DAG1

Chr 3AR

dystroglycan 1

Also known as: 156DAG, A3a, AGRNR, DAG, LGMDR16, MDDGA9, MDDGC7, MDDGC9

NCBI Gene: 1605ENSG00000173402UniProt: Q14118

This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]

Primary Disease Associations & Inheritance

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9MIM #616538
AR
Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9MIM #613818
AR
494
ClinVar variants
21
Pathogenic / LP
0.98
pLI score· haploinsufficient
1
Active trials
Clinical Summary— DAG1
🧬
Gene-Disease Validity (ClinGen)
qualitative or quantitative defects of alpha-dystroglycan · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
21 Pathogenic / Likely Pathogenic· 293 VUS of 494 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.30LOEUF
pLI 0.981
Z-score 3.84
OE 0.10 (0.04–0.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.63Z-score
OE missense 0.92 (0.86–0.99)
494 obs / 534.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.10 (0.04–0.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.86–0.99)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.11
0≤1.21.6
LoF obs/exp: 2 / 20.9Missense obs/exp: 494 / 534.7Syn Z: -1.34

ClinVar Variant Classifications

494 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic15
Likely Pathogenic6
VUS293
Likely Benign156
Benign11
Conflicting13
15
Pathogenic
6
Likely Pathogenic
293
VUS
156
Likely Benign
11
Benign
13
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
0
11
0
15
Likely Pathogenic
4
0
2
0
6
VUS
14
268
7
4
293
Likely Benign
0
0
11
145
156
Benign
0
0
11
0
11
Conflicting
—13
Total2226842149494

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

DAG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

DAG1-related congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies

definitive
ARLoss Of FunctionAbsent Gene Product
Eye
G2P ↗

DAG1-related muscular dystrophy-dystroglycanopathy limb-girdle

definitive
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
DYSTROGLYCAN 1; DAG1
MIM #128239 · *

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9

MIM #616538

Molecular basis of disorder known

Autosomal recessive

Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 9

MIM #613818

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variations and clinical spectrum of dystroglycanopathy in a large cohort of Chinese patients.
Song D et al.·Clin Genet
2021Cohort
DAG1 haploinsufficiency is associated with sporadic and familial isolated or pauci-symptomatic hyperCKemia.
Traverso M et al.·Eur J Hum Genet
2024
Endogenous stimuli-responsive separating microneedles to inhibit hypertrophic scar through remodeling the pathological microenvironment.
Yang ZR et al.·Nat Commun
2024Functional
DAG1 mutations associated with asymptomatic hyperCKemia and hypoglycosylation of α-dystroglycan.
Dong M et al.·Neurology
2015
Expert panel curation of 31 genes in relation to limb girdle muscular dystrophy.
Mohan S et al.·Ann Clin Transl Neurol
2024
NAD+ improves neuromuscular development in a zebrafish model of FKRP-associated dystroglycanopathy.
Bailey EC et al.·Skelet Muscle
2019Review
Walker-Warburg syndrome and tectocerebellar dysraphia: A novel association caused by a homozygous DAG1 mutation.
Leibovitz Z et al.·Eur J Paediatr Neurol
2018
Circular RNA circ-TNRC6B inhibits the proliferation and invasion of esophageal squamous cell carcinoma cells by regulating the miR-452-5p/DAG1 axis.
Xu R et al.·Mol Oncol
2023
Genetic Engineering of Dystroglycan in Animal Models of Muscular Dystrophy.
Sciandra F et al.·Biomed Res Int
2015Review
Absence of α- and β-dystroglycan is associated with Walker-Warburg syndrome.
Riemersma M et al.·Neurology
2015Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Muscular Dystrophy

Clinical Trial Readiness for the Dystroglycanopathies

RECRUITING
NCT00313677Katherine MathewsStarted 2006-04

External Resources

Links to major genomics databases and tools