European (Non-Finnish)	0.000170	0.000159
Middle Eastern	0.000167	0.000167
South Asian	0.000788	0.000785
Other	0.000669	0.000661

dbNSFP

Source: dbNSFP

Function: FUNCTION: Essential for the organization of sarcomeric actin thin filaments in skeletal muscle (PubMed:25250574). Increases the rate of actin polymerization (PubMed:25250574). {ECO:0000269|PubMed:25250574}.;
Disease: DISEASE: Nemaline myopathy 10 (NEM10) [MIM:616165]: An autosomal recessive severe form of nemaline myopathy. Nemaline myopathies are muscular disorders characterized by muscle weakness of varying severity and onset, and abnormal thread-like or rod-shaped structures in muscle fibers on histologic examination. NEM10 is characterized by early-onset generalized muscle weakness and hypotonia with respiratory insufficiency and feeding difficulties. Additional features include arthrogryposis or congenital contractures, ophthalmoplegia, a history of prematurity, reduced fetal movements, and polyhydramnios. Most patients die of respiratory failure in early infancy. {ECO:0000269|PubMed:25250574}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Intolerance Scores

loftool
rvis_EVS: 2.29
rvis_percentile_EVS: 98.31

Haploinsufficiency Scores

pHI: 0.0464
hipred: N
hipred_score: 0.196
ghis

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.209

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Lmod3
Phenotype: homeostasis/metabolism phenotype; muscle phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: lmod3
Affected structure: muscle cell
Phenotype tag: abnormal
Phenotype quality: increased distance

Gene ontology

Biological process: muscle contraction;striated muscle contraction;myofibril assembly;skeletal muscle thin filament assembly;actin nucleation;skeletal muscle fiber development;positive regulation of skeletal muscle fiber development;pointed-end actin filament capping
Cellular component: cytoplasm;striated muscle thin filament;myofibril;M band
Molecular function: actin monomer binding;tropomyosin binding