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DYSF

dysferlin

The DYSF gene provides instructions for producing the dysferlin protein, which is critical for muscle fibre repair and maintaining muscle integrity. The DYSF gene encodes the dysferlin protein, found in the sarcolemma, the membrane surrounding muscle fibres.

Chromosome 2p13.2 Autosomal recessive HGNC:3097 Tier C
DYSF 2p13.2 p arm q arm 2

DYSF is located on the short (p) arm of chromosome 2, at band 2p13.2. Arm ratio per GRCh38 - banding schematic.

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Clinical tests that include this

Carrier Screening panel
DYSF is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The DYSF gene is responsible for manufacturing dysferlin, a protein predominantly located in the sarcolemma, the protective membrane encasing muscle fibres. Dysferlin is essential for the repair processes that muscle cells undergo, particularly following strain or injury. Understanding the DYSF gene's function is important for comprehending the mechanisms behind certain inherited muscle disorders.

What the gene does

The dysferlin protein, encoded by the DYSF gene, is primarily involved in maintaining the integrity of muscle fibres. Its key role is thought to be in sarcolemma repair, where it helps to patch up damage to the muscle cell membrane caused by mechanical stress or injury. Dysferlin may also facilitate the transport of various substances within muscle fibres, contributing to their overall cellular function. Furthermore, research indicates that dysferlin could interact with calcium, influencing cell signalling pathways crucial for muscle health. This multifaceted role underscores its importance in preventing muscle degeneration.

Video: Genetics 101

Chromosome location

The DYSF gene is situated on the short arm of chromosome 2, specifically at position 2p13.2. This genomic location specifies where the gene resides within the human genome.

Protein structure

The dysferlin protein is composed of 2080 amino acids and features several distinct domains critical for its function. It contains multiple C2 domains, specifically C2 1 (amino acids 1-101), C2 2 (amino acids 203-321), C2 3 (amino acids 360-496), C2 4 (amino acids 1136-1262), C2 5 (amino acids 1310-1438), C2 6 (amino acids 1561-1679), and C2 7 (amino acids 1795-1943). Additionally, there are two notable disordered regions within the protein, located at amino acids 132-215 and 1995-2017.

Domain map · 2,080 amino acids
C2 1 (1–101)C2 2 (203–321)C2 3 (360–496)C2 4 (1136–1262)C2 5 (1310–1438)C2 6 (1561–1679)C2 7 (1795–1943)C2 3360–496C2 51310–1438C2 71795–19431~1,0402,080
Domain - independent functional unit
🧬 Explore 3D structure on AlphaFold
UniProt:O75923Length:2,080 aaStructure:AlphaFold

Key variants

Genetic variations, or variants, within the DYSF gene can lead to altered or non-functional dysferlin protein. These changes can impair the protein's ability to perform its crucial roles in muscle repair and maintenance, ultimately contributing to the development of various muscle diseases. The impact of a variant depends on its specific nature and location within the gene.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for DYSF.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
g.71567951_71570741del
Deletion
 - Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.3085G>C
single nucleotide variant
 p.Gly1029Arg Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.345+1del
Deletion
 - Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.3531C>A
single nucleotide variant
 p.Tyr1177Ter Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.3756+905_3897+151del
Deletion
 - Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.3844_3851del
Deletion
 p.Ser1282fs Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.4726del
Deletion
 p.Glu1576fs Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.5643-1G>A
single nucleotide variant
 - Pathogenic ★★★☆ Limb-girdle muscular dystrophy
c.5885-51_6063+50del
Deletion
 - Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy
c.6017del
Deletion
 p.Gly2006fs Pathogenic ★★★☆ Autosomal recessive limb-girdle muscular dystrophy

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Pathogenic variants in the DYSF gene are associated with several inherited muscle disorders, inherited in an autosomal recessive pattern. These include Limb-girdle muscular dystrophy type 2B (Miyoshi), a condition characterised by progressive muscle weakness and wasting. Other conditions linked to DYSF variants include Miyoshi myopathy and distal myopathy with anterior tibial onset, both primarily affecting muscles further from the body's centre.

Inheritance pattern

Conditions caused by pathogenic DYSF variants typically follow autosomal recessive inheritance.

♀ Carrier parent 1 altered copy ♂ Carrier parent 1 altered copy Affected Carrier Carrier Unaffected Affected Carrier Unaffected Circles = females · Squares = males

When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.

Carrier frequency by population How common is heterozygous DYSF carrier status across ancestry groups?

UK clinical status

The DYSF gene is included in several NHS Genomic Medicine Service national test directories, reflecting its clinical significance within the UK. It is assessed on panels for Acute rhabdomyolysis (R419), Distal myopathies, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), and Rhabdomyolysis and metabolic muscle disorders.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Acute rhabdomyolysis · R419 NHS GMS → Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies · R82 NHS GMS → Distal myopathies NHS GMS → Rhabdomyolysis and metabolic muscle disorders NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the main function of the DYSF gene?

The DYSF gene provides instructions for making the dysferlin protein, which is vital for repairing the sarcolemma (muscle cell membrane) when it gets damaged and for transporting materials within muscle fibres.

What conditions are associated with DYSF gene variants?

Variants in the DYSF gene are linked to several inherited muscular dystrophies, including Limb-girdle muscular dystrophy type 2B (Miyoshi), Miyoshi myopathy, and distal myopathy with anterior tibial onset.

How are DYSF-related conditions inherited?

Conditions associated with DYSF gene variants, such as Limb-girdle muscular dystrophy type 2B, are inherited in an autosomal recessive pattern. This means an individual must inherit two copies of the altered gene (one from each parent) to develop the condition.

References

  1. Klinge L, Aboumousa A, Eagle M. New aspects on patients affected by dysferlin deficient muscular dystrophy. Journal of neurology, neurosurgery, and psychiatry. 2010. PMID: 19528035
  2. Paradas C, Llauger J, Diaz-Manera J. Redefining dysferlinopathy phenotypes based on clinical findings and muscle imaging studies. Neurology. 2010. PMID: 20574037
  3. Broglio L, Tentorio M, Cotelli MS. Limb-girdle muscular dystrophy-associated protein diseases. The neurologist. 2010. PMID: 21150381
  4. Krahn M, Béroud C, Labelle V. Analysis of the DYSF mutational spectrum in a large cohort of patients. Human mutation. 2009. PMID: 18853459
  5. Chiu YH, Hornsey MA, Klinge L. Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy. Human molecular genetics. 2009. PMID: 19286669
  6. Glover L, Brown RH Jr. Dysferlin in membrane trafficking and patch repair. Traffic (Copenhagen, Denmark). 2007. PMID: 17547707
  7. Han R, Campbell KP. Dysferlin and muscle membrane repair. Current opinion in cell biology. 2007. PMID: 17662592
  8. Nguyen K, Bassez G, Krahn M. Phenotypic study in 40 patients with dysferlin gene mutations: high frequency of atypical phenotypes. Archives of neurology. 2007. PMID: 17698709
  9. Straub V, Bushby K. The childhood limb-girdle muscular dystrophies. Seminars in pediatric neurology. 2006. PMID: 17027860
  10. Bansal D, Campbell KP. Dysferlin and the plasma membrane repair in muscular dystrophy. Trends in cell biology. 2004. PMID: 15066638
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 23 August 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .