View source for Desmin

{{Short description|Mammalian protein found in humans}}
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{{Infobox_gene}}
'''Desmin''' is a [[protein]] that in humans is encoded by the ''DES'' [[gene]].<ref name="pmid9736733">{{cite journal | vauthors = Muñoz-Mármol AM, Strasser G, Isamat M, Coulombe PA, Yang Y, Roca X, Vela E, Mate JL, Coll J, Fernández-Figueras MT, Navas-Palacios JJ, Ariza A, Fuchs E | title = A dysfunctional desmin mutation in a patient with severe generalized myopathy | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 19 | pages = 11312–11317 | date = September 1998 | pmid = 9736733 | pmc = 21639 | doi = 10.1073/pnas.95.19.11312 | doi-access = free | bibcode = 1998PNAS...9511312M }}</ref><ref name="pmid2673923">{{cite journal | vauthors = Li ZL, Lilienbaum A, Butler-Browne G, Paulin D | title = Human desmin-coding gene: complete nucleotide sequence, characterization and regulation of expression during myogenesis and development | journal = Gene | volume = 78 | issue = 2 | pages = 243–254 | date = May 1989 | pmid = 2673923 | doi = 10.1016/0378-1119(89)90227-8 }}</ref> Desmin is a muscle-specific, [[Intermediate filament#Type III|type III intermediate filament]]<ref>[http://www.proteinatlas.org/gene_info.php?ensembl_gene_id=ENSG00000175084&antibody_id=34 "Desmin"], The [[Human Protein Atlas]]. Proteinatlas.org. Retrieved on 2013-07-29.</ref> that integrates the [[sarcolemma]], [[sarcomere#Bands|Z disk]], and [[nuclear membrane]] in [[sarcomere]]s and regulates sarcomere architecture.<ref name = "Brodehl_2018">{{cite journal | vauthors = Brodehl A, Gaertner-Rommel A, Milting H | title = Molecular insights into cardiomyopathies associated with desmin (DES) mutations | journal = Biophysical Reviews | volume = 10 | issue = 4 | pages = 983–1006 | date = August 2018 | pmid = 29926427 | pmc = 6082305 | doi = 10.1007/s12551-018-0429-0 }}</ref><ref>{{cite journal | vauthors = Sequeira V, Nijenkamp LL, Regan JA, van der Velden J | title = The physiological role of cardiac cytoskeleton and its alterations in heart failure | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 1838 | issue = 2 | pages = 700–722 | date = February 2014 | pmid = 23860255 | doi = 10.1016/j.bbamem.2013.07.011 | doi-access = free }}</ref>

== Structure ==

Desmin is a 53.5 kD protein composed of 470 amino acids, encoded by the human ''DES'' gene located on the [[Locus (genetics)#Nomenclature|long arm]] of [[chromosome 2]].<ref>{{cite web |url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P17661 |title=Mass spectrometry characterization of human DES at COPaKB |access-date=2015-03-19 |archive-url=https://web.archive.org/web/20150924025518/http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P17661 |archive-date=2015-09-24 }}</ref><ref name="Zong_2013">{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–1053 | date = October 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref> There are three major domains to the desmin protein: a conserved [[alpha helix]] rod, a variable non alpha helix head, and a carboxy-terminal tail.<ref name="Bar"/> Desmin, as all [[intermediate filaments]], shows no polarity when assembled.<ref name="Bar"/> The rod domain consists of 308 amino acids with parallel alpha helical coiled coil dimers and three linkers to disrupt it.<ref name="Bar"/> The rod domain connects to the head domain. The head domain 84 amino acids with many arginine, serine, and aromatic residues is important in filament assembly and dimer-dimer interactions.<ref name="Bar"/> The tail domain is responsible for the integration of filaments and interaction with proteins and organelles. Desmin is only expressed in vertebrates, however homologous proteins are found in many organisms.<ref name="Bar">{{cite journal | vauthors = Bär H, Strelkov SV, Sjöberg G, Aebi U, Herrmann H | title = The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation? | journal = Journal of Structural Biology | volume = 148 | issue = 2 | pages = 137–152 | date = November 2004 | pmid = 15477095 | doi = 10.1016/j.jsb.2004.04.003 }}</ref> Desmin is a subunit of intermediate filaments in [[cardiac muscle]], [[skeletal muscle]] and [[smooth muscle]] tissue.<ref name="Li">{{cite journal | vauthors = Li Z, Mericskay M, Agbulut O, Butler-Browne G, Carlsson L, Thornell LE, Babinet C, Paulin D | title = Desmin is essential for the tensile strength and integrity of myofibrils but not for myogenic commitment, differentiation, and fusion of skeletal muscle | journal = The Journal of Cell Biology | volume = 139 | issue = 1 | pages = 129–144 | date = October 1997 | pmid = 9314534 | pmc = 2139820 | doi = 10.1083/jcb.139.1.129 }}</ref> In cardiac muscle, desmin is present in [[sarcomere|Z-discs]] and [[intercalated discs]]. Desmin has been shown to [[Protein-protein interaction|interact]] with [[desmoplakin]]<ref name="pmid9261168">{{cite journal | vauthors = Meng JJ, Bornslaeger EA, Green KJ, Steinert PM, Ip W | title = Two-hybrid analysis reveals fundamental differences in direct interactions between desmoplakin and cell type-specific intermediate filaments | journal = The Journal of Biological Chemistry | volume = 272 | issue = 34 | pages = 21495–21503 | date = August 1997 | pmid = 9261168 | doi = 10.1074/jbc.272.34.21495 | doi-access = free }}</ref> and [[CRYAB|αB-crystallin]].<ref>{{cite journal | vauthors = Bennardini F, Wrzosek A, Chiesi M | title = Alpha B-crystallin in cardiac tissue. Association with actin and desmin filaments | journal = Circulation Research | volume = 71 | issue = 2 | pages = 288–294 | date = August 1992 | pmid = 1628387 | doi = 10.1161/01.res.71.2.288 | doi-access = free }}</ref>

== Function ==

Desmin was first described in 1976,<ref name="pmid1069986">{{cite journal | vauthors = Lazarides E, Hubbard BD | title = Immunological characterization of the subunit of the 100 A filaments from muscle cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 73 | issue = 12 | pages = 4344–4348 | date = December 1976 | pmid = 1069986 | pmc = 431448 | doi = 10.1073/pnas.73.12.4344 | doi-access = free }}</ref> first purified in 1977,<ref name="pmid266185">{{cite journal | vauthors = Izant JG, Lazarides E | title = Invariance and heterogeneity in the major structural and regulatory proteins of chick muscle cells revealed by two-dimensional gel electrophoresis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 74 | issue = 4 | pages = 1450–1454 | date = April 1977 | pmid = 266185 | pmc = 430794 | doi = 10.1073/pnas.74.4.1450 | doi-access = free | bibcode = 1977PNAS...74.1450I }}</ref> the [[gene]] was cloned in 1989,<ref name="pmid2673923"/> and the first [[knockout mouse]] was created in 1996. The function of desmin has been deduced through studies in knockout mice. Desmin is one of the earliest protein markers for muscle tissue in embryogenesis as it is detected in the [[somite]]s.<ref name="Bar"/><ref name="Costa">{{cite journal |vauthors=Costa ML, Escaleira R, Cataldo A, Oliveira F, Mermelstein CS |date=December 2004 |title=Desmin: molecular interactions and putative functions of the muscle intermediate filament protein |journal=Brazilian Journal of Medical and Biological Research |volume=37 |issue=12 |pages=1819–1830 |doi=10.1590/S0100-879X2004001200007 |pmid=15558188 |doi-access=free}}</ref> Although it is present early in the development of muscle cells, it is only expressed at low levels, and increases as the cell nears terminal differentiation. A similar protein, [[vimentin]], is present in higher amounts during embryogenesis while desmin is present in higher amounts after differentiation. This suggests that there may be some interaction between the two in determining muscle cell differentiation. However desmin knockout mice develop normally and only experience defects later in life.<ref name="Li"/> Since desmin is expressed at a low level during differentiation another protein may be able to compensate for desmin's function early in development but not later on.<ref>{{cite web | url = http://www.cbil.upenn.edu/MTIR/dys-toc.html | title = Dystrophin | date = 1997-03-16 | access-date = 2010-06-28 | work = Catalogue of Regulatory Elements | author = Stoeckert C | publisher = University of Pennsylvania | archive-url = https://web.archive.org/web/20070608025838/http://www.cbil.upenn.edu/MTIR/dys-toc.html | archive-date = 2007-06-08 }}</ref>

In adult desmin-null mice, hearts from 10 week-old animals showed drastic alterations in muscle architecture, including a misalignment of myofibrils and disorganization and swelling of mitochondria; findings that were more severe in cardiac relative to skeletal muscle. Cardiac tissue also exhibited progressive necrosis and calcification of the myocardium.<ref>{{cite journal | vauthors = Milner DJ, Weitzer G, Tran D, Bradley A, Capetanaki Y | title = Disruption of muscle architecture and myocardial degeneration in mice lacking desmin | journal = The Journal of Cell Biology | volume = 134 | issue = 5 | pages = 1255–1270 | date = September 1996 | pmid = 8794866 | pmc = 2120972 | doi = 10.1083/jcb.134.5.1255 }}</ref> A separate study examined this in more detail in cardiac tissue and found that murine hearts lacking desmin developed [[hypertrophic cardiomyopathy]] and chamber dilation combined with systolic dysfunction.<ref>{{cite journal | vauthors = Milner DJ, Taffet GE, Wang X, Pham T, Tamura T, Hartley C, Gerdes AM, Capetanaki Y | title = The absence of desmin leads to cardiomyocyte hypertrophy and cardiac dilation with compromised systolic function | journal = Journal of Molecular and Cellular Cardiology | volume = 31 | issue = 11 | pages = 2063–2076 | date = November 1999 | pmid = 10591032 | doi = 10.1006/jmcc.1999.1037 }}</ref> In adult muscle, desmin forms a scaffold around the Z-disk of the sarcomere and connects the Z-disk to the [[sarcolemma|subsarcolemmal]] cytoskeleton.<ref name="Paulin">{{cite journal | vauthors = Paulin D, Li Z | title = Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle | journal = Experimental Cell Research | volume = 301 | issue = 1 | pages = 1–7 | date = November 2004 | pmid = 15501438 | doi = 10.1016/j.yexcr.2004.08.004 }}</ref> It links the [[myofibril]]s laterally by connecting the Z-disks.<ref name="Bar"/> Through its connection to the sarcomere, desmin connects the contractile apparatus to the [[cell nucleus]], [[mitochondria]], and post-synaptic areas of motor endplates.<ref name="Bar"/> These connections maintain the structural and mechanical integrity of the cell during contraction while also helping in force transmission and longitudinal load bearing.<ref name="Paulin"/><ref name="Shah">{{cite journal | vauthors = Shah SB, Davis J, Weisleder N, Kostavassili I, McCulloch AD, Ralston E, Capetanaki Y, Lieber RL | title = Structural and functional roles of desmin in mouse skeletal muscle during passive deformation | journal = Biophysical Journal | volume = 86 | issue = 5 | pages = 2993–3008 | date = May 2004 | pmid = 15111414 | pmc = 1304166 | doi = 10.1016/S0006-3495(04)74349-0 | bibcode = 2004BpJ....86.2993S }}</ref>

In human heart failure, desmin expression is upregulated, which has been hypothesized to be a defense mechanism in an attempt to maintain normal sarcomere alignment amidst disease pathogenesis.<ref>{{cite journal | vauthors = Heling A, Zimmermann R, Kostin S, Maeno Y, Hein S, Devaux B, Bauer E, Klövekorn WP, Schlepper M, Schaper W, Schaper J | title = Increased expression of cytoskeletal, linkage, and extracellular proteins in failing human myocardium | journal = Circulation Research | volume = 86 | issue = 8 | pages = 846–853 | date = April 2000 | pmid = 10785506 | doi = 10.1161/01.res.86.8.846 | doi-access = free }}</ref>  There is some evidence that desmin may also connect the sarcomere to the [[extracellular matrix]] (ECM) through [[desmosomes]] which could be important in signalling between the ECM and the sarcomere which could regulate muscle contraction and movement.<ref name="Shah"/> Finally, desmin may be important in [[mitochondria]] function. When desmin is not functioning properly there is improper mitochondrial distribution, number, morphology and function.<ref name="Milner">{{cite journal | vauthors = Milner DJ, Mavroidis M, Weisleder N, Capetanaki Y | title = Desmin cytoskeleton linked to muscle mitochondrial distribution and respiratory function | journal = The Journal of Cell Biology | volume = 150 | issue = 6 | pages = 1283–1298 | date = September 2000 | pmid = 10995435 | pmc = 2150713 | doi = 10.1083/jcb.150.6.1283 | citeseerx = 10.1.1.273.9903 }}</ref><ref name="Goldfarb">{{cite journal | vauthors = Goldfarb LG, Vicart P, Goebel HH, Dalakas MC | title = Desmin myopathy | journal = Brain | volume = 127 | issue = Pt 4 | pages = 723–734 | date = April 2004 | pmid = 14724127 | doi = 10.1093/brain/awh033 | doi-access = free }}</ref> Since desmin links the mitochondria to the sarcomere it may transmit information about contractions and energy need and through this regulate the aerobic respiration rate of the muscle cell.

== Clinical significance ==

[[Desmin-related myofibrillar myopathy]] (DRM or desminopathy) is a subgroup of the myofibrillar myopathy diseases <ref>{{cite journal | vauthors = Fichna JP, Maruszak A, Żekanowski C | title = Myofibrillar myopathy in the genomic context | journal = Journal of Applied Genetics | volume = 59 | issue = 4 | pages = 431–439 | date = November 2018 | pmid = 30203143 | doi = 10.1007/s13353-018-0463-4 | doi-access = free }}</ref> and is the result of a mutation in the gene that codes for desmin which by changing the protein structure <ref>{{cite journal | vauthors = Fichna JP, Karolczak J, Potulska-Chromik A, Miszta P, Berdynski M, Sikorska A, Filipek S, Redowicz MJ, Kaminska A, Zekanowski C | title = Two desmin gene mutations associated with myofibrillar myopathies in Polish families | journal = PLOS ONE | volume = 9 | issue = 12 | article-number = e115470 | date = December 2014 | pmid = 25541946 | doi = 10.1371/journal.pone.0115470 | pmc = 4277352 | bibcode = 2014PLoSO...9k5470F | doi-access = free }}</ref> prevents it from forming [[protein filament]]s, and rather, forms aggregates of desmin and other proteins throughout the cell.<ref name = "Brodehl_2018" /><ref name="Bar"/> Desmin (''DES'') mutations have been associated with restrictive,<ref>{{cite journal | vauthors = Brodehl A, Pour Hakimi SA, Stanasiuk C, Ratnavadivel S, Hendig D, Gaertner A, Gerull B, Gummert J, Paluszkiewicz L, Milting H | title = Restrictive Cardiomyopathy is Caused by a Novel Homozygous Desmin (''DES'') Mutation p.Y122H Leading to a Severe Filament Assembly Defect | journal = Genes | volume = 10 | issue = 11 | page = 918 | date = November 2019 | pmid = 31718026 | pmc = 6896098 | doi = 10.3390/genes10110918 | doi-access = free }}</ref> dilated,<ref>{{cite journal | vauthors = Fischer B, Dittmann S, Brodehl A, Unger A, Stallmeyer B, Paul M, Seebohm G, Kayser A, Peischard S, Linke WA, Milting H, Schulze-Bahr E | title = Functional characterization of novel alpha-helical rod domain desmin (DES) pathogenic variants associated with dilated cardiomyopathy, atrioventricular block and a risk for sudden cardiac death | journal = International Journal of Cardiology | volume = 329 | pages = 167–174 | date = April 2021 | pmid = 33373648 | doi = 10.1016/j.ijcard.2020.12.050 | s2cid = 229719883 }}</ref><ref>{{cite journal | vauthors = Brodehl A, Dieding M, Biere N, Unger A, Klauke B, Walhorn V, Gummert J, Schulz U, Linke WA, Gerull B, Vorgert M, Anselmetti D, Milting H | title = Functional characterization of the novel DES mutation p.L136P associated with dilated cardiomyopathy reveals a dominant filament assembly defect | journal = Journal of Molecular and Cellular Cardiology | volume = 91 | pages = 207–214 | date = February 2016 | pmid = 26724190 | doi = 10.1016/j.yjmcc.2015.12.015 }}</ref> idiopathic,<ref>{{cite journal | vauthors = Li D, Tapscoft T, Gonzalez O, Burch PE, Quiñones MA, Zoghbi WA, Hill R, Bachinski LL, Mann DL, Roberts R | title = Desmin mutation responsible for idiopathic dilated cardiomyopathy | journal = Circulation | volume = 100 | issue = 5 | pages = 461–464 | date = August 1999 | pmid = 10430757 | doi = 10.1161/01.cir.100.5.461 | author-link6 = William Zoghbi | doi-access = free }}</ref><ref>{{cite journal | vauthors = Goldfarb LG, Park KY, Cervenáková L, Gorokhova S, Lee HS, Vasconcelos O, Nagle JW, Semino-Mora C, Sivakumar K, Dalakas MC | title = Missense mutations in desmin associated with familial cardiac and skeletal myopathy | journal = Nature Genetics | volume = 19 | issue = 4 | pages = 402–403 | date = August 1998 | pmid = 9697706 | doi = 10.1038/1300 | s2cid = 23313873 }}</ref> arrhythmogenic <ref>{{cite journal | vauthors = Protonotarios A, Brodehl A, Asimaki A, Jager J, Quinn E, Stanasiuk C, Ratnavadivel S, Futema M, Akhtar MM, Gossios TD, Ashworth M, Savvatis K, Walhorn V, Anselmetti D, Elliott PM, Syrris P, Milting H, Lopes LR | title = The Novel Desmin Variant p.Leu115Ile Is Associated With a Unique Form of Biventricular Arrhythmogenic Cardiomyopathy | journal = The Canadian Journal of Cardiology | volume = 37 | issue = 6 | pages = 857–866 | date = June 2021 | pmid = 33290826 | doi = 10.1016/j.cjca.2020.11.017 | s2cid = 228078648 | url = https://discovery.ucl.ac.uk/id/eprint/10117120/ }}</ref><ref>{{cite journal | vauthors = Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J | title = Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia | journal = Circulation | volume = 137 | issue = 15 | pages = 1595–1610 | date = April 2018 | pmid = 29212896 | doi = 10.1161/CIRCULATIONAHA.117.028719 | s2cid = 4715358 | doi-access = free | hdl = 10481/89514 | hdl-access = free }}</ref><ref name="pmid20829228">{{cite journal | vauthors = Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H | title = De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy | journal = Human Molecular Genetics | volume = 19 | issue = 23 | pages = 4595–4607 | date = December 2010 | pmid = 20829228 | doi = 10.1093/hmg/ddq387 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Lorenzon A, Beffagna G, Bauce B, De Bortoli M, Li Mura IE, Calore M, Dazzo E, Basso C, Nava A, Thiene G, Rampazzo A | title = Desmin mutations and arrhythmogenic right ventricular cardiomyopathy | journal = The American Journal of Cardiology | volume = 111 | issue = 3 | pages = 400–405 | date = February 2013 | pmid = 23168288 | pmc = 3554957 | doi = 10.1016/j.amjcard.2012.10.017 }}</ref> and non-compaction cardimyopathy.<ref>{{cite journal | vauthors = Kulikova O, Brodehl A, Kiseleva A, Myasnikov R, Meshkov A, Stanasiuk C, Gärtner A, Divashuk M, Sotnikova E, Koretskiy S, Kharlap M, Kozlova V, Mershina E, Pilus P, Sinitsyn V, Milting H, Boytsov S, Drapkina O | title = The Desmin (''DES'') Mutation p.A337P Is Associated with Left-Ventricular Non-Compaction Cardiomyopathy | journal = Genes | volume = 12 | issue = 1 | page = 121 | date = January 2021 | pmid = 33478057 | pmc = 7835827 | doi = 10.3390/genes12010121 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Marakhonov AV, Brodehl A, Myasnikov RP, Sparber PA, Kiseleva AV, Kulikova OV, Meshkov AN, Zharikova AA, Koretsky SN, Kharlap MS, Stanasiuk C, Mershina EA, Sinitsyn VE, Shevchenko AO, Mozheyko NP, Drapkina OM, Boytsov SA, Milting H, Skoblov MY | title = Noncompaction cardiomyopathy is caused by a novel in-frame desmin (DES) deletion mutation within the 1A coiled-coil rod segment leading to a severe filament assembly defect | journal = Human Mutation | volume = 40 | issue = 6 | pages = 734–741 | date = June 2019 | pmid = 30908796 | doi = 10.1002/humu.23747 | s2cid = 85515283 | doi-access = free }}</ref> Even within the same family the observed cardiac phenotype could be broad and diverse. The N-terminal part of the 1A desmin subdomain is a genetic hot spot region for mutations affecting filament assembly.<ref>{{cite journal | vauthors = Voß S, Walhorn V, Holler S, Gärtner A, Pohl G, Tiesmeier J, Gummert J, Anselmetti D, Milting H, Brodehl A | title = Functional impact of the head domain variants of <i>DES</i> (Desmin) on filament assembly | journal = Genes & Diseases | volume = 12 | issue = 1 | article-number = 101238 | date = January 2025 | pmid = 39650696 | pmc = 11620975 | doi = 10.1016/j.gendis.2024.101238 }}</ref><ref name="Brodehl 3906">{{cite journal | vauthors = Borchers A, Pieler T | title = Programming pluripotent precursor cells derived from Xenopus embryos to generate specific tissues and organs | journal = Genes | volume = 1 | issue = 3 | pages = 413–426 | date = November 2010 | doi = 10.3390/cells11233906 | pmid = 36497166 | pmc = 9738904 | doi-access = free }}</ref> Some of these ''DES'' mutations cause an aggregation of desmin within the [[cytoplasm]].<ref name="Brodehl 3906"/><ref name="pmid22403400">{{cite journal | vauthors = Brodehl A, Hedde PN, Dieding M, Fatima A, Walhorn V, Gayda S, Šarić T, Klauke B, Gummert J, Anselmetti D, Heilemann M, Nienhaus GU, Milting H | title = Dual color photoactivation localization microscopy of cardiomyopathy-associated desmin mutants | journal = The Journal of Biological Chemistry | volume = 287 | issue = 19 | pages = 16047–16057 | date = May 2012 | pmid = 22403400 | pmc = 3346104 | doi = 10.1074/jbc.M111.313841 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Brodehl A, Ebbinghaus H, Gaertner-Rommel A, Stanasiuk C, Klauke B, Milting H | title = Functional analysis of DES-p.L398P and RBM20-p.R636C | journal = Genetics in Medicine | volume = 21 | issue = 5 | pages = 1246–1247 | date = May 2019 | pmid = 30262925 | doi = 10.1038/s41436-018-0291-2 | s2cid = 52877855 | doi-access = free }}</ref> Some mutations like p.A120D or p.R127P were discovered in families, where several members had sudden cardiac death.<ref name="pmid24200904">{{cite journal | vauthors = Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T, Gargus J, Fatima A, Saric T, Cakar H, Walhorn V, Tönsing K, Skrzipczyk T, Cebulla R, Gerdes D, Schulz U, Gummert J, Svendsen JH, Olesen MS, Anselmetti D, Christensen AH, Kimonis V, Milting H | title = The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death | journal = Circulation: Cardiovascular Genetics | volume = 6 | issue = 6 | pages = 615–623 | date = December 2013 | pmid = 24200904 | doi = 10.1161/CIRCGENETICS.113.000103 | doi-access = free }}</ref> In addition, ''DES'' mutations cause frequently cardiac conduction diseases.<ref>{{cite journal | vauthors = Schirmer I, Dieding M, Klauke B, Brodehl A, Gaertner-Rommel A, Walhorn V, Gummert J, Schulz U, Paluszkiewicz L, Anselmetti D, Milting H | title = A novel desmin (DES) indel mutation causes severe atypical cardiomyopathy in combination with atrioventricular block and skeletal myopathy | journal = Molecular Genetics & Genomic Medicine | volume = 6 | issue = 2 | pages = 288–293 | date = March 2018 | pmid = 29274115 | pmc = 5902401 | doi = 10.1002/mgg3.358 }}</ref>

Desmin has been evaluated for role in assessing the depth of invasion of [[urothelial carcinoma]] in [[TURBT]] specimens.<ref>{{cite journal | vauthors = Saha K, Saha A, Datta C, Chatterjee U, Ray S, Bera M |title=Does desmin immunohistochemistry have a role in assessing stage of urothelial carcinoma in transurethral resection of bladder tumor specimens? |journal=Clinical Cancer Investigation Journal |date=2014 |volume=3 |issue=6 |page=502 |doi=10.4103/2278-0513.142634 |doi-access=free }}</ref>

== References ==
{{reflist}}

== External links ==
* [https://www.ncbi.nlm.nih.gov/books/NBK1499/ GeneReviews/NIH/NCBI/UW entry on Myofibrillar Myopathy]
* {{MeshName|Desmin}}
* [[LOVD]] mutation database: [http://www.dmd.nl/nmdb2/?select_db=DES DES]

{{Cytoskeletal Proteins}}
{{Muscle tissue}}
{{Tumor markers}}

[[Category:Tumor markers]]