DAG1

dystroglycan 1

Basic information

Region (hg38): 3:49468712-49535618

Links

ENSG00000173402 ∙ NCBI:1605 ∙ OMIM:128239 ∙ HGNC:2666 ∙ Uniprot:Q14118 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive limb-girdle muscular dystrophy type 2P (Definitive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2P (Strong), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy, type A (Supportive), mode of inheritance: AR
• autosomal recessive limb-girdle muscular dystrophy type 2P (Supportive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (Definitive), mode of inheritance: AR
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9; Muscular dystrophy-dystroglycanopathy, type C, 9	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic; Ophthalmologic	14678799; 21388311; 25503980; 25934851

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DAG1 gene.

• Autosomal recessive limb-girdle muscular dystrophy type 2P;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (267 variants)
• not provided (247 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;Autosomal recessive limb-girdle muscular dystrophy type 2P (221 variants)
• Inborn genetic diseases (42 variants)
• not specified (38 variants)
• Autosomal recessive limb-girdle muscular dystrophy type 2P (9 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (8 variants)
• Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 (1 variants)
• Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DAG1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			12	117	3	132
missense			356	5	3	364
nonsense	3	2	4			9
start loss						0
frameshift	2	6	14			22
inframe indel			6			6
splice donor/acceptor (+/-2bp)	1		2			3
splice region			1	2	1	4
non coding			1	11	11	23
Total	6	8	395	133	17

Variants in DAG1

This is a list of pathogenic ClinVar variants found in the DAG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-49468836-C-CA			Benign (Jul 03, 2018)
3-49468840-A-AT			Benign (Nov 19, 2019)
3-49468866-C-T			Benign (Jul 03, 2018)
3-49469056-G-T		Intellectual disability	Uncertain significance (May 29, 2019)
3-49470079-T-G			Benign (Jul 03, 2018)
3-49470414-G-A		not specified	Benign (Jan 26, 2016)
3-49470420-C-T		not specified	Likely benign (Jan 28, 2016)
3-49477102-A-G			Likely benign (Aug 10, 2020)
3-49487345-G-C			Benign (Oct 02, 2018)
3-49487663-A-G			Benign (Jul 01, 2019)
3-49488525-T-C			Benign (Jul 01, 2019)
3-49488529-G-T			Benign (Jul 03, 2018)
3-49488610-TA-T			Likely benign (Jul 03, 2018)
3-49488611-A-T			Benign (Jul 03, 2018)
3-49488867-C-T			Benign (Jul 03, 2018)
3-49510128-T-C			Benign (Jun 14, 2018)
3-49510128-T-G			not provided (May 13, 2011)
3-49510406-C-CT			Benign (Jan 29, 2019)
3-49510501-C-T		not specified	Likely benign (Mar 21, 2017)
3-49510511-G-T			Likely benign (May 07, 2018)
3-49510539-G-A		Autosomal recessive limb-girdle muscular dystrophy type 2P;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9	Uncertain significance (Dec 28, 2023)
3-49510539-G-C		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;Autosomal recessive limb-girdle muscular dystrophy type 2P	Uncertain significance (Mar 19, 2022)
3-49510548-T-G		Autosomal recessive limb-girdle muscular dystrophy type 2P;Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9	Uncertain significance (Jun 13, 2022)
3-49510549-G-A		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;Autosomal recessive limb-girdle muscular dystrophy type 2P	Conflicting classifications of pathogenicity (Jun 01, 2021)
3-49510555-C-G		Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;Autosomal recessive limb-girdle muscular dystrophy type 2P	Likely benign (Sep 08, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DAG1	protein_coding	protein_coding	ENST00000545947	2	66903

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0188	125744	0	4	125748	0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.625	494	535	0.924	0.0000340	5771
Missense in Polyphen		177	228.52	0.77456		2597
Synonymous	-1.34	246	221	1.11	0.0000147	2002
Loss of Function	3.84	2	20.9	0.0955	0.00000124	241

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.; FUNCTION: Beta-dystroglycan is a transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity.
• Disease: DISEASE: Muscular dystrophy-dystroglycanopathy limb-girdle C9 (MDDGC9) [MIM:613818]: An autosomal recessive muscular dystrophy showing onset in early childhood, and associated with mental retardation without structural brain anomalies. {ECO:0000269|PubMed:21388311, ECO:0000269|PubMed:25503980}. Note=The disease is caused by mutations affecting the gene represented in this entry. MDDGC7 is caused by DAG1 mutations that interfere with normal post-translational processing, resulting in defective DAG1 glycosylation and impaired interactions with extracellular-matrix components. Other muscular dystrophy- dystroglycanopathies are caused by defects in enzymes involved in protein O-glycosylation.; DISEASE: Muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A9 (MDDGA9) [MIM:616538]: An autosomal recessive disorder characterized by congenital muscular dystrophy associated with cobblestone lissencephaly and other brain anomalies, eye malformations, profound mental retardation, and death usually in the first years of life. Included diseases are the more severe Walker-Warburg syndrome and the slightly less severe muscle-eye-brain disease. {ECO:0000269|PubMed:24052401, ECO:0000269|PubMed:25934851}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: ECM-receptor interaction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Viral myocarditis - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Integrated Breast Cancer Pathway;Angiogenesis overview;Arrhythmogenic Right Ventricular Cardiomyopathy;Primary Focal Segmental Glomerulosclerosis FSGS;Developmental Biology;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;agrin in postsynaptic differentiation;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Non-integrin membrane-ECM interactions;Axon guidance;ECM proteoglycans;O-linked glycosylation (Consensus)

Recessive Scores

• pRec: 0.625

Intolerance Scores

• loftool: 0.00152
• rvis_EVS: -0.57
• rvis_percentile_EVS: 19.04

Haploinsufficiency Scores

• pHI: 0.319
• hipred: Y
• hipred_score: 0.825
• ghis: 0.510

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.706

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dag1
• Phenotype: nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); vision/eye phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: dag1
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: detached from

Gene ontology

• Biological process: positive regulation of cell-matrix adhesion;morphogenesis of an epithelial sheet;membrane protein ectodomain proteolysis;cytoskeletal anchoring at plasma membrane;aging;regulation of gastrulation;regulation of epithelial to mesenchymal transition;response to denervation involved in regulation of muscle adaptation;calcium-dependent cell-matrix adhesion;regulation of embryonic cell shape;modulation by virus of host morphology or physiology;nerve maturation;myelination in peripheral nervous system;extracellular matrix organization;negative regulation of cell migration;axon regeneration;positive regulation of myelination;microtubule anchoring;skeletal muscle tissue regeneration;negative regulation of MAPK cascade;response to peptide hormone;positive regulation of protein kinase activity;viral entry into host cell;positive regulation of oligodendrocyte differentiation;regulation of synapse organization;negative regulation of protein kinase B signaling;angiogenesis involved in wound healing;epithelial tube branching involved in lung morphogenesis;branching involved in salivary gland morphogenesis;cellular response to mechanical stimulus;cellular response to cholesterol;commissural neuron axon guidance;basement membrane organization;regulation of neurotransmitter receptor localization to postsynaptic specialization membrane;retrograde trans-synaptic signaling by trans-synaptic protein complex;positive regulation of basement membrane assembly involved in embryonic body morphogenesis
• Cellular component: extracellular region;basement membrane;extracellular space;nucleoplasm;cytoplasm;endoplasmic reticulum lumen;Golgi lumen;cytosol;cytoskeleton;plasma membrane;cell-cell adherens junction;focal adhesion;external side of plasma membrane;dystrophin-associated glycoprotein complex;dystroglycan complex;integral component of membrane;basolateral plasma membrane;lamellipodium;filopodium;node of Ranvier;nuclear periphery;sarcolemma;costamere;plasma membrane raft;postsynaptic membrane;collagen-containing extracellular matrix;extracellular exosome;contractile ring;glutamatergic synapse;GABA-ergic synapse;postsynaptic cytosol
• Molecular function: virus receptor activity;dystroglycan binding;actin binding;calcium ion binding;protein binding;structural constituent of muscle;tubulin binding;vinculin binding;SH2 domain binding;laminin-1 binding;alpha-actinin binding