Nemaline myopathy 7

Summary

Nemaline myopathy 7 (MONDO:0012538) is a disease caused by CFL2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: CFL2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 133

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	nemaline myopathy 7
Mondo ID	MONDO:0012538
MeSH	C565198
OMIM	610687
DOID	DOID:0110934
UMLS	C1853154
MedGen	343979
GARD	0015493
Is cancer (heuristic)	no

Also known as: CFL2 nemaline myopathy · NEM7 · nemaline myopathy 7 · nemaline myopathy caused by mutation in CFL2 · nemaline myopathy type 7

Data availability: 133 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › typical nemaline myopathy › nemaline myopathy 7

Related subtypes (5): congenital myopathy 2a, typical, autosomal dominant, nemaline myopathy 2, congenital myopathy 23, nemaline myopathy 9, nemaline myopathy 10

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

133 retrieved; paginated sample, class counts are floors:

71 uncertain significance, 40 likely benign, 9 benign, 8 pathogenic, 3 conflicting classifications of pathogenicity, 2 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1395680	NM_138638.5(CFL2):c.100_103del (p.Lys34fs)	CFL2	Pathogenic	criteria provided, multiple submitters, no conflicts
2000758	NM_138638.5(CFL2):c.154_157del (p.Ala52fs)	CFL2	Pathogenic	criteria provided, single submitter
2073433	NM_138638.5(CFL2):c.4-115A>C	CFL2	Pathogenic	criteria provided, single submitter
2722427	NM_138638.5(CFL2):c.4-115A>G	CFL2	Pathogenic	criteria provided, single submitter
657372	NC_000014.9:g.(?34710372)(34713686_?)del	CFL2	Pathogenic	criteria provided, single submitter
800930	NM_138638.5(CFL2):c.338del (p.Ser113fs)	CFL2	Pathogenic	criteria provided, single submitter
8160	NM_138638.5(CFL2):c.103G>A (p.Ala35Thr)	CFL2	Pathogenic	no assertion criteria provided
583485	NC_000014.9:g.(?34712845)(34714560_?)del	LOC130055474	Pathogenic	criteria provided, single submitter
195369	NM_138638.5(CFL2):c.21G>A (p.Val7=)	CFL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
313086	NM_138638.5(CFL2):c.*1036G>A	CFL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
971564	NM_138638.5(CFL2):c.242G>A (p.Arg81Gln)	CFL2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1001719	NM_138638.5(CFL2):c.475G>T (p.Val159Phe)	CFL2	Uncertain significance	criteria provided, single submitter
1006980	NM_138638.5(CFL2):c.355A>T (p.Ser119Cys)	CFL2	Uncertain significance	criteria provided, single submitter
1017814	NM_138638.5(CFL2):c.349del (p.Tyr117fs)	CFL2	Uncertain significance	criteria provided, single submitter
1030772	NM_138638.5(CFL2):c.316C>A (p.Pro106Thr)	CFL2	Uncertain significance	criteria provided, single submitter
1061574	NM_138638.5(CFL2):c.203A>G (p.Tyr68Cys)	CFL2	Uncertain significance	criteria provided, single submitter
1062469	NM_138638.5(CFL2):c.93G>C (p.Lys31Asn)	CFL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
128713	NM_138638.5(CFL2):c.457T>G (p.Leu153Val)	CFL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1349460	NM_138638.5(CFL2):c.78_80del (p.Glu28del)	CFL2	Uncertain significance	criteria provided, single submitter
1355538	NM_138638.5(CFL2):c.268G>A (p.Glu90Lys)	CFL2	Uncertain significance	criteria provided, single submitter
1374330	NM_138638.5(CFL2):c.467A>G (p.Asn156Ser)	CFL2	Uncertain significance	criteria provided, single submitter
1377548	NM_138638.5(CFL2):c.276A>C (p.Lys92Asn)	CFL2	Uncertain significance	criteria provided, single submitter
1401361	NM_138638.5(CFL2):c.73A>G (p.Thr25Ala)	CFL2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1422535	NM_138638.5(CFL2):c.304A>G (p.Ile102Val)	CFL2	Uncertain significance	criteria provided, single submitter
1428070	NM_138638.5(CFL2):c.452A>G (p.Glu151Gly)	CFL2	Uncertain significance	criteria provided, single submitter
1444456	NM_138638.5(CFL2):c.22A>G (p.Asn8Asp)	CFL2	Uncertain significance	criteria provided, single submitter
1469897	NM_138638.5(CFL2):c.127G>A (p.Asp43Asn)	CFL2	Uncertain significance	criteria provided, single submitter
1713372	NM_138638.5(CFL2):c.114C>A (p.Phe38Leu)	CFL2	Uncertain significance	criteria provided, single submitter
1713798	NM_138638.5(CFL2):c.497T>C (p.Leu166Ser)	CFL2	Uncertain significance	criteria provided, single submitter
1713911	NM_138638.5(CFL2):c.469G>A (p.Val157Ile)	CFL2	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · 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
CFL2	Definitive	Autosomal recessive	nemaline myopathy 7	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFL2	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
CFL2	HGNC:1875	ENSG00000165410	Q9Y281	Cofilin-2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFL2	Cofilin-2	Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner.

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)
CFL2	Other/Unknown	no		ADF-H, ADF/Cofilin, ADF-H/Gelsolin-like_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
cardiac muscle of right atrium	1
left ventricle myocardium	1
tibialis anterior	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFL2	261	ubiquitous	marker	cardiac muscle of right atrium, left ventricle myocardium, tibialis anterior

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFL2	4,226

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFL2	Q9Y281	11

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
actin filament fragmentation	1	4213.0×	0.001	CFL2
positive regulation of actin filament depolymerization	1	1872.4×	0.001	CFL2
actin filament depolymerization	1	1296.3×	0.001	CFL2
actin filament severing	1	1203.7×	0.001	CFL2
muscle cell cellular homeostasis	1	648.1×	0.002	CFL2
sarcomere organization	1	383.0×	0.003	CFL2
skeletal muscle tissue development	1	290.6×	0.003	CFL2

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
CFL2	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	CFL2

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)
CFL2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.