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DYSF

dysferlin, the group of Ferlin family

Basic information

Region (hg38): 2:71453561-71686763

Previous symbols: [ "LGMD2B" ]

Links

ENSG00000135636 ∙ NCBI:8291 ∙ OMIM:603009 ∙ HGNC:3097 ∙ Uniprot:O75923 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Transcripts

Transcript IDs starting with ENST are treated as Ensembl, all others as RefSeq. Showing 4 of 32.

Transcript IDProtein IDCoding exonsMANE SelectMANE Plus Clinical
NM_001130987.2NP_001124459.156yes-
ENST00000410020.8ENSP00000386881.356yes-
NM_003494.4NP_003485.155-yes
NM_001130455.2NP_001123927.155--

Phenotypes

GenCC

Source: genCC

  • autosomal recessive limb-girdle muscular dystrophy (Definitive), mode of inheritance: AR
  • distal myopathy with anterior tibial onset (Strong), mode of inheritance: AR
  • autosomal recessive limb-girdle muscular dystrophy type 2B (Strong), mode of inheritance: AR
  • neuromuscular disease caused by qualitative or quantitative defects of dysferlin (Definitive), mode of inheritance: AR
  • autosomal recessive limb-girdle muscular dystrophy type 2B (Supportive), mode of inheritance: AR
  • Miyoshi myopathy (Supportive), mode of inheritance: AR
  • congenital myopathy, Paradas type (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Miyoshi muscular dystrophy 1; Muscular dystrophy, limb-girdle, autosomal recessive, 2; Myopathy, distal, with anterior tibial onsetARCardiovascularIndividuals may have mild cardiac anomalies, as well as more severe cardiac manifestations such as dilated cardiomyopathy, and surveillance (eg, with echocardiogram) may allow early detection and management of sequelaeCardiovascular; Musculoskeletal3942856; 9009996; 8808603; 9731527; 9731526; 10196377; 10469840; 11134403; 10766988; 11198284; 16087766; 17287450; 17994539; 18306167; 19084402; 20535123; 21522182; 22297152; 22517428; 21816046
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ClinVar

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

  • Neuromuscular_disease_caused_by_qualitative_or_quantitative_defects_of_dysferlin (3309 variants)
  • not_provided (1245 variants)
  • Autosomal_recessive_limb-girdle_muscular_dystrophy_type_2B (1174 variants)
  • Miyoshi_muscular_dystrophy_1 (505 variants)
  • Distal_myopathy_with_anterior_tibial_onset (283 variants)
  • Inborn_genetic_diseases (273 variants)
  • Autosomal_recessive_limb-girdle_muscular_dystrophy (244 variants)
  • not_specified (195 variants)
  • DYSF-related_disorder (108 variants)
  • Abnormality_of_the_musculature (12 variants)
  • Muscular_dystrophy (3 variants)
  • Miyoshi_myopathy (3 variants)
  • Distal_lower_limb_muscle_weakness (2 variants)
  • Other_rare_neuromuscular_disorders (2 variants)
  • See_cases (2 variants)
  • Limb-girdle_muscular_dystrophy (2 variants)
  • EMG:_myopathic_abnormalities (1 variants)
  • Peripheral_neuropathy (1 variants)
  • Arthralgia (1 variants)
  • Restrictive_cardiomyopathy (1 variants)
  • Schizophrenia (1 variants)
  • Peroneal_muscle_atrophy (1 variants)
  • Primary_dilated_cardiomyopathy (1 variants)
  • Muscle_weakness (1 variants)
  • Foot_dorsiflexor_weakness (1 variants)
  • Proximal_muscle_weakness (1 variants)
  • Myalgia (1 variants)
  • Absent_muscle_fiber_dysferlin (1 variants)
  • Myopathy (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DYSF gene is commonly pathogenic or not. These statistics are base on transcript: NM_001130987.2. Only rare variants are included in the table.

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.

EffectPLPVUSLBBSum
synonymous
4
clinvar
48
clinvar
1043
clinvar
7
clinvar
 1102
missense
64
clinvar
98
clinvar
1002
clinvar
205
clinvar
17
clinvar
 1386
nonsense
130
clinvar
96
clinvar
2
clinvar
 228
start loss
0
frameshift
204
clinvar
152
clinvar
3
clinvar
2
clinvar
 361
splice donor/acceptor (+/-2bp)
74
clinvar
122
clinvar
10
clinvar
1
clinvar
 207
Total 472 472 1065 1251 24

Highest pathogenic variant AF is 0.0010766431

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
DYSFprotein_codingprotein_codingENST00000410020 56233047
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
12547702711257480.00108
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.038912321.24e+30.9970.000083413861
Missense in Polyphen433437.060.990714677
Synonymous-1.865514981.110.00003384112
Loss of Function4.01721190.6030.000006161350

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.004460.00440
Ashkenazi Jewish0.00009940.0000992
East Asian0.001740.00174
Finnish0.0001400.000139
European (Non-Finnish)0.0008540.000853
Middle Eastern0.001740.00174
South Asian0.001120.00111
Other0.0008160.000815

dbNSFP

Source: dbNSFP

Function
FUNCTION: Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity). {ECO:0000250}.;
Disease
DISEASE: Limb-girdle muscular dystrophy 2B (LGMD2B) [MIM:253601]: An autosomal recessive degenerative myopathy characterized by weakness and atrophy starting in the proximal pelvifemoral muscles, with onset in the late teens or later, massive elevation of serum creatine kinase levels and slow progression. Scapular muscle involvement is minor and not present at onset. Upper limb girdle involvement follows some years after the onset in lower limbs. {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403, ECO:0000269|PubMed:14678801, ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:16705711, ECO:0000269|PubMed:16996541, ECO:0000269|PubMed:17185750, ECO:0000269|PubMed:17287450, ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Miyoshi muscular dystrophy 1 (MMD1) [MIM:254130]: A late- onset muscular dystrophy involving the distal lower limb musculature. It is characterized by weakness that initially affects the gastrocnemius muscle during early adulthood. {ECO:0000269|PubMed:10196377, ECO:0000269|PubMed:11134403, ECO:0000269|PubMed:11468312, ECO:0000269|PubMed:11959863, ECO:0000269|PubMed:12796534, ECO:0000269|PubMed:15116377, ECO:0000269|PubMed:15469449, ECO:0000269|PubMed:15477515, ECO:0000269|PubMed:15515206, ECO:0000269|PubMed:16010686, ECO:0000269|PubMed:16100712, ECO:0000269|PubMed:17287450, ECO:0000269|PubMed:18306167, ECO:0000269|PubMed:18853459, ECO:0000269|PubMed:9731526, ECO:0000269|Ref.27}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Distal myopathy with anterior tibial onset (DMAT) [MIM:606768]: Onset of the disorder is between 14 and 28 years of age and the anterior tibial muscles are the first muscle group to be involved. Inheritance is autosomal recessive. {ECO:0000269|PubMed:11198284}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Smooth Muscle Contraction;Muscle contraction (Consensus)

Recessive Scores

pRec
0.307

Intolerance Scores

loftool
0.00220
rvis_EVS
-1.31
rvis_percentile_EVS
4.85

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.776

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Zebrafish Information Network

Gene name
dysf
Affected structure
muscle
Phenotype tag
abnormal
Phenotype quality
refractivity

Gene ontology

Biological process
angiogenesis;plasma membrane repair;positive regulation of endothelial cell proliferation;monocyte activation involved in immune response;macrophage activation involved in immune response;glycerol metabolic process;vesicle fusion;muscle contraction;negative regulation of gene expression;lipid storage;T-tubule organization;negative regulation of protein catabolic process;skeletal muscle tissue regeneration;fat cell differentiation;positive regulation of cell adhesion;muscle fiber development;cytokine secretion;negative regulation of phagocytosis;cellular response to osmotic stress;positive regulation of neutrophil chemotaxis;regulation of calcium ion import;negative regulation of high voltage-gated calcium channel activity;negative regulation of protein polyubiquitination
Cellular component
nucleus;endosome;early endosome;late endosome;Golgi apparatus;microtubule organizing center;microtubule;plasma membrane;integral component of membrane;lamellipodium;endocytic vesicle;T-tubule;cytoplasmic vesicle membrane;sarcolemma;extracellular exosome;membrane microdomain
Molecular function
calcium ion binding;protein binding;phospholipid binding;calcium-dependent phospholipid binding;microtubule binding;alpha-tubulin binding
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