RBCC Red Blood Cell Collection

FLNC (ABPL, FLN2) [Confidence: low (only semi-automatic identification from reviews)]
Filamin-C; FLN-C; FLNc (ABP-280-like protein; ABP-L; Actin-binding-like protein; Filamin-2; Gamma-filamin)

UniProt Q14315
ID FLNC_HUMAN Reviewed; 2725 AA.
AC Q14315; B2ZZ88; O95303; Q07985; Q9NS12; Q9NYE5; Q9UMR8; Q9Y503;
read moreDT 16-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 3.
DT 22-JAN-2014, entry version 149.
DE RecName: Full=Filamin-C;
DE Short=FLN-C;
DE Short=FLNc;
DE AltName: Full=ABP-280-like protein;
DE AltName: Full=ABP-L;
DE AltName: Full=Actin-binding-like protein;
DE AltName: Full=Filamin-2;
DE AltName: Full=Gamma-filamin;
GN Name=FLNC; Synonyms=ABPL, FLN2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANTS GLY-1580; ALA-1599 AND PRO-2203.
RC TISSUE=Heart;
RX PubMed=9791010; DOI=10.1006/bbrc.1998.9506;
RA Xie Z.-W., Xu W.-F., Davie E.W., Chung D.W.;
RT "Molecular cloning of human ABPL, an actin-binding protein
RT homologue.";
RL Biochem. Biophys. Res. Commun. 251:914-919(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), GENE ORGANIZATION, AND
RP SIMILARITY TO OTHER MEMBERS OF THE FAMILY.
RX PubMed=11153914; DOI=10.1007/s004390000414;
RA Chakarova C., Wehnert M.S., Uhl K., Sakthivel S., Vosberg H.-P.,
RA van der Ven P.F.M., Fuerst D.O.;
RT "Genomic structure and fine mapping of the two human filamin gene
RT paralogues FLNB and FLNC and comparative analysis of the filamin gene
RT family.";
RL Hum. Genet. 107:597-611(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND VARIANTS GLY-1580;
RP ALA-1599; ARG-2135 AND PRO-2203.
RX PubMed=10658210;
RX DOI=10.1002/(SICI)1097-0169(200002)45:2<149::AID-CM6>3.0.CO;2-G;
RA van der Ven P.F.M., Obermann W.M.J., Lemke B., Gautel M., Weber K.,
RA Fuerst D.O.;
RT "Characterization of muscle filamin isoforms suggests a possible role
RT of gamma-filamin/ABP-L in sarcomeric Z-disc formation.";
RL Cell Motil. Cytoskeleton 45:149-162(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND INTERACTION WITH SGCD AND
RP SGCG.
RC TISSUE=Skeletal muscle;
RX PubMed=10629222; DOI=10.1083/jcb.148.1.115;
RA Thompson T.G., Chan Y.-M., Hack A.A., Brosius M., Rajala M.,
RA Lidov H.G.W., McNally E.M., Watkins S., Kunkel L.M.;
RT "Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting
RT protein.";
RL J. Cell Biol. 148:115-126(2000).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Kato S.;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R.,
RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H.,
RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A.,
RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J.,
RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A.,
RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S.,
RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M.,
RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C.,
RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P.,
RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J.,
RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L.,
RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R.,
RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K.,
RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S.,
RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M.,
RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R.,
RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D.,
RA Waterston R.H., Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP PROTEIN SEQUENCE OF 70-81; 165-183; 335-343; 350-377; 422-437;
RP 559-573; 576-588; 718-727; 880-895; 900-911; 917-968; 978-991;
RP 1015-1027; 1074-1088; 1147-1157; 1242-1278; 1300-1313; 1355-1367;
RP 1377-1394; 1475-1494; 1568-1586; 1616-1627; 1658-1671; 1714-1719;
RP 1809-1825; 1840-1860; 1886-1901; 1932-1945; 1954-1968; 2000-2008;
RP 2031-2043; 2050-2083; 2114-2127; 2231-2291; 2294-2316; 2327-2356;
RP 2411-2437; 2577-2589; 2597-2616; 2642-2653 AND 2691-2699,
RP PHOSPHORYLATION AT SER-2233, AND MASS SPECTROMETRY.
RC TISSUE=Lung fibroblast;
RA Bienvenut W.V., Pchelintsev N., Adams P.D.;
RL Submitted (OCT-2009) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 585-815 AND 1638-2101 (ISOFORM 2), AND
RP TISSUE SPECIFICITY.
RX PubMed=7689010; DOI=10.1093/hmg/2.6.761;
RA Maestrini E., Patrosso C., Mancini M., Rivella S., Rocchi M.,
RA Repetto M., Villa A., Frattini A., Zoppe M., Vezzoni P., Toniolo D.;
RT "Mapping of two genes encoding isoforms of the actin binding protein
RT ABP-280, a dystrophin like protein, to Xq28 and to chromosome 7.";
RL Hum. Mol. Genet. 2:761-766(1993).
RN [10]
RP INTERACTION WITH MYOZ1.
RX PubMed=10984498; DOI=10.1074/jbc.M007493200;
RA Faulkner G., Pallavicini A., Comelli A., Salamon M., Bortoletto G.,
RA Ievolella C., Trevisan S., Kojic' S., Dalla Vecchia F., Laveder P.,
RA Valle G., Lanfranchi G.;
RT "FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-
RT disc of skeletal muscle.";
RL J. Biol. Chem. 275:41234-41242(2000).
RN [11]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DOMAIN, AND INTERACTION WITH
RP MYOT.
RX PubMed=11038172; DOI=10.1083/jcb.151.2.235;
RA van der Ven P.F.M., Wiesner S., Salmikangas P., Auerbach D.,
RA Himmel M., Kempa S., Hayess K., Pacholsky D., Taivainen A.,
RA Schroeder R., Carpen O., Fuerst D.O.;
RT "Indications for a novel muscular dystrophy pathway: gamma-filamin,
RT the muscle-specific filamin isoform, interacts with myotilin.";
RL J. Cell Biol. 151:235-248(2000).
RN [12]
RP INTERACTION WITH KCND2.
RX PubMed=11102480;
RA Petrecca K., Miller D.M., Shrier A.;
RT "Localization and enhanced current density of the Kv4.2 potassium
RT channel by interaction with the actin-binding protein filamin.";
RL J. Neurosci. 20:8736-8744(2000).
RN [13]
RP INTERACTION WITH MYOZ1.
RX PubMed=11171996; DOI=10.1073/pnas.041609698;
RA Takada F., Vander Woude D.L., Tong H.-Q., Thompson T.G., Watkins S.C.,
RA Kunkel L.M., Beggs A.H.;
RT "Myozenin: an alpha-actinin- and gamma-filamin-binding protein of
RT skeletal muscle Z lines.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:1595-1600(2001).
RN [14]
RP INTERACTION WITH INPPL1.
RX PubMed=11739414; DOI=10.1083/jcb.200104005;
RA Dyson J.M., O'Malley C.J., Becanovic J., Munday A.D., Berndt M.C.,
RA Coghill I.D., Nandurkar H.H., Ooms L.M., Mitchell C.A.;
RT "The SH2-containing inositol polyphosphate 5-phosphatase, SHIP-2,
RT binds filamin and regulates submembraneous actin.";
RL J. Cell Biol. 155:1065-1079(2001).
RN [15]
RP REVIEW.
RX PubMed=11252955; DOI=10.1038/35052082;
RA Stossel T.P., Condeelis J., Cooley L., Hartwig J.H., Noegel A.,
RA Schleicher M., Shapiro S.S.;
RT "Filamins as integrators of cell mechanics and signalling.";
RL Nat. Rev. Mol. Cell Biol. 2:138-145(2001).
RN [16]
RP SILENCING IN CANCER CELL LINES MKN28 AND MKN74.
RX PubMed=12438262;
RA Kaneda A., Kaminishi M., Yanagihara K., Sugimura T., Ushijima T.;
RT "Identification of silencing of nine genes in human gastric cancers.";
RL Cancer Res. 62:6645-6650(2002).
RN [17]
RP INTERACTION WITH MYOZ3.
RX PubMed=11842093; DOI=10.1074/jbc.M200712200;
RA Frey N., Olson E.N.;
RT "Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin
RT family, interacts with multiple Z-disc proteins.";
RL J. Biol. Chem. 277:13998-14004(2002).
RN [18]
RP DIMERIZATION, AND INTERACTION WITH FLNB.
RX PubMed=12525170; DOI=10.1021/bi026501+;
RA Himmel M., van der Ven P.F.M., Stoecklein W., Fuerst D.O.;
RT "The limits of promiscuity: isoform-specific dimerization of
RT filamins.";
RL Biochemistry 42:430-439(2003).
RN [19]
RP INVOLVEMENT IN MFM5.
RX PubMed=15929027; DOI=10.1086/431959;
RA Vorgerd M., van der Ven P.F.M., Bruchertseifer V., Loewe T.,
RA Kley R.A., Schroeder R., Lochmueller H., Himmel M., Koehler K.,
RA Fuerst D.O., Huebner A.;
RT "A mutation in the dimerization domain of filamin C causes a novel
RT type of autosomal dominant myofibrillar myopathy.";
RL Am. J. Hum. Genet. 77:297-304(2005).
RN [20]
RP INTERACTION WITH ITGB1; MYOT AND MYOZ1.
RX PubMed=16076904; DOI=10.1242/jcs.02484;
RA Gontier Y., Taivainen A., Fontao L., Sonnenberg A., van der Flier A.,
RA Carpen O., Faulkner G., Borradori L.;
RT "The Z-disc proteins myotilin and FATZ-1 interact with each other and
RT are connected to the sarcolemma via muscle-specific filamins.";
RL J. Cell Sci. 118:3739-3749(2005).
RN [21]
RP INTERACTION WITH USP25.
RX PubMed=16501887; DOI=10.1007/s00018-005-5533-1;
RA Bosch-Comas A., Lindsten K., Gonzalez-Duarte R., Masucci M.G.,
RA Marfany G.;
RT "The ubiquitin-specific protease USP25 interacts with three sarcomeric
RT proteins.";
RL Cell. Mol. Life Sci. 63:723-734(2006).
RN [22]
RP INTERACTION WITH XIRP1.
RX PubMed=16631741; DOI=10.1016/j.yexcr.2006.03.015;
RA van der Ven P.F.M., Ehler E., Vakeel P., Eulitz S., Schenk J.A.,
RA Milting H., Micheel B., Fuerst D.O.;
RT "Unusual splicing events result in distinct Xin isoforms that
RT associate differentially with filamin c and Mena/VASP.";
RL Exp. Cell Res. 312:2154-2167(2006).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1161, AND MASS
RP SPECTROMETRY.
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2233, AND MASS
RP SPECTROMETRY.
RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [25]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2233, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP UBIQUITINATION BY FBXL22.
RX PubMed=22972877; DOI=10.1161/CIRCRESAHA.112.271007;
RA Spaich S., Will R.D., Just S., Spaich S., Kuhn C., Frank D.,
RA Berger I.M., Wiemann S., Korn B., Koegl M., Backs J., Katus H.A.,
RA Rottbauer W., Frey N.;
RT "F-box and leucine-rich repeat protein 22 is a cardiac-enriched F-box
RT protein that regulates sarcomeric protein turnover and is essential
RT for maintenance of contractile function in vivo.";
RL Circ. Res. 111:1504-1516(2012).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 2633-2725, AND MUTAGENESIS
RP OF MET-2669.
RX PubMed=15642266; DOI=10.1016/j.str.2004.10.014;
RA Pudas R., Kiema T.-R., Butler P.J.G., Stewart M., Ylaenne J.;
RT "Structural basis for vertebrate filamin dimerization.";
RL Structure 13:111-119(2005).
RN [29]
RP STRUCTURE BY NMR OF 1536-2599.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the filamin domains from human filamin C.";
RL Submitted (NOV-2006) to the PDB data bank.
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 2495-2598, AND SUBUNIT.
RX PubMed=17379241; DOI=10.1016/j.jmb.2007.02.018;
RA Sjekloca L., Pudas R., Sjoblom B., Konarev P., Carugo O., Rybin V.,
RA Kiema T.R., Svergun D., Ylanne J., Djinovic Carugo K.;
RT "Crystal structure of human filamin C domain 23 and small angle
RT scattering model for filamin C 23-24 dimer.";
RL J. Mol. Biol. 368:1011-1023(2007).
RN [31]
RP STRUCTURE BY NMR OF 2302-2415 IN COMPLEX WITH FBLIM1.
RX PubMed=19074766; DOI=10.1074/jbc.M807719200;
RA Ithychanda S.S., Das M., Ma Y.Q., Ding K., Wang X., Gupta S., Wu C.,
RA Plow E.F., Qin J.;
RT "Migfilin, a molecular switch in regulation of integrin activation.";
RL J. Biol. Chem. 284:4713-4722(2009).
RN [32]
RP VARIANTS MPD4 THR-193 AND THR-251, AND CHARACTERIZATION OF VARIANTS
RP MPD4 THR-193 AND THR-251.
RX PubMed=21620354; DOI=10.1016/j.ajhg.2011.04.021;
RA Duff R.M., Tay V., Hackman P., Ravenscroft G., McLean C., Kennedy P.,
RA Steinbach A., Schoffler W., van der Ven P.F., Furst D.O., Song J.,
RA Djinovic-Carugo K., Penttila S., Raheem O., Reardon K., Malandrini A.,
RA Gambelli S., Villanova M., Nowak K.J., Williams D.R., Landers J.E.,
RA Brown R.H. Jr., Udd B., Laing N.G.;
RT "Mutations in the N-terminal actin-binding domain of filamin C cause a
RT distal myopathy.";
RL Am. J. Hum. Genet. 88:729-740(2011).
CC -!- FUNCTION: Muscle-specific filamin, which plays a central role in
CC muscle cells, probably by functioning as a large actin-cross-
CC linking protein. May be involved in reorganizing the actin
CC cytoskeleton in response to signaling events, and may also display
CC structural functions at the Z lines in muscle cells. Critical for
CC normal myogenesis and for maintaining the structural integrity of
CC the muscle fibers.
CC -!- SUBUNIT: Homodimer. Interacts with KY. Interacts with IGFN1 (By
CC similarity). Interacts with MICALL2 (By similarity). Interacts
CC with FLNB, KCND2, ITGB1A, INPPL1, MYOT, MYOZ1 and MYOZ3. Interacts
CC with sarcoglycans SGCD and SGCG. Interacts (via filament repeats
CC 17-18, 20-21 and 24) with USP25 (isoform USP25m only). Interacts
CC with FBLIM1.
CC -!- INTERACTION:
CC P00519:ABL1; NbExp=2; IntAct=EBI-489954, EBI-375543;
CC P46108:CRK; NbExp=2; IntAct=EBI-489954, EBI-886;
CC O75923:DYSF; NbExp=3; IntAct=EBI-489954, EBI-2799016;
CC P62993:GRB2; NbExp=2; IntAct=EBI-489954, EBI-401755;
CC Q9UBF9:MYOT; NbExp=6; IntAct=EBI-489954, EBI-296701;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane
CC protein. Cytoplasm, cytoskeleton. Cytoplasm, myofibril, sarcomere,
CC Z line. Note=A small amount localizes at membranes. In striated
CC muscle cells, it predominantly localizes in myofibrillar Z lines,
CC while a minor fraction localizes with subsarcolemme.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14315-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14315-2; Sequence=VSP_007579;
CC -!- TISSUE SPECIFICITY: Highly expressed in striated muscles. Weakly
CC expressed in thyroid, fetal brain, fetal lung, retina, spinal cord
CC and bone marrow. Not expressed in testis, pancreas, adrenal gland,
CC placenta, liver and kidney.
CC -!- DEVELOPMENTAL STAGE: Expressed in both differentiating and adult
CC muscles.
CC -!- DOMAIN: The intradomain insert is specific to FLNC and mediates
CC the targeting to developing and mature Z lines.
CC -!- DOMAIN: Comprised of a N-terminal actin-binding domain, 24
CC internally homologous repeats and two hinge regions. Repeat 24 and
CC the second hinge domain are important for dimer formation.
CC -!- DOMAIN: The filamin 20 repeat mediates interaction with XIRP1.
CC -!- PTM: Ubiquitinated by FBXL22, leading to proteasomal degradation.
CC -!- DISEASE: Myopathy, myofibrillar, 5 (MFM5) [MIM:609524]: A
CC neuromuscular disorder, usually with an adult onset, characterized
CC by focal myofibrillar destruction, pathological cytoplasmic
CC protein aggregations, and clinical features of a limb-girdle
CC myopathy. Note=The disease is caused by mutations affecting the
CC gene represented in this entry.
CC -!- DISEASE: Myopathy, distal, 4 (MPD4) [MIM:614065]: A slowly
CC progressive muscular disorder characterized by distal muscle
CC weakness and atrophy affecting the upper and lower limbs. Onset
CC occurs around the third to fourth decades of life, and patients
CC remain ambulatory even after long disease duration. Muscle biopsy
CC shows non-specific changes with no evidence of rods, necrosis, or
CC inflammation. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- MISCELLANEOUS: Silenced in MKN28 and MKN74 gastric cancer cell
CC lines due to aberrant methylation of the gene.
CC -!- SIMILARITY: Belongs to the filamin family.
CC -!- SIMILARITY: Contains 1 actin-binding domain.
CC -!- SIMILARITY: Contains 2 CH (calponin-homology) domains.
CC -!- SIMILARITY: Contains 24 filamin repeats.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD12245.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAF68195.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
CC Sequence=AAF80245.1; Type=Frameshift; Positions=2578, 2580, 2590;
CC Sequence=CAA49688.1; Type=Frameshift; Positions=778, 787;
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/FLNC";
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DR EMBL; AF089841; AAD12245.1; ALT_INIT; mRNA.
DR EMBL; AF184126; AAF68195.1; ALT_INIT; Genomic_DNA.
DR EMBL; AF184119; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184120; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184121; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184122; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184123; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184124; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF184125; AAF68195.1; JOINED; Genomic_DNA.
DR EMBL; AF252549; AAF67190.1; -; Genomic_DNA.
DR EMBL; AJ132990; CAB51535.1; -; Genomic_DNA.
DR EMBL; AJ012737; CAB46442.1; -; mRNA.
DR EMBL; AB371585; BAG48314.1; -; mRNA.
DR EMBL; AC025594; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471070; EAW83691.1; -; Genomic_DNA.
DR EMBL; AF146692; AAF80245.1; ALT_FRAME; mRNA.
DR EMBL; X70083; CAA49688.1; ALT_FRAME; mRNA.
DR EMBL; X70084; CAA49689.1; -; mRNA.
DR PIR; S37775; S37775.
DR PIR; S37778; S37778.
DR RefSeq; NP_001120959.1; NM_001127487.1.
DR RefSeq; NP_001449.3; NM_001458.4.
DR UniGene; Hs.58414; -.
DR PDB; 1V05; X-ray; 1.43 A; A=2633-2725.
DR PDB; 2D7M; NMR; -; A=1536-1637.
DR PDB; 2D7N; NMR; -; A=1782-1861.
DR PDB; 2D7O; NMR; -; A=1856-1953.
DR PDB; 2D7P; NMR; -; A=2405-2500.
DR PDB; 2D7Q; NMR; -; A=2502-2599.
DR PDB; 2K9U; NMR; -; A=2302-2415.
DR PDB; 2NQC; X-ray; 2.05 A; A=2495-2598.
DR PDB; 3V8O; X-ray; 2.80 A; A/B=569-761.
DR PDBsum; 1V05; -.
DR PDBsum; 2D7M; -.
DR PDBsum; 2D7N; -.
DR PDBsum; 2D7O; -.
DR PDBsum; 2D7P; -.
DR PDBsum; 2D7Q; -.
DR PDBsum; 2K9U; -.
DR PDBsum; 2NQC; -.
DR PDBsum; 3V8O; -.
DR ProteinModelPortal; Q14315; -.
DR SMR; Q14315; 22-2725.
DR DIP; DIP-33398N; -.
DR IntAct; Q14315; 38.
DR MINT; MINT-5004555; -.
DR STRING; 9606.ENSP00000327145; -.
DR PhosphoSite; Q14315; -.
DR DMDM; 254763419; -.
DR PaxDb; Q14315; -.
DR PRIDE; Q14315; -.
DR Ensembl; ENST00000325888; ENSP00000327145; ENSG00000128591.
DR Ensembl; ENST00000346177; ENSP00000344002; ENSG00000128591.
DR GeneID; 2318; -.
DR KEGG; hsa:2318; -.
DR UCSC; uc003vnz.4; human.
DR CTD; 2318; -.
DR GeneCards; GC07P128470; -.
DR HGNC; HGNC:3756; FLNC.
DR HPA; HPA006135; -.
DR MIM; 102565; gene.
DR MIM; 609524; phenotype.
DR MIM; 614065; phenotype.
DR neXtProt; NX_Q14315; -.
DR Orphanet; 63273; Distal myopathy with posterior leg and anterior hand involvement.
DR Orphanet; 171445; Muscle filaminopathy.
DR PharmGKB; PA28174; -.
DR eggNOG; COG5069; -.
DR HOVERGEN; HBG004163; -.
DR InParanoid; Q14315; -.
DR KO; K04437; -.
DR OMA; EPTGCIV; -.
DR OrthoDB; EOG76T9QC; -.
DR Reactome; REACT_111155; Cell-Cell communication.
DR EvolutionaryTrace; Q14315; -.
DR GeneWiki; FLNC_(gene); -.
DR GenomeRNAi; 2318; -.
DR NextBio; 9413; -.
DR PRO; PR:Q14315; -.
DR ArrayExpress; Q14315; -.
DR Bgee; Q14315; -.
DR CleanEx; HS_FLNC; -.
DR Genevestigator; Q14315; -.
DR GO; GO:0043034; C:costamere; TAS:BHF-UCL.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0042383; C:sarcolemma; IDA:BHF-UCL.
DR GO; GO:0016528; C:sarcoplasm; IEA:Ensembl.
DR GO; GO:0030018; C:Z disc; IEA:UniProtKB-SubCell.
DR GO; GO:0034329; P:cell junction assembly; TAS:Reactome.
DR GO; GO:0048747; P:muscle fiber development; IEA:Ensembl.
DR Gene3D; 1.10.418.10; -; 2.
DR Gene3D; 2.60.40.10; -; 24.
DR InterPro; IPR001589; Actinin_actin-bd_CS.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR003961; Fibronectin_type3.
DR InterPro; IPR017868; Filamin/ABP280_repeat-like.
DR InterPro; IPR001298; Filamin/ABP280_rpt.
DR InterPro; IPR028559; FLN.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR PANTHER; PTHR11915:SF172; PTHR11915:SF172; 1.
DR Pfam; PF00307; CH; 2.
DR Pfam; PF00630; Filamin; 23.
DR SMART; SM00033; CH; 2.
DR SMART; SM00060; FN3; 2.
DR SMART; SM00557; IG_FLMN; 24.
DR SUPFAM; SSF47576; SSF47576; 1.
DR SUPFAM; SSF81296; SSF81296; 24.
DR PROSITE; PS00019; ACTININ_1; 1.
DR PROSITE; PS00020; ACTININ_2; 1.
DR PROSITE; PS50021; CH; 2.
DR PROSITE; PS50194; FILAMIN_REPEAT; 24.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative splicing; Complete proteome;
KW Cytoplasm; Cytoskeleton; Direct protein sequencing; Disease mutation;
KW Membrane; Myofibrillar myopathy; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 2725 Filamin-C.
FT /FTId=PRO_0000087301.
FT DOMAIN 1 259 Actin-binding.
FT DOMAIN 36 142 CH 1.
FT DOMAIN 159 259 CH 2.
FT REPEAT 270 368 Filamin 1.
FT REPEAT 370 468 Filamin 2.
FT REPEAT 469 565 Filamin 3.
FT REPEAT 566 658 Filamin 4.
FT REPEAT 662 758 Filamin 5.
FT REPEAT 759 861 Filamin 6.
FT REPEAT 862 960 Filamin 7.
FT REPEAT 961 1056 Filamin 8.
FT REPEAT 1057 1149 Filamin 9.
FT REPEAT 1150 1244 Filamin 10.
FT REPEAT 1245 1344 Filamin 11.
FT REPEAT 1345 1437 Filamin 12.
FT REPEAT 1438 1533 Filamin 13.
FT REPEAT 1534 1630 Filamin 14.
FT REPEAT 1635 1734 Filamin 15.
FT REPEAT 1759 1853 Filamin 16.
FT REPEAT 1854 1946 Filamin 17.
FT REPEAT 1947 2033 Filamin 18.
FT REPEAT 2036 2128 Filamin 19.
FT REPEAT 2244 2306 Filamin 20.
FT REPEAT 2309 2401 Filamin 21.
FT REPEAT 2403 2496 Filamin 22.
FT REPEAT 2500 2592 Filamin 23.
FT REPEAT 2630 2724 Filamin 24.
FT REGION 1735 1758 Hinge 1.
FT REGION 2162 2243 Intradomain insert.
FT REGION 2403 2724 Interaction with INPPL1.
FT REGION 2593 2725 Self-association site, tail (By
FT similarity).
FT REGION 2593 2629 Hinge 2.
FT MOD_RES 1161 1161 Phosphoserine.
FT MOD_RES 2233 2233 Phosphoserine.
FT VAR_SEQ 1734 1766 Missing (in isoform 2).
FT /FTId=VSP_007579.
FT VARIANT 193 193 A -> T (in MPD4; results in slightly
FT decreased thermal stability and increased
FT actin-binding activity; results in
FT significantly decreased nuclear
FT localization with formation of
FT intracellular protein aggregates).
FT /FTId=VAR_066212.
FT VARIANT 251 251 M -> T (in MPD4; results in slightly
FT decreased thermal stability and increased
FT actin-binding activity; results in the
FT formation of intracellular protein
FT aggregates).
FT /FTId=VAR_066213.
FT VARIANT 1567 1567 R -> Q (in dbSNP:rs2291569).
FT /FTId=VAR_015705.
FT VARIANT 1580 1580 D -> G (in dbSNP:rs2643766).
FT /FTId=VAR_015706.
FT VARIANT 1599 1599 T -> A (in dbSNP:rs2643767).
FT /FTId=VAR_015707.
FT VARIANT 2135 2135 K -> R (in dbSNP:rs1063261).
FT /FTId=VAR_015708.
FT VARIANT 2203 2203 R -> P (in dbSNP:rs1063262).
FT /FTId=VAR_015709.
FT VARIANT 2626 2626 S -> N (in dbSNP:rs2639142).
FT /FTId=VAR_015710.
FT VARIANT 2637 2637 K -> Q (in dbSNP:rs2291572).
FT /FTId=VAR_015711.
FT MUTAGEN 2669 2669 M->D: Abolishes dimerization.
FT CONFLICT 138 138 I -> T (in Ref. 3; CAB46442).
FT CONFLICT 189 189 K -> E (in Ref. 3; CAB46442).
FT CONFLICT 194 194 L -> Q (in Ref. 3; CAB46442).
FT CONFLICT 218 218 A -> S (in Ref. 1; AAD12245 and 2;
FT AAF68195).
FT CONFLICT 233 233 Q -> L (in Ref. 3; CAB46442).
FT CONFLICT 484 484 L -> P (in Ref. 3; CAB46442).
FT CONFLICT 585 585 Q -> V (in Ref. 9; CAA49688).
FT CONFLICT 723 723 D -> N (in Ref. 1; AAD12245, 2; AAF68195
FT and 9; CAA49688).
FT CONFLICT 1091 1091 G -> D (in Ref. 3; CAB46442).
FT CONFLICT 1640 1640 L -> T (in Ref. 9; CAA49689).
FT CONFLICT 1668 1668 V -> M (in Ref. 3; CAB46442).
FT CONFLICT 2101 2101 C -> S (in Ref. 3; CAB46442 and 9;
FT CAA49689).
FT CONFLICT 2321 2322 GT -> RA (in Ref. 1; AAD12245 and 2;
FT AAF68195).
FT CONFLICT 2355 2355 S -> N (in Ref. 4; AAF80245).
FT CONFLICT 2382 2382 E -> K (in Ref. 4; AAF80245).
FT CONFLICT 2484 2484 G -> C (in Ref. 4; AAF80245).
FT CONFLICT 2491 2491 P -> L (in Ref. 4; AAF80245).
FT CONFLICT 2499 2499 Q -> H (in Ref. 4; AAF80245).
FT CONFLICT 2514 2514 G -> E (in Ref. 4; AAF80245).
FT CONFLICT 2528 2530 VNT -> DDH (in Ref. 4; AAF80245).
FT CONFLICT 2535 2535 S -> F (in Ref. 4; AAF80245).
FT CONFLICT 2547 2547 K -> N (in Ref. 4; AAF80245).
FT CONFLICT 2557 2557 E -> G (in Ref. 4; AAF80245).
FT CONFLICT 2601 2602 HS -> QH (in Ref. 4; AAF80245).
FT STRAND 574 578
FT HELIX 579 581
FT STRAND 583 585
FT STRAND 590 599
FT HELIX 601 603
FT STRAND 604 612
FT STRAND 617 620
FT STRAND 622 630
FT STRAND 636 644
FT STRAND 653 659
FT HELIX 667 669
FT STRAND 671 674
FT HELIX 675 677
FT STRAND 678 680
FT STRAND 688 693
FT STRAND 697 699
FT STRAND 702 708
FT STRAND 717 720
FT STRAND 722 730
FT STRAND 734 744
FT STRAND 753 759
FT HELIX 1539 1541
FT STRAND 1542 1547
FT STRAND 1554 1558
FT STRAND 1560 1569
FT STRAND 1574 1579
FT STRAND 1588 1592
FT STRAND 1594 1596
FT STRAND 1598 1602
FT STRAND 1608 1618
FT STRAND 1625 1631
FT STRAND 1785 1789
FT STRAND 1794 1796
FT STRAND 1798 1803
FT STRAND 1813 1816
FT STRAND 1818 1820
FT STRAND 1822 1826
FT STRAND 1832 1843
FT STRAND 1849 1854
FT STRAND 1863 1866
FT HELIX 1867 1870
FT STRAND 1871 1873
FT STRAND 1878 1883
FT TURN 1885 1887
FT STRAND 1895 1900
FT STRAND 1910 1918
FT STRAND 1924 1929
FT STRAND 1931 1934
FT STRAND 1941 1947
FT STRAND 2303 2308
FT TURN 2313 2316
FT STRAND 2318 2322
FT TURN 2323 2325
FT STRAND 2332 2338
FT STRAND 2344 2355
FT STRAND 2358 2362
FT STRAND 2365 2374
FT STRAND 2377 2389
FT STRAND 2396 2404
FT HELIX 2407 2410
FT STRAND 2427 2432
FT STRAND 2440 2445
FT STRAND 2447 2449
FT STRAND 2463 2468
FT STRAND 2474 2484
FT STRAND 2491 2496
FT HELIX 2505 2507
FT STRAND 2509 2512
FT HELIX 2513 2515
FT STRAND 2517 2519
FT STRAND 2524 2529
FT TURN 2531 2533
FT STRAND 2538 2546
FT STRAND 2549 2555
FT STRAND 2558 2564
FT STRAND 2569 2580
FT STRAND 2587 2594
FT HELIX 2635 2637
FT STRAND 2639 2642
FT HELIX 2643 2645
FT STRAND 2654 2659
FT STRAND 2663 2665
FT STRAND 2668 2673
FT STRAND 2675 2677
FT STRAND 2680 2686
FT STRAND 2691 2697
FT STRAND 2702 2710
FT STRAND 2719 2724
SQ SEQUENCE 2725 AA; 291022 MW; B7C8516C2366E75D CRC64;
MMNNSGYSDA GLGLGDETDE MPSTEKDLAE DAPWKKIQQN TFTRWCNEHL KCVGKRLTDL
QRDLSDGLRL IALLEVLSQK RMYRKFHPRP NFRQMKLENV SVALEFLERE HIKLVSIDSK
AIVDGNLKLI LGLIWTLILH YSISMPMWED EDDEDARKQT PKQRLLGWIQ NKVPQLPITN
FNRDWQDGKA LGALVDNCAP GLCPDWEAWD PNQPVENARE AMQQADDWLG VPQVIAPEEI
VDPNVDEHSV MTYLSQFPKA KLKPGAPVRS KQLNPKKAIA YGPGIEPQGN TVLQPAHFTV
QTVDAGVGEV LVYIEDPEGH TEEAKVVPNN DKDRTYAVSY VPKVAGLHKV TVLFAGQNIE
RSPFEVNVGM ALGDANKVSA RGPGLEPVGN VANKPTYFDI YTAGAGTGDV AVVIVDPQGR
RDTVEVALED KGDSTFRCTY RPAMEGPHTV HVAFAGAPIT RSPFPVHVSE ACNPNACRAS
GRGLQPKGVR VKEVADFKVF TKGAGSGELK VTVKGPKGTE EPVKVREAGD GVFECEYYPV
VPGKYVVTIT WGGYAIPRSP FEVQVSPEAG VQKVRAWGPG LETGQVGKSA DFVVEAIGTE
VGTLGFSIEG PSQAKIECDD KGDGSCDVRY WPTEPGEYAV HVICDDEDIR DSPFIAHILP
APPDCFPDKV KAFGPGLEPT GCIVDKPAEF TIDARAAGKG DLKLYAQDAD GCPIDIKVIP
NGDGTFRCSY VPTKPIKHTI IISWGGVNVP KSPFRVNVGE GSHPERVKVY GPGVEKTGLK
ANEPTYFTVD CSEAGQGDVS IGIKCAPGVV GPAEADIDFD IIKNDNDTFT VKYTPPGAGR
YTIMVLFANQ EIPASPFHIK VDPSHDASKV KAEGPGLNRT GVEVGKPTHF TVLTKGAGKA
KLDVQFAGTA KGEVVRDFEI IDNHDYSYTV KYTAVQQGNM AVTVTYGGDP VPKSPFVVNV
APPLDLSKIK VQGLNSKVAV GQEQAFSVNT RGAGGQGQLD VRMTSPSRRP IPCKLEPGGG
AEAQAVRYMP PEEGPYKVDI TYDGHPVPGS PFAVEGVLPP DPSKVCAYGP GLKGGLVGTP
APFSIDTKGA GTGGLGLTVE GPCEAKIECQ DNGDGSCAVS YLPTEPGEYT INILFAEAHI
PGSPFKATIR PVFDPSKVRA SGPGLERGKV GEAATFTVDC SEAGEAELTI EILSDAGVKA
EVLIHNNADG TYHITYSPAF PGTYTITIKY GGHPVPKFPT RVHVQPAVDT SGVKVSGPGV
EPHGVLREVT TEFTVDARSL TATGGNHVTA RVLNPSGAKT DTYVTDNGDG TYRVQYTAYE
EGVHLVEVLY DEVAVPKSPF RVGVTEGCDP TRVRAFGPGL EGGLVNKANR FTVETRGAGT
GGLGLAIEGP SEAKMSCKDN KDGSCTVEYI PFTPGDYDVN ITFGGRPIPG SPFRVPVKDV
VDPGKVKCSG PGLGAGVRAR VPQTFTVDCS QAGRAPLQVA VLGPTGVAEP VEVRDNGDGT
HTVHYTPATD GPYTVAVKYA DQEVPRSPFK IKVLPAHDAS KVRASGPGLN ASGIPASLPV
EFTIDARDAG EGLLTVQILD PEGKPKKANI RDNGDGTYTV SYLPDMSGRY TITIKYGGDE
IPYSPFRIHA LPTGDASKCL VTVSIGGHGL GACLGPRIQI GQETVITVDA KAAGEGKVTC
TVSTPDGAEL DVDVVENHDG TFDIYYTAPE PGKYVITIRF GGEHIPNSPF HVLACDPLPH
EEEPSEVPQL RQPYAPPRPG ARPTHWATEE PVVPVEPMES MLRPFNLVIP FAVQKGELTG
EVRMPSGKTA RPNITDNKDG TITVRYAPTE KGLHQMGIKY DGNHIPGSPL QFYVDAINSR
HVSAYGPGLS HGMVNKPATF TIVTKDAGEG GLSLAVEGPS KAEITCKDNK DGTCTVSYLP
TAPGDYSIIV RFDDKHIPGS PFTAKITGDD SMRTSQLNVG TSTDVSLKIT ESDLSQLTAS
IRAPSGNEEP CLLKRLPNRH IGISFTPKEV GEHVVSVRKS GKHVTNSPFK ILVGPSEIGD
ASKVRVWGKG LSEGHTFQVA EFIVDTRNAG YGGLGLSIEG PSKVDINCED MEDGTCKVTY
CPTEPGTYII NIKFADKHVP GSPFTVKVTG EGRMKESITR RRQAPSIATI GSTCDLNLKI
PGNWFQMVSA QERLTRTFTR SSHTYTRTER TEISKTRGGE TKREVRVEES TQVGGDPFPA
VFGDFLGRER LGSFGSITRQ QEGEASSQDM TAQVTSPSGK VEAAEIVEGE DSAYSVRFVP
QEMGPHTVAV KYRGQHVPGS PFQFTVGPLG EGGAHKVRAG GTGLERGVAG VPAEFSIWTR
EAGAGGLSIA VEGPSKAEIA FEDRKDGSCG VSYVVQEPGD YEVSIKFNDE HIPDSPFVVP
VASLSDDARR LTVTSLQETG LKVNQPASFA VQLNGARGVI DARVHTPSGA VEECYVSELD
SDKHTIRFIP HENGVHSIDV KFNGAHIPGS PFKIRVGEQS QAGDPGLVSA YGPGLEGGTT
GVSSEFIVNT LNAGSGALSV TIDGPSKVQL DCRECPEGHV VTYTPMAPGN YLIAIKYGGP
QHIVGSPFKA KVTGPRLSGG HSLHETSTVL VETVTKSSSS RGSSYSSIPK FSSDASKVVT
RGPGLSQAFV GQKNSFTVDC SKAGTNMMMV GVHGPKTPCE EVYVKHMGNR VYNVTYTVKE
KGDYILIVKW GDESVPGSPF KVKVP
//

MIM 102565
*RECORD*
*FIELD* NO
102565
*FIELD* TI
*102565 FILAMIN C; FLNC
;;FILAMIN, GAMMA;;
FILAMIN 2; FLN2;;
ACTIN-BINDING PROTEIN 280, AUTOSOMAL FORM; ABP280A;;
read moreABPA;;
ACTIN-BINDING PROTEIN-LIKE; ABPL
*FIELD* TX

DESCRIPTION

Filamins, such as FLNC, are a family of actin (see ACTA1;
102610)-binding proteins involved in reshaping of the cytoskeleton. See
FLN1 (FLNA; 300017) for background information on the filamin gene
family.

CLONING

Xie et al. (1998) cloned FLNC, which they called ABPL, from a heart cDNA
library. The deduced 2,705-amino acid protein has a calculated molecular
mass of 289 kD. ABPL contains an N-terminal actin-binding domain,
followed by 24 repeats of about 94 amino acids. It has hinge sequences
prior to repeats 16 and 24. Xie et al. (1998) also identified an
alternatively spliced transcript that encodes a protein lacking hinge 1.
PCR analysis detected transcripts encoding the hinge 1-containing
isoform in stomach, uterus, umbilical vein endothelial cells, and
prostate. Transcripts encoding both isoforms were detected in heart,
thyroid, fetal brain, fetal lung, retina, spinal cord, skeletal muscle,
and bone marrow.

Using sarcoglycan-gamma (SGCG; 608896) as bait in a yeast 2-hybrid
screen of a skeletal muscle cDNA library, followed by EST database
analysis and screening of a skeletal muscle cDNA library, Thompson et
al. (2000) cloned FLNC, which they called FLN2. The deduced 2,688-amino
acid protein shares 74% and 71% identity with FLN1 and filamin-beta
(FLNB; 603381), respectively, and the 3 proteins are nearly 100%
identical in the actin-binding domains. FLN2 lacks the first hinge
region present in FLN1 and FLNB, but it has the second hinge region.
Like FLN1 and FLNB, FLNC has a C-terminal domain containing binding
sites for several receptor proteins. Western blot analysis detected a
280-kD protein in heart and skeletal muscle.

GENE FUNCTION

By yeast 2-hybrid analysis, Thompson et al. (2000) found that
sarcoglycan-gamma and -delta (SGCD; 601411) interacted with FLN2, but
sarcoglycan-alpha (SGCA; 600119) and -beta (SGCB; 600900) did not. In
vitro binding assays indicated that FLN2 interacted directly with
sarcoglycan-gamma and -delta, but not with dystrophin (DMD; 300377) and
syntrophin beta-1 (SNTB1; 600026). Coimmunoprecipitation analysis of
transfected proteins and of endogenous proteins in mouse myotube lysates
confirmed that FLN2 interacted with sarcoglycans-gamma and -delta. Fln2
was detected predominantly in the soluble fraction of lysed mouse
myotube cultures. Immunoelectron microscopy detected 2 pools of Fln2,
one adjacent to the sarcolemmal membrane and the other more diffuse.
Thompson et al. (2000) found elevated levels of membrane-associated FLN2
in 2 patients with limb-girdle muscular dystrophy type 2C (LGMD2C;
253700), a patient with Duchenne muscular dystrophy (DMD; 310200), and
dystrophic mice.

The KY protein (605739) has been implicated in a neuromuscular dystrophy
in the mouse, but its role in muscle function remains unclear. Beatham
et al. (2004) showed that KY interacted with several sarcomeric
cytoskeletal proteins including filamin C and the slow isoform of the
myosin-binding protein C (MYBPC1; 160794). A role for KY in regulating
filamin C function in vivo was supported by the expression analysis of
filamin C in the Ky-null mouse mutant, where distinct irregular
subcellular localization of filamin C was found in subsets of muscle
fibers, which appeared to be a specific outcome of KY deficiency. In
vitro assays showed that KY has protease activity, and specific
degradation of filamin C by KY was shown in transfected cells. Beatham
et al. (2004) suggested that KY may be an intrinsic part of the protein
networks underlying the molecular mechanism of several limb-girdle
muscular dystrophies, particularly those where interactions between
filamin C and disease-causing proteins have been shown.

MAPPING

Gariboldi et al. (1994) mapped the FLN2 gene to human chromosome
7q32-q35 by analysis of somatic cell hybrids containing portions of
chromosome 7. Chakarova et al. (2000) assigned the FLNC gene to 7q32 by
radiation hybrid analysis.

By interspecific backcross analysis, Gariboldi et al. (1994) mapped the
mouse homolog to chromosome 6 in a region showing homology of synteny to
human chromosome 7.

- Pseudogene

An FLNC pseudogene maps to chromosome 7q32-q35 about 53.7 kb downstream
from the functional FLNC gene. The pseudogene is 98% homologous to exons
46, 47, and 48 of the functional gene (van der Ven et al., 2010).

MOLECULAR GENETICS

- Myofibrillar Myopathy 5

In affected members of a German family with autosomal dominant
myofibrillar myopathy-5 (MFM5; 609524), Vorgerd et al. (2005) identified
a heterozygous mutation in the FLNC gene (102565.0001).

In a German mother and daughter with adult-onset limb-girdle muscle
weakness, Shatunov et al. (2009) identified a heterozygous deletion in
the FLNC gene (102565.0002). This family was the only 1 of 127 families
with a myopathy examined that was found to have an FLNC mutation,
indicating that this subtype of myofibrillar myopathy is rare.

- Distal Myopathy 4

By linkage analysis followed by candidate gene sequencing of an
Australian family with distal myopathy-4 (MPD4; 614065), reported by
Williams et al. (2005), Duff et al. (2011) identified a heterozygous
mutation in the FLNC gene (M251T; 102565.0003). A different heterozygous
mutation (A193T; 102565.0004) was found in affected members of an
Italian family with the same phenotype. Both mutations occurred in the
actin-binding domain, and in vitro cellular expression studies showed
that both mutations resulted in increased affinity for actin.

HISTORY

Kono et al. (2010) identified a heterozygous 1-bp deletion (8107delG) in
exon 48 of the FLNC gene in affected members of a Japanese family with
adult-onset myofibrillar myopathy primarily affecting the distal limbs,
with later involvement of proximal muscles. However, the paper was later
retracted by the authors after the mutation was found to occur in the
FLNC pseudogene, based on the report of van der Ven et al. (2010). Van
der Ven et al. (2010) noted that the pseudogene is 98% homologous to
exons 46, 47, and 48 of the functional FLNC gene and that the pseudogene
contains the 8107delG variant.

*FIELD* AV
.0001
MYOPATHY, MYOFIBRILLAR, 5
FLNC, TRP2710TER

In affected members of a German family with autosomal dominant
myofibrillar myopathy-5 (MFM5; 609524), Vorgerd et al. (2005) identified
a heterozygous 8130G-A transition in exon 48 of the FLNC gene, resulting
in a trp2710-to-ter (W2710X) substitution. The mutation leads to a
truncation of the filamin C immunoglobulin domain that is responsible
for dimerization. Functional expression studies showed that the W2710X
protein had improper folding, was unable to form dimers, and showed
abnormal aggregation. The findings implied that dimer formation is
essential for the biologic function of filamin. The mutation was not
identified in 220 control chromosomes.

By in vitro functional expression studies, Lowe et al. (2007) showed
that W2710X-mutant protein was less stable and more susceptible to
proteolysis compared to wildtype. The mutant protein did not dimerize
properly and formed filamin aggregates in cultured cells. Aggregation of
mutant protein did not affect dimerization of wildtype filamin C, and
the mutant protein still showed normal binding to actin and
sarcoglycans.

.0002
MYOPATHY, MYOFIBRILLAR, 5
FLNC, 12-BP DEL, NT2997

In a German mother and daughter with autosomal dominant myofibrillar
myopathy-5 (609524), Shatunov et al. (2009) identified a heterozygous
12-bp deletion (2997_3008del) in exon 18 of the FLNC gene, predicted to
result in an in-frame deletion of 4 residues (val930 to thr933) in the
seventh repeat and confirmed by RT-PCR analysis of muscle tissue from
the affected daughter. The phenotype was characterized by adult-onset
muscle weakness initially involving proximal muscles of the lower limbs
and spreading to the upper limbs and distal muscles of lower
extremities. Both had paraspinal and abdominal muscle involvement and
winging of the scapula. Cardiac and respiratory muscles were not
affected. Skeletal muscle biopsy from the daughter showed marked
variation in fiber size, some fibers with internal nuclei, and type 1
fiber predominance. Several fibers showed polymorphous hyaline and
nonhyaline myofibrillary FLNC-positive inclusions with a convoluted,
serpentine appearance. Ultrastructural examination showed major
myofibrillar abnormalities, with accumulation of Z disc debris,
granulofilamentous material, and nemaline rods. There were also
mitochondrial aggregates.

.0003
MYOPATHY, DISTAL, 4
FLNC, MET251THR

In affected members of a large Australian family with autosomal dominant
distal myopathy-4 (MPD4; 614065) originally reported by Williams et al.
(2005), Duff et al. (2011) identified a heterozygous 752T-C transition
in exon 4 of the FLNC gene, resulting in a met251-to-thr (M251T)
substitution in a highly conserved residue in the CH2 domain in the
actin-binding domain. The mutation was not found in 400 control
chromosomes. The mutant protein had slightly decreased thermal stability
and showed increased actin-binding activity compared to the wildtype
protein. Transfection of the mutant M251T protein into cells showed
significantly decreased nuclear localization compared to wildtype and
resulted in the formation of intracellular protein aggregates. Duff et
al. (2011) concluded that the disease mechanism somehow involves
increased affinity for actin. The phenotype was characterized by adult
onset of distal muscle weakness and atrophy affecting the upper and
lower limbs, with nonspecific findings on muscle biopsy.

.0004
MYOPATHY, DISTAL, 4
FLNC, ALA193THR

In affected members of an Italian family with autosomal dominant distal
myopathy-4 (MPD4; 614065), Duff et al. (2011) identified a heterozygous
577G-A transition in exon 2 of the FLNC gene, resulting in an
ala193-to-thr (A193T) substitution in a highly conserved residue in the
CH2 domain in the actin-binding domain. The mutation was not found in
204 control chromosomes. The mutant protein had slightly decreased
thermal stability and showed increased actin-binding activity compared
to the wildtype protein. Nuclear localization was unaltered, but
transfection resulted in the formation of intracellular protein
aggregates. Duff et al. (2011) concluded that the disease mechanism
somehow involves increased affinity for actin. The phenotype was
characterized by adult onset of distal muscle weakness and atrophy
affecting the upper and lower limbs, with nonspecific findings on muscle
biopsy.

*FIELD* RF
1. Beatham, J.; Romero, R.; Townsend, S. K. M.; Hacker, T.; van der
Ven, P. F. M.; Blanco, G.: Filamin C interacts with the muscular
dystrophy KY protein and is abnormally distributed in mouse KY deficient
muscle fibres. Hum. Molec. Genet. 13: 2863-2874, 2004.

2. Chakarova, C.; Wehnert, M. S.; Uhl, K.; Sakthivel, S.; Vosberg,
H.-P.; van der Ven, P. F. M.; Furst, D. O.: Genomic structure and
fine mapping of the two human filamin gene paralogues FLNB and FLNC
and comparative analysis of the filamin gene family. Hum. Genet. 107:
597-611, 2000.

3. Duff, R. M.; Tay, V.; Hackman, P.; Ravenscroft, G.; McLean, C.;
Kennedy, P.; Steinbach, A.; Schoffler, W.; van der Ven, P. F.; Furst,
D. O.; Song, J.; Djinovic-Carugo, K.; and 12 others: Mutations
in the N-terminal actin-binding domain of filamin C cause a distal
myopathy. Am. J. Hum. Genet. 88: 729-740, 2011.

4. Gariboldi, M.; Maestrini, E.; Canzian, F.; Manenti, G.; De Gregorio,
L.; Rivella, S.; Chatterjee, A.; Herman, G. E.; Archidiacono, N.;
Antonacci, R.; Pierotti, M. A.; Dragani, T. A.; Toniolo, D.: Comparative
mapping of the actin-binding protein 280 genes in human and mouse. Genomics 21:
428-430, 1994.

5. Kono, S.; Nishio, T.; Takahashi, Y.; Goto-Inoue, N.; Kinoshita,
M.; Zaima, N.; Suzuki, H.; Fukutoku-Otsuji, A.; Setou, M.; Miyajima,
H.: Dominant-negative effects of a novel mutation in the filamin
myopathy. Neurology 75: 547-554, 2010. Note: Retraction: Neurology
75: 2138 only, 2010.

6. Lowe, T.; Kley, R. A.; van der Ven, P. F. M.; Himmel, M.; Huebner,
A.; Vorgerd, M.; Furst, D. O.: The pathomechanism of filaminopathy:
altered biochemical properties explain the cellular phenotype of a
protein aggregation myopathy. Hum. Molec. Genet. 16: 1351-1358,
2007.

7. Shatunov, A.; Olive, M.; Odgerel, Z.; Stadelmann-Nessler, C.; Irlbacher,
K.; van Landeghem, F.; Bayarsaikhan, M.; Lee, H.-S.; Goudeau, B.;
Chinnery, P. F.; Straub, V.; Hilton-Jones, D.; and 9 others: In-frame
deletion in the seventh immunoglobulin-like repeat of filamin C in
a family with myofibrillar myopathy. Europ. J. Hum. Genet. 17: 656-663,
2009.

8. Thompson, T. G.; Chan, Y.-M.; Hack, A. A.; Brosius, M.; Rajala,
M.; Lidov, H. G. W.; McNally, E. M.; Watkins, S.; Kunkel, L. M.:
Filamin 2 (FLN2): a muscle-specific sarcoglycan interacting protein. J.
Cell Biol. 148: 115-126, 2000.

9. Van der Ven, P. F. M.; Odgerel, Z.; Furst, D. O.; Goldfarb, L.
G.: Dominant-negative effects of a novel mutation in the filamin
myopathy. (Letter) Neurology 75: 2137-2138, 2010.

10. Vorgerd, M.; van der Ven, P. F. M.; Bruchertseifer, V.; Lowe,
T.; Kley, R. A.; Schroder, R.; Lochmuller, H.; Himmel, M.; Koehler,
K.; Furst, D. O.; Huebner, A.: A mutation in the dimerization domain
of filamin C causes a novel type of autosomal dominant myofibrillar
myopathy. Am. J. Hum. Genet. 77: 297-304, 2005.

11. Williams, D. R.; Reardon, K.; Roberts, L.; Dennet, X.; Duff, R.;
Laing, N. G.; Byrne, E.: A new dominant distal myopathy affecting
posterior leg and anterior upper limb muscles. Neurology 64: 1245-1254,
2005.

12. Xie, Z.; Xu, W.; Davie, E. W.; Chung, D. W.: Molecular cloning
of human ABPL, an actin-binding protein homologue. Biochem. Biophys.
Res. Commun. 251: 914-919, 1998.

*FIELD* CN
Cassandra L. Kniffin - updated: 6/29/2011
Cassandra L. Kniffin - updated: 1/28/2011
Cassandra L. Kniffin - updated: 11/2/2010
Cassandra L. Kniffin - updated: 2/22/2010
George E. Tiller - updated: 5/22/2007
Patricia A. Hartz - updated: 9/21/2005
Cassandra L. Kniffin - updated: 8/9/2005
Victor A. McKusick - updated: 12/18/2000

*FIELD* CD
Victor A. McKusick: 7/8/1993

*FIELD* ED
carol: 08/07/2013
alopez: 2/3/2012
wwang: 7/1/2011
ckniffin: 6/29/2011
wwang: 2/24/2011
wwang: 2/21/2011
ckniffin: 1/28/2011
wwang: 12/7/2010
ckniffin: 11/2/2010
wwang: 2/23/2010
ckniffin: 2/22/2010
wwang: 6/15/2007
terry: 5/22/2007
mgross: 10/10/2005
terry: 9/21/2005
wwang: 8/30/2005
wwang: 8/12/2005
ckniffin: 8/9/2005
mcapotos: 1/18/2001
terry: 12/18/2000
alopez: 9/5/2000
alopez: 10/20/1999
carol: 3/30/1999
alopez: 12/4/1998
dkim: 7/17/1998
mark: 4/10/1997
jason: 6/8/1994
carol: 4/13/1994
carol: 8/16/1993
carol: 7/8/1993

MIM 609524
*RECORD*
*FIELD* NO
609524
*FIELD* TI
#609524 MYOPATHY, MYOFIBRILLAR, 5; MFM5
;;MYOPATHY, MYOFIBRILLAR, FILAMIN C-RELATED;;
read moreFILAMINOPATHY, AUTOSOMAL DOMINANT
*FIELD* TX
A number sign (#) is used with this entry because myofibrillar
myopathy-5 (MFM5) is caused by heterozygous mutation in the FLNC gene
(102565) on chromosome 7q32.

For a general phenotypic description and a discussion of genetic
heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419).

Mutation in the FLNC gene can also cause distal myopathy-4 (MPD4;
614065), which shows a different pattern of muscle involvement and
different histologic changes.

CLINICAL FEATURES

Vorgerd et al. (2005) reported a German family in which 17 members had
adult-onset of slowly progressive skeletal muscle weakness with
autosomal dominant inheritance. Although most patients had proximal
involvement of the lower limbs with lesser involvement of the upper
extremities, 1 patient had distal weakness of the calf muscles only.
Initial symptoms included weakness when climbing stairs, waddling gait,
and lower back pain. Several patients also had respiratory
insufficiency, and 3 patients had evidence of peripheral nerve
involvement. Only 1 patient had evidence of cardiac involvement. All
patients showed increased serum creatine kinase. Skeletal muscle biopsy
showed MFM with amorphous, granular, or hyaline deposits and occasional
vacuoles. Other features included internal nuclei, fiber splitting, and
necrotic fibers. Oxidative enzymes were decreased. Immunohistochemical
analysis showed accumulation of desmin (DES; 125660) and filamin C.
Electron microscopy of skeletal muscle biopsy from 1 patient showed Z
disc streaming, nemaline rod formation, and intermyofibrillar and
subsarcolemmal granulofilamentous protein aggregates. Vorgerd et al.
(2005) noted that the features in their family were distinct from those
reported by Gamez et al. (2001) (see LGMD1F; 608423).

Shatunov et al. (2009) reported a German mother and daughter with adult
onset of slowly progressive muscle weakness at ages 60 and 34 years,
respectively. Symptoms in the mother began with difficulty climbing
stairs and paresis of the pelvic muscles, with proximal upper extremity
muscles becoming involved 4 years later. She later had paresis of the
neck muscles, muscles surrounding the knees, and distal leg muscles,
with hypo- or areflexia. She could not stand or walk on heels or toes,
and used a walking frame. The daughter first developed muscle pain
increasing with exercise and difficulty climbing stairs. Two years
later, she had limb-girdle paresis and hypotrophy of the proximal
muscles of the upper limb. Both patients had winging of the scapula and
involvement of the paraspinal and abdominal muscles; neither patient had
evidence of cardiac or respiratory muscle involvement. Family history
indicated that a maternal grandmother, maternal uncle, and a brother had
slowly progressive muscle weakness. Skeletal muscle biopsy from the
daughter showed marked variation in fiber size and some fibers with
internal nuclei. There was type 1 fiber predominance. Several fibers
showed polymorphous hyaline and nonhyaline myofibrillary FLNC-positive
inclusions with a convoluted, serpentine appearance. Ultrastructural
examination showed major myofibrillar abnormalities, with accumulation
of Z disc debris, granulofilamentous material, and nemaline rods. There
were also mitochondrial aggregates.

MOLECULAR GENETICS

In affected members of a German family with autosomal dominant MFM,
Vorgerd et al. (2005) identified a heterozygous mutation in the FLNC
gene (102565.0001).

In a German mother and daughter with adult-onset limb-girdle muscle
weakness, Shatunov et al. (2009) identified a heterozygous deletion in
the FLNC gene (102565.0002). This family was the only 1 of 127 families
with a myopathy examined that was found to have an FLNC mutation,
indicating that this subtype of myofibrillar myopathy is rare.

*FIELD* RF
1. Gamez, J.; Navarro, C.; Andreu, A. L.; Fernandez, J. M.; Palenzuela,
L.; Tejeira, S.; Fernandez-Hojas, R.; Schwartz, S.; Karadimas, C.;
DiMauro, S.; Hirano, M.; Cervera, C.: Autosomal dominant limb-girdle
muscular dystrophy: a large kindred with evidence for anticipation. Neurology 56:
450-454, 2001.

2. Shatunov, A.; Olive, M.; Odgerel, Z.; Stadelmann-Nessler, C.; Irlbacher,
K.; van Landeghem, F.; Bayarsaikhan, M.; Lee, H.-S.; Goudeau, B.;
Chinnery, P. F.; Straub, V.; Hilton-Jones, D.; and 9 others: In-frame
deletion in the seventh immunoglobulin-like repeat of filamin C in
a family with myofibrillar myopathy. Europ. J. Hum. Genet. 17: 656-663,
2009.

3. Vorgerd, M.; van der Ven, P. F. M.; Bruchertseifer, V.; Lowe, T.;
Kley, R. A.; Schroder, R.; Lochmuller, H.; Himmel, M.; Koehler, K.;
Furst, D. O.; Huebner, A.: A mutation in the dimerization domain
of filamin C causes a novel type of autosomal dominant myofibrillar
myopathy. Am. J. Hum. Genet. 77: 297-304, 2005.

*FIELD* CS
INHERITANCE:
Autosomal dominant

RESPIRATORY:
Respiratory insufficiency

MUSCLE, SOFT TISSUE:
Muscle weakness, proximal, slowly progressive;
Lower limbs more affected than upper limbs;
Distal muscles may be affected;
Difficulty climbing stairs;
Waddling gait;
Muscle biopsy shows myofibrillar myopathy;
Abnormal muscle fibers with amorphous, granular, or hyaline deposits;
Increased internal nuclei;
Fiber splitting;
Necrotic fibers;
Abnormal aggregates of desmin and filamin C;
Electron microscopy showed Z-disk streaming;
Nemaline rod formation;
Intermyofibrillar and subsarcolemmal granulofilamentous protein aggregates

NEUROLOGIC:
[Peripheral nervous system];
Peripheral nerve involvement may occur

LABORATORY ABNORMALITIES:
Increased serum creatine kinase

MISCELLANEOUS:
Adult onset (37 to 57 years);
Slowly progressive

MOLECULAR BASIS:
Caused by mutations in the filamin C gene (FLNC, 102565.0001)

*FIELD* CD
Cassandra L. Kniffin: 8/9/2005

*FIELD* ED
ckniffin: 08/09/2005

*FIELD* CN
Cassandra L. Kniffin - updated: 11/2/2010

*FIELD* CD
Cassandra L. Kniffin: 8/9/2005

*FIELD* ED
carol: 08/07/2013
alopez: 2/3/2012
wwang: 7/1/2011
ckniffin: 6/29/2011
terry: 6/3/2011
wwang: 12/7/2010
ckniffin: 11/2/2010
terry: 7/30/2008
wwang: 8/12/2005
ckniffin: 8/9/2005

MIM 614065
*RECORD*
*FIELD* NO
614065
*FIELD* TI
#614065 MYOPATHY, DISTAL, 4; MPD4
;;WILLIAMS DISTAL MYOPATHY
*FIELD* TX
A number sign (#) is used with this entry because distal myopathy-4
read more(MPD4), also known as Williams distal myopathy, is caused by
heterozygous mutation in the FLNC gene (102565) on chromosome 7q32.

DESCRIPTION

Williams distal myopathy is an autosomal dominant slowly progressive
muscular disorder characterized by distal muscle weakness and atrophy
affecting the upper and lower limbs. Onset occurs around the third to
fourth decades of life, and patients remain ambulatory even after long
disease duration. Muscle biopsy shows nonspecific changes with no
evidence of rods, necrosis, or inflammation (summary by Duff et al.,
2011).

Mutation in the FLNC gene can also cause myofibrillar myopathy-5 (MFM5;
609524), which shows a different pattern of muscle involvement and
different histologic changes.

CLINICAL FEATURES

Williams et al. (2005) reported an Australian family in which at least
12 members had adult onset of a slowly progressive myopathy first
affecting the distal muscles of the hand and leg. Patients reported
insidious onset of muscle weakness before the fifth decade, with 5
having onset in their teenage years. There was a variable pattern of
muscle weakness at onset, including wasting of the small muscles of the
hand and weak grip strength or wasting of the posterior leg muscles.
There was also weakness of the forearm muscles and ankle plantar
flexors. Five had weakness of knee flexion, and 8 had weakness of hip
flexion, resulting in abnormal gait. Three had late onset of facial
muscle weakness. All reported muscle pain, which was worse after
exercise, and most had hyporeflexia in the lower limbs. None had
dysphagia, respiratory, or cardiac involvement, and all remained
ambulatory. Serum creatine kinase was normal or mildly elevated. Sensory
examination was normal. Muscle imaging in some patients was normal,
others with longstanding disease had atrophy and fatty replacement. The
anterior compartment of the legs was normal. Biopsy of 1 patient at age
75 years showed no dystrophic features, but did show some increased
fiber size variation and increased numbers of type 1 fibers. There were
no rimmed vacuoles and electron microscopy was normal. Linkage analysis
excluded known distal myopathy genes, and Williams et al. (2005)
concluded that the disorder in this family represented a novel type of
autosomal dominant distal myopathy.

Duff et al. (2011) provided follow-up of the family reported by Williams
et al. (2005), noting that disease most often started in the third
decade of life in the hands and was characterized by thenar muscle
weakness leading to reduced grip strength. This was followed by calf
muscle weakness beginning around the fourth decade of life and leading
to difficulties in running and jumping. Progression to proximal muscles
was evident in the fifth decade of life and usually required a stick for
walking by the sixth decade of life. Muscle biopsies showed a spectrum
of findings, such as fiber size variation and atrophy, but no necrosis,
vacuoles, inclusions, regeneration, or inflammation.

Duff et al. (2011) also reported an Italian family in which 4
individuals had a similar phenotype. Three living patients had onset of
reduced finger skills and running performance at about 30 years of age.
This was followed by slow progression to the proximal lower limb muscle
over the next 20 years, with atrophy of the hand muscles, inability to
squat, and use of a stick for walking by age 60. None had respiratory
features, but 2 of the 4 patients had cardiomyopathy. Muscle biopsies
were unremarkable and showed no protein aggregates.

INHERITANCE

The transmission pattern in the Australian family reported by Williams
et al. (2005) and the Italian family reported by Duff et al. (2011) was
consistent with autosomal dominant inheritance.

MOLECULAR GENETICS

By linkage analysis followed by candidate gene sequencing of the
Australian family with distal myopathy previously reported by Williams
et al. (2005), Duff et al. (2011) identified a heterozygous mutation in
the FLNC gene (M251T; 102565.0003). A different heterozygous mutation
(A193T; 102565.0004) was found in affected members of an Italian family
with the same phenotype and linkage to the same region of chromosome 7q.
Both mutations occurred in the actin-binding domain, and in vitro
cellular expression studies showed that both mutations resulted in
increased affinity for actin.

*FIELD* RF
1. Duff, R. M.; Tay, V.; Hackman, P.; Ravenscroft, G.; McLean, C.;
Kennedy, P.; Steinbach, A.; Schoffler, W.; van der Ven, P. F. M.;
Furst, D. O.; Song, J.; Djinovic-Carugo, K.; and 12 others: Mutations
in the N-terminal actin-binding domain of filamin C cause a distal
myopathy. Am. J. Hum. Genet. 88: 729-740, 2011.

2. Williams, D. R.; Reardon, K.; Roberts, L.; Dennet, X.; Duff, R.;
Laing, N. G.; Byrne, E.: A new dominant distal myopathy affecting
posterior leg and anterior upper limb muscles. Neurology 64: 1245-1254,
2005.

*FIELD* CS
INHERITANCE:
Autosomal dominant

CARDIOVASCULAR:
[Heart];
Cardiomyopathy (in 2 of 4 patients from 1 family)

MUSCLE, SOFT TISSUE:
Muscle weakness, distal upper and lower limbs;
Muscle atrophy, distal upper and lower limbs;
Calf muscle weakness;
Sparing of the anterior tibial compartment;
Decreased hand grip strength;
Forearm muscle weakness;
Weakness of ankle plantar flexion;
Weakness of hip flexors;
Decreased ability to run;
Inability to jump or squat;
Progression to proximal muscle weakness;
Imaging shows muscle atrophy and fatty replacement;
Muscle biopsy shows variation in fiber size;
Type 1 fiber predominance;
No rods;
No necrosis;
No dystrophic changes

NEUROLOGIC:
[Peripheral nervous system];
Hyporeflexia in the lower limbs

LABORATORY ABNORMALITIES:
Normal or mildly increased serum creatine kinase

MISCELLANEOUS:
Variable age at onset, mostly in third decade (range teenage years
to fourth decade);
Slowly progressive;
Patients remain ambulatory;
Two families have been reported (as of 6/2011)

MOLECULAR BASIS:
Caused by mutation in the filamin C gene (FLNC, 102565.0003)

*FIELD* CD
Cassandra L. Kniffin: 6/29/2011

*FIELD* ED
joanna: 07/26/2011
ckniffin: 6/29/2011

*FIELD* CD
Cassandra L. Kniffin: 6/29/2011

*FIELD* ED
terry: 07/05/2011
wwang: 7/1/2011
ckniffin: 6/29/2011