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DYSF

dysferlin

The DYSF gene provides instructions for producing dysferlin, a protein critical for maintaining the integrity of muscle cell membranes. DYSF encodes dysferlin, a protein located in the sarcolemma, the protective 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.

Explore chromosome 2 in the library →

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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, also known as dysferlin, is responsible for creating a protein vital for muscle health. This protein, dysferlin, is predominantly found within the sarcolemma, the specialised outer membrane of muscle fibres. Its primary function involves repairing this membrane when it sustains damage, often due to the stresses of muscle use. Understanding DYSF is important for diagnosing and researching inherited muscle disorders, particularly those affecting the limbs and extremities.

What the gene does

Dysferlin, the protein encoded by the DYSF gene, is primarily involved in the repair of the sarcolemma, the plasma membrane enclosing muscle cells. When muscle fibres experience strain or injury, dysferlin is thought to facilitate the rapid patching of these membrane lesions, preventing further damage and maintaining muscle integrity. Beyond its role in membrane repair, dysferlin may also contribute to the transport of materials within muscle fibres and participate in calcium-dependent cell signalling pathways, suggesting a broader involvement in muscle cell physiology.

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Chromosome location

The DYSF gene is situated on the short arm of chromosome 2, specifically at position 13.2, which is designated as 2p13.2. This genomic location indicates where the gene is found within the human genome. The gene spans a significant region on this chromosome, contributing to its complex protein product.

Protein structure

The dysferlin protein is composed of 2080 amino acids and features several distinct structural elements. It includes seven C2 domains, which are often involved in calcium-dependent membrane binding. These are distributed throughout the protein: 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, the protein contains two disordered regions: one between amino acids 132-215 and another from 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

Variants within the DYSF gene can alter the structure or function of the dysferlin protein. These changes can impair the protein's ability to perform its essential roles, particularly in muscle membrane repair. The specific clinical presentation can vary depending on the type and location of the variant, ranging from proximal to distal muscle weakness.

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 a group of inherited muscle disorders known collectively as dysferlinopathies. These include Limb-girdle muscular dystrophy type 2B (Miyoshi), characterised by progressive weakness and wasting of muscles, primarily affecting those closer to the body's centre such as the shoulders and hips. DYSF variants can also cause Miyoshi myopathy, which typically presents with distal muscle weakness, particularly in the lower legs, and distal myopathy with anterior tibial onset.

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

In the UK, the DYSF gene is part of several NHS Genomic Medicine Service national test directories. It is included in panels related to Acute rhabdomyolysis (R419), Distal myopathies, Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies (R82), and Rhabdomyolysis and metabolic muscle disorders. This indicates its clinical relevance for diagnosing these conditions within the NHS.

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 role of dysferlin in the body?

Dysferlin is a protein primarily found in the sarcolemma, the membrane surrounding muscle fibres. Its main function is to repair this membrane when it gets damaged, which is crucial for maintaining healthy muscle function. It may also help transport substances within muscle cells and regulate cell signalling.

What conditions are associated with DYSF gene variants?

Variants in the DYSF gene are linked to several inherited muscle disorders, collectively called dysferlinopathies. These include Limb-girdle muscular dystrophy type 2B (Miyoshi), Miyoshi myopathy, and distal myopathy with anterior tibial onset. All these conditions involve progressive muscle weakness and wasting.

How is DYSF gene information used clinically in the UK?

In the UK, the DYSF gene is part of diagnostic testing panels for various muscle conditions through the NHS Genomic Medicine Service. These panels cover conditions like acute rhabdomyolysis, distal myopathies, and limb-girdle muscular dystrophies, helping with diagnosis and management.

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 11 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .