autosomal recessive limb-girdle muscular dystrophy type 2W

Summary

autosomal recessive limb-girdle muscular dystrophy type 2W (MONDO:0014788) is a disease with 2 cohort genes and 1 clinical trial.

At a glance

• Cohort genes: 2
• ClinVar variants: 323
• Clinical trials: 1

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal recessive limb-girdle muscular dystrophy type 2W
Mondo ID	MONDO:0014788
OMIM	616827
Orphanet	466801
DOID	DOID:0110288
UMLS	C4225192
MedGen	897675
GARD	0017834
Is cancer (heuristic)	no

Also known as: autosomal recessive limb-girdle muscular dystrophy caused by mutation in LIMS2 · LGMD2W · LIMS2 autosomal recessive limb-girdle muscular dystrophy · muscular dystrophy, autosomal recessive, with cardiomyopathy and triangular tongue · muscular dystrophy, limb-girdle, type 2W · muscular dystrophy, limb-girdle, type 2w

Data availability: 323 ClinVar variants · 4 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 2W

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 R18, 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 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

323 retrieved; paginated sample, class counts are floors:

181 uncertain significance, 118 likely benign, 13 benign, 4 benign/likely benign, 3 conflicting classifications of pathogenicity, 2 pathogenic, 2 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
222901	NM_001161404.1(LIMS2):c.[261C>G;275C>T]		Pathogenic	no assertion criteria provided
222902	NM_001161403.3(LIMS2):c.968T>C (p.Leu323Pro)	LIMS2	Pathogenic	no assertion criteria provided
2585055	NM_001161403.3(LIMS2):c.238+1G>T	LIMS2	Likely pathogenic	criteria provided, single submitter
3065195	NM_001161403.3(LIMS2):c.430del (p.His144fs)	LIMS2	Likely pathogenic	criteria provided, single submitter
3118917	NM_001161403.3(LIMS2):c.494A>G (p.Asn165Ser)	LIMS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
542250	NM_001161403.3(LIMS2):c.882C>A (p.Asn294Lys)	LIMS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
571615	NM_001161403.3(LIMS2):c.12-6748A>G	LIMS2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1007133	NC_000002.11:g.(?128396846)(128432608_?)dup	GPR17	Uncertain significance	criteria provided, single submitter
1029142	NM_001161403.3(LIMS2):c.359+2701C>T	GPR17	Uncertain significance	criteria provided, single submitter
475542	NC_000002.11:g.(?128396836)(128432618_?)dup	GPR17	Uncertain significance	criteria provided, single submitter
1000166	NM_001161403.3(LIMS2):c.764A>C (p.Asp255Ala)	LIMS2	Uncertain significance	criteria provided, single submitter
1013948	NM_001161403.3(LIMS2):c.802G>T (p.Val268Leu)	LIMS2	Uncertain significance	criteria provided, single submitter
1018587	NM_001161403.3(LIMS2):c.927C>G (p.Tyr309Ter)	LIMS2	Uncertain significance	criteria provided, single submitter
1027050	NM_001161403.3(LIMS2):c.238G>A (p.Gly80Ser)	LIMS2	Uncertain significance	criteria provided, single submitter
1036588	NM_001161403.3(LIMS2):c.61C>T (p.Arg21Cys)	LIMS2	Uncertain significance	criteria provided, single submitter
1041213	NM_001161403.3(LIMS2):c.345GAA[1] (p.Lys116del)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1046324	NM_001161403.3(LIMS2):c.237C>T (p.Cys79=)	LIMS2	Uncertain significance	criteria provided, single submitter
1047114	NM_001161403.3(LIMS2):c.14A>G (p.Asn5Ser)	LIMS2	Uncertain significance	criteria provided, single submitter
1053867	NM_001161403.3(LIMS2):c.454C>T (p.Leu152Phe)	LIMS2	Uncertain significance	criteria provided, single submitter
1053971	NM_001161403.3(LIMS2):c.167A>G (p.Tyr56Cys)	LIMS2	Uncertain significance	criteria provided, single submitter
1054460	NM_001161403.3(LIMS2):c.49C>T (p.Arg17Cys)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1054901	NM_001161403.3(LIMS2):c.79C>T (p.Arg27Cys)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1056461	NM_001161403.3(LIMS2):c.385C>G (p.Arg129Gly)	LIMS2	Uncertain significance	criteria provided, single submitter
1058817	NM_001161403.3(LIMS2):c.181C>T (p.Arg61Trp)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1061830	NM_001161403.3(LIMS2):c.145C>A (p.Pro49Thr)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1323235	NM_001161403.3(LIMS2):c.661-2A>C	LIMS2	Uncertain significance	criteria provided, single submitter
1354331	NM_001161403.3(LIMS2):c.971C>T (p.Ser324Leu)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1358409	NM_001161403.3(LIMS2):c.11+1305G>A	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts
1361142	NM_001161403.3(LIMS2):c.334C>G (p.Leu112Val)	LIMS2	Uncertain significance	criteria provided, single submitter
1362387	NM_001161403.3(LIMS2):c.20C>T (p.Ser7Leu)	LIMS2	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
LIMS2	Supportive	Autosomal recessive	autosomal recessive limb-girdle muscular dystrophy type 2W	4

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
LIMS2	HGNC:16084	ENSG00000072163	Q7Z4I7	LIM and senescent cell antigen-like-containing domain protein 2	gencc,clinvar
GPR17	HGNC:4471	ENSG00000144230	Q13304	Uracil nucleotide/cysteinyl leukotriene receptor	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
LIMS2	LIM and senescent cell antigen-like-containing domain protein 2	Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.
GPR17	Uracil nucleotide/cysteinyl leukotriene receptor	Dual specificity receptor for uracil nucleotides and cysteinyl leukotrienes (CysLTs).

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
GPCR	1	12.0×	0.164
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
LIMS2	Transcription factor	no		Znf_LIM, PINCH-1-4-like, LIMS1/2-like_LIM1
GPR17	GPCR	yes		GPCR_Rhodpsn, GPCR_Rhodpsn_7TM

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
apex of heart	2
lower esophagus	1
lower esophagus muscularis layer	1
mucosa of stomach	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
LIMS2	237	ubiquitous	marker	apex of heart, lower esophagus muscularis layer, lower esophagus
GPR17	182	tissue_specific	marker	apex of heart, sural nerve, mucosa of stomach

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GPR17	1,154
LIMS2	743

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
LIMS2	Q7Z4I7	1
GPR17	Q13304	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 7. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Leukotriene receptors	1	951.7×	0.007	GPR17
P2Y receptors	1	475.8×	0.007	GPR17
Cell-extracellular matrix interactions	1	335.9×	0.007	LIMS2
Cell junction organization	1	93.6×	0.019	LIMS2
Cell-Cell communication	1	68.8×	0.020	LIMS2
G alpha (q) signalling events	1	28.7×	0.040	GPR17
G alpha (i) signalling events	1	19.5×	0.051	GPR17

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
negative regulation of cholangiocyte proliferation	1	8426.0×	0.002	LIMS2
cholangiocyte proliferation	1	4213.0×	0.002	LIMS2
negative regulation of hepatocyte proliferation	1	2808.7×	0.002	LIMS2
negative regulation of neural precursor cell proliferation	1	766.0×	0.004	LIMS2
positive regulation of integrin-mediated signaling pathway	1	648.1×	0.004	LIMS2
neural precursor cell proliferation	1	337.0×	0.006	LIMS2
cell-cell junction organization	1	312.1×	0.006	LIMS2
negative regulation of inflammatory response to antigenic stimulus	1	300.9×	0.006	GPR17
oligodendrocyte differentiation	1	210.7×	0.007	GPR17
positive regulation of substrate adhesion-dependent cell spreading	1	187.2×	0.007	LIMS2
integrin-mediated signaling pathway	1	80.2×	0.016	LIMS2
cell-cell adhesion	1	50.8×	0.023	LIMS2
G protein-coupled receptor signaling pathway	1	18.1×	0.057	GPR17
negative regulation of apoptotic process	1	17.4×	0.057	LIMS2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
GPR17	CANGRELOR TETRASODIUM

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GPR17	5	4
LIMS2	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
CANGRELOR TETRASODIUM	4	GPR17
PRANLUKAST	4	GPR17
INDOMETHACIN	4	GPR17
MONTELUKAST	4	GPR17
GAVESTINEL	2	GPR17

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GPR17	78	Functional:57, Binding:21

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

5 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.

Compound	Max phase	Cohort target (bioactivity)
CANGRELOR TETRASODIUM	4	GPR17
PRANLUKAST	4	GPR17
INDOMETHACIN	4	GPR17
MONTELUKAST	4	GPR17
GAVESTINEL	2	GPR17

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	GPR17
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	LIMS2

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)
LIMS2	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