autosomal dominant limb-girdle muscular dystrophy type 1G

Summary

autosomal dominant limb-girdle muscular dystrophy type 1G (MONDO:0012193) is a disease caused by HNRNPDL (GenCC Strong), with 1 cohort gene and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: HNRNPDL (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 442
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		2	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	autosomal dominant limb-girdle muscular dystrophy type 1G
Mondo ID	MONDO:0012193
MeSH	C563794
OMIM	609115
Orphanet	55596
DOID	DOID:0110306
SNOMED CT	719990003
UMLS	C1836765
MedGen	322993
GARD	0012531
Is cancer (heuristic)	no

Also known as: autosomal dominant limb-girdle muscular dystrophy caused by mutation in HNRNPDL · HNRNPDL autosomal dominant limb-girdle muscular dystrophy · LGMD1G · limb-girdle muscular dystrophy type 1G · limb-girdle muscular dystrophy, type 1G · muscular dystrophy, limb-girdle, autosomal dominant 3

Data availability: 442 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 dominant disease › muscular dystrophy, limb-girdle, autosomal dominant › autosomal dominant limb-girdle muscular dystrophy type 1G

Related subtypes (7): autosomal dominant limb-girdle muscular dystrophy type 1F, myofibrillar myopathy 3, autosomal dominant limb-girdle muscular dystrophy type 1H, autosomal dominant limb-girdle muscular dystrophy type 1E (DES), autosomal dominant limb-girdle muscular dystrophy type 1D (DNAJB6), Emery-Dreifuss muscular dystrophy 2, autosomal dominant, muscular dystrophy, limb-girdle, autosomal dominant 4

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

442 retrieved; paginated sample, class counts are floors:

240 uncertain significance, 176 likely benign, 10 conflicting classifications of pathogenicity, 10 benign, 4 benign/likely benign, 2 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
144073	NM_031372.4(HNRNPDL):c.1132G>A (p.Asp378Asn)	HNRNPDL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
144074	NM_031372.4(HNRNPDL):c.1132G>C (p.Asp378His)	HNRNPDL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1016195	NM_031372.4(HNRNPDL):c.274T>C (p.Ser92Pro)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1026627	NM_031372.4(HNRNPDL):c.92GGCCGC[3] (p.31RP[3])	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464378	NM_031372.4(HNRNPDL):c.110A>C (p.Gln37Pro)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464379	NM_031372.4(HNRNPDL):c.113T>C (p.Leu38Pro)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464382	NM_031372.4(HNRNPDL):c.124_125delinsTC (p.Leu42Ser)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
464386	NM_031372.4(HNRNPDL):c.314C>T (p.Thr105Ile)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
533022	NM_031372.4(HNRNPDL):c.248C>T (p.Pro83Leu)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
660483	NM_031372.4(HNRNPDL):c.245G>T (p.Arg82Leu)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
704526	NM_031372.4(HNRNPDL):c.1097G>C (p.Gly366Ala)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
938978	NM_031372.4(HNRNPDL):c.324_341del (p.Arg109_Ala114del)	HNRNPDL	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1009487	NM_031372.4(HNRNPDL):c.86A>G (p.His29Arg)	HNRNPDL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1020727	NM_031372.4(HNRNPDL):c.303TGC[3] (p.Ala104dup)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1020822	NM_031372.4(HNRNPDL):c.698A>G (p.Lys233Arg)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1034574	NM_031372.4(HNRNPDL):c.70T>G (p.Ser24Ala)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1047059	NM_031372.4(HNRNPDL):c.61A>G (p.Thr21Ala)	HNRNPDL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1051825	NM_031372.4(HNRNPDL):c.191A>G (p.Gln64Arg)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1052546	NM_031372.4(HNRNPDL):c.317G>C (p.Arg106Pro)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1052812	NM_031372.4(HNRNPDL):c.176G>T (p.Arg59Leu)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1059508	NM_031372.4(HNRNPDL):c.444-10_444-9del	HNRNPDL	Uncertain significance	criteria provided, single submitter
1062117	NM_031372.4(HNRNPDL):c.793C>G (p.Pro265Ala)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1062242	NM_031372.4(HNRNPDL):c.255_256del (p.Phe86fs)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1063451	NM_031372.4(HNRNPDL):c.73C>G (p.Arg25Gly)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1063649	NM_031372.4(HNRNPDL):c.397G>A (p.Ala133Thr)	HNRNPDL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1309105	NM_031372.4(HNRNPDL):c.241C>T (p.Arg81Trp)	HNRNPDL	Uncertain significance	criteria provided, multiple submitters, no conflicts
1346798	NM_031372.4(HNRNPDL):c.612+5G>A	HNRNPDL	Uncertain significance	criteria provided, single submitter
1351696	NM_031372.4(HNRNPDL):c.355A>G (p.Thr119Ala)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1354152	NM_031372.4(HNRNPDL):c.7G>A (p.Val3Ile)	HNRNPDL	Uncertain significance	criteria provided, single submitter
1354476	NM_031372.4(HNRNPDL):c.283A>C (p.Ile95Leu)	HNRNPDL	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
HNRNPDL	Strong	Autosomal dominant	autosomal dominant limb-girdle muscular dystrophy type 1G	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
HNRNPDL	Orphanet:55596	HNRNPDL-related limb-girdle muscular dystrophy D3

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
HNRNPDL	HGNC:5037	ENSG00000152795	O14979	Heterogeneous nuclear ribonucleoprotein D-like	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
HNRNPDL	Heterogeneous nuclear ribonucleoprotein D-like	Acts as a transcriptional regulator.

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)
HNRNPDL	Other/Unknown	no		RRM_dom, Nucleotide-bd_a/b_plait_sf, hnRPDL_RRM1

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
embryo	1
primordial germ cell in gonad	1
tendon of biceps brachii	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
HNRNPDL	306	ubiquitous	marker	primordial germ cell in gonad, tendon of biceps brachii, embryo

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
HNRNPDL	4,869

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
HNRNPDL	O14979	1

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
Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation	1	300.5×	0.003	HNRNPDL

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
RNA processing	1	218.9×	0.009	HNRNPDL
regulation of gene expression	1	83.4×	0.012	HNRNPDL

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
HNRNPDL	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
HNRNPDL	1	Binding:1

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	HNRNPDL

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)
HNRNPDL	1	—

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