autosomal recessive limb-girdle muscular dystrophy type R18

Summary

autosomal recessive limb-girdle muscular dystrophy type R18 (MONDO:0014144) is a disease caused by TRAPPC11 (GenCC Definitive), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: TRAPPC11 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 878
• Phenotypes (HPO): 27
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		3	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

27 HPO clinical features (Orphanet curated; top 27 by frequency):

HPO ID	Term	Frequency
HP:0000518	Cataract	Frequent (30-79%)
HP:0001265	Hyporeflexia	Frequent (30-79%)
HP:0001288	Gait disturbance	Frequent (30-79%)
HP:0001344	Absent speech	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002515	Waddling gait	Frequent (30-79%)
HP:0002910	Elevated circulating hepatic transaminase concentration	Frequent (30-79%)
HP:0003198	Myopathy	Frequent (30-79%)
HP:0003307	Hyperlordosis	Frequent (30-79%)
HP:0003326	Myalgia	Frequent (30-79%)
HP:0003394	Muscle spasm	Frequent (30-79%)
HP:0003560	Muscular dystrophy	Frequent (30-79%)
HP:0003701	Proximal muscle weakness	Frequent (30-79%)
HP:0006785	Limb-girdle muscular dystrophy	Frequent (30-79%)
HP:0006889	Intellectual disability, borderline	Frequent (30-79%)
HP:0012762	Cerebral white matter atrophy	Frequent (30-79%)
HP:0040081	Abnormal circulating creatine kinase concentration	Frequent (30-79%)
HP:0100295	Muscle fiber atrophy	Frequent (30-79%)
HP:0000252	Microcephaly	Occasional (5-29%)
HP:0001397	Hepatic steatosis	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002072	Chorea	Occasional (5-29%)
HP:0002078	Truncal ataxia	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0025313	Exophoria	Occasional (5-29%)
HP:0002091	Restrictive ventilatory defect	Excluded (0%)
HP:0005133	Right ventricular dilatation	Excluded (0%)

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type R18
Mondo ID	MONDO:0014144
OMIM	615356
Orphanet	369840
DOID	DOID:0110287
UMLS	C4517996
MedGen	1385598
GARD	0012543
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in TRAPPC11 · autosomal recessive limb-girdle muscular dystrophy type 2S · LGMD2S · limb-girdle muscular dystrophy type 2S · muscular dystrophy, limb-girdle, autosomal recessive 18 · muscular dystrophy, limb-girdle, type 2S · TRAPPC11 autosomal recessive limb-girdle muscular dystrophy

Data availability: 878 ClinVar variants · 6 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › autosomal recessive limb-girdle muscular dystrophy › autosomal recessive limb-girdle muscular dystrophy type R18

Related subtypes (31): epidermolysis bullosa simplex 5B, with muscular dystrophy, autosomal recessive limb-girdle muscular dystrophy type 2A, autosomal recessive limb-girdle muscular dystrophy type 2B, autosomal recessive limb-girdle muscular dystrophy type 2C, autosomal recessive limb-girdle muscular dystrophy type 2H, autosomal recessive limb-girdle muscular dystrophy type 2F, autosomal recessive limb-girdle muscular dystrophy type 2G, autosomal recessive limb-girdle muscular dystrophy type 2E, autosomal recessive limb-girdle muscular dystrophy type 2I, autosomal recessive limb-girdle muscular dystrophy type 2D, autosomal recessive limb-girdle muscular dystrophy type 2J, autosomal recessive limb-girdle muscular dystrophy type 2K, autosomal recessive limb-girdle muscular dystrophy type 2L, autosomal recessive limb-girdle muscular dystrophy type 2M, autosomal recessive limb-girdle muscular dystrophy type 2O, autosomal recessive limb-girdle muscular dystrophy type 2N, autosomal recessive limb-girdle muscular dystrophy type 2Q, autosomal recessive limb-girdle muscular dystrophy type 2P, autosomal recessive limb-girdle muscular dystrophy type 2T, autosomal recessive limb-girdle muscular dystrophy type 2U, limb-girdle muscular dystrophy due to POMK deficiency, autosomal recessive limb-girdle muscular dystrophy type 2X, autosomal recessive limb-girdle muscular dystrophy type 2W, autosomal recessive limb-girdle muscular dystrophy type 2Y, autosomal recessive limb-girdle muscular dystrophy type 2R1, muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 8, muscular dystrophy, limb-girdle, autosomal recessive 23, muscular dystrophy, limb-girdle, autosomal recessive 26, muscular dystrophy, limb-girdle, autosomal recessive 27, muscular dystrophy, limb-girdle, autosomal recessive 28, muscular dystrophy, limb-girdle, autosomal recessive 29

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

600 retrieved; paginated sample, class counts are floors:

275 likely benign, 244 uncertain significance, 27 pathogenic, 19 benign, 9 conflicting classifications of pathogenicity, 9 benign/likely benign, 9 likely pathogenic, 8 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1452649	NM_021942.6(TRAPPC11):c.2281dup (p.Glu761fs)	LOC126807238	Pathogenic	criteria provided, single submitter
1458638	NM_021942.6(TRAPPC11):c.2389C>T (p.Gln797Ter)	LOC126807238	Pathogenic	criteria provided, single submitter
373300	NM_021942.6(TRAPPC11):c.2407C>T (p.Gln803Ter)	LOC126807238	Pathogenic	criteria provided, multiple submitters, no conflicts
1033577	NM_021942.6(TRAPPC11):c.1568-1G>T	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1033578	NM_021942.6(TRAPPC11):c.2625del (p.His875fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
1033986	NM_021942.6(TRAPPC11):c.518_521del (p.Phe173fs)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323707	NM_021942.6(TRAPPC11):c.2579del (p.Leu860fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
1325225	NM_021942.6(TRAPPC11):c.512_515del (p.Ser171fs)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1425984	NM_021942.6(TRAPPC11):c.630_631del (p.His210fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
1429017	NM_021942.6(TRAPPC11):c.1381G>T (p.Glu461Ter)	TRAPPC11	Pathogenic	criteria provided, single submitter
1452398	NM_021942.6(TRAPPC11):c.1466G>A (p.Trp489Ter)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454783	NM_021942.6(TRAPPC11):c.1051C>T (p.Gln351Ter)	TRAPPC11	Pathogenic	criteria provided, single submitter
1456744	NC_000004.11:g.(?184622830)(184633797_?)del	TRAPPC11	Pathogenic	criteria provided, single submitter
1457515	NM_021942.6(TRAPPC11):c.1291_1297del (p.Glu430_Ile431insTer)	TRAPPC11	Pathogenic	criteria provided, multiple submitters, no conflicts
1458177	NM_021942.6(TRAPPC11):c.3173_3180del (p.Phe1058fs)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1972684	NM_021942.6(TRAPPC11):c.171_174dup (p.Asp59delinsArgTer)	TRAPPC11	Pathogenic	criteria provided, single submitter
2041292	NM_021942.6(TRAPPC11):c.886C>T (p.Arg296Ter)	TRAPPC11	Pathogenic	criteria provided, single submitter
2055283	NM_021942.6(TRAPPC11):c.1348C>T (p.Arg450Ter)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2135671	NM_021942.6(TRAPPC11):c.370del (p.Val124fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
2141268	NM_021942.6(TRAPPC11):c.913_914del (p.Lys305fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
2418901	NM_021942.6(TRAPPC11):c.1702C>T (p.Arg568Ter)	TRAPPC11	Pathogenic	criteria provided, multiple submitters, no conflicts
2426695	NC_000004.11:g.(?184585021)(184585244_?)del	TRAPPC11	Pathogenic	criteria provided, single submitter
2580783	NM_021942.6(TRAPPC11):c.1522C>T (p.Gln508Ter)	TRAPPC11	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
268054	NM_021942.6(TRAPPC11):c.661-1G>T	TRAPPC11	Pathogenic	no assertion criteria provided
268055	NM_021942.6(TRAPPC11):c.1893+3A>G	TRAPPC11	Pathogenic	criteria provided, single submitter
2729079	NM_021942.6(TRAPPC11):c.2173del (p.Arg725fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
2756727	NM_021942.6(TRAPPC11):c.1816C>T (p.Gln606Ter)	TRAPPC11	Pathogenic	criteria provided, single submitter
2810365	NM_021942.6(TRAPPC11):c.1131del (p.Asn378fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
2850813	NM_021942.6(TRAPPC11):c.666_669del (p.Phe223fs)	TRAPPC11	Pathogenic	criteria provided, single submitter
2858941	NM_021942.6(TRAPPC11):c.725del (p.Asn242fs)	TRAPPC11	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · 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.

Gene	Classification	Inheritance	Disease	Records
TRAPPC11	Definitive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type R18	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TRAPPC11	Orphanet:369840	TRAPPC11-related limb-girdle muscular dystrophy R18
TRAPPC11	Orphanet:369847	Intellectual disability-hyperkinetic movement-truncal ataxia syndrome
TRAPPC11	Orphanet:869	Triple A syndrome

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
TRAPPC11	HGNC:25751	ENSG00000168538	Q7Z392	Trafficking protein particle complex subunit 11	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TRAPPC11	Trafficking protein particle complex subunit 11	Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.

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)
TRAPPC11	Other/Unknown	no		TPC11, TRAPPC11_C

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
adrenal tissue	1
calcaneal tendon	1
primordial germ cell in gonad	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TRAPPC11	277	ubiquitous	marker	calcaneal tendon, adrenal tissue, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TRAPPC11	1,442

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TRAPPC11	Q7Z392	87.76

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.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
RAB GEFs exchange GTP for GDP on RABs	1	124.1×	0.008	TRAPPC11

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
constitutive secretory pathway	1	2808.7×	0.002	TRAPPC11
regulation of protein complex stability	1	1053.2×	0.002	TRAPPC11
obsolete vesicle tethering	1	991.3×	0.002	TRAPPC11
COPII vesicle coat assembly	1	702.2×	0.002	TRAPPC11
endoplasmic reticulum to Golgi vesicle-mediated transport	1	135.9×	0.007	TRAPPC11
Golgi organization	1	133.8×	0.007	TRAPPC11

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
TRAPPC11	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	TRAPPC11

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)
TRAPPC11	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
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments