LMOD1

protein-coding

leiomodin 1, the group of Leiomodins

Gene summary

The leiomodin 1 protein has a putative membrane-spanning region and 2 types of tandemly repeated blocks. The transcript is expressed in all tissues tested, with the highest levels in thyroid, eye muscle, skeletal muscle, and ovary. Increased expression of leiomodin 1 may be linked to Graves' disease and thyroid-associated ophthalmopathy. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012134.3

Inheritance

AR, AD

ClinVar variants

P:3U:72B:14

Top phenotype

Megacystis-microcolon-intestinal hypoperistalsis syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr1:201,896,456-201,946,548

External References & Databases

Ensembl (ENSG00000163431)

Transcript & Mutation Effects

hg38 • Region Span ~50.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

megacystis-microcolon-intestinal hypoperistalsis syndrome 3LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0030294

Submitter: Labcorp Genetics (formerly Invitae)

megacystis-microcolon-intestinal hypoperistalsis syndrome 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030294

Submitter: Ambry Genetics

megacystis-microcolon-intestinal hypoperistalsis syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007960

Submitter: Orphanet

megacystis-microcolon-intestinal hypoperistalsis syndrome 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0030294

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Megacystis-microcolon-intestinal hypoperistalsis syndrome 3AR

Manifestation: Genitourinary; Gastrointestinal; Renal

Intervention: General

Rationale: 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

Refs: 28292896

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LMOD1 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 64

not providedTotal: 15

Megacystis-microcolon-intestinal hypoperistalsis syndrome 3Total: 5

LMOD1-related conditionTotal: 3

Visceral myopathy 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012134.3. 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			1 clinvar	7 clinvar		8
missense	2 clinvar		69 clinvar	5 clinvar	2 clinvar	78
nonsense	1 clinvar					1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	3	0	72	12	2	89

Highest pathogenic variant AF is 0.00000495752

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012134.3	RefSeq	NP_036266.2	3	MANE Select
ENST00000367288.5	Ensembl	ENSP00000356257.4	3	MANE Select
ENST00000869075.1	Ensembl	ENSP00000539134.1	2	Standard
ENST00000869075.2	Ensembl	ENSP00000539134.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Smooth Muscle Contraction
Muscle contraction

Biological Process

muscle contraction
myofibril assembly
positive regulation of actin filament polymerization
actin nucleation
pointed-end actin filament capping

Molecular Function

actin binding
tropomyosin binding

Cellular Component

cytosol
striated muscle thin filament
actin filament
membrane
myofibril

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000367288
Coding exons: 3
Length: 50136
Individuals with no LoFs: 124640
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 124643
p: 0.0000120

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.19	271	332	0.816	0.0000185	3952
Missense (PolyPhen)		73	130.25	0.56046		1521
Synonymous	-0.966	147	133	1.11	0.00000774	1170
Loss of Function	3.17	2	15.5	0.129	9.25e-7	238

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)	0.000018	0.000018	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mediates nucleation of actin filaments. {ECO:0000269|PubMed:26370058}.;

Recessive Scores

pRec: 0.231

Intolerance Scores

RVIS EVS: 0.18
RVIS percentile EVS: 66.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.167

Gene Damage Prediction

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