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GeneBe

DES

desmin, the group of Intermediate filaments Type III

Basic information

Region (hg38): 2:219418376-219426735

Links

ENSG00000175084 ∙ NCBI:1674 ∙ OMIM:125660 ∙ HGNC:2770 ∙ Uniprot:P17661 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • atrioventricular block (Strong), mode of inheritance: AD
  • atrioventricular block (Strong), mode of inheritance: AR
  • myofibrillar myopathy 1 (Definitive), mode of inheritance: Semidominant
  • dilated cardiomyopathy 1I (Strong), mode of inheritance: AD
  • familial isolated dilated cardiomyopathy (Supportive), mode of inheritance: AD
  • neurogenic scapuloperoneal syndrome, Kaeser type (Supportive), mode of inheritance: AD
  • dilated cardiomyopathy 1I (Definitive), mode of inheritance: AD
  • myofibrillar myopathy 1 (Definitive), mode of inheritance: AD
  • myofibrillar myopathy 1 (Definitive), mode of inheritance: AR
  • dilated cardiomyopathy 1I (Strong), mode of inheritance: AD
  • myofibrillar myopathy 1 (Strong), mode of inheritance: AD
  • myofibrillar myopathy 1 (Strong), mode of inheritance: AR
  • dilated cardiomyopathy (Definitive), mode of inheritance: AD
  • arrhythmogenic right ventricular cardiomyopathy (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Myopathy, myofibrillar 1; Cardiomyopathy, dilated, 1IAD/ARCardiovascularIn myofibrillar myopathy, individuals typically present with slowly progressive weakness, and a significant proportion of individuals demonstrate cardiomyopathy, such that surveillance for arrhythmia or conduction defects may allow early treatment (eg, pacemaker, ICD); Cardiac transplantation may be necessary in individuals with severe forms of cardiomyopathy; In dilated cardiomyopathy, surveillance (eg, with electrocardiogram and echocardiogram) can allow early detection and interventions (including medications) in order to ameliorate morbidity and mortalityCardiovascular; Musculoskeletal; Neurologic5828910; 8114783; 7672786; 9697706; 9736733; 10430757; 10545598; 11073539; 17221859; 17439987; 19433360; 19879535; 20301672; 20664348; 20718792; 22215463; 23687351; 24200904; 31024060

ClinVar

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

  • Desmin-related myofibrillar myopathy (723 variants)
  • not provided (314 variants)
  • Cardiovascular phenotype (229 variants)
  • not specified (111 variants)
  • Dilated cardiomyopathy 1I (61 variants)
  • Neurogenic scapuloperoneal syndrome, Kaeser type (48 variants)
  • Cardiomyopathy (45 variants)
  • Myofibrillar Myopathy, Dominant (28 variants)
  • Dilated cardiomyopathy 1I;Desmin-related myofibrillar myopathy;Neurogenic scapuloperoneal syndrome, Kaeser type (17 variants)
  • Dilated cardiomyopathy 1I;Neurogenic scapuloperoneal syndrome, Kaeser type;Desmin-related myofibrillar myopathy (13 variants)
  • Desmin-related myofibrillar myopathy;Dilated cardiomyopathy 1I;Neurogenic scapuloperoneal syndrome, Kaeser type (9 variants)
  • Primary dilated cardiomyopathy (8 variants)
  • DES-related condition (7 variants)
  • Desmin-related myofibrillar myopathy;Neurogenic scapuloperoneal syndrome, Kaeser type;Dilated cardiomyopathy 1I (7 variants)
  • Neurogenic scapuloperoneal syndrome, Kaeser type;Desmin-related myofibrillar myopathy;Dilated cardiomyopathy 1I (6 variants)
  • Inborn genetic diseases (6 variants)
  • Arrhythmogenic right ventricular cardiomyopathy (5 variants)
  • Neurogenic scapuloperoneal syndrome, Kaeser type;Dilated cardiomyopathy 1I;Desmin-related myofibrillar myopathy (5 variants)
  • Myofibrillar myopathy (4 variants)
  • Dilated cardiomyopathy 1I;Desmin-related myofibrillar myopathy (3 variants)
  • Primary dilated cardiomyopathy;Neuromuscular disease (3 variants)
  • Primary familial hypertrophic cardiomyopathy (3 variants)
  • Dilated Cardiomyopathy, Dominant (2 variants)
  • Scapuloperoneal weakness (2 variants)
  • Primary familial dilated cardiomyopathy (1 variants)
  • Arrhythmogenic right ventricular dysplasia 9 (1 variants)
  • See cases (1 variants)
  • 14 conditions (1 variants)
  • Abnormality of the musculature (1 variants)
  • Congenital diaphragmatic hernia (1 variants)
  • Progressive familial heart block;Bradycardia (1 variants)
  • Dilated cardiomyopathy 1S (1 variants)
  • Neuromuscular disease;Primary dilated cardiomyopathy;Desmin-related myofibrillar myopathy (1 variants)
  • Megacolon (1 variants)
  • Hypertrophic cardiomyopathy (1 variants)
  • Desmin-related myofibrillar myopathy;Primary dilated cardiomyopathy (1 variants)
  • Left ventricular noncompaction cardiomyopathy (1 variants)
  • Dilated cardiomyopathy 1A (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DES 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
8
clinvar
169
clinvar
5
clinvar
 182
missense
8
clinvar
22
clinvar
418
clinvar
2
clinvar
 450
nonsense
10
clinvar
5
clinvar
2
clinvar
 17
start loss
2
clinvar
 2
frameshift
12
clinvar
5
clinvar
5
clinvar
 22
inframe indel
2
clinvar
2
clinvar
17
clinvar
 21
splice donor/acceptor (+/-2bp)
1
clinvar
8
clinvar
4
clinvar
 13
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
1
19
16
 36
non coding
?
    UTR, intron and other, non coding variants
1
clinvar
12
clinvar
62
clinvar
16
clinvar
 91
Total 34 44 466 233 21

Highest pathogenic variant AF is 0.0000329

Variants in DES

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

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

Position Type Phenotype Significance ClinVar
2-219418389-C-T Neurogenic scapuloperoneal syndrome, Kaeser type • Dilated cardiomyopathy 1I • Myofibrillar Myopathy, Dominant • Desmin-related myofibrillar myopathy Uncertain significance (Jan 12, 2018)334449
2-219418409-C-T Dilated cardiomyopathy 1I • Neurogenic scapuloperoneal syndrome, Kaeser type • Desmin-related myofibrillar myopathy Uncertain significance (Jan 13, 2018)895278
2-219418416-C-T not specified Likely benign (Mar 08, 2018)516001
2-219418419-G-A not specified • Myofibrillar Myopathy, Dominant • Dilated cardiomyopathy 1I • Neurogenic scapuloperoneal syndrome, Kaeser type • Desmin-related myofibrillar myopathy Benign/Likely benign (Apr 27, 2017)201698
2-219418432-T-A Likely benign (Apr 03, 2018)670193
2-219418432-T-TGCGCCCGCCAGCC not specified Benign (Oct 19, 2020)201699
2-219418446-T-TGCGCCCGCCAGCC Benign (Mar 03, 2015)1297205
2-219418454-G-A not specified Uncertain significance (Feb 11, 2022)1343552
2-219418456-C-G not specified • Dilated cardiomyopathy 1I Conflicting classifications of pathogenicity (Jul 25, 2019)290155
2-219418457-G-A Dilated cardiomyopathy 1I • Neurogenic scapuloperoneal syndrome, Kaeser type • Myofibrillar Myopathy, Dominant • not specified • Desmin-related myofibrillar myopathy Uncertain significance (Feb 01, 2021)334450
2-219418461-C-T Cardiomyopathy Uncertain significance (-)1802376
2-219418463-A-G Desmin-related myofibrillar myopathy Likely pathogenic (Sep 21, 2023)388926
2-219418464-T-C Desmin-related myofibrillar myopathy Likely pathogenic (Jun 29, 2020)1066470
2-219418467-G-T Desmin-related myofibrillar myopathy Pathogenic/Likely pathogenic (Feb 08, 2023)66414
2-219418469-C-G DES-related disorder Uncertain significance (Dec 29, 2023)2631293
2-219418469-C-T Desmin-related myofibrillar myopathy Pathogenic/Likely pathogenic (May 04, 2023)836201
2-219418470-A-G Desmin-related myofibrillar myopathy Uncertain significance (Oct 03, 2022)1025467
2-219418471-G-A Cardiovascular phenotype • Desmin-related myofibrillar myopathy Likely benign (Dec 01, 2023)1768930
2-219418472-G-A Desmin-related myofibrillar myopathy Uncertain significance (Dec 21, 2020)1054531
2-219418473-C-A Desmin-related myofibrillar myopathy Uncertain significance (Mar 12, 2022)2110362
2-219418474-C-A Desmin-related myofibrillar myopathy • Cardiovascular phenotype Likely benign (Dec 17, 2023)416615
2-219418474-C-G Desmin-related myofibrillar myopathy Likely benign (Feb 03, 2020)1097857
2-219418477-C-A Cardiovascular phenotype Uncertain significance (Jan 23, 2023)2497629
2-219418479-C-G Desmin-related myofibrillar myopathy • Cardiovascular phenotype Uncertain significance (Oct 12, 2021)1436615
2-219418479-C-T Desmin-related myofibrillar myopathy Uncertain significance (Jan 09, 2018)572025

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DESprotein_codingprotein_codingENST00000373960 98363
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.008830.9911257260221257480.0000875
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense1.772062910.7080.00001912986
Missense in Polyphen79106.970.738551097
Synonymous1.111081240.8730.00000789923
Loss of Function3.05824.20.3310.00000141249

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0001230.000123
Ashkenazi Jewish0.0008270.000794
East Asian0.0001160.000109
Finnish0.000.00
European (Non-Finnish)0.00007030.0000703
Middle Eastern0.0001160.000109
South Asian0.00003270.0000327
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Muscle-specific type III intermediate filament essential for proper muscular structure and function. Plays a crucial role in maintaining the structure of sarcomeres, inter-connecting the Z-disks and forming the myofibrils, linking them not only to the sarcolemmal cytoskeleton, but also to the nucleus and mitochondria, thus providing strength for the muscle fiber during activity (PubMed:25358400). In adult striated muscle they form a fibrous network connecting myofibrils to each other and to the plasma membrane from the periphery of the Z-line structures (PubMed:24200904, PubMed:25394388, PubMed:26724190). May act as a sarcomeric microtubule-anchoring protein: specifically associates with detyrosinated tubulin-alpha chains, leading to buckled microtubules and mechanical resistance to contraction. Contributes to the transcriptional regulation of the NKX2-5 gene in cardiac progenitor cells during a short period of cardiomyogenesis and in cardiac side population stem cells in the adult. Plays a role in maintaining an optimal conformation of nebulette (NEB) on heart muscle sarcomeres to bind and recruit cardiac alpha-actin (By similarity). {ECO:0000250|UniProtKB:P31001, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:26724190, ECO:0000303|PubMed:25358400}.;
Disease
DISEASE: Myopathy, myofibrillar, 1 (MFM1) [MIM:601419]: A form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disk and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM1 is characterized by skeletal muscle weakness associated with cardiac conduction blocks, arrhythmias, restrictive heart failure, and accumulation of desmin-reactive deposits in cardiac and skeletal muscle cells. {ECO:0000269|PubMed:10545598, ECO:0000269|PubMed:10717012, ECO:0000269|PubMed:10905661, ECO:0000269|PubMed:11061256, ECO:0000269|PubMed:11668632, ECO:0000269|PubMed:12620971, ECO:0000269|PubMed:12766977, ECO:0000269|PubMed:14648196, ECO:0000269|PubMed:14711882, ECO:0000269|PubMed:14724127, ECO:0000269|PubMed:15495235, ECO:0000269|PubMed:15800015, ECO:0000269|PubMed:16009553, ECO:0000269|PubMed:16376610, ECO:0000269|PubMed:16865695, ECO:0000269|PubMed:17221859, ECO:0000269|PubMed:18061454, ECO:0000269|PubMed:19879535, ECO:0000269|PubMed:20829228, ECO:0000269|PubMed:22106715, ECO:0000269|PubMed:22395865, ECO:0000269|PubMed:23615443, ECO:0000269|PubMed:25394388, ECO:0000269|PubMed:27733623, ECO:0000269|PubMed:28470624, ECO:0000269|PubMed:9697706, ECO:0000269|PubMed:9736733}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations in the DES gene are associated with a variable clinical phenotype which encompasses isolated myopathies, pure cardiac phenotypes (including dilated cardiomyopathy, restrictive cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy), cardiac conduction disease, and combinations of these disorders. If both cardiologic and neurologic features occur, they can manifest in any order, as cardiologic features can precede, occur simultaneously with, or follow manifestation of generalized neuromuscular disease (PubMed:19879535). {ECO:0000269|PubMed:19879535}.; DISEASE: Cardiomyopathy, dilated 1I (CMD1I) [MIM:604765]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death. {ECO:0000269|PubMed:10430757, ECO:0000269|PubMed:24200904, ECO:0000269|PubMed:26724190}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Neurogenic scapuloperoneal syndrome Kaeser type (Kaeser syndrome) [MIM:181400]: Autosomal dominant disorder with a peculiar scapuloperoneal distribution of weakness and atrophy. A large clinical variability is observed ranging from scapuloperoneal, limb grindle and distal phenotypes with variable cardiac or respiratory involvement. Facial weakness, dysphagia and gynaecomastia are frequent additional symptoms. Affected men seemingly bear a higher risk of sudden, cardiac death as compared to affected women. Histological and immunohistochemical examination of muscle biopsy specimens reveal a wide spectrum of findings ranging from near normal or unspecific pathology to typical, myofibrillar changes with accumulation of desmin. {ECO:0000269|PubMed:17439987, ECO:0000269|PubMed:25394388}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Limb-girdle muscular dystrophy 2R (LGMD2R) [MIM:615325]: A form of limb-girdle muscular dystrophy, a disease characterized by proximal weakness, weakness of the hip and shoulder girdles and prominent asymmetrical quadriceps femoris and biceps brachii atrophy. {ECO:0000269|PubMed:23687351}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Arrhythmogenic Right Ventricular Cardiomyopathy;Striated Muscle Contraction;Striated Muscle Contraction;Muscle contraction;Aurora B signaling (Consensus)

Recessive Scores

pRec
0.122

Intolerance Scores

loftool
0.0939
rvis_EVS
-0.51
rvis_percentile_EVS
21.56

Haploinsufficiency Scores

pHI
0.787
hipred
Y
hipred_score
0.790
ghis
0.575

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.785

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Des
Phenotype
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); 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype;

Zebrafish Information Network

Gene name
desma
Affected structure
cardiac muscle cell
Phenotype tag
abnormal
Phenotype quality
decreased amount

Gene ontology

Biological process
muscle contraction;cytoskeleton organization;regulation of heart contraction;muscle filament sliding;intermediate filament organization
Cellular component
nucleus;cytosol;intermediate filament;fascia adherens;intercalated disc;Z disc;neuromuscular junction;sarcolemma;intermediate filament cytoskeleton;extracellular exosome;cardiac myofibril
Molecular function
structural constituent of cytoskeleton;protein binding;cytoskeletal protein binding;identical protein binding