neurogenic scapuloperoneal syndrome, Kaeser type

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Also known as Kaeser syndromescapuloperoneal syndrome, neurogenic, Kaeser typeSCPNKstark-Kaeser syndrome

Summary

neurogenic scapuloperoneal syndrome, Kaeser type (MONDO:0008407) is a disease with 1 cohort gene.

At a glance

  • Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
  • Cohort genes: 1
  • ClinVar variants: 109

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Cases/families15WorldwideValidated
Point prevalence<1 / 1 000 000WorldwideValidated

Identifiers

Disease identifiers

FieldValue
Canonical nameneurogenic scapuloperoneal syndrome, Kaeser type
Mondo IDMONDO:0008407
MeSHC566695
OMIM181400
Orphanet85146
DOIDDOID:0111551
UMLSC1867005
MedGen356670
GARD0010312
Is cancer (heuristic)no

Also known as: Kaeser syndrome · scapuloperoneal syndrome, neurogenic, Kaeser type · SCPNK · stark-Kaeser syndrome

Data availability: 109 ClinVar variants · 1 GenCC gene-disease record.

Disease family

Classification path: disease › human disease › disease by body system or component › nervous system disorderqualitative or quantitative protein defects in neuromuscular diseasesneuromuscular disease caused by qualitative or quantitative defects of myofibrillar proteins › qualitative or quantitative defects of desmin › neurogenic scapuloperoneal syndrome, Kaeser type

Related subtypes (4): myofibrillar myopathy 1, dilated cardiomyopathy 1I, autosomal dominant limb-girdle muscular dystrophy type 1E (DES), rigid spine syndrome

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

109 retrieved; paginated sample, class counts are floors:

53 uncertain significance, 25 conflicting classifications of pathogenicity, 13 benign/likely benign, 7 benign, 5 likely pathogenic, 3 pathogenic/likely pathogenic, 2 pathogenic, 1 likely benign

ClinVarVariant (HGVS)GeneClassificationReview
16835NM_001927.4(DES):c.1049G>C (p.Arg350Pro)DESPathogeniccriteria provided, multiple submitters, no conflicts
201722NM_001927.4(DES):c.634C>T (p.Arg212Ter)DESPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
643624NM_001927.4(DES):c.226del (p.Thr76fs)DESPathogeniccriteria provided, multiple submitters, no conflicts
66402NM_001927.4(DES):c.1360C>T (p.Arg454Trp)DESPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
66411NM_001927.4(DES):c.347A>G (p.Asn116Ser)DESPathogenic/Likely pathogeniccriteria provided, multiple submitters, no conflicts
1471108NM_001927.4(DES):c.1130T>C (p.Leu377Pro)DESLikely pathogeniccriteria provided, multiple submitters, no conflicts
3382173NM_001927.4(DES):c.944dup (p.Gln316fs)DESLikely pathogeniccriteria provided, single submitter
3585680NM_001927.4(DES):c.322del (p.Glu108fs)DESLikely pathogeniccriteria provided, single submitter
3896834NM_001927.4(DES):c.1237del (p.Glu413fs)DESLikely pathogeniccriteria provided, single submitter
522692NM_001927.4(DES):c.1151A>G (p.His384Arg)DESLikely pathogeniccriteria provided, multiple submitters, no conflicts
1071184NM_001927.4(DES):c.885G>A (p.Trp295Ter)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
178015NM_001927.4(DES):c.635G>A (p.Arg212Gln)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
178016NM_001927.4(DES):c.665G>A (p.Arg222His)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
193219NM_001927.4(DES):c.216C>A (p.Ser72Arg)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
201709NM_001927.4(DES):c.1243C>T (p.Arg415Trp)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
222542NM_001927.4(DES):c.643G>A (p.Val215Met)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
283467NM_001927.4(DES):c.924C>T (p.Asn308=)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
334451NM_001927.4(DES):c.*198G>ADESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
411141NM_001927.4(DES):c.679C>T (p.Arg227Cys)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44254NM_001927.4(DES):c.170C>T (p.Ser57Leu)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44255NM_001927.4(DES):c.18G>A (p.Ser6=)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44256NM_001927.4(DES):c.193G>A (p.Gly65Ser)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44265NM_001927.4(DES):c.638C>T (p.Ala213Val)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44266NM_001927.4(DES):c.642C>T (p.Asp214=)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
44274NM_001927.4(DES):c.934G>A (p.Asp312Asn)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
498347NM_001927.4(DES):c.1148G>A (p.Arg383His)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
498618NM_001927.4(DES):c.229A>G (p.Thr77Ala)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
639517NM_001927.4(DES):c.1288+1G>ADESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
66408NM_001927.4(DES):c.322G>A (p.Glu108Lys)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications
66423NM_001927.4(DES):c.893C>T (p.Ser298Leu)DESConflicting classifications of pathogenicitycriteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 15 · Orphanet: 3 · 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.

GeneClassificationInheritanceDiseaseRecords
DESSupportiveAutosomal dominantneurogenic scapuloperoneal syndrome, Kaeser type15

Orphanet rare-disease linkage (cohort genes)

GeneOrphanet IDRare disease
DESOrphanet:154Familial isolated dilated cardiomyopathy
DESOrphanet:85146Neurogenic scapuloperoneal syndrome, Kaeser type
DESOrphanet:98909Desminopathy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

SubsetGenes
multi_evidence1

Cohort genes (full)

SymbolHGNCEnsemblUniProtNameEvidence
DESHGNC:2770ENSG00000175084P17661Desmingencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

SymbolProtein nameFunction (lead sentence)
DESDesminMuscle-specific type III intermediate filament essential for proper muscular structure and function.

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.

FamilyGenesFoldFDR
Other/Unknown11.8×0.558

Per-gene assignment

SymbolFamilyDruggable?ECInterPro (top 3)
DESOther/UnknownnoIntermed_filament_DNA-bd, IF_conserved, IF_rod_dom

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)

BucketGenes
narrow (1-5 tissues)0
moderate (6-20)0
broad (>20)1
unknown0

Top tissues across cohort

TissueCohort genes
apex of heart1
gastrocnemius1
saphenous vein1

Per-gene tissue summary (top 30)

SymbolBgee breadthFANTOM5 breadthSCXATop tissues
DES280broadmarkerapex of heart, saphenous vein, gastrocnemius

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

SymbolInteractor count
DES2,486

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

SymbolUniProtpLDDT
DESP1766177.73

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 1. Enrichment computed across 1 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.

PathwayCohort genesFoldFDRSample cohort genes
Striated Muscle Contraction1308.6×0.003DES

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 termCohort genesFoldFDRSample cohort genes
skeletal muscle organ development12106.5×0.003DES
nuclear envelope organization1991.3×0.003DES
regulation of heart contraction1495.6×0.004DES
intermediate filament organization1240.7×0.006DES
muscle contraction1208.1×0.006DES
cytoskeleton organization1132.7×0.008DES

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

SymbolMoleculesMax phase
DES00

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):

TierDefinitionGenesSymbols
AApproved (phase 4 drug)0
BPhased (≥1) drug, not yet approved0
CDruggable family + PDB, no drug0
DDruggable family + AlphaFold only, no drug0
EDifficult family or no structure, no drug1DES

Undrugged target profiles

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

SymbolChEMBL assaysDrugged partners (top 3)
DES0

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

  • Cohort genes: DES