MDA5 (anti-melanoma differentiation-associated protein 5)

MDA5 (anti-melanoma differentiation-associated protein 5) is a RIG-I-like receptor dsRNA helicase enzyme that is encoded by the IFIH1 gene.

MDA5 is part of the RIG-I-like receptor (RLR) family, which also includes RIG-I and LGP2, and functions as a pattern recognition receptor capable of detecting viruses. 

It is generally believed that MDA5 recognizes double stranded RNA (dsRNA) over 2000nts in length.

MDA5 can detect and bind to cytoplasmic dsRNA.

MDA5 is activated by a high molecular weight RNA complex composed of ssRNA and dsRNA.

Some observations made in cancer cells show that MDA5 also interacts with cellular RNA is able to induce an autoinflammatory response.

Gene location Chromosome 2.

Expressed in:

palpebral conjunctiva

parotid gland

jejunal mucosa



parietal pleura

visceral pleura


Germinal epithelium

superficial temporal artery

MDA5 is able to detect long dsRNA, the genomic RNA of dsRNA viruses as well as replicative intermediates of both positive and negative sense RNA viruses.

It interacts with a number of chemical modifications of RNA to bind to this type of RNA and initiate an immune response.

Activated MDA5 interacts with the mitochondrial antiviral signalling proteins.

Mutations in IFIH1/MDA5 are associated to Singleton-Merten Syndrome, and to Aicardi–Goutières syndrome, and 

some IFIH1 SNPs are associated with increased risk of type 1 diabetes.

Antibodies against MDA5 are associated to amyopathic dermatomyositis with rapidly progressive interstitial lung disease.

Melanoma differentiation–associated gene 5 (MDA5) is a autoantigen target in a subset of patients with dermatomyositis. 

Anti-MDA5 dermatomyositis is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, an elevated risk of interstitial lung disease with a potentially fatal course. 

The clinical features can differ substantially from those typically observed in cutaneous dermatomyositis: the diagnosis is often overlooked, which might negatively affect patient outcomes. 

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