Nemaline myopathy 10

Summary

Nemaline myopathy 10 (MONDO:0014513) is a disease caused by LMOD3 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: LMOD3 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 404

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nemaline myopathy 10
Mondo ID	MONDO:0014513
OMIM	616165
DOID	DOID:0110931
UMLS	C4015360
MedGen	863797
GARD	0016066
Is cancer (heuristic)	no

Also known as: LMOD3 nemaline myopathy · NEM10 · nemaline myopathy 10 · nemaline myopathy caused by mutation in LMOD3 · nemaline myopathy type 10

Data availability: 404 ClinVar variants · 3 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › severe congenital nemaline myopathy › nemaline myopathy 10

Related subtypes (4): congenital myopathy 2a, typical, autosomal dominant, nemaline myopathy 2, nemaline myopathy 8, nemaline myopathy 9

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

404 retrieved; paginated sample, class counts are floors:

203 uncertain significance, 121 likely benign, 39 pathogenic, 12 benign, 11 conflicting classifications of pathogenicity, 11 benign/likely benign, 5 likely pathogenic, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1323241	NM_198271.5(LMOD3):c.1342C>T (p.Gln448Ter)	LMOD3	Pathogenic	criteria provided, single submitter
1323243	NM_198271.5(LMOD3):c.1020_1023del (p.Thr341fs)	LMOD3	Pathogenic	criteria provided, single submitter
1354391	NM_198271.5(LMOD3):c.1192del (p.Arg398fs)	LMOD3	Pathogenic	criteria provided, single submitter
1395938	NM_198271.5(LMOD3):c.1472dup (p.Arg492fs)	LMOD3	Pathogenic	criteria provided, single submitter
1417273	NM_198271.5(LMOD3):c.971del (p.Gly324fs)	LMOD3	Pathogenic	criteria provided, single submitter
1451345	NM_198271.5(LMOD3):c.704C>G (p.Ser235Ter)	LMOD3	Pathogenic	criteria provided, single submitter
1451618	NM_198271.5(LMOD3):c.1219C>T (p.Gln407Ter)	LMOD3	Pathogenic	criteria provided, single submitter
1457468	NM_198271.5(LMOD3):c.80_95del (p.Asn26_Leu27insTer)	LMOD3	Pathogenic	criteria provided, single submitter
162215	NM_198271.5(LMOD3):c.138dup (p.Ser47fs)	LMOD3	Pathogenic	no assertion criteria provided
162217	NM_198271.5(LMOD3):c.1201C>T (p.Arg401Ter)	LMOD3	Pathogenic	criteria provided, single submitter
162218	NM_198271.5(LMOD3):c.1099_1100del (p.Asn367fs)	LMOD3	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
162219	NM_198271.5(LMOD3):c.1069G>T (p.Glu357Ter)	LMOD3	Pathogenic	no assertion criteria provided
2149678	NM_198271.5(LMOD3):c.1330C>T (p.Gln444Ter)	LMOD3	Pathogenic	criteria provided, single submitter
2169511	NM_198271.5(LMOD3):c.882dup (p.Asp295fs)	LMOD3	Pathogenic	criteria provided, single submitter
2176069	NM_198271.5(LMOD3):c.278_288del (p.Thr93fs)	LMOD3	Pathogenic	criteria provided, single submitter
2501771	NM_198271.5(LMOD3):c.944_945del (p.Leu315fs)	LMOD3	Pathogenic	criteria provided, single submitter
2712484	NM_198271.5(LMOD3):c.131_132del (p.Pro44fs)	LMOD3	Pathogenic	criteria provided, single submitter
2898508	NM_198271.5(LMOD3):c.780del (p.Asn261fs)	LMOD3	Pathogenic	criteria provided, single submitter
3012412	NM_198271.5(LMOD3):c.637dup (p.Ile213fs)	LMOD3	Pathogenic	criteria provided, multiple submitters, no conflicts
3643646	NM_198271.5(LMOD3):c.1434C>G (p.Tyr478Ter)	LMOD3	Pathogenic	criteria provided, single submitter
3656192	NM_198271.5(LMOD3):c.1543_1544del (p.Ile515fs)	LMOD3	Pathogenic	criteria provided, single submitter
3691947	NM_198271.5(LMOD3):c.1012G>T (p.Glu338Ter)	LMOD3	Pathogenic	criteria provided, single submitter
3720520	NM_198271.5(LMOD3):c.1372C>T (p.Gln458Ter)	LMOD3	Pathogenic	criteria provided, single submitter
374498	NM_198271.5(LMOD3):c.1648C>T (p.Leu550Phe)	LMOD3	Pathogenic	criteria provided, multiple submitters, no conflicts
374499	NM_198271.5(LMOD3):c.1004A>G (p.Gln335Arg)	LMOD3	Pathogenic	criteria provided, single submitter
3906263	NM_198271.5(LMOD3):c.112del (p.Glu38fs)	LMOD3	Pathogenic	criteria provided, single submitter
4070600	NM_198271.5(LMOD3):c.106C>T (p.Gln36Ter)	LMOD3	Pathogenic	criteria provided, multiple submitters, no conflicts
4726249	NM_198271.5(LMOD3):c.658A>T (p.Lys220Ter)	LMOD3	Pathogenic	criteria provided, single submitter
4731299	NM_198271.5(LMOD3):c.319G>T (p.Glu107Ter)	LMOD3	Pathogenic	criteria provided, single submitter
4738488	NM_198271.5(LMOD3):c.1284del (p.Met430fs)	LMOD3	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 2 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
LMOD3	Definitive	Autosomal recessive	nemaline myopathy 10	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
LMOD3	Orphanet:171430	Severe congenital nemaline myopathy
LMOD3	Orphanet:171436	Typical nemaline myopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
LMOD3	HGNC:6649	ENSG00000163380	Q0VAK6	Leiomodin-3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LMOD3	Leiomodin-3	Essential for the organization of sarcomeric actin thin filaments in skeletal muscle.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LMOD3	Other/Unknown	no		TMOD, LRR_dom_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
biceps brachii	1
quadriceps femoris	1
vastus lateralis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LMOD3	170	tissue_specific	marker	biceps brachii, vastus lateralis, quadriceps femoris

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LMOD3	838

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
LMOD3	Q0VAK6	67.79

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
skeletal muscle thin filament assembly	1	2808.7×	0.001	LMOD3
pointed-end actin filament capping	1	2407.4×	0.001	LMOD3
positive regulation of skeletal muscle fiber development	1	2106.5×	0.001	LMOD3
actin nucleation	1	1872.4×	0.001	LMOD3
myofibril assembly	1	1123.5×	0.002	LMOD3
striated muscle contraction	1	842.6×	0.002	LMOD3
skeletal muscle fiber development	1	543.6×	0.002	LMOD3
muscle contraction	1	208.1×	0.005	LMOD3
actin filament organization	1	118.7×	0.008	LMOD3

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
LMOD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	LMOD3

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
LMOD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.