Rigid spine muscular dystrophy 1

Summary

Rigid spine muscular dystrophy 1 (MONDO:0011271) is a disease caused by SELENON (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Causal gene: SELENON (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 589
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	rigid spine muscular dystrophy 1
Mondo ID	MONDO:0011271
OMIM	602771
DOID	DOID:0110633
NCIT	C126691
SNOMED CT	240063002
UMLS	C0410180
MedGen	98047
GARD	0024786
Is cancer (heuristic)	no

Also known as: classic MmD · classic multiminicore disease · classic multiminicore myopathy · MDRS1 · minicore myopathy, severe classic form · multicore myopathy, severe classic form · multiminicore disease, severe classic form · muscular dystrophy, congenital, Eichsfeld type · muscular dystrophy, congenital, merosin-positive, with early spine rigidity · muscular dystrophy, rigid spine, 1 · myopathy, SEPN1-related · rigid spine muscular dystrophy 1 · rigid spine muscular dystrophy type 1 · rigid spine syndrome · rigid spine syndrome caused by mutation in SELENON · RSMD1 · RSS · SELENON rigid spine syndrome

Data availability: 589 ClinVar variants · 3 GenCC gene-disease records · 13 cell lines.

Disease family

An umbrella term covering 1 Mondo subtype.

Classification path: disease › human disease › disease by body system or component › nervous system disorder › qualitative or quantitative protein defects in neuromuscular diseases › neuromuscular disease caused by qualitative or quantitative defects of selenoprotein N1 › multiminicore myopathy › rigid spine muscular dystrophy 1

Related subtypes (4): congenital multicore myopathy with external ophthalmoplegia, moderate multiminicore disease with hand involvement, antenatal multiminicore disease with arthrogryposis multiplex congenita, classic multiminicore myopathy

Subtypes (1): desmin-related myopathy with Mallory body-like inclusions

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

589 retrieved; paginated sample, class counts are floors:

215 uncertain significance, 204 likely benign, 60 pathogenic, 39 conflicting classifications of pathogenicity, 33 pathogenic/likely pathogenic, 16 likely pathogenic, 12 benign, 9 benign/likely benign, 1 no classifications from unflagged records

ClinVar	Variant (HGVS)	Gene	Classification	Review
3897883	NM_020451.3:c.[713dupA];[1397G>A]		Pathogenic	criteria provided, single submitter
1365639	NC_000001.10:g.(?25870190)(26142209_?)del	LDLRAP1	Pathogenic	criteria provided, single submitter
1028166	NM_206926.2(SELENON):c.1285+1G>A	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1075320	NM_206926.2(SELENON):c.1212_1215del (p.Asp404fs)	SELENON	Pathogenic	criteria provided, single submitter
1076253	NM_206926.2(SELENON):c.984dup (p.Pro329fs)	SELENON	Pathogenic	criteria provided, single submitter
1180703	NM_206926.2(SELENON):c.1344del (p.Asn449fs)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323573	NM_206926.2(SELENON):c.344_345del (p.Pro115fs)	SELENON	Pathogenic	criteria provided, single submitter
1323574	NM_206926.2(SELENON):c.646-2_658del	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1411446	NM_206926.2(SELENON):c.18_46del (p.Gly7fs)	SELENON	Pathogenic	criteria provided, single submitter
1415561	NM_206926.2(SELENON):c.1294C>T (p.Arg432Trp)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1420223	NM_206926.2(SELENON):c.470G>A (p.Trp157Ter)	SELENON	Pathogenic	criteria provided, single submitter
1445921	NM_206926.2(SELENON):c.8_9insTGCCGGGCCG (p.Arg5fs)	SELENON	Pathogenic	criteria provided, single submitter
1451790	NM_206926.2(SELENON):c.598_599insC (p.Tyr200fs)	SELENON	Pathogenic	criteria provided, single submitter
1453339	NM_206926.2(SELENON):c.160G>T (p.Glu54Ter)	SELENON	Pathogenic	criteria provided, single submitter
1701096	NM_206926.2(SELENON):c.2T>A (p.Met1Lys)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1701097	NM_206926.2(SELENON):c.715G>A (p.Gly239Arg)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704255	NM_206926.2(SELENON):c.671del (p.Met224fs)	SELENON	Pathogenic	no assertion criteria provided
193429	NM_206926.2(SELENON):c.44_72dup (p.Arg25fs)	SELENON	Pathogenic	criteria provided, multiple submitters, no conflicts
193432	NM_206926.2(SELENON):c.13_22dup (p.Gln8fs)	SELENON	Pathogenic	criteria provided, multiple submitters, no conflicts
198238	NM_206926.2(SELENON):c.770+2T>C	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
199156	NM_206926.2(SELENON):c.994G>T (p.Glu332Ter)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2001607	NM_206926.2(SELENON):c.861dup (p.Asp288fs)	SELENON	Pathogenic	criteria provided, single submitter
2094929	NM_206926.2(SELENON):c.1180-1G>T	SELENON	Pathogenic	criteria provided, single submitter
2113172	NM_206926.2(SELENON):c.-21_183+6del	SELENON	Pathogenic	criteria provided, single submitter
2159320	NM_206926.2(SELENON):c.1087C>T (p.Gln363Ter)	SELENON	Pathogenic	criteria provided, single submitter
2412662	NM_206926.2(SELENON):c.69_76dup (p.Arg26fs)	SELENON	Pathogenic	criteria provided, multiple submitters, no conflicts
2412672	NM_206926.2(SELENON):c.1074del (p.Glu360fs)	SELENON	Pathogenic	criteria provided, single submitter
2418838	NM_206926.2(SELENON):c.-30_64del (p.Met1fs)	SELENON	Pathogenic	criteria provided, single submitter
2419559	NM_206926.2(SELENON):c.142del (p.Val48fs)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2444322	NM_206926.2(SELENON):c.1120G>T (p.Glu374Ter)	SELENON	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 5 · 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
SELENON	Definitive	Autosomal recessive	rigid spine muscular dystrophy 1	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SELENON	Orphanet:2020	Congenital fiber-type disproportion myopathy
SELENON	Orphanet:324604	Classic multiminicore myopathy
SELENON	Orphanet:84132	Desmin-related myopathy with Mallory body-like inclusions
SELENON	Orphanet:97244	Rigid spine syndrome
LDLRAP1	Orphanet:391665	Homozygous familial hypercholesterolemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SELENON	HGNC:15999	ENSG00000162430	Q9NZV5	Selenoprotein N	gencc,clinvar
LDLRAP1	HGNC:18640	ENSG00000157978	Q5SW96	Low density lipoprotein receptor adapter protein 1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SELENON	Selenoprotein N	Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis.
LDLRAP1	Low density lipoprotein receptor adapter protein 1	Adapter protein (clathrin-associated sorting protein (CLASP)) required for efficient endocytosis of the LDL receptor (LDLR) in polarized cells such as hepatocytes and lymphocytes, but not in non-polarized cells (fibroblasts).

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 2 · 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	2	1.8×	0.312

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SELENON	Other/Unknown	no		EF_hand_dom
LDLRAP1	Other/Unknown	no		PTB/PI_dom, PH-like_dom_sf, Adapter_Engulfment-Domain

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ganglionic eminence	1
stromal cell of endometrium	1
ventricular zone	1
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SELENON	244	ubiquitous	marker	stromal cell of endometrium, ventricular zone, ganglionic eminence
LDLRAP1	271	ubiquitous	marker	cerebellar hemisphere, cerebellar cortex, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
LDLRAP1	1,055
SELENON	800

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LDLRAP1	Q5SW96	1

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SELENON	Q9NZV5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. Enrichment computed across 2 evidence-associated genes (1 with Reactome annotation).

Pathways 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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Chylomicron clearance	1	2284.0×	0.006	LDLRAP1
Transport of RCbl within the body	1	1427.5×	0.006	LDLRAP1
Vitamin D (calciferol) metabolism	1	878.5×	0.006	LDLRAP1
Cobalamin (Cbl, vitamin B12) transport and metabolism	1	634.4×	0.006	LDLRAP1
LDL clearance	1	543.8×	0.006	LDLRAP1
Plasma lipoprotein clearance	1	475.8×	0.006	LDLRAP1
Plasma lipoprotein assembly, remodeling, and clearance	1	228.4×	0.011	LDLRAP1
Metabolism of water-soluble vitamins and cofactors	1	181.3×	0.012	LDLRAP1
Metabolism of steroids	1	137.6×	0.014	LDLRAP1
Metabolism of vitamins and cofactors	1	116.5×	0.015	LDLRAP1
Cargo recognition for clathrin-mediated endocytosis	1	104.8×	0.015	LDLRAP1
Clathrin-mediated endocytosis	1	85.2×	0.017	LDLRAP1
Membrane Trafficking	1	37.1×	0.035	LDLRAP1
Vesicle-mediated transport	1	34.8×	0.035	LDLRAP1
Metabolism of lipids	1	31.6×	0.036	LDLRAP1
Transport of small molecules	1	25.1×	0.042	LDLRAP1
Metabolism	1	11.6×	0.086	LDLRAP1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of skeletal muscle cell proliferation	1	4213.0×	0.002	SELENON
regulation of protein binding	1	4213.0×	0.002	LDLRAP1
receptor-mediated endocytosis involved in cholesterol transport	1	4213.0×	0.002	LDLRAP1
positive regulation of response to oxidative stress	1	4213.0×	0.002	SELENON
positive regulation of receptor-mediated endocytosis involved in cholesterol transport	1	4213.0×	0.002	LDLRAP1
L-ascorbic acid transmembrane transport	1	2808.7×	0.002	SELENON
regulation of ryanodine-sensitive calcium-release channel activity	1	2808.7×	0.002	SELENON
diaphragm contraction	1	2106.5×	0.002	SELENON
response to muscle activity involved in regulation of muscle adaptation	1	2106.5×	0.002	SELENON
positive regulation of low-density lipoprotein particle clearance	1	2106.5×	0.002	LDLRAP1
membrane biogenesis	1	1685.2×	0.002	SELENON
skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration	1	1404.3×	0.002	SELENON
membrane to membrane docking	1	1404.3×	0.002	SELENON
skeletal muscle satellite cell differentiation	1	1053.2×	0.003	SELENON
positive regulation of cholesterol metabolic process	1	1053.2×	0.003	LDLRAP1
obsolete mitochondrion-endoplasmic reticulum membrane tethering	1	1053.2×	0.003	SELENON
L-ascorbic acid metabolic process	1	766.0×	0.003	SELENON
cellular response to caffeine	1	766.0×	0.003	SELENON
multicellular organismal response to stress	1	648.1×	0.003	SELENON
amyloid precursor protein metabolic process	1	648.1×	0.003	LDLRAP1
energy reserve metabolic process	1	526.6×	0.004	SELENON
mitochondrial calcium ion transmembrane transport	1	495.6×	0.004	SELENON
low-density lipoprotein particle clearance	1	495.6×	0.004	LDLRAP1
positive regulation of receptor-mediated endocytosis	1	401.2×	0.004	LDLRAP1
calcium ion import	1	401.2×	0.004	SELENON
cholesterol transport	1	366.4×	0.005	LDLRAP1
regulation of protein localization to plasma membrane	1	324.1×	0.005	LDLRAP1
skeletal muscle fiber development	1	271.8×	0.006	SELENON
cellular response to cytokine stimulus	1	271.8×	0.006	LDLRAP1
membrane organization	1	255.3×	0.006	SELENON

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
SELENON	0	0
LDLRAP1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	SELENON, LDLRAP1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
SELENON	0	—
LDLRAP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04745247	Not specified	UNKNOWN	Stimulate the Face to Improve Tactile Acuity on the Hand