Full text data of HSPB8
HSPB8
(CRYAC, E2IG1, HSP22)
[Confidence: low (only semi-automatic identification from reviews)]
Heat shock protein beta-8; HspB8 (Alpha-crystallin C chain; E2-induced gene 1 protein; Protein kinase H11; Small stress protein-like protein HSP22)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Heat shock protein beta-8; HspB8 (Alpha-crystallin C chain; E2-induced gene 1 protein; Protein kinase H11; Small stress protein-like protein HSP22)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9UJY1
ID HSPB8_HUMAN Reviewed; 196 AA.
AC Q9UJY1; B2R6A6; Q6FIH3; Q9UKS3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Heat shock protein beta-8;
DE Short=HspB8;
DE AltName: Full=Alpha-crystallin C chain;
DE AltName: Full=E2-induced gene 1 protein;
DE AltName: Full=Protein kinase H11;
DE AltName: Full=Small stress protein-like protein HSP22;
GN Name=HSPB8; Synonyms=CRYAC, E2IG1, HSP22; ORFNames=PP1629;
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].
RX PubMed=11085516;
RA Charpentier A.H., Bednarek A.K., Daniel R.L., Hawkins K.A.,
RA Laflin K.J., Gaddis S., MacLeod M.C., Aldaz C.M.;
RT "Effects of estrogen on global gene expression: identification of
RT novel targets of estrogen action.";
RL Cancer Res. 60:5977-5983(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH HSPB1.
RX PubMed=11342557; DOI=10.1074/jbc.M103001200;
RA Benndorf R., Sun X., Gilmont R.R., Biederman K.J., Molloy M.P.,
RA Goodmurphy C.W., Cheng H., Andrews P.C., Welsh M.J.;
RT "HSP22, a new member of the small heat shock protein superfamily,
RT interacts with mimic of phosphorylated HSP27 (3DHSP27).";
RL J. Biol. Chem. 276:26753-26761(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Melanoma;
RX PubMed=10833516; DOI=10.1074/jbc.M002140200;
RA Smith C.C., Yu Y.X., Kulka M., Aurelian L.;
RT "A novel human gene similar to the protein kinase (PK) coding domain
RT of the large subunit of herpes simplex virus type 2 ribonucleotide
RT reductase (ICP10) codes for a serine-threonine PK and is expressed in
RT melanoma cells.";
RL J. Biol. Chem. 275:25690-25699(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PHOSPHORYLATION AT THR-63, AND MASS SPECTROMETRY.
RX PubMed=11816564; DOI=10.1021/ac0104227;
RA Molloy M.P., Andrews P.C.;
RT "Phosphopeptide derivatization signatures to identify serine and
RT threonine phosphorylated peptides by mass spectrometry.";
RL Anal. Chem. 73:5387-5394(2001).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=11470154;
RA Kappe G., Verschuure P., Philipsen R.L.A., Staalduinen A.A.,
RA Van de Boogaart P., Boelens W.C., de Jong W.W.;
RT "Characterization of two novel human small heat shock proteins:
RT protein kinase-related HspB8 and testis-specific HspB9.";
RL Biochim. Biophys. Acta 1520:1-6(2001).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=19464326; DOI=10.1016/j.bbamcr.2009.05.005;
RA Vos M.J., Kanon B., Kampinga H.H.;
RT "HSPB7 is a SC35 speckle resident small heat shock protein.";
RL Biochim. Biophys. Acta 1793:1343-1353(2009).
RN [16]
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 [17]
RP INTERACTION WITH DNAJB6.
RX PubMed=22366786; DOI=10.1038/ng.1103;
RA Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H.,
RA Screen M., McDonald K., Stajich J.M., Mahjneh I., Vihola A.,
RA Raheem O., Penttila S., Lehtinen S., Huovinen S., Palmio J., Tasca G.,
RA Ricci E., Hackman P., Hauser M., Katsanis N., Udd B.;
RT "Mutations affecting the cytoplasmic functions of the co-chaperone
RT DNAJB6 cause limb-girdle muscular dystrophy.";
RL Nat. Genet. 44:450-455(2012).
RN [18]
RP VARIANTS HMN2A GLU-141 AND ASN-141.
RX PubMed=15122253; DOI=10.1038/ng1328;
RA Irobi J., Van Impe K., Seeman P., Jordanova A., Dierick I.,
RA Verpoorten N., Michalik A., De Vriendt E., Jacobs A., Van Gerwen V.,
RA Vennekens K., Mazanec R., Tournev I., Hilton-Jones D., Talbot K.,
RA Kremensky I., Van Den Bosch L., Robberecht W., Van Vandekerckhove J.,
RA Broeckhoven C., Gettemans J., De Jonghe P., Timmerman V.;
RT "Hot-spot residue in small heat-shock protein 22 causes distal motor
RT neuropathy.";
RL Nat. Genet. 36:597-601(2004).
RN [19]
RP VARIANT CMT2L ASN-141.
RX PubMed=15565283; DOI=10.1007/s00439-004-1218-3;
RA Tang B.-S., Zhao G.-H., Luo W., Xia K., Cai F., Pan Q., Zhang R.-X.,
RA Zhang F.F., Liu X.-M., Chen B., Zhang C., Shen L., Jiang H.,
RA Long Z.G., Dai H.-P.;
RT "Small heat-shock protein 22 mutated in autosomal dominant Charcot-
RT Marie-Tooth disease type 2L.";
RL Hum. Genet. 116:222-224(2005).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-67 AND MET-78.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Displays temperature-dependent chaperone activity.
CC -!- SUBUNIT: Monomer. Interacts with HSPB1. Interacts with DNAJB6.
CC -!- INTERACTION:
CC Self; NbExp=6; IntAct=EBI-739074, EBI-739074;
CC P02511:CRYAB; NbExp=2; IntAct=EBI-739074, EBI-739060;
CC P04792:HSPB1; NbExp=3; IntAct=EBI-739074, EBI-352682;
CC Q16082:HSPB2; NbExp=3; IntAct=EBI-739074, EBI-739395;
CC O14558:HSPB6; NbExp=2; IntAct=EBI-739074, EBI-739095;
CC Q9UBY9:HSPB7; NbExp=5; IntAct=EBI-739074, EBI-739361;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to
CC nuclear foci during heat shock.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and
CC heart.
CC -!- INDUCTION: By 17-beta-estradiol.
CC -!- DISEASE: Neuronopathy, distal hereditary motor, 2A (HMN2A)
CC [MIM:158590]: A neuromuscular disorder. Distal hereditary motor
CC neuronopathies constitute a heterogeneous group of neuromuscular
CC disorders caused by selective degeneration of motor neurons in the
CC anterior horn of the spinal cord, without sensory deficit in the
CC posterior horn. The overall clinical picture consists of a
CC classical distal muscular atrophy syndrome in the legs without
CC clinical sensory loss. The disease starts with weakness and
CC wasting of distal muscles of the anterior tibial and peroneal
CC compartments of the legs. Later on, weakness and atrophy may
CC expand to the proximal muscles of the lower limbs and/or to the
CC distal upper limbs. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2L (CMT2L) [MIM:608673]: An
CC axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the
CC distal muscles of the arms. Charcot-Marie-Tooth disease is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies (designated CMT1 when they are dominantly inherited)
CC and primary peripheral axonal neuropathies (CMT2). Neuropathies of
CC the CMT2 group are characterized by signs of axonal degeneration
CC in the absence of obvious myelin alterations, normal or slightly
CC reduced nerve conduction velocities, and progressive distal muscle
CC weakness and atrophy. Nerve conduction velocities are normal or
CC slightly reduced. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small heat shock protein (HSP20)
CC family.
CC -!- CAUTION: Was reported (PubMed:10833516) to have a protein kinase
CC activity and to act as a Mn(2+)-dependent serine-threonine-
CC specific protein kinase.
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="http://www.molgen.ua.ac.be/CMTMutations/";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HSPB8";
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DR EMBL; AF191017; AAF09481.1; -; mRNA.
DR EMBL; AF250138; AAF65562.1; -; mRNA.
DR EMBL; AF133207; AAD55359.1; -; mRNA.
DR EMBL; AL136936; CAB66870.1; -; mRNA.
DR EMBL; AF217987; AAG17230.1; -; mRNA.
DR EMBL; BT006876; AAP35522.1; -; mRNA.
DR EMBL; CR533453; CAG38484.1; -; mRNA.
DR EMBL; AK312501; BAG35403.1; -; mRNA.
DR EMBL; CH471054; EAW98144.1; -; Genomic_DNA.
DR EMBL; BC002673; AAH02673.1; -; mRNA.
DR RefSeq; NP_055180.1; NM_014365.2.
DR UniGene; Hs.400095; -.
DR ProteinModelPortal; Q9UJY1; -.
DR SMR; Q9UJY1; 6-170.
DR IntAct; Q9UJY1; 10.
DR MINT; MINT-1456822; -.
DR STRING; 9606.ENSP00000281938; -.
DR PhosphoSite; Q9UJY1; -.
DR DMDM; 13431576; -.
DR PaxDb; Q9UJY1; -.
DR PRIDE; Q9UJY1; -.
DR DNASU; 26353; -.
DR Ensembl; ENST00000281938; ENSP00000281938; ENSG00000152137.
DR GeneID; 26353; -.
DR KEGG; hsa:26353; -.
DR UCSC; uc001txb.3; human.
DR CTD; 26353; -.
DR GeneCards; GC12P119616; -.
DR HGNC; HGNC:30171; HSPB8.
DR HPA; HPA015876; -.
DR MIM; 158590; phenotype.
DR MIM; 608014; gene.
DR MIM; 608673; phenotype.
DR neXtProt; NX_Q9UJY1; -.
DR Orphanet; 99945; Autosomal dominant Charcot-Marie-Tooth disease type 2L.
DR Orphanet; 139525; Distal hereditary motor neuropathy type 2.
DR PharmGKB; PA134900173; -.
DR eggNOG; NOG271659; -.
DR HOGENOM; HOG000233955; -.
DR HOVERGEN; HBG054766; -.
DR InParanoid; Q9UJY1; -.
DR KO; K08879; -.
DR OMA; PFGESSF; -.
DR OrthoDB; EOG7WHHBK; -.
DR PhylomeDB; Q9UJY1; -.
DR ChiTaRS; HSPB8; human.
DR GeneWiki; HSPB8; -.
DR GenomeRNAi; 26353; -.
DR NextBio; 48689; -.
DR PRO; PR:Q9UJY1; -.
DR Bgee; Q9UJY1; -.
DR CleanEx; HS_HSPB8; -.
DR Genevestigator; Q9UJY1; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0006950; P:response to stress; IEA:UniProtKB-KW.
DR InterPro; IPR002068; a-crystallin/Hsp20_dom.
DR InterPro; IPR001436; Alpha-crystallin/HSP.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR Pfam; PF00011; HSP20; 1.
DR PIRSF; PIRSF036514; Sm_HSP_B1; 1.
DR PRINTS; PR00299; ACRYSTALLIN.
DR SUPFAM; SSF49764; SSF49764; 1.
DR PROSITE; PS01031; HSP20; 1.
PE 1: Evidence at protein level;
KW Chaperone; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm;
KW Disease mutation; Neurodegeneration; Neuropathy; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Stress response.
FT CHAIN 1 196 Heat shock protein beta-8.
FT /FTId=PRO_0000125945.
FT MOD_RES 24 24 Phosphoserine.
FT MOD_RES 63 63 Phosphothreonine; by PKC; in vitro.
FT VARIANT 67 67 G -> S (in a glioblastoma multiforme
FT sample; somatic mutation).
FT /FTId=VAR_042244.
FT VARIANT 78 78 R -> M (in dbSNP:rs55826713).
FT /FTId=VAR_042245.
FT VARIANT 141 141 K -> E (in HMN2A; strengthen interaction
FT with HSPB1).
FT /FTId=VAR_018504.
FT VARIANT 141 141 K -> N (in HMN2A and CMT2L; strengthen
FT interaction with HSPB1).
FT /FTId=VAR_018505.
FT CONFLICT 51 51 W -> C (in Ref. 3; AAD55359).
SQ SEQUENCE 196 AA; 21604 MW; B76058CED52292CB CRC64;
MADGQMPFSC HYPSRLRRDP FRDSPLSSRL LDDGFGMDPF PDDLTASWPD WALPRLSSAW
PGTLRSGMVP RGPTATARFG VPAEGRTPPP FPGEPWKVCV NVHSFKPEEL MVKTKDGYVE
VSGKHEEKQQ EGGIVSKNFT KKIQLPAEVD PVTVFASLSP EGLLIIEAPQ VPPYSTFGES
SFNNELPQDS QEVTCT
//
ID HSPB8_HUMAN Reviewed; 196 AA.
AC Q9UJY1; B2R6A6; Q6FIH3; Q9UKS3;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-MAY-2000, sequence version 1.
DT 22-JAN-2014, entry version 130.
DE RecName: Full=Heat shock protein beta-8;
DE Short=HspB8;
DE AltName: Full=Alpha-crystallin C chain;
DE AltName: Full=E2-induced gene 1 protein;
DE AltName: Full=Protein kinase H11;
DE AltName: Full=Small stress protein-like protein HSP22;
GN Name=HSPB8; Synonyms=CRYAC, E2IG1, HSP22; ORFNames=PP1629;
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].
RX PubMed=11085516;
RA Charpentier A.H., Bednarek A.K., Daniel R.L., Hawkins K.A.,
RA Laflin K.J., Gaddis S., MacLeod M.C., Aldaz C.M.;
RT "Effects of estrogen on global gene expression: identification of
RT novel targets of estrogen action.";
RL Cancer Res. 60:5977-5983(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH HSPB1.
RX PubMed=11342557; DOI=10.1074/jbc.M103001200;
RA Benndorf R., Sun X., Gilmont R.R., Biederman K.J., Molloy M.P.,
RA Goodmurphy C.W., Cheng H., Andrews P.C., Welsh M.J.;
RT "HSP22, a new member of the small heat shock protein superfamily,
RT interacts with mimic of phosphorylated HSP27 (3DHSP27).";
RL J. Biol. Chem. 276:26753-26761(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Melanoma;
RX PubMed=10833516; DOI=10.1074/jbc.M002140200;
RA Smith C.C., Yu Y.X., Kulka M., Aurelian L.;
RT "A novel human gene similar to the protein kinase (PK) coding domain
RT of the large subunit of herpes simplex virus type 2 ribonucleotide
RT reductase (ICP10) codes for a serine-threonine PK and is expressed in
RT melanoma cells.";
RL J. Biol. Chem. 275:25690-25699(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=11230166; DOI=10.1101/gr.GR1547R;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thalamus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
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 [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP PHOSPHORYLATION AT THR-63, AND MASS SPECTROMETRY.
RX PubMed=11816564; DOI=10.1021/ac0104227;
RA Molloy M.P., Andrews P.C.;
RT "Phosphopeptide derivatization signatures to identify serine and
RT threonine phosphorylated peptides by mass spectrometry.";
RL Anal. Chem. 73:5387-5394(2001).
RN [12]
RP TISSUE SPECIFICITY.
RX PubMed=11470154;
RA Kappe G., Verschuure P., Philipsen R.L.A., Staalduinen A.A.,
RA Van de Boogaart P., Boelens W.C., de Jong W.W.;
RT "Characterization of two novel human small heat shock proteins:
RT protein kinase-related HspB8 and testis-specific HspB9.";
RL Biochim. Biophys. Acta 1520:1-6(2001).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-24, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP SUBCELLULAR LOCATION.
RX PubMed=19464326; DOI=10.1016/j.bbamcr.2009.05.005;
RA Vos M.J., Kanon B., Kampinga H.H.;
RT "HSPB7 is a SC35 speckle resident small heat shock protein.";
RL Biochim. Biophys. Acta 1793:1343-1353(2009).
RN [16]
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 [17]
RP INTERACTION WITH DNAJB6.
RX PubMed=22366786; DOI=10.1038/ng.1103;
RA Sarparanta J., Jonson P.H., Golzio C., Sandell S., Luque H.,
RA Screen M., McDonald K., Stajich J.M., Mahjneh I., Vihola A.,
RA Raheem O., Penttila S., Lehtinen S., Huovinen S., Palmio J., Tasca G.,
RA Ricci E., Hackman P., Hauser M., Katsanis N., Udd B.;
RT "Mutations affecting the cytoplasmic functions of the co-chaperone
RT DNAJB6 cause limb-girdle muscular dystrophy.";
RL Nat. Genet. 44:450-455(2012).
RN [18]
RP VARIANTS HMN2A GLU-141 AND ASN-141.
RX PubMed=15122253; DOI=10.1038/ng1328;
RA Irobi J., Van Impe K., Seeman P., Jordanova A., Dierick I.,
RA Verpoorten N., Michalik A., De Vriendt E., Jacobs A., Van Gerwen V.,
RA Vennekens K., Mazanec R., Tournev I., Hilton-Jones D., Talbot K.,
RA Kremensky I., Van Den Bosch L., Robberecht W., Van Vandekerckhove J.,
RA Broeckhoven C., Gettemans J., De Jonghe P., Timmerman V.;
RT "Hot-spot residue in small heat-shock protein 22 causes distal motor
RT neuropathy.";
RL Nat. Genet. 36:597-601(2004).
RN [19]
RP VARIANT CMT2L ASN-141.
RX PubMed=15565283; DOI=10.1007/s00439-004-1218-3;
RA Tang B.-S., Zhao G.-H., Luo W., Xia K., Cai F., Pan Q., Zhang R.-X.,
RA Zhang F.F., Liu X.-M., Chen B., Zhang C., Shen L., Jiang H.,
RA Long Z.G., Dai H.-P.;
RT "Small heat-shock protein 22 mutated in autosomal dominant Charcot-
RT Marie-Tooth disease type 2L.";
RL Hum. Genet. 116:222-224(2005).
RN [20]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-67 AND MET-78.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Displays temperature-dependent chaperone activity.
CC -!- SUBUNIT: Monomer. Interacts with HSPB1. Interacts with DNAJB6.
CC -!- INTERACTION:
CC Self; NbExp=6; IntAct=EBI-739074, EBI-739074;
CC P02511:CRYAB; NbExp=2; IntAct=EBI-739074, EBI-739060;
CC P04792:HSPB1; NbExp=3; IntAct=EBI-739074, EBI-352682;
CC Q16082:HSPB2; NbExp=3; IntAct=EBI-739074, EBI-739395;
CC O14558:HSPB6; NbExp=2; IntAct=EBI-739074, EBI-739095;
CC Q9UBY9:HSPB7; NbExp=5; IntAct=EBI-739074, EBI-739361;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Translocates to
CC nuclear foci during heat shock.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in skeletal muscle and
CC heart.
CC -!- INDUCTION: By 17-beta-estradiol.
CC -!- DISEASE: Neuronopathy, distal hereditary motor, 2A (HMN2A)
CC [MIM:158590]: A neuromuscular disorder. Distal hereditary motor
CC neuronopathies constitute a heterogeneous group of neuromuscular
CC disorders caused by selective degeneration of motor neurons in the
CC anterior horn of the spinal cord, without sensory deficit in the
CC posterior horn. The overall clinical picture consists of a
CC classical distal muscular atrophy syndrome in the legs without
CC clinical sensory loss. The disease starts with weakness and
CC wasting of distal muscles of the anterior tibial and peroneal
CC compartments of the legs. Later on, weakness and atrophy may
CC expand to the proximal muscles of the lower limbs and/or to the
CC distal upper limbs. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- DISEASE: Charcot-Marie-Tooth disease 2L (CMT2L) [MIM:608673]: An
CC axonal form of Charcot-Marie-Tooth disease, a disorder of the
CC peripheral nervous system, characterized by progressive weakness
CC and atrophy, initially of the peroneal muscles and later of the
CC distal muscles of the arms. Charcot-Marie-Tooth disease is
CC classified in two main groups on the basis of electrophysiologic
CC properties and histopathology: primary peripheral demyelinating
CC neuropathies (designated CMT1 when they are dominantly inherited)
CC and primary peripheral axonal neuropathies (CMT2). Neuropathies of
CC the CMT2 group are characterized by signs of axonal degeneration
CC in the absence of obvious myelin alterations, normal or slightly
CC reduced nerve conduction velocities, and progressive distal muscle
CC weakness and atrophy. Nerve conduction velocities are normal or
CC slightly reduced. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the small heat shock protein (HSP20)
CC family.
CC -!- CAUTION: Was reported (PubMed:10833516) to have a protein kinase
CC activity and to act as a Mn(2+)-dependent serine-threonine-
CC specific protein kinase.
CC -!- WEB RESOURCE: Name=Inherited peripheral neuropathies mutation db;
CC URL="http://www.molgen.ua.ac.be/CMTMutations/";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HSPB8";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF191017; AAF09481.1; -; mRNA.
DR EMBL; AF250138; AAF65562.1; -; mRNA.
DR EMBL; AF133207; AAD55359.1; -; mRNA.
DR EMBL; AL136936; CAB66870.1; -; mRNA.
DR EMBL; AF217987; AAG17230.1; -; mRNA.
DR EMBL; BT006876; AAP35522.1; -; mRNA.
DR EMBL; CR533453; CAG38484.1; -; mRNA.
DR EMBL; AK312501; BAG35403.1; -; mRNA.
DR EMBL; CH471054; EAW98144.1; -; Genomic_DNA.
DR EMBL; BC002673; AAH02673.1; -; mRNA.
DR RefSeq; NP_055180.1; NM_014365.2.
DR UniGene; Hs.400095; -.
DR ProteinModelPortal; Q9UJY1; -.
DR SMR; Q9UJY1; 6-170.
DR IntAct; Q9UJY1; 10.
DR MINT; MINT-1456822; -.
DR STRING; 9606.ENSP00000281938; -.
DR PhosphoSite; Q9UJY1; -.
DR DMDM; 13431576; -.
DR PaxDb; Q9UJY1; -.
DR PRIDE; Q9UJY1; -.
DR DNASU; 26353; -.
DR Ensembl; ENST00000281938; ENSP00000281938; ENSG00000152137.
DR GeneID; 26353; -.
DR KEGG; hsa:26353; -.
DR UCSC; uc001txb.3; human.
DR CTD; 26353; -.
DR GeneCards; GC12P119616; -.
DR HGNC; HGNC:30171; HSPB8.
DR HPA; HPA015876; -.
DR MIM; 158590; phenotype.
DR MIM; 608014; gene.
DR MIM; 608673; phenotype.
DR neXtProt; NX_Q9UJY1; -.
DR Orphanet; 99945; Autosomal dominant Charcot-Marie-Tooth disease type 2L.
DR Orphanet; 139525; Distal hereditary motor neuropathy type 2.
DR PharmGKB; PA134900173; -.
DR eggNOG; NOG271659; -.
DR HOGENOM; HOG000233955; -.
DR HOVERGEN; HBG054766; -.
DR InParanoid; Q9UJY1; -.
DR KO; K08879; -.
DR OMA; PFGESSF; -.
DR OrthoDB; EOG7WHHBK; -.
DR PhylomeDB; Q9UJY1; -.
DR ChiTaRS; HSPB8; human.
DR GeneWiki; HSPB8; -.
DR GenomeRNAi; 26353; -.
DR NextBio; 48689; -.
DR PRO; PR:Q9UJY1; -.
DR Bgee; Q9UJY1; -.
DR CleanEx; HS_HSPB8; -.
DR Genevestigator; Q9UJY1; -.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008219; P:cell death; IEA:UniProtKB-KW.
DR GO; GO:0006950; P:response to stress; IEA:UniProtKB-KW.
DR InterPro; IPR002068; a-crystallin/Hsp20_dom.
DR InterPro; IPR001436; Alpha-crystallin/HSP.
DR InterPro; IPR008978; HSP20-like_chaperone.
DR Pfam; PF00011; HSP20; 1.
DR PIRSF; PIRSF036514; Sm_HSP_B1; 1.
DR PRINTS; PR00299; ACRYSTALLIN.
DR SUPFAM; SSF49764; SSF49764; 1.
DR PROSITE; PS01031; HSP20; 1.
PE 1: Evidence at protein level;
KW Chaperone; Charcot-Marie-Tooth disease; Complete proteome; Cytoplasm;
KW Disease mutation; Neurodegeneration; Neuropathy; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Stress response.
FT CHAIN 1 196 Heat shock protein beta-8.
FT /FTId=PRO_0000125945.
FT MOD_RES 24 24 Phosphoserine.
FT MOD_RES 63 63 Phosphothreonine; by PKC; in vitro.
FT VARIANT 67 67 G -> S (in a glioblastoma multiforme
FT sample; somatic mutation).
FT /FTId=VAR_042244.
FT VARIANT 78 78 R -> M (in dbSNP:rs55826713).
FT /FTId=VAR_042245.
FT VARIANT 141 141 K -> E (in HMN2A; strengthen interaction
FT with HSPB1).
FT /FTId=VAR_018504.
FT VARIANT 141 141 K -> N (in HMN2A and CMT2L; strengthen
FT interaction with HSPB1).
FT /FTId=VAR_018505.
FT CONFLICT 51 51 W -> C (in Ref. 3; AAD55359).
SQ SEQUENCE 196 AA; 21604 MW; B76058CED52292CB CRC64;
MADGQMPFSC HYPSRLRRDP FRDSPLSSRL LDDGFGMDPF PDDLTASWPD WALPRLSSAW
PGTLRSGMVP RGPTATARFG VPAEGRTPPP FPGEPWKVCV NVHSFKPEEL MVKTKDGYVE
VSGKHEEKQQ EGGIVSKNFT KKIQLPAEVD PVTVFASLSP EGLLIIEAPQ VPPYSTFGES
SFNNELPQDS QEVTCT
//
MIM
158590
*RECORD*
*FIELD* NO
158590
*FIELD* TI
#158590 NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA; HMN2A
;;HMN IIA;;
NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA; DHMN2A;;
read moreSPINAL MUSCULAR ATROPHY, DISTAL, ADULT, AUTOSOMAL DOMINANT, IIA;;
CHARCOT-MARIE-TOOTH DISEASE, SPINAL, IIA
*FIELD* TX
A number sign (#) is used with this entry because distal hereditary
motor neuronopathy type IIA (dHMN2A or HMN2A) is caused by heterozygous
mutation in the gene encoding heat-shock 22-kD protein-8 (HSPB8; 608014)
on chromosome 12q24. Charcot-Marie-Tooth disease type 2L (CMT2L; 608673)
is an allelic disorder with an overlapping phenotype.
For a general phenotypic description and a discussion of genetic
heterogeneity of distal HMN, see HMN type I (HMN1; 182960).
CLINICAL FEATURES
Nelson and Amick (1966) reported a family in which 6 members had
insidious onset and gradual progression of symmetrical distal atrophy
and weakness of the extremities associated with hyporeflexia. Age at
onset ranged from 20 to 40 years and the inheritance appeared to be
autosomal dominant. The lack of sensory changes and normal motor nerve
conduction velocities distinguished the disorder from peroneal muscular
atrophy. Progression was slow, so that affected persons survived until
at least middle life.
D'Alessandro et al. (1982) described a 59-year-old father and
20-year-old son with a distal form of spinal muscular atrophy. EMG and
muscle biopsy confirmed motor neuron disease in both. Muscle cramps were
the only symptom. The disorder was associated with hypertrophy of the
calves. The father-to-son transmission excluded Kennedy disease
(313200), an X-linked disorder, unless the mother was a heterozygous
carrier. No comment on consanguinity was made. Groen et al. (1993)
described a family in which a 26-year-old man had typical signs of
distal spinal muscular atrophy accompanied by atrophic muscles of the
lower leg, whereas the father and sister had the picture of benign
spinal muscular atrophy with hypertrophy of the calves as described by
D'Alessandro et al. (1982).
Timmerman et al. (1992) described a kindred in which many members in 6
generations were affected with what the authors labeled autosomal
dominant distal hereditary motor neuropathy type II. Age at onset,
determined for 11 patients, ranged from 14 to 35 years with a mean age
at onset of 21.6 +/- 6.0 years. The first clinical symptoms appeared
with a weakness of the extensor hallux longus muscle. Over the next 10
years, the disease progressed to complete paralysis and atrophy of all
distal leg muscles with some weakness of the thigh muscles. The distal
arm muscles were also affected but weakness was less pronounced. In a
few elderly patients, vibratory sense was impaired but no other sensory
losses were noted. Deep tendon reflexes were preserved but were
sometimes diminished or even absent in the legs. Some of the older
patients needed walking-aids or were wheelchair-bound. Motor and sensory
nerve conduction velocities were normal. Chronic neurogenic alterations
were demonstrated by electromyography. Linkage studies with markers on
1q, 5q, 17p, and 19q, excluded Charcot-Marie-Tooth disease type I
(118220; 118200) and autosomal recessive SMA.
Jansen et al. (1986) reported an autosomal dominant scapulohumeral form
of SMA beginning between the end of the fourth and the sixth decade and
showing rapid progression without evidence of corticospinal tract
dysfunction. Death from respiratory failure occurred within 2 years of
onset. Jansen et al. (1986) thought that this entity was separate from
amyotrophic lateral sclerosis (ALS; 105400).
MAPPING
Timmerman et al. (1996) performed additional clinical and genetic study
of a 6-generation family reported by Timmerman et al. (1992). Data
obtained from a genomewide search of polymorphic markers revealed
significant linkage with D12S86 and dHMN2. To refine the location of the
gene, they analyzed an additional 5 (CA)n dinucleotide repeat markers.
Based on informative recombinants, the candidate region for the dHMN2
gene comprised a region of 13 cM and approximately 5 Mb between the
markers D12S86 and D12S340 on chromosome 12q24.
Irobi et al. (2000) constructed a clone contig map of the critical 13-cM
interval on 12q24.3 where the distal HMN2 gene is located.
MOLECULAR GENETICS
In affected members of 4 families with dHMN2, Irobi et al. (2004)
identified heterozygous mutations in the same codon of the HSPB8 gene
(608014.0001-608014.0002). One of the families had previously been
reported by Timmerman et al. (1992).
Irobi et al. (2010) compared the effect of mutant HSPB8 in primary
neuronal and glial cell cultures. In motor neurons, expression of both
HSPB8 K141N (608014.0001) and K141E (608014.0002) mutations resulted in
neurite degeneration, as manifested by a reduction in number of neurites
per cell, as well as in a reduction in average length of the neurites.
Expression of the K141E, and to a lesser extent the K141N, mutation also
induced spheroids in the neurites. There were no signs of apoptosis in
motor neurons, showing that mutant HSPB8 resulted in neurite
degeneration without inducing neuronal death. While overt in motor
neurons, these phenotypes were only very mildly present in sensory
neurons and completely absent in cortical neurons and glial cells.
- Reviews
Irobi et al. (2004) reviewed the molecular genetics of the distal motor
neuropathies.
*FIELD* RF
1. D'Alessandro, R.; Montagna, P.; Govoni, E.; Pazzaglia, P.: Benign
familial spinal muscular atrophy with hypertrophy of the calves. Arch.
Neurol. 39: 657-660, 1982.
2. Groen, R. J. M.; Sie, O. G.; van Weerden, T. W.: Dominant inherited
distal spinal muscular atrophy with atrophic and hypertrophic calves. J.
Neurol. Sci. 114: 81-84, 1993.
3. Irobi, J.; Almeida-Souza, L.; Asselbergh, B.; De Winter, V.; Goethals,
S.; Dierick, I.; Krishnan, J.; Timmermans, J.-P.; Robberecht, W.;
De Jonghe, P.; Van Den Bosch, L.; Janssens, S.; Timmerman, V.: Mutant
HSPB8 causes motor neuron-specific neurite degeneration. Hum. Molec.
Genet. 19: 3254-3265, 2010.
4. Irobi, J.; De Jonghe, P.; Timmerman, V.: Molecular genetics of
distal hereditary motor neuropathies. Hum. Molec. Genet. 13: R195-R202,
2004.
5. Irobi, J.; Tissir, F.; De Jonghe, P.; De Vriendt, E.; Van Broeckhoven,
C.; Timmerman, V.; Beuten, J.: A clone contig of 12q24.3 encompassing
the distal hereditary motor neuropathy type II gene. Genomics 65:
34-43, 2000.
6. Irobi, J.; Van Impe, K.; Seeman, P.; Jordanova, A.; Dierick, I,.;
Verpoorten, N.; Michalik, A.; De Vriendt, E.; Jacobs, A.; Van Gerwen,
V.; Vennekens, K.; Mazanec, R.; and 11 others: Hot-spot residue
in small heat-shock protein 22 causes distal motor neuropathy. Nature
Genet. 36: 597-601, 2004.
7. Jansen, P. H. P.; Joosten, E. M. G.; Jaspar, H. H. J.; Vingerhoets,
H. M.: A rapidly progressive autosomal dominant scapulohumeral form
of spinal muscular atrophy. Ann. Neurol. 20: 538-540, 1986.
8. Nelson, J. W.; Amick, L. D.: Heredofamilial progressive spinal
muscular atrophy: a clinical and electromyographic study of a kinship.
(Abstract) Neurology 16: 306 only, 1966.
9. Timmerman, V.; De Jonghe, P.; Simokovic, S.; Lofgren, A.; Beuten,
J.; Nelis, E.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.:
Distal hereditary motor neuropathy type II (distal HMN II): mapping
of a locus to chromosome 12q24. Hum. Molec. Genet. 5: 1065-1069,
1996.
10. Timmerman, V.; Raeymaekers, P.; Nelis, E.; De Jonghe, P.; Muylle,
L.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.: Linkage analysis
of distal hereditary motor neuropathy type II (distal HMN II) in a
single pedigree. J. Neurol. Sci. 109: 41-48, 1992.
*FIELD* CS
INHERITANCE:
Autosomal dominant
NEUROLOGIC:
[Central nervous system];
Paresis of extensor muscles of the big toe is presenting symptom;
Muscle weakness, distal (lower limbs more affected than upper limbs),
due to motor neuronopathy;
Progression to paralysis and atrophy of distal lower limb muscles;
EMG shows neurogenic abnormalities;
Hyporeflexia of lower limbs;
Areflexia of lower limbs;
No sensory deficit
MISCELLANEOUS:
Mean age of onset 21 years (range 14-35 years);
Rapid disease progression;
Charcot-Marie-Tooth disease type 2L (CMT2L, 608673) is an allelic
disorder with an overlapping phenotype;
See also HMN2B (608634)
MOLECULAR BASIS:
Caused by mutation in the heat-shock 22-kD protein 8 gene (HSPB8,
608014.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 5/3/2004
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
ckniffin: 03/16/2007
joanna: 4/18/2005
ckniffin: 5/3/2004
ckniffin: 3/29/2004
*FIELD* CN
George E. Tiller - updated: 9/17/2013
George E. Tiller - updated: 4/5/2007
Cassandra L. Kniffin - updated: 5/3/2004
Cassandra L. Kniffin - reorganized: 3/31/2004
Cassandra L. Kniffin - updated: 3/29/2004
Victor A. McKusick - updated: 9/28/2000
Moyra Smith - updated: 8/26/1996
*FIELD* CD
Victor A. McKusick: 12/15/1986
*FIELD* ED
carol: 12/20/2013
alopez: 9/17/2013
wwang: 4/29/2010
ckniffin: 4/23/2010
terry: 4/5/2007
carol: 3/16/2007
ckniffin: 3/16/2007
ckniffin: 3/13/2007
alopez: 5/28/2004
tkritzer: 5/4/2004
ckniffin: 5/3/2004
ckniffin: 3/31/2004
carol: 3/31/2004
ckniffin: 3/31/2004
ckniffin: 3/29/2004
joanna: 3/18/2004
tkritzer: 2/17/2004
carol: 6/13/2001
terry: 9/28/2000
dkim: 12/10/1998
terry: 7/31/1998
mark: 8/26/1996
marlene: 8/22/1996
mark: 10/31/1995
mimadm: 11/6/1994
carol: 7/14/1993
carol: 3/11/1993
carol: 6/25/1992
carol: 6/23/1992
*RECORD*
*FIELD* NO
158590
*FIELD* TI
#158590 NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA; HMN2A
;;HMN IIA;;
NEUROPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA; DHMN2A;;
read moreSPINAL MUSCULAR ATROPHY, DISTAL, ADULT, AUTOSOMAL DOMINANT, IIA;;
CHARCOT-MARIE-TOOTH DISEASE, SPINAL, IIA
*FIELD* TX
A number sign (#) is used with this entry because distal hereditary
motor neuronopathy type IIA (dHMN2A or HMN2A) is caused by heterozygous
mutation in the gene encoding heat-shock 22-kD protein-8 (HSPB8; 608014)
on chromosome 12q24. Charcot-Marie-Tooth disease type 2L (CMT2L; 608673)
is an allelic disorder with an overlapping phenotype.
For a general phenotypic description and a discussion of genetic
heterogeneity of distal HMN, see HMN type I (HMN1; 182960).
CLINICAL FEATURES
Nelson and Amick (1966) reported a family in which 6 members had
insidious onset and gradual progression of symmetrical distal atrophy
and weakness of the extremities associated with hyporeflexia. Age at
onset ranged from 20 to 40 years and the inheritance appeared to be
autosomal dominant. The lack of sensory changes and normal motor nerve
conduction velocities distinguished the disorder from peroneal muscular
atrophy. Progression was slow, so that affected persons survived until
at least middle life.
D'Alessandro et al. (1982) described a 59-year-old father and
20-year-old son with a distal form of spinal muscular atrophy. EMG and
muscle biopsy confirmed motor neuron disease in both. Muscle cramps were
the only symptom. The disorder was associated with hypertrophy of the
calves. The father-to-son transmission excluded Kennedy disease
(313200), an X-linked disorder, unless the mother was a heterozygous
carrier. No comment on consanguinity was made. Groen et al. (1993)
described a family in which a 26-year-old man had typical signs of
distal spinal muscular atrophy accompanied by atrophic muscles of the
lower leg, whereas the father and sister had the picture of benign
spinal muscular atrophy with hypertrophy of the calves as described by
D'Alessandro et al. (1982).
Timmerman et al. (1992) described a kindred in which many members in 6
generations were affected with what the authors labeled autosomal
dominant distal hereditary motor neuropathy type II. Age at onset,
determined for 11 patients, ranged from 14 to 35 years with a mean age
at onset of 21.6 +/- 6.0 years. The first clinical symptoms appeared
with a weakness of the extensor hallux longus muscle. Over the next 10
years, the disease progressed to complete paralysis and atrophy of all
distal leg muscles with some weakness of the thigh muscles. The distal
arm muscles were also affected but weakness was less pronounced. In a
few elderly patients, vibratory sense was impaired but no other sensory
losses were noted. Deep tendon reflexes were preserved but were
sometimes diminished or even absent in the legs. Some of the older
patients needed walking-aids or were wheelchair-bound. Motor and sensory
nerve conduction velocities were normal. Chronic neurogenic alterations
were demonstrated by electromyography. Linkage studies with markers on
1q, 5q, 17p, and 19q, excluded Charcot-Marie-Tooth disease type I
(118220; 118200) and autosomal recessive SMA.
Jansen et al. (1986) reported an autosomal dominant scapulohumeral form
of SMA beginning between the end of the fourth and the sixth decade and
showing rapid progression without evidence of corticospinal tract
dysfunction. Death from respiratory failure occurred within 2 years of
onset. Jansen et al. (1986) thought that this entity was separate from
amyotrophic lateral sclerosis (ALS; 105400).
MAPPING
Timmerman et al. (1996) performed additional clinical and genetic study
of a 6-generation family reported by Timmerman et al. (1992). Data
obtained from a genomewide search of polymorphic markers revealed
significant linkage with D12S86 and dHMN2. To refine the location of the
gene, they analyzed an additional 5 (CA)n dinucleotide repeat markers.
Based on informative recombinants, the candidate region for the dHMN2
gene comprised a region of 13 cM and approximately 5 Mb between the
markers D12S86 and D12S340 on chromosome 12q24.
Irobi et al. (2000) constructed a clone contig map of the critical 13-cM
interval on 12q24.3 where the distal HMN2 gene is located.
MOLECULAR GENETICS
In affected members of 4 families with dHMN2, Irobi et al. (2004)
identified heterozygous mutations in the same codon of the HSPB8 gene
(608014.0001-608014.0002). One of the families had previously been
reported by Timmerman et al. (1992).
Irobi et al. (2010) compared the effect of mutant HSPB8 in primary
neuronal and glial cell cultures. In motor neurons, expression of both
HSPB8 K141N (608014.0001) and K141E (608014.0002) mutations resulted in
neurite degeneration, as manifested by a reduction in number of neurites
per cell, as well as in a reduction in average length of the neurites.
Expression of the K141E, and to a lesser extent the K141N, mutation also
induced spheroids in the neurites. There were no signs of apoptosis in
motor neurons, showing that mutant HSPB8 resulted in neurite
degeneration without inducing neuronal death. While overt in motor
neurons, these phenotypes were only very mildly present in sensory
neurons and completely absent in cortical neurons and glial cells.
- Reviews
Irobi et al. (2004) reviewed the molecular genetics of the distal motor
neuropathies.
*FIELD* RF
1. D'Alessandro, R.; Montagna, P.; Govoni, E.; Pazzaglia, P.: Benign
familial spinal muscular atrophy with hypertrophy of the calves. Arch.
Neurol. 39: 657-660, 1982.
2. Groen, R. J. M.; Sie, O. G.; van Weerden, T. W.: Dominant inherited
distal spinal muscular atrophy with atrophic and hypertrophic calves. J.
Neurol. Sci. 114: 81-84, 1993.
3. Irobi, J.; Almeida-Souza, L.; Asselbergh, B.; De Winter, V.; Goethals,
S.; Dierick, I.; Krishnan, J.; Timmermans, J.-P.; Robberecht, W.;
De Jonghe, P.; Van Den Bosch, L.; Janssens, S.; Timmerman, V.: Mutant
HSPB8 causes motor neuron-specific neurite degeneration. Hum. Molec.
Genet. 19: 3254-3265, 2010.
4. Irobi, J.; De Jonghe, P.; Timmerman, V.: Molecular genetics of
distal hereditary motor neuropathies. Hum. Molec. Genet. 13: R195-R202,
2004.
5. Irobi, J.; Tissir, F.; De Jonghe, P.; De Vriendt, E.; Van Broeckhoven,
C.; Timmerman, V.; Beuten, J.: A clone contig of 12q24.3 encompassing
the distal hereditary motor neuropathy type II gene. Genomics 65:
34-43, 2000.
6. Irobi, J.; Van Impe, K.; Seeman, P.; Jordanova, A.; Dierick, I,.;
Verpoorten, N.; Michalik, A.; De Vriendt, E.; Jacobs, A.; Van Gerwen,
V.; Vennekens, K.; Mazanec, R.; and 11 others: Hot-spot residue
in small heat-shock protein 22 causes distal motor neuropathy. Nature
Genet. 36: 597-601, 2004.
7. Jansen, P. H. P.; Joosten, E. M. G.; Jaspar, H. H. J.; Vingerhoets,
H. M.: A rapidly progressive autosomal dominant scapulohumeral form
of spinal muscular atrophy. Ann. Neurol. 20: 538-540, 1986.
8. Nelson, J. W.; Amick, L. D.: Heredofamilial progressive spinal
muscular atrophy: a clinical and electromyographic study of a kinship.
(Abstract) Neurology 16: 306 only, 1966.
9. Timmerman, V.; De Jonghe, P.; Simokovic, S.; Lofgren, A.; Beuten,
J.; Nelis, E.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.:
Distal hereditary motor neuropathy type II (distal HMN II): mapping
of a locus to chromosome 12q24. Hum. Molec. Genet. 5: 1065-1069,
1996.
10. Timmerman, V.; Raeymaekers, P.; Nelis, E.; De Jonghe, P.; Muylle,
L.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.: Linkage analysis
of distal hereditary motor neuropathy type II (distal HMN II) in a
single pedigree. J. Neurol. Sci. 109: 41-48, 1992.
*FIELD* CS
INHERITANCE:
Autosomal dominant
NEUROLOGIC:
[Central nervous system];
Paresis of extensor muscles of the big toe is presenting symptom;
Muscle weakness, distal (lower limbs more affected than upper limbs),
due to motor neuronopathy;
Progression to paralysis and atrophy of distal lower limb muscles;
EMG shows neurogenic abnormalities;
Hyporeflexia of lower limbs;
Areflexia of lower limbs;
No sensory deficit
MISCELLANEOUS:
Mean age of onset 21 years (range 14-35 years);
Rapid disease progression;
Charcot-Marie-Tooth disease type 2L (CMT2L, 608673) is an allelic
disorder with an overlapping phenotype;
See also HMN2B (608634)
MOLECULAR BASIS:
Caused by mutation in the heat-shock 22-kD protein 8 gene (HSPB8,
608014.0001)
*FIELD* CN
Cassandra L. Kniffin - updated: 5/3/2004
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
ckniffin: 03/16/2007
joanna: 4/18/2005
ckniffin: 5/3/2004
ckniffin: 3/29/2004
*FIELD* CN
George E. Tiller - updated: 9/17/2013
George E. Tiller - updated: 4/5/2007
Cassandra L. Kniffin - updated: 5/3/2004
Cassandra L. Kniffin - reorganized: 3/31/2004
Cassandra L. Kniffin - updated: 3/29/2004
Victor A. McKusick - updated: 9/28/2000
Moyra Smith - updated: 8/26/1996
*FIELD* CD
Victor A. McKusick: 12/15/1986
*FIELD* ED
carol: 12/20/2013
alopez: 9/17/2013
wwang: 4/29/2010
ckniffin: 4/23/2010
terry: 4/5/2007
carol: 3/16/2007
ckniffin: 3/16/2007
ckniffin: 3/13/2007
alopez: 5/28/2004
tkritzer: 5/4/2004
ckniffin: 5/3/2004
ckniffin: 3/31/2004
carol: 3/31/2004
ckniffin: 3/31/2004
ckniffin: 3/29/2004
joanna: 3/18/2004
tkritzer: 2/17/2004
carol: 6/13/2001
terry: 9/28/2000
dkim: 12/10/1998
terry: 7/31/1998
mark: 8/26/1996
marlene: 8/22/1996
mark: 10/31/1995
mimadm: 11/6/1994
carol: 7/14/1993
carol: 3/11/1993
carol: 6/25/1992
carol: 6/23/1992
MIM
608014
*RECORD*
*FIELD* NO
608014
*FIELD* TI
*608014 HEAT-SHOCK 22-KD PROTEIN 8; HSPB8
;;HSP22;;
PROTEIN KINASE H11; H11;;
E2-INDUCED GENE 1; E2IG1;;
read moreHEAT-SHOCK 27-KD PROTEIN 8
*FIELD* TX
CLONING
To identify genes that are regulated by or associated with estrogen
action, Charpentier et al. (2000) performed serial analysis of gene
expression (SAGE) on estrogen-responsive breast cancer cells after
exposure to estrogen. Using transcript-specific PCR primers for novel
sequences that increased more than 10-fold upon treatment with 17-beta
estradiol (E2), they cloned 5 cDNAs, designated E2-induced genes (E2IG)
1-5, from a human placenta cDNA library. The E2IG1 cDNA encodes a
deduced 196-amino acid protein that contains a central portion
homologous to a highly conserved HSP-alpha crystallin domain common to
all HSP20 family members. It shows 54% sequence homology to HSP27
(602195), suggesting that it is a member of the small HSP family.
By searching an EST database for sequences containing the
alpha-crystallin domain characteristic of small heat-shock proteins,
followed by PCR of a placenta cDNA library, Kappe et al. (2001) cloned
HSPB8. Northern blot analysis detected broad expression of a 2.2-kb
transcript, with highest abundance in skeletal muscle, heart, and
placenta. Expression of HSPB8 was intermediate in several other tissues,
but it was not detected in blood.
GENE STRUCTURE
Kappe et al. (2001) determined that the HSPB8 gene contains at least 3
exons.
MAPPING
By sequence analysis, Charpentier et al. (2000) mapped the E2IG1 gene to
chromosome 12 between markers D12S366 and D12S340.
GENE FUNCTION
Carra et al. (2005) investigated the capacity of HSPB8 to prevent
protein aggregation in cells using Htt (613004) protein containing 43
glutamine residues (Htt43Q) as a model. In control conditions, Htt43Q
accumulated in perinuclear inclusions composed of SDS-insoluble
aggregates. In most cells, cotransfection with HSPB8 blocked inclusion
formation. Biochemical analyses indicated that HSPB8 inhibited the
accumulation of insoluble Htt43Q as efficiently as HSP40 (DNAJB1;
604572), which was taken as a positive control. Htt43Q then accumulated
in the SDS-soluble fraction, provided that protein degradation was
blocked by proteasome and autophagy inhibitors. In contrast, HSPB1
(602195) and alpha-B-crystallin (CRYAB; 123590) had no effect. Analyses
of HSPB1/HSPB8 chimeric proteins indicated that the C-terminal domain of
HSPB8 contains the specific sequence necessary for chaperone activity.
The K141N mutation (608014.0001) significantly reduced the chaperone
activity of the protein. Carra et al. (2005) hypothesized that a
decrease in HSPB8 chaperone activity may contribute to the development
of some neuropathies.
MOLECULAR GENETICS
In affected members of 4 families with autosomal dominant distal
hereditary motor neuronopathy type IIA (dHMN2A; 158590), Irobi et al.
(2004) identified heterozygous mutations in the same codon of the HSPB8
gene (608104.0001-608014.0002).
Benndorf and Welsh (2004) reviewed the role of heat-shock proteins in
neuromuscular function, as indicated by the association of mutations in
2 of these genes, HSP22 and HSP27, with human neuromuscular disorders.
In affected members of a Chinese family with axonal Charcot-Marie-Tooth
disease type 2L (608673), Tang et al. (2005) identified a mutation in
the HSPB8 gene (608014.0003).
Irobi et al. (2010) compared the effect of mutant HSPB8 in primary
neuronal and glial cell cultures. In motor neurons, expression of both
HSPB8 K141N (608014.0001) and K141E (608014.0002) mutations resulted in
neurite degeneration, as manifested by a reduction in number of neurites
per cell, as well as in a reduction in average length of the neurites.
Expression of the K141E, and to a lesser extent the K141N, mutation also
induced spheroids in the neurites. There were no signs of apoptosis in
motor neurons, showing that mutant HSPB8 resulted in neurite
degeneration without inducing neuronal death. While overt in motor
neurons, these phenotypes were only very mildly present in sensory
neurons and completely absent in cortical neurons and glial cells.
*FIELD* AV
.0001
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA
HSPB8, 423G-C, LYS141ASN
In affected members of a Belgian family with autosomal dominant distal
hereditary motor neuronopathy type II (158590) previously reported by
Timmerman et al. (1992), and in affected members of a large Czech family
with dHMN2, Irobi et al. (2004) identified a heterozygous 423G-C
transversion in exon 2 of the HSPB8 gene, resulting in a lys141-to-asn
(K141N) substitution. The mutation cosegregated with the disease in both
families. The K141N mutation affects a highly conserved residue in the
central alpha-crystallin domain of the protein. Normally, HSPB8
interacts with HSPB1 (602195). Expression studies of the K141N mutant
protein in COS cells showed an increased interaction between HSPB8 and
HSPB1, leading to the formation of intracellular aggregates. A different
mutation in the same codon was identified in 2 other families with dHMN2
(608014.0002).
.0002
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA
HSPB8, LYS141GLU
In affected members of an English family and a Bulgarian family with
distal hereditary motor neuronopathy type II (158590), Irobi et al.
(2004) identified a heterozygous 421A-G transition in exon 2 of the
HSPB8 gene, resulting in a lys141-to-glu (K141E) substitution. The
mutation cosegregated with the disease in both families. The K141E
mutation affects a highly conserved residue in the central
alpha-crystallin domain of the protein. Normally, HSPB8 interacts with
HSPB1 (602195). Expression studies of the mutant K141E protein in COS
cells showed an increased interaction between HSPB8 and HSPB1, leading
to the formation of intracellular aggregates. A different mutation in
the same codon was identified in 2 other families with dHMN2
(608014.0001).
.0003
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2L
HSPB8, 423G-T, LYS141ASN
In affected members of a large Chinese family with axonal
Charcot-Marie-Tooth disease type 2L (608673) in which Tang et al. (2004)
assigned the underlying locus to 12q24, Tang et al. (2005) identified a
423G-T transversion in exon 2 of the HSPB8 gene, resulting in a
lys141-to-asn (K141N) substitution.
*FIELD* RF
1. Benndorf, R.; Welsh, M. J.: Shocking degeneration. Nature Genet. 36:
547-548, 2004.
2. Carra, S.; Sivilotti, M.; Chavez Zobel, A. T.; Lambert, H.; Landry,
J.: HspB8, a small heat shock protein mutated in human neuromuscular
disorders, has in vivo chaperone activity in cultured cells. Hum.
Molec. Genet. 14: 1659-1669, 2005.
3. Charpentier, A. H.; Bednarek, A. K.; Daniel, R. L.; Hawkins, K.
A.; Laflin, K. J.; Gaddis, S.; MacLeod, M. C.; Aldaz, C. M.: Effects
of estrogen on global gene expression: identification of novel targets
of estrogen action. Cancer Res. 60: 5977-5983, 2000.
4. Irobi, J.; Almeida-Souza, L.; Asselbergh, B.; De Winter, V.; Goethals,
S.; Dierick, I.; Krishnan, J.; Timmermans, J.-P.; Robberecht, W.;
De Jonghe, P.; Van Den Bosch, L.; Janssens, S.; Timmerman, V.: Mutant
HSPB8 causes motor neuron-specific neurite degeneration. Hum. Molec.
Genet. 19: 3254-3265, 2010.
5. Irobi, J.; Van Impe, K.; Seeman, P.; Jordanova, A.; Dierick, I,.;
Verpoorten, N.; Michalik, A.; De Vriendt, E.; Jacobs, A.; Van Gerwen,
V.; Vennekens, K.; Mazanec, R.; and 11 others: Hot-spot residue
in small heat-shock protein 22 causes distal motor neuropathy. Nature
Genet. 36: 597-601, 2004.
6. Kappe, G.; Verschuure, P.; Philipsen, R. L. A.; Staalduinen, A.
A.; Van de Boogaart, P.; Boelens, W. C.; De Jong, W. W.: Characterization
of two novel human small heat shock proteins: protein kinase-related
HspB8 and testis-specific HspB9. Biochim. Biophys. Acta 1520: 1-6,
2001.
7. Tang, B.; Luo, W.; Xia, K.; Xiao, J.; Jiang, H.; Shen, L.; Tang,
J.; Zhao, G.; Cai, F.; Pan, Q.; Dai, H.; Yang, Q.; Xia, J.; Evgrafov,
O. V.: A new locus for autosomal dominant Charcot-Marie-Tooth disease
type 2 (CMT2L) maps to chromosome 12q24. Hum. Genet. 114: 527-533,
2004.
8. Tang, B.; Zhao, G.; Luo, W.; Xia, K.; Cai, F.; Pan, Q.; Zhang,
R.; Zhang, F.; Liu, X.; Chen, B.; Zhang, C.; Shen, L.; Jiang, H.;
Long, Z.; Dai, H.: Small heat-shock protein 22 mutated in autosomal
dominant Charcot-Marie-Tooth disease type 2L. Hum. Genet. 116: 222-224,
2005.
9. Timmerman, V.; Raeymaekers, P.; Nelis, E.; De Jonghe, P.; Muylle,
L.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.: Linkage analysis
of distal hereditary motor neuropathy type II (distal HMN II) in a
single pedigree. J. Neurol. Sci. 109: 41-48, 1992.
*FIELD* CN
George E. Tiller - updated: 09/17/2013
George E. Tiller - updated: 6/16/2008
Victor A. McKusick - updated: 4/15/2005
Victor A. McKusick - updated: 6/14/2004
Cassandra L. Kniffin - updated: 5/3/2004
Patricia A. Hartz - updated: 12/16/2003
*FIELD* CD
Carol A. Bocchini: 8/6/2003
*FIELD* ED
alopez: 09/17/2013
ckniffin: 1/24/2013
wwang: 9/15/2009
wwang: 6/19/2008
terry: 6/16/2008
ckniffin: 3/16/2007
tkritzer: 4/18/2005
terry: 4/15/2005
tkritzer: 6/29/2004
terry: 6/14/2004
alopez: 5/28/2004
tkritzer: 5/5/2004
tkritzer: 5/4/2004
ckniffin: 5/3/2004
mgross: 12/17/2003
mgross: 12/16/2003
tkritzer: 8/7/2003
carol: 8/6/2003
*RECORD*
*FIELD* NO
608014
*FIELD* TI
*608014 HEAT-SHOCK 22-KD PROTEIN 8; HSPB8
;;HSP22;;
PROTEIN KINASE H11; H11;;
E2-INDUCED GENE 1; E2IG1;;
read moreHEAT-SHOCK 27-KD PROTEIN 8
*FIELD* TX
CLONING
To identify genes that are regulated by or associated with estrogen
action, Charpentier et al. (2000) performed serial analysis of gene
expression (SAGE) on estrogen-responsive breast cancer cells after
exposure to estrogen. Using transcript-specific PCR primers for novel
sequences that increased more than 10-fold upon treatment with 17-beta
estradiol (E2), they cloned 5 cDNAs, designated E2-induced genes (E2IG)
1-5, from a human placenta cDNA library. The E2IG1 cDNA encodes a
deduced 196-amino acid protein that contains a central portion
homologous to a highly conserved HSP-alpha crystallin domain common to
all HSP20 family members. It shows 54% sequence homology to HSP27
(602195), suggesting that it is a member of the small HSP family.
By searching an EST database for sequences containing the
alpha-crystallin domain characteristic of small heat-shock proteins,
followed by PCR of a placenta cDNA library, Kappe et al. (2001) cloned
HSPB8. Northern blot analysis detected broad expression of a 2.2-kb
transcript, with highest abundance in skeletal muscle, heart, and
placenta. Expression of HSPB8 was intermediate in several other tissues,
but it was not detected in blood.
GENE STRUCTURE
Kappe et al. (2001) determined that the HSPB8 gene contains at least 3
exons.
MAPPING
By sequence analysis, Charpentier et al. (2000) mapped the E2IG1 gene to
chromosome 12 between markers D12S366 and D12S340.
GENE FUNCTION
Carra et al. (2005) investigated the capacity of HSPB8 to prevent
protein aggregation in cells using Htt (613004) protein containing 43
glutamine residues (Htt43Q) as a model. In control conditions, Htt43Q
accumulated in perinuclear inclusions composed of SDS-insoluble
aggregates. In most cells, cotransfection with HSPB8 blocked inclusion
formation. Biochemical analyses indicated that HSPB8 inhibited the
accumulation of insoluble Htt43Q as efficiently as HSP40 (DNAJB1;
604572), which was taken as a positive control. Htt43Q then accumulated
in the SDS-soluble fraction, provided that protein degradation was
blocked by proteasome and autophagy inhibitors. In contrast, HSPB1
(602195) and alpha-B-crystallin (CRYAB; 123590) had no effect. Analyses
of HSPB1/HSPB8 chimeric proteins indicated that the C-terminal domain of
HSPB8 contains the specific sequence necessary for chaperone activity.
The K141N mutation (608014.0001) significantly reduced the chaperone
activity of the protein. Carra et al. (2005) hypothesized that a
decrease in HSPB8 chaperone activity may contribute to the development
of some neuropathies.
MOLECULAR GENETICS
In affected members of 4 families with autosomal dominant distal
hereditary motor neuronopathy type IIA (dHMN2A; 158590), Irobi et al.
(2004) identified heterozygous mutations in the same codon of the HSPB8
gene (608104.0001-608014.0002).
Benndorf and Welsh (2004) reviewed the role of heat-shock proteins in
neuromuscular function, as indicated by the association of mutations in
2 of these genes, HSP22 and HSP27, with human neuromuscular disorders.
In affected members of a Chinese family with axonal Charcot-Marie-Tooth
disease type 2L (608673), Tang et al. (2005) identified a mutation in
the HSPB8 gene (608014.0003).
Irobi et al. (2010) compared the effect of mutant HSPB8 in primary
neuronal and glial cell cultures. In motor neurons, expression of both
HSPB8 K141N (608014.0001) and K141E (608014.0002) mutations resulted in
neurite degeneration, as manifested by a reduction in number of neurites
per cell, as well as in a reduction in average length of the neurites.
Expression of the K141E, and to a lesser extent the K141N, mutation also
induced spheroids in the neurites. There were no signs of apoptosis in
motor neurons, showing that mutant HSPB8 resulted in neurite
degeneration without inducing neuronal death. While overt in motor
neurons, these phenotypes were only very mildly present in sensory
neurons and completely absent in cortical neurons and glial cells.
*FIELD* AV
.0001
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA
HSPB8, 423G-C, LYS141ASN
In affected members of a Belgian family with autosomal dominant distal
hereditary motor neuronopathy type II (158590) previously reported by
Timmerman et al. (1992), and in affected members of a large Czech family
with dHMN2, Irobi et al. (2004) identified a heterozygous 423G-C
transversion in exon 2 of the HSPB8 gene, resulting in a lys141-to-asn
(K141N) substitution. The mutation cosegregated with the disease in both
families. The K141N mutation affects a highly conserved residue in the
central alpha-crystallin domain of the protein. Normally, HSPB8
interacts with HSPB1 (602195). Expression studies of the K141N mutant
protein in COS cells showed an increased interaction between HSPB8 and
HSPB1, leading to the formation of intracellular aggregates. A different
mutation in the same codon was identified in 2 other families with dHMN2
(608014.0002).
.0002
NEURONOPATHY, DISTAL HEREDITARY MOTOR, TYPE IIA
HSPB8, LYS141GLU
In affected members of an English family and a Bulgarian family with
distal hereditary motor neuronopathy type II (158590), Irobi et al.
(2004) identified a heterozygous 421A-G transition in exon 2 of the
HSPB8 gene, resulting in a lys141-to-glu (K141E) substitution. The
mutation cosegregated with the disease in both families. The K141E
mutation affects a highly conserved residue in the central
alpha-crystallin domain of the protein. Normally, HSPB8 interacts with
HSPB1 (602195). Expression studies of the mutant K141E protein in COS
cells showed an increased interaction between HSPB8 and HSPB1, leading
to the formation of intracellular aggregates. A different mutation in
the same codon was identified in 2 other families with dHMN2
(608014.0001).
.0003
CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2L
HSPB8, 423G-T, LYS141ASN
In affected members of a large Chinese family with axonal
Charcot-Marie-Tooth disease type 2L (608673) in which Tang et al. (2004)
assigned the underlying locus to 12q24, Tang et al. (2005) identified a
423G-T transversion in exon 2 of the HSPB8 gene, resulting in a
lys141-to-asn (K141N) substitution.
*FIELD* RF
1. Benndorf, R.; Welsh, M. J.: Shocking degeneration. Nature Genet. 36:
547-548, 2004.
2. Carra, S.; Sivilotti, M.; Chavez Zobel, A. T.; Lambert, H.; Landry,
J.: HspB8, a small heat shock protein mutated in human neuromuscular
disorders, has in vivo chaperone activity in cultured cells. Hum.
Molec. Genet. 14: 1659-1669, 2005.
3. Charpentier, A. H.; Bednarek, A. K.; Daniel, R. L.; Hawkins, K.
A.; Laflin, K. J.; Gaddis, S.; MacLeod, M. C.; Aldaz, C. M.: Effects
of estrogen on global gene expression: identification of novel targets
of estrogen action. Cancer Res. 60: 5977-5983, 2000.
4. Irobi, J.; Almeida-Souza, L.; Asselbergh, B.; De Winter, V.; Goethals,
S.; Dierick, I.; Krishnan, J.; Timmermans, J.-P.; Robberecht, W.;
De Jonghe, P.; Van Den Bosch, L.; Janssens, S.; Timmerman, V.: Mutant
HSPB8 causes motor neuron-specific neurite degeneration. Hum. Molec.
Genet. 19: 3254-3265, 2010.
5. Irobi, J.; Van Impe, K.; Seeman, P.; Jordanova, A.; Dierick, I,.;
Verpoorten, N.; Michalik, A.; De Vriendt, E.; Jacobs, A.; Van Gerwen,
V.; Vennekens, K.; Mazanec, R.; and 11 others: Hot-spot residue
in small heat-shock protein 22 causes distal motor neuropathy. Nature
Genet. 36: 597-601, 2004.
6. Kappe, G.; Verschuure, P.; Philipsen, R. L. A.; Staalduinen, A.
A.; Van de Boogaart, P.; Boelens, W. C.; De Jong, W. W.: Characterization
of two novel human small heat shock proteins: protein kinase-related
HspB8 and testis-specific HspB9. Biochim. Biophys. Acta 1520: 1-6,
2001.
7. Tang, B.; Luo, W.; Xia, K.; Xiao, J.; Jiang, H.; Shen, L.; Tang,
J.; Zhao, G.; Cai, F.; Pan, Q.; Dai, H.; Yang, Q.; Xia, J.; Evgrafov,
O. V.: A new locus for autosomal dominant Charcot-Marie-Tooth disease
type 2 (CMT2L) maps to chromosome 12q24. Hum. Genet. 114: 527-533,
2004.
8. Tang, B.; Zhao, G.; Luo, W.; Xia, K.; Cai, F.; Pan, Q.; Zhang,
R.; Zhang, F.; Liu, X.; Chen, B.; Zhang, C.; Shen, L.; Jiang, H.;
Long, Z.; Dai, H.: Small heat-shock protein 22 mutated in autosomal
dominant Charcot-Marie-Tooth disease type 2L. Hum. Genet. 116: 222-224,
2005.
9. Timmerman, V.; Raeymaekers, P.; Nelis, E.; De Jonghe, P.; Muylle,
L.; Ceuterick, C.; Martin, J.-J.; Van Broeckhoven, C.: Linkage analysis
of distal hereditary motor neuropathy type II (distal HMN II) in a
single pedigree. J. Neurol. Sci. 109: 41-48, 1992.
*FIELD* CN
George E. Tiller - updated: 09/17/2013
George E. Tiller - updated: 6/16/2008
Victor A. McKusick - updated: 4/15/2005
Victor A. McKusick - updated: 6/14/2004
Cassandra L. Kniffin - updated: 5/3/2004
Patricia A. Hartz - updated: 12/16/2003
*FIELD* CD
Carol A. Bocchini: 8/6/2003
*FIELD* ED
alopez: 09/17/2013
ckniffin: 1/24/2013
wwang: 9/15/2009
wwang: 6/19/2008
terry: 6/16/2008
ckniffin: 3/16/2007
tkritzer: 4/18/2005
terry: 4/15/2005
tkritzer: 6/29/2004
terry: 6/14/2004
alopez: 5/28/2004
tkritzer: 5/5/2004
tkritzer: 5/4/2004
ckniffin: 5/3/2004
mgross: 12/17/2003
mgross: 12/16/2003
tkritzer: 8/7/2003
carol: 8/6/2003
MIM
608673
*RECORD*
*FIELD* NO
608673
*FIELD* TI
#608673 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2L; CMT2L
;;CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2L;;
read moreCHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2L
*FIELD* TX
A number sign (#) is used with this entry because axonal
Charcot-Marie-Tooth disease type 2L (CMT2L) is caused by mutation in the
HSPB8 gene (608014). Distal hereditary motor neuronopathy IIA (HMN2A;
158590) is an allelic disorder with an overlapping phenotype.
For a phenotypic description and a discussion of genetic heterogeneity
of axonal CMT type 2, see CMT2A (118210).
MAPPING
In an extensively affected Chinese family, Tang et al. (2004) found
linkage of an axonal form of autosomal dominant Charcot-Marie-Tooth
disease, designated CMT2L, to a locus on chromosome 12q24. A maximum
2-point lod score of 6.35 and multipoint lod score of 8.08 for marker
D12S76 at a recombination of 0.0 strongly supported linkage.
MOLECULAR GENETICS
In affected members of the CMT2L family described by Tang et al. (2004),
Tang et al. (2005) sequenced all known exons and intron-exon boundaries
of 26 known candidate genes in the 12q24 region and identified a
lys141-to-asn substitution in the HSPB8 gene (K141N; 608014.0003). Tang
et al. (2005) stated that this was the third time that a gene was shown
to be mutant in both Charcot-Marie-Tooth disease and distal hereditary
motor neuropathy (dHMN). Dominant mutations in the GARS gene (600287)
are associated with CMT2D (601472) and dHMNVA (600794), and dominant
mutations in the HSPB1 gene (602195) are associated with CMT2F (606595)
and dHMN2B (608634).
*FIELD* RF
1. Tang, B.; Luo, W.; Xia, K.; Xiao, J.; Jiang, H.; Shen, L.; Tang,
J.; Zhao, G.; Cai, F.; Pan, Q.; Dai, H.; Yang, Q.; Xia, J.; Evgrafov,
O. V.: A new locus for autosomal dominant Charcot-Marie-Tooth disease
type 2 (CMT2L) maps to chromosome 12q24. Hum. Genet. 114: 527-533,
2004.
2. Tang, B.; Zhao, G.; Luo, W.; Xia, K.; Cai, F.; Pan, Q.; Zhang,
R.; Zhang, F.; Liu, X.; Chen, B.; Zhang, C.; Shen, L.; Jiang, H.;
Long, Z.; Dai, H.: Small heat-shock protein 22 mutated in autosomal
dominant Charcot-Marie-Tooth disease type 2L. Hum. Genet. 116: 222-224,
2005.
*FIELD* CS
INHERITANCE:
Autosomal dominant
SKELETAL:
[Spine];
Scoliosis;
[Feet];
Pes cavus
NEUROLOGIC:
[Peripheral nervous system];
Distal limb muscle weakness due to peripheral neuropathy;
Distal limb muscle atrophy due to peripheral neuropathy;
Progresses to involve upper distal limb muscles;
Proximal muscle involvement rarely occurs;
Distal sensory impairment;
Hyporeflexia;
Areflexia;
Normal motor nerve conduction velocity (NCV) (greater than 38 m/s);
Decreased or absent sensory nerve action potentials;
EMG shows denervation and fibrillation potentials;
Nerve biopsy shows axonal neuropathy;
Loss of large myelinated fibers;
Thin myelinated axons
MISCELLANEOUS:
Age at onset 15 to 33 years;
Usually begins in feet and legs (peroneal distribution);
Genetic heterogeneity (see CMT2A 118210)
MOLECULAR BASIS:
Caused by mutations in the heat-shock 22-kD protein 8 gene (HSPB8,
608014.0003)
*FIELD* CN
Joanna S. Amberger - updated: 04/18/2005
*FIELD* CD
Cassandra L. Kniffin: 12/21/2004
*FIELD* ED
joanna: 04/18/2005
ckniffin: 12/21/2004
*FIELD* CD
Victor A. McKusick: 5/20/2004
*FIELD* ED
carol: 08/01/2012
terry: 3/3/2010
ckniffin: 3/16/2007
tkritzer: 4/18/2005
carol: 5/20/2004
*RECORD*
*FIELD* NO
608673
*FIELD* TI
#608673 CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2L; CMT2L
;;CHARCOT-MARIE-TOOTH NEUROPATHY, AXONAL, TYPE 2L;;
read moreCHARCOT-MARIE-TOOTH DISEASE, AXONAL, AUTOSOMAL DOMINANT, TYPE 2L
*FIELD* TX
A number sign (#) is used with this entry because axonal
Charcot-Marie-Tooth disease type 2L (CMT2L) is caused by mutation in the
HSPB8 gene (608014). Distal hereditary motor neuronopathy IIA (HMN2A;
158590) is an allelic disorder with an overlapping phenotype.
For a phenotypic description and a discussion of genetic heterogeneity
of axonal CMT type 2, see CMT2A (118210).
MAPPING
In an extensively affected Chinese family, Tang et al. (2004) found
linkage of an axonal form of autosomal dominant Charcot-Marie-Tooth
disease, designated CMT2L, to a locus on chromosome 12q24. A maximum
2-point lod score of 6.35 and multipoint lod score of 8.08 for marker
D12S76 at a recombination of 0.0 strongly supported linkage.
MOLECULAR GENETICS
In affected members of the CMT2L family described by Tang et al. (2004),
Tang et al. (2005) sequenced all known exons and intron-exon boundaries
of 26 known candidate genes in the 12q24 region and identified a
lys141-to-asn substitution in the HSPB8 gene (K141N; 608014.0003). Tang
et al. (2005) stated that this was the third time that a gene was shown
to be mutant in both Charcot-Marie-Tooth disease and distal hereditary
motor neuropathy (dHMN). Dominant mutations in the GARS gene (600287)
are associated with CMT2D (601472) and dHMNVA (600794), and dominant
mutations in the HSPB1 gene (602195) are associated with CMT2F (606595)
and dHMN2B (608634).
*FIELD* RF
1. Tang, B.; Luo, W.; Xia, K.; Xiao, J.; Jiang, H.; Shen, L.; Tang,
J.; Zhao, G.; Cai, F.; Pan, Q.; Dai, H.; Yang, Q.; Xia, J.; Evgrafov,
O. V.: A new locus for autosomal dominant Charcot-Marie-Tooth disease
type 2 (CMT2L) maps to chromosome 12q24. Hum. Genet. 114: 527-533,
2004.
2. Tang, B.; Zhao, G.; Luo, W.; Xia, K.; Cai, F.; Pan, Q.; Zhang,
R.; Zhang, F.; Liu, X.; Chen, B.; Zhang, C.; Shen, L.; Jiang, H.;
Long, Z.; Dai, H.: Small heat-shock protein 22 mutated in autosomal
dominant Charcot-Marie-Tooth disease type 2L. Hum. Genet. 116: 222-224,
2005.
*FIELD* CS
INHERITANCE:
Autosomal dominant
SKELETAL:
[Spine];
Scoliosis;
[Feet];
Pes cavus
NEUROLOGIC:
[Peripheral nervous system];
Distal limb muscle weakness due to peripheral neuropathy;
Distal limb muscle atrophy due to peripheral neuropathy;
Progresses to involve upper distal limb muscles;
Proximal muscle involvement rarely occurs;
Distal sensory impairment;
Hyporeflexia;
Areflexia;
Normal motor nerve conduction velocity (NCV) (greater than 38 m/s);
Decreased or absent sensory nerve action potentials;
EMG shows denervation and fibrillation potentials;
Nerve biopsy shows axonal neuropathy;
Loss of large myelinated fibers;
Thin myelinated axons
MISCELLANEOUS:
Age at onset 15 to 33 years;
Usually begins in feet and legs (peroneal distribution);
Genetic heterogeneity (see CMT2A 118210)
MOLECULAR BASIS:
Caused by mutations in the heat-shock 22-kD protein 8 gene (HSPB8,
608014.0003)
*FIELD* CN
Joanna S. Amberger - updated: 04/18/2005
*FIELD* CD
Cassandra L. Kniffin: 12/21/2004
*FIELD* ED
joanna: 04/18/2005
ckniffin: 12/21/2004
*FIELD* CD
Victor A. McKusick: 5/20/2004
*FIELD* ED
carol: 08/01/2012
terry: 3/3/2010
ckniffin: 3/16/2007
tkritzer: 4/18/2005
carol: 5/20/2004