Full text data of KRT6A
KRT6A
(K6A, KRT6D)
[Confidence: low (only semi-automatic identification from reviews)]
Keratin, type II cytoskeletal 6A (Cytokeratin-6A; CK-6A; Cytokeratin-6D; CK-6D; Keratin-6A; K6A; Type-II keratin Kb6; Hom s 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Keratin, type II cytoskeletal 6A (Cytokeratin-6A; CK-6A; Cytokeratin-6D; CK-6D; Keratin-6A; K6A; Type-II keratin Kb6; Hom s 5)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P02538
ID K2C6A_HUMAN Reviewed; 564 AA.
AC P02538; A4QPC1; P48667; Q08AR4; Q6NT67; Q96CL4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Keratin, type II cytoskeletal 6A;
DE AltName: Full=Cytokeratin-6A;
DE Short=CK-6A;
DE AltName: Full=Cytokeratin-6D;
DE Short=CK-6D;
DE AltName: Full=Keratin-6A;
DE Short=K6A;
DE AltName: Full=Type-II keratin Kb6;
DE AltName: Allergen=Hom s 5;
GN Name=KRT6A; Synonyms=K6A, KRT6D;
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 [GENOMIC DNA].
RC TISSUE=Skin;
RX PubMed=7543104; DOI=10.1074/jbc.270.31.18581;
RA Takahashi K., Paladini R.D., Coulombe P.A.;
RT "Cloning and characterization of multiple human genes and cDNAs
RT encoding highly related type II keratin 6 isoforms.";
RL J. Biol. Chem. 270:18581-18592(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-21.
RC TISSUE=Brain, Ovary, and Pancreas;
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 [4]
RP PROTEIN SEQUENCE OF 2-9; 31-40; 43-86; 169-204; 208-232; 241-347;
RP 350-369; 379-386; 425-436; 447-475 AND 534-550, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N., Lilla S., Lange E.,
RA Sumpton D.P.;
RL Submitted (MAR-2008) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 208-564.
RX PubMed=6191871; DOI=10.1016/0092-8674(83)90034-X;
RA Hanukoglu I., Fuchs E.;
RT "The cDNA sequence of a type II cytoskeletal keratin reveals constant
RT and variable structural domains among keratins.";
RL Cell 33:915-924(1983).
RN [6]
RP INTERACTION WITH TCHP.
RX PubMed=15731013; DOI=10.1242/jcs.01667;
RA Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T.,
RA Usukura J., Inagaki M.;
RT "Identification of trichoplein, a novel keratin filament-binding
RT protein.";
RL J. Cell Sci. 118:1081-1090(2005).
RN [7]
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 [8]
RP VARIANT PC1 ASN-171 DEL.
RX PubMed=7545493; DOI=10.1038/ng0795-363;
RA Bowden P.E., Haley J.L., Kansky A., Rothnagel J.A., Jones D.O.,
RA Turner R.J.;
RT "Mutation of a type II keratin gene (K6a) in pachyonychia congenita.";
RL Nat. Genet. 10:363-365(1995).
RN [9]
RP VARIANTS PC1 VAL-174; ARG-469 AND LYS-472.
RX PubMed=11886499; DOI=10.1046/j.0022-202x.2001.01565.x;
RA Terrinoni A., Smith F.J.D., Didona B., Canzona F., Paradisi M.,
RA Huber M., Hohl D., David A., Verloes A., Leigh I.M., Munro C.S.,
RA Melino G., McLean W.H.I.;
RT "Novel and recurrent mutations in the genes encoding keratins K6a, K16
RT and K17 in 13 cases of pachyonychia congenita.";
RL J. Invest. Dermatol. 117:1391-1396(2001).
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. KRT6
CC isomers associate with KRT16 and/or KRT17. Interacts with TCHP.
CC -!- INTERACTION:
CC Q15834:CCDC85B; NbExp=2; IntAct=EBI-702198, EBI-739674;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in distinct types of
CC epithelia such as those in oral mucosa, esophagus, papillae of
CC tongue and hair follicle outer root sheath.
CC -!- DISEASE: Pachyonychia congenita 1 (PC1) [MIM:167200]: An autosomal
CC dominant ectodermal dysplasia characterized by hypertrophic nail
CC dystrophy resulting in onchyogryposis (thickening and increase in
CC curvature of the nail), palmoplantar keratoderma, follicular
CC hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the
CC hands and feet is usually present. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE from
CC atopic dermatitis (AD) patients. Identified as an IgE autoantigen
CC in atopic dermatitis (AD) patients with severe skin
CC manifestations.
CC -!- MISCELLANEOUS: There are at least six isoforms of human type II
CC keratin-6 (K6), K6A being the most abundant representing about 77%
CC of all forms found in epithelia.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and
CC microfibrillar keratin, I (acidic) and II (neutral to basic) (40-
CC 55 and 56-70 kDa, respectively).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRT6A";
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; L42583; AAC41767.1; -; Genomic_DNA.
DR EMBL; L42575; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42576; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42577; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42578; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42579; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42580; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42581; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; AH005420; AAB60696.1; -; Genomic_DNA.
DR EMBL; BT006899; AAP35545.1; -; mRNA.
DR EMBL; BC008807; AAH08807.1; -; mRNA.
DR EMBL; BC014152; AAH14152.1; -; mRNA.
DR EMBL; BC069269; AAH69269.1; -; mRNA.
DR EMBL; BC125058; AAI25059.1; -; mRNA.
DR EMBL; BC139753; AAI39754.1; -; mRNA.
DR EMBL; V01516; CAA24760.1; -; Genomic_DNA.
DR PIR; A57398; KRHUEA.
DR PIR; I61769; I61769.
DR RefSeq; NP_005545.1; NM_005554.3.
DR UniGene; Hs.700779; -.
DR ProteinModelPortal; P02538; -.
DR SMR; P02538; 160-313, 329-471.
DR DIP; DIP-533N; -.
DR IntAct; P02538; 12.
DR STRING; 9606.ENSP00000369317; -.
DR Allergome; 3326; Hom s 5.0101.
DR Allergome; 415; Hom s 5.
DR PhosphoSite; P02538; -.
DR DMDM; 1346344; -.
DR PaxDb; P02538; -.
DR PeptideAtlas; P02538; -.
DR PRIDE; P02538; -.
DR DNASU; 3853; -.
DR Ensembl; ENST00000330722; ENSP00000369317; ENSG00000205420.
DR GeneID; 3853; -.
DR KEGG; hsa:3853; -.
DR UCSC; uc001sam.3; human.
DR CTD; 3853; -.
DR GeneCards; GC12M052880; -.
DR HGNC; HGNC:6443; KRT6A.
DR HPA; HPA045697; -.
DR MIM; 148041; gene.
DR MIM; 167200; phenotype.
DR neXtProt; NX_P02538; -.
DR Orphanet; 2309; Pachyonychia congenita.
DR PharmGKB; PA30231; -.
DR eggNOG; NOG315845; -.
DR HOGENOM; HOG000230976; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; P02538; -.
DR KO; K07605; -.
DR OMA; MQDQVED; -.
DR OrthoDB; EOG7FV3Q8; -.
DR ChiTaRS; KRT6A; human.
DR GeneWiki; Keratin_6A; -.
DR GenomeRNAi; 3853; -.
DR NextBio; 15161; -.
DR PRO; PR:P02538; -.
DR Bgee; P02538; -.
DR CleanEx; HS_KRT6A; -.
DR Genevestigator; P02538; -.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0045095; C:keratin filament; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0007398; P:ectoderm development; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell proliferation; NAS:UniProtKB.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR003054; Keratin_II.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allergen; Coiled coil; Complete proteome;
KW Direct protein sequencing; Disease mutation; Ectodermal dysplasia;
KW Intermediate filament; Keratin; Palmoplantar keratoderma;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 564 Keratin, type II cytoskeletal 6A.
FT /FTId=PRO_0000063731.
FT REGION 2 162 Head.
FT REGION 163 472 Rod.
FT REGION 163 198 Coil 1A.
FT REGION 199 217 Linker 1.
FT REGION 218 309 Coil 1B.
FT REGION 310 333 Linker 12.
FT REGION 334 472 Coil 2.
FT REGION 473 564 Tail.
FT SITE 414 414 Stutter.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 21 21 N -> S (in dbSNP:rs17845411).
FT /FTId=VAR_021264.
FT VARIANT 111 111 G -> D (in dbSNP:rs681063).
FT /FTId=VAR_035030.
FT VARIANT 171 171 Missing (in PC1).
FT /FTId=VAR_003878.
FT VARIANT 174 174 F -> V (in PC1; dbSNP:rs28933087).
FT /FTId=VAR_017075.
FT VARIANT 469 469 L -> R (in PC1; dbSNP:rs57052654).
FT /FTId=VAR_017076.
FT VARIANT 472 472 E -> K (in PC1; dbSNP:rs60554162).
FT /FTId=VAR_017077.
FT CONFLICT 192 192 E -> D (in Ref. 1; AAB60696).
FT CONFLICT 241 241 G -> N (in Ref. 1; AAB60696).
FT CONFLICT 249 249 F -> L (in Ref. 1; AAB60696).
FT CONFLICT 395 395 I -> S (in Ref. 5; CAA24760).
FT CONFLICT 404 404 N -> S (in Ref. 1; AAB60696).
FT CONFLICT 443 443 R -> W (in Ref. 3; AAH69269).
FT CONFLICT 486 486 I -> V (in Ref. 1; AAB60696).
SQ SEQUENCE 564 AA; 60045 MW; 26708916C7DC923A CRC64;
MASTSTTIRS HSSSRRGFSA NSARLPGVSR SGFSSVSVSR SRGSGGLGGA CGGAGFGSRS
LYGLGGSKRI SIGGGSCAIS GGYGSRAGGS YGFGGAGSGF GFGGGAGIGF GLGGGAGLAG
GFGGPGFPVC PPGGIQEVTV NQSLLTPLNL QIDPTIQRVR AEEREQIKTL NNKFASFIDK
VRFLEQQNKV LETKWTLLQE QGTKTVRQNL EPLFEQYINN LRRQLDSIVG ERGRLDSELR
GMQDLVEDFK NKYEDEINKR TAAENEFVTL KKDVDAAYMN KVELQAKADT LTDEINFLRA
LYDAELSQMQ THISDTSVVL SMDNNRNLDL DSIIAEVKAQ YEEIAQRSRA EAESWYQTKY
EELQVTAGRH GDDLRNTKQE IAEINRMIQR LRSEIDHVKK QCANLQAAIA DAEQRGEMAL
KDAKNKLEGL EDALQKAKQD LARLLKEYQE LMNVKLALDV EIATYRKLLE GEECRLNGEG
VGQVNISVVQ STVSSGYGGA SGVGSGLGLG GGSSYSYGSG LGVGGGFSSS SGRAIGGGLS
SVGGGSSTIK YTTTSSSSRK SYKH
//
ID K2C6A_HUMAN Reviewed; 564 AA.
AC P02538; A4QPC1; P48667; Q08AR4; Q6NT67; Q96CL4;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 3.
DT 22-JAN-2014, entry version 144.
DE RecName: Full=Keratin, type II cytoskeletal 6A;
DE AltName: Full=Cytokeratin-6A;
DE Short=CK-6A;
DE AltName: Full=Cytokeratin-6D;
DE Short=CK-6D;
DE AltName: Full=Keratin-6A;
DE Short=K6A;
DE AltName: Full=Type-II keratin Kb6;
DE AltName: Allergen=Hom s 5;
GN Name=KRT6A; Synonyms=K6A, KRT6D;
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 [GENOMIC DNA].
RC TISSUE=Skin;
RX PubMed=7543104; DOI=10.1074/jbc.270.31.18581;
RA Takahashi K., Paladini R.D., Coulombe P.A.;
RT "Cloning and characterization of multiple human genes and cDNAs
RT encoding highly related type II keratin 6 isoforms.";
RL J. Biol. Chem. 270:18581-18592(1995).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-21.
RC TISSUE=Brain, Ovary, and Pancreas;
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 [4]
RP PROTEIN SEQUENCE OF 2-9; 31-40; 43-86; 169-204; 208-232; 241-347;
RP 350-369; 379-386; 425-436; 447-475 AND 534-550, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND MASS SPECTROMETRY.
RC TISSUE=Lung carcinoma;
RA Bienvenut W.V., Vousden K.H., Lukashchuk N., Lilla S., Lange E.,
RA Sumpton D.P.;
RL Submitted (MAR-2008) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 208-564.
RX PubMed=6191871; DOI=10.1016/0092-8674(83)90034-X;
RA Hanukoglu I., Fuchs E.;
RT "The cDNA sequence of a type II cytoskeletal keratin reveals constant
RT and variable structural domains among keratins.";
RL Cell 33:915-924(1983).
RN [6]
RP INTERACTION WITH TCHP.
RX PubMed=15731013; DOI=10.1242/jcs.01667;
RA Nishizawa M., Izawa I., Inoko A., Hayashi Y., Nagata K., Yokoyama T.,
RA Usukura J., Inagaki M.;
RT "Identification of trichoplein, a novel keratin filament-binding
RT protein.";
RL J. Cell Sci. 118:1081-1090(2005).
RN [7]
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 [8]
RP VARIANT PC1 ASN-171 DEL.
RX PubMed=7545493; DOI=10.1038/ng0795-363;
RA Bowden P.E., Haley J.L., Kansky A., Rothnagel J.A., Jones D.O.,
RA Turner R.J.;
RT "Mutation of a type II keratin gene (K6a) in pachyonychia congenita.";
RL Nat. Genet. 10:363-365(1995).
RN [9]
RP VARIANTS PC1 VAL-174; ARG-469 AND LYS-472.
RX PubMed=11886499; DOI=10.1046/j.0022-202x.2001.01565.x;
RA Terrinoni A., Smith F.J.D., Didona B., Canzona F., Paradisi M.,
RA Huber M., Hohl D., David A., Verloes A., Leigh I.M., Munro C.S.,
RA Melino G., McLean W.H.I.;
RT "Novel and recurrent mutations in the genes encoding keratins K6a, K16
RT and K17 in 13 cases of pachyonychia congenita.";
RL J. Invest. Dermatol. 117:1391-1396(2001).
CC -!- SUBUNIT: Heterodimer of a type I and a type II keratin. KRT6
CC isomers associate with KRT16 and/or KRT17. Interacts with TCHP.
CC -!- INTERACTION:
CC Q15834:CCDC85B; NbExp=2; IntAct=EBI-702198, EBI-739674;
CC -!- TISSUE SPECIFICITY: Constitutively expressed in distinct types of
CC epithelia such as those in oral mucosa, esophagus, papillae of
CC tongue and hair follicle outer root sheath.
CC -!- DISEASE: Pachyonychia congenita 1 (PC1) [MIM:167200]: An autosomal
CC dominant ectodermal dysplasia characterized by hypertrophic nail
CC dystrophy resulting in onchyogryposis (thickening and increase in
CC curvature of the nail), palmoplantar keratoderma, follicular
CC hyperkeratosis, and oral leukokeratosis. Hyperhidrosis of the
CC hands and feet is usually present. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- ALLERGEN: Causes an allergic reaction in human. Binds to IgE from
CC atopic dermatitis (AD) patients. Identified as an IgE autoantigen
CC in atopic dermatitis (AD) patients with severe skin
CC manifestations.
CC -!- MISCELLANEOUS: There are at least six isoforms of human type II
CC keratin-6 (K6), K6A being the most abundant representing about 77%
CC of all forms found in epithelia.
CC -!- MISCELLANEOUS: There are two types of cytoskeletal and
CC microfibrillar keratin, I (acidic) and II (neutral to basic) (40-
CC 55 and 56-70 kDa, respectively).
CC -!- SIMILARITY: Belongs to the intermediate filament family.
CC -!- WEB RESOURCE: Name=Human Intermediate Filament Mutation Database;
CC URL="http://www.interfil.org";
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/KRT6A";
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; L42583; AAC41767.1; -; Genomic_DNA.
DR EMBL; L42575; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42576; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42577; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42578; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42579; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42580; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; L42581; AAC41767.1; JOINED; Genomic_DNA.
DR EMBL; AH005420; AAB60696.1; -; Genomic_DNA.
DR EMBL; BT006899; AAP35545.1; -; mRNA.
DR EMBL; BC008807; AAH08807.1; -; mRNA.
DR EMBL; BC014152; AAH14152.1; -; mRNA.
DR EMBL; BC069269; AAH69269.1; -; mRNA.
DR EMBL; BC125058; AAI25059.1; -; mRNA.
DR EMBL; BC139753; AAI39754.1; -; mRNA.
DR EMBL; V01516; CAA24760.1; -; Genomic_DNA.
DR PIR; A57398; KRHUEA.
DR PIR; I61769; I61769.
DR RefSeq; NP_005545.1; NM_005554.3.
DR UniGene; Hs.700779; -.
DR ProteinModelPortal; P02538; -.
DR SMR; P02538; 160-313, 329-471.
DR DIP; DIP-533N; -.
DR IntAct; P02538; 12.
DR STRING; 9606.ENSP00000369317; -.
DR Allergome; 3326; Hom s 5.0101.
DR Allergome; 415; Hom s 5.
DR PhosphoSite; P02538; -.
DR DMDM; 1346344; -.
DR PaxDb; P02538; -.
DR PeptideAtlas; P02538; -.
DR PRIDE; P02538; -.
DR DNASU; 3853; -.
DR Ensembl; ENST00000330722; ENSP00000369317; ENSG00000205420.
DR GeneID; 3853; -.
DR KEGG; hsa:3853; -.
DR UCSC; uc001sam.3; human.
DR CTD; 3853; -.
DR GeneCards; GC12M052880; -.
DR HGNC; HGNC:6443; KRT6A.
DR HPA; HPA045697; -.
DR MIM; 148041; gene.
DR MIM; 167200; phenotype.
DR neXtProt; NX_P02538; -.
DR Orphanet; 2309; Pachyonychia congenita.
DR PharmGKB; PA30231; -.
DR eggNOG; NOG315845; -.
DR HOGENOM; HOG000230976; -.
DR HOVERGEN; HBG013015; -.
DR InParanoid; P02538; -.
DR KO; K07605; -.
DR OMA; MQDQVED; -.
DR OrthoDB; EOG7FV3Q8; -.
DR ChiTaRS; KRT6A; human.
DR GeneWiki; Keratin_6A; -.
DR GenomeRNAi; 3853; -.
DR NextBio; 15161; -.
DR PRO; PR:P02538; -.
DR Bgee; P02538; -.
DR CleanEx; HS_KRT6A; -.
DR Genevestigator; P02538; -.
DR GO; GO:0005882; C:intermediate filament; TAS:ProtInc.
DR GO; GO:0045095; C:keratin filament; IEA:InterPro.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; NAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; NAS:UniProtKB.
DR GO; GO:0007398; P:ectoderm development; TAS:ProtInc.
DR GO; GO:0008284; P:positive regulation of cell proliferation; NAS:UniProtKB.
DR InterPro; IPR001664; IF.
DR InterPro; IPR018039; Intermediate_filament_CS.
DR InterPro; IPR003054; Keratin_II.
DR PANTHER; PTHR23239; PTHR23239; 1.
DR Pfam; PF00038; Filament; 1.
DR PRINTS; PR01276; TYPE2KERATIN.
DR PROSITE; PS00226; IF; 1.
PE 1: Evidence at protein level;
KW Acetylation; Allergen; Coiled coil; Complete proteome;
KW Direct protein sequencing; Disease mutation; Ectodermal dysplasia;
KW Intermediate filament; Keratin; Palmoplantar keratoderma;
KW Polymorphism; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 564 Keratin, type II cytoskeletal 6A.
FT /FTId=PRO_0000063731.
FT REGION 2 162 Head.
FT REGION 163 472 Rod.
FT REGION 163 198 Coil 1A.
FT REGION 199 217 Linker 1.
FT REGION 218 309 Coil 1B.
FT REGION 310 333 Linker 12.
FT REGION 334 472 Coil 2.
FT REGION 473 564 Tail.
FT SITE 414 414 Stutter.
FT MOD_RES 2 2 N-acetylalanine.
FT VARIANT 21 21 N -> S (in dbSNP:rs17845411).
FT /FTId=VAR_021264.
FT VARIANT 111 111 G -> D (in dbSNP:rs681063).
FT /FTId=VAR_035030.
FT VARIANT 171 171 Missing (in PC1).
FT /FTId=VAR_003878.
FT VARIANT 174 174 F -> V (in PC1; dbSNP:rs28933087).
FT /FTId=VAR_017075.
FT VARIANT 469 469 L -> R (in PC1; dbSNP:rs57052654).
FT /FTId=VAR_017076.
FT VARIANT 472 472 E -> K (in PC1; dbSNP:rs60554162).
FT /FTId=VAR_017077.
FT CONFLICT 192 192 E -> D (in Ref. 1; AAB60696).
FT CONFLICT 241 241 G -> N (in Ref. 1; AAB60696).
FT CONFLICT 249 249 F -> L (in Ref. 1; AAB60696).
FT CONFLICT 395 395 I -> S (in Ref. 5; CAA24760).
FT CONFLICT 404 404 N -> S (in Ref. 1; AAB60696).
FT CONFLICT 443 443 R -> W (in Ref. 3; AAH69269).
FT CONFLICT 486 486 I -> V (in Ref. 1; AAB60696).
SQ SEQUENCE 564 AA; 60045 MW; 26708916C7DC923A CRC64;
MASTSTTIRS HSSSRRGFSA NSARLPGVSR SGFSSVSVSR SRGSGGLGGA CGGAGFGSRS
LYGLGGSKRI SIGGGSCAIS GGYGSRAGGS YGFGGAGSGF GFGGGAGIGF GLGGGAGLAG
GFGGPGFPVC PPGGIQEVTV NQSLLTPLNL QIDPTIQRVR AEEREQIKTL NNKFASFIDK
VRFLEQQNKV LETKWTLLQE QGTKTVRQNL EPLFEQYINN LRRQLDSIVG ERGRLDSELR
GMQDLVEDFK NKYEDEINKR TAAENEFVTL KKDVDAAYMN KVELQAKADT LTDEINFLRA
LYDAELSQMQ THISDTSVVL SMDNNRNLDL DSIIAEVKAQ YEEIAQRSRA EAESWYQTKY
EELQVTAGRH GDDLRNTKQE IAEINRMIQR LRSEIDHVKK QCANLQAAIA DAEQRGEMAL
KDAKNKLEGL EDALQKAKQD LARLLKEYQE LMNVKLALDV EIATYRKLLE GEECRLNGEG
VGQVNISVVQ STVSSGYGGA SGVGSGLGLG GGSSYSYGSG LGVGGGFSSS SGRAIGGGLS
SVGGGSSTIK YTTTSSSSRK SYKH
//
MIM
148041
*RECORD*
*FIELD* NO
148041
*FIELD* TI
*148041 KERATIN 6A; KRT6A
;;KERATIN, EPIDERMAL TYPE II, K6A; K6A;;
K6C;;
K6D
*FIELD* TX
read more
CLONING
Keratin 6A (K6A) is the dominant K6 isoform. Takahashi et al. (1995)
screened human genomic and skin cDNA libraries with probes derived from
the K6B gene (148042), and isolated clones containing the full-length
gene and cDNA predicted to encode K6a. As many as 6 different human K6
protein isoforms that are highly related at the gene structure,
nucleotide sequence, and predicted amino acid sequence levels were
identified. Takahashi et al. (1995) proposed an evolutionary model in
which the multiplicity of human K6 genes is explained by successive gene
duplication events. They confirmed that K6A is clearly the dominant K6
isoform in skin tissue samples and cultured epithelial cell lines and
that the various isoforms are differentially regulated within and
between epithelial tissue types.
GENE STRUCTURE
Tyner et al. (1985) provided information on the structure of a type II
keratin gene. A recent duplication in the basic keratin gene family gave
rise to 2 copies of the human K6 gene. One of the copies is expressed at
very low levels and may be at a still unextinguished step on the way to
becoming a traditional pseudogene.
Takahashi et al. (1995) determined that the KRT6A gene contains 9 exons.
MAPPING
Rosenberg et al. (1991) assigned the KRT6A gene to chromosome 12 by use
of Southern blot analysis of somatic cell hybrids. By in situ
hybridization of metaphase chromosomes, they demonstrated that the KRT6A
gene is located in region 12q12-q14.
MOLECULAR GENETICS
In affected members of a Slovenian family segregating type 1
pachyonychia congenita (PC1; 167200), a rare autosomal dominant disorder
characterized by multiple ectodermal abnormalities, Bowden et al. (1995)
identified heterozygosity for a mutation in the KRT6A gene
(148041.0001).
ANIMAL MODEL
Wong et al. (2000) found that K6-null mice have changes in the oral
mucosa resembling those of pachyonychia congenita. They speculated on
why the mice lacked obvious alterations in nail morphology, the
conspicuous feature in pachyonychia congenita.
Wojcik et al. (2001) generated mice deficient in both K6a and K6b. The
majority of K6a/K6b double-null mice died of starvation within the first
2 weeks of life. The starvation was due to a localized disintegration of
the dorsal tongue epithelium, which resulted in the buildup of a plaque
of cell debris that severely impaired feeding. However, about 25% of
K6a/K6b double-null mice survived to adulthood and had normal hair and
nails. Wojcik et al. (2001) identified a third K6 gene expressed in hair
follicles, K6hf (609025), and suggested that its presence offers an
explanation for the absence of hair and nail defects in K6a/K6b
double-null mice.
*FIELD* AV
.0001
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, 3-BP DEL, ASN8
In a Slovenian family, Bowden et al. (1995) observed type 1 pachyonychia
congenita (167200) in the grandfather, father, and daughter. The father
and daughter had classic changes with thickened nails, palmoplantar
keratoderma, and leukokeratosis of the tongue. The grandfather had only
minor nail changes and mild keratoderma (raising the possibility of
somatic and germinal mosaicism). No mutation was found in KRT16 and
KRT17 in which mutations had been found in other patients with
pachyonychia congenita. They identified heterozygosity for a 3-bp
deletion (AAC) in exon 1 of the K6A gene, which removed a highly
conserved asparagine residue from position 8 of the 1A helical domain.
The mutation was present in heterozygous state.
Terrinoni et al. (2001) found this mutation, which they designated
N171del, in 1 familial and 2 sporadic cases of PC1. The analogous
mutation in the KRT4 gene (123940.0001) was reported in 2 cases of white
sponge nevus (Rugg et al., 1995). This mutation is consistent with DNA
polymerase slippage during replication of 3 tandem CAA repeats present
in exon 1 of several type II keratin genes, including KRT4 and KRT6A.
.0002
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, PHE174VAL
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 520T-G transversion in the KRT6A gene that resulted in a
phe174-to-val (F174V) amino acid substitution. This mutation is F10V in
the 1A domain of the protein.
.0003
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, GLU472LYS
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 1414G-to-A transition in the KRT6A gene that resulted in a
glu472-to-lys (E472K) amino acid substitution. This mutation is E117K in
the 2B domain of the protein.
.0004
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, LEU469ARG
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 1406T-G transversion in the KRT6A gene that resulted in a
leu469-to-arg (L469R) amino acid substitution. This mutation is L114R in
the 2B domain of the protein.
*FIELD* RF
1. Bowden, P. E.; Haley, J. L.; Kansky, A.; Rothnagel, J. A.; Jones,
D. O.; Turner, R. J.: Mutation of a type II keratin gene (K6a) in
pachyonychia congenita. Nature Genet. 10: 363-365, 1995.
2. Rosenberg, M.; Fuchs, E.; Le Beau, M. M.; Eddy, R. L.; Shows, T.
B.: Three epidermal and one simple epithelial type II keratin genes
map to human chromosome 12. Cytogenet. Cell Genet. 57: 33-38, 1991.
3. Rugg, E. L.; McLean, W. H. I.; Allison, W. E.; Lunny, D. P.; Macleod,
R. I.; Felix, D. H.; Lane, E. B.; Munro, C. S.: A mutation in the
mucosal keratin K4 is associated with oral white sponge nevus. Nature
Genet. 11: 450-452, 1995.
4. Takahashi, K.; Paladini, R. D.; Coulombe, P. A.: Cloning and characterization
of multiple human genes and cDNAs encoding highly related type II
keratin 6 isoforms. J. Biol. Chem. 270: 18581-18592, 1995.
5. Terrinoni, A.; Smith, F. J. D.; Didona, B.; Canzona, F.; Paradisi,
M.; Huber, M.; Hohl, D.; David, A.; Verloes, A.; Leigh, I. M.; Munro,
C. S.; Melino, G.; McLean, W. H. I.: Novel and recurrent mutations
in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia
congenita. J. Invest. Derm. 117: 1391-1396, 2001.
6. Tyner, A.; Eichman, M.; Fuchs, E.: The sequence of a type II keratin
gene expressed in human skin: conservation of structure among all
intermediate filament genes. Proc. Nat. Acad. Sci. 82: 4683-4687,
1985.
7. Wojcik, S. M.; Longley, M. A.; Roop, D. R.: Discovery of a novel
murine keratin 6 (K6) isoform explains the absence of hair and nail
defects in mice deficient for K6a and K6b. J. Cell Biol. 154: 619-630,
2001.
8. Wong, P.; Colucci-Guyon, E.; Takahashi, K.; Gu, C.; Babinet, C.;
Coulombe, P. A.: Introducing a null mutation in the mouse K6-alpha
and K6-beta genes reveals their essential structural role in the oral
mucosa. J. Cell Biol. 150: 921-928, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 9/24/2008
Matthew B. Gross - updated: 11/12/2004
Gary A. Bellus - updated: 5/19/2003
Victor A. McKusick - updated: 9/28/2000
*FIELD* CD
Victor A. McKusick: 7/11/1990
*FIELD* ED
alopez: 09/08/2010
mgross: 9/24/2008
terry: 9/24/2008
carol: 8/28/2006
mgross: 11/12/2004
alopez: 5/19/2003
mcapotos: 10/17/2000
mcapotos: 10/16/2000
terry: 9/28/2000
terry: 3/10/1998
mark: 1/5/1998
alopez: 6/2/1997
mark: 9/27/1995
terry: 6/30/1995
supermim: 3/16/1992
carol: 10/9/1991
carol: 2/20/1991
carol: 7/11/1990
*RECORD*
*FIELD* NO
148041
*FIELD* TI
*148041 KERATIN 6A; KRT6A
;;KERATIN, EPIDERMAL TYPE II, K6A; K6A;;
K6C;;
K6D
*FIELD* TX
read more
CLONING
Keratin 6A (K6A) is the dominant K6 isoform. Takahashi et al. (1995)
screened human genomic and skin cDNA libraries with probes derived from
the K6B gene (148042), and isolated clones containing the full-length
gene and cDNA predicted to encode K6a. As many as 6 different human K6
protein isoforms that are highly related at the gene structure,
nucleotide sequence, and predicted amino acid sequence levels were
identified. Takahashi et al. (1995) proposed an evolutionary model in
which the multiplicity of human K6 genes is explained by successive gene
duplication events. They confirmed that K6A is clearly the dominant K6
isoform in skin tissue samples and cultured epithelial cell lines and
that the various isoforms are differentially regulated within and
between epithelial tissue types.
GENE STRUCTURE
Tyner et al. (1985) provided information on the structure of a type II
keratin gene. A recent duplication in the basic keratin gene family gave
rise to 2 copies of the human K6 gene. One of the copies is expressed at
very low levels and may be at a still unextinguished step on the way to
becoming a traditional pseudogene.
Takahashi et al. (1995) determined that the KRT6A gene contains 9 exons.
MAPPING
Rosenberg et al. (1991) assigned the KRT6A gene to chromosome 12 by use
of Southern blot analysis of somatic cell hybrids. By in situ
hybridization of metaphase chromosomes, they demonstrated that the KRT6A
gene is located in region 12q12-q14.
MOLECULAR GENETICS
In affected members of a Slovenian family segregating type 1
pachyonychia congenita (PC1; 167200), a rare autosomal dominant disorder
characterized by multiple ectodermal abnormalities, Bowden et al. (1995)
identified heterozygosity for a mutation in the KRT6A gene
(148041.0001).
ANIMAL MODEL
Wong et al. (2000) found that K6-null mice have changes in the oral
mucosa resembling those of pachyonychia congenita. They speculated on
why the mice lacked obvious alterations in nail morphology, the
conspicuous feature in pachyonychia congenita.
Wojcik et al. (2001) generated mice deficient in both K6a and K6b. The
majority of K6a/K6b double-null mice died of starvation within the first
2 weeks of life. The starvation was due to a localized disintegration of
the dorsal tongue epithelium, which resulted in the buildup of a plaque
of cell debris that severely impaired feeding. However, about 25% of
K6a/K6b double-null mice survived to adulthood and had normal hair and
nails. Wojcik et al. (2001) identified a third K6 gene expressed in hair
follicles, K6hf (609025), and suggested that its presence offers an
explanation for the absence of hair and nail defects in K6a/K6b
double-null mice.
*FIELD* AV
.0001
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, 3-BP DEL, ASN8
In a Slovenian family, Bowden et al. (1995) observed type 1 pachyonychia
congenita (167200) in the grandfather, father, and daughter. The father
and daughter had classic changes with thickened nails, palmoplantar
keratoderma, and leukokeratosis of the tongue. The grandfather had only
minor nail changes and mild keratoderma (raising the possibility of
somatic and germinal mosaicism). No mutation was found in KRT16 and
KRT17 in which mutations had been found in other patients with
pachyonychia congenita. They identified heterozygosity for a 3-bp
deletion (AAC) in exon 1 of the K6A gene, which removed a highly
conserved asparagine residue from position 8 of the 1A helical domain.
The mutation was present in heterozygous state.
Terrinoni et al. (2001) found this mutation, which they designated
N171del, in 1 familial and 2 sporadic cases of PC1. The analogous
mutation in the KRT4 gene (123940.0001) was reported in 2 cases of white
sponge nevus (Rugg et al., 1995). This mutation is consistent with DNA
polymerase slippage during replication of 3 tandem CAA repeats present
in exon 1 of several type II keratin genes, including KRT4 and KRT6A.
.0002
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, PHE174VAL
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 520T-G transversion in the KRT6A gene that resulted in a
phe174-to-val (F174V) amino acid substitution. This mutation is F10V in
the 1A domain of the protein.
.0003
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, GLU472LYS
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 1414G-to-A transition in the KRT6A gene that resulted in a
glu472-to-lys (E472K) amino acid substitution. This mutation is E117K in
the 2B domain of the protein.
.0004
PACHYONYCHIA CONGENITA, TYPE 1
KRT6A, LEU469ARG
In a patient with sporadic PC1 (167200), Terrinoni et al. (2001)
reported a 1406T-G transversion in the KRT6A gene that resulted in a
leu469-to-arg (L469R) amino acid substitution. This mutation is L114R in
the 2B domain of the protein.
*FIELD* RF
1. Bowden, P. E.; Haley, J. L.; Kansky, A.; Rothnagel, J. A.; Jones,
D. O.; Turner, R. J.: Mutation of a type II keratin gene (K6a) in
pachyonychia congenita. Nature Genet. 10: 363-365, 1995.
2. Rosenberg, M.; Fuchs, E.; Le Beau, M. M.; Eddy, R. L.; Shows, T.
B.: Three epidermal and one simple epithelial type II keratin genes
map to human chromosome 12. Cytogenet. Cell Genet. 57: 33-38, 1991.
3. Rugg, E. L.; McLean, W. H. I.; Allison, W. E.; Lunny, D. P.; Macleod,
R. I.; Felix, D. H.; Lane, E. B.; Munro, C. S.: A mutation in the
mucosal keratin K4 is associated with oral white sponge nevus. Nature
Genet. 11: 450-452, 1995.
4. Takahashi, K.; Paladini, R. D.; Coulombe, P. A.: Cloning and characterization
of multiple human genes and cDNAs encoding highly related type II
keratin 6 isoforms. J. Biol. Chem. 270: 18581-18592, 1995.
5. Terrinoni, A.; Smith, F. J. D.; Didona, B.; Canzona, F.; Paradisi,
M.; Huber, M.; Hohl, D.; David, A.; Verloes, A.; Leigh, I. M.; Munro,
C. S.; Melino, G.; McLean, W. H. I.: Novel and recurrent mutations
in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia
congenita. J. Invest. Derm. 117: 1391-1396, 2001.
6. Tyner, A.; Eichman, M.; Fuchs, E.: The sequence of a type II keratin
gene expressed in human skin: conservation of structure among all
intermediate filament genes. Proc. Nat. Acad. Sci. 82: 4683-4687,
1985.
7. Wojcik, S. M.; Longley, M. A.; Roop, D. R.: Discovery of a novel
murine keratin 6 (K6) isoform explains the absence of hair and nail
defects in mice deficient for K6a and K6b. J. Cell Biol. 154: 619-630,
2001.
8. Wong, P.; Colucci-Guyon, E.; Takahashi, K.; Gu, C.; Babinet, C.;
Coulombe, P. A.: Introducing a null mutation in the mouse K6-alpha
and K6-beta genes reveals their essential structural role in the oral
mucosa. J. Cell Biol. 150: 921-928, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 9/24/2008
Matthew B. Gross - updated: 11/12/2004
Gary A. Bellus - updated: 5/19/2003
Victor A. McKusick - updated: 9/28/2000
*FIELD* CD
Victor A. McKusick: 7/11/1990
*FIELD* ED
alopez: 09/08/2010
mgross: 9/24/2008
terry: 9/24/2008
carol: 8/28/2006
mgross: 11/12/2004
alopez: 5/19/2003
mcapotos: 10/17/2000
mcapotos: 10/16/2000
terry: 9/28/2000
terry: 3/10/1998
mark: 1/5/1998
alopez: 6/2/1997
mark: 9/27/1995
terry: 6/30/1995
supermim: 3/16/1992
carol: 10/9/1991
carol: 2/20/1991
carol: 7/11/1990
MIM
167200
*RECORD*
*FIELD* NO
167200
*FIELD* TI
#167200 PACHYONYCHIA CONGENITA, TYPE 1; PC1
;;PACHYONYCHIA CONGENITA, JADASSOHN-LEWANDOWSKY TYPE;;
read moreJADASSOHN-LEWANDOWSKY SYNDROME
PACHYONYCHIA CONGENITA TARDA, TYPE 1, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
pachyonychia congenita type 1 (PC1) can be caused by heterozygous
mutation in the keratin-16 gene (KRT16; 148067) on chromosome 17 or in
the keratin-6A gene (KRT6A; 148041) on chromosome 12.
Pachyonychia congenita type 2, or the Jackson-Lawler (PC2; 167210), can
be caused by mutation in the KRT17 gene (148069) on chromosome 17 or in
the KRT6B gene (148042) on chromosome 12.
See 260130 for a possible autosomal recessive form of pachyonychia
congenita.
CLINICAL FEATURES
Pachyonychia congenita is characterized by onychogryposis,
hyperkeratosis of the palms, soles, knees and elbows, tiny cutaneous
horns in many areas, and leukoplakia of the oral mucous membranes.
Hyperhidrosis of the hands and feet is usually present. Murray (1921)
found 7 affected in 3 generations. Kumer and Loos (1935) found 24
affected in 5 generations. McKusick (1971) observed an apparent new
mutation with transmission from father to son in a Jewish family.
Laryngeal changes requiring tracheostomy for respiratory distress during
childhood were reported by Stieglitz and Centerwall (1983) in father and
son. Feinstein et al. (1988) classified 168 reported cases into 4 types,
of which type IV, present in 7.2% of the cases, had laryngeal lesions,
hoarseness, mental retardation, hair anomalies, and alopecia. Paller et
al. (1991) described a late-onset form in which typical subungual
hyperkeratoses began during the teenage years. Leukokeratosis and
keratoderma of the palms and soles were associated. The family history
of 3 of the 5 patients was consistent with autosomal dominant
inheritance.
Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed
under the designation pachyonychia congenita. PC1, the
Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC2, the Jackson
and Lawler type, has natal teeth and epidermoid cysts (cylindromas), but
no oral leukoplakia. Corneal dystrophy may be a feature exclusively of
the Jackson-Lawler type. Both disorders are clearly autosomal dominant.
On the basis of a study of 13 patients with PC1 or PC2, Terrinoni et al.
(2001) concluded that the presence of pilosebaceous cysts following
puberty is the best indicator of PC2; prepubescent patients are more
difficult to classify due to the lack of cysts. Natal teeth are
indicative of PC2, although their absence does not preclude the PC2
diagnosis.
Leachman et al. (2005) analyzed clinical, pathologic, and genetic data
from the literature in 2 research registries. They found that more than
97% of PC cases exhibited fingernail and toenail thickening, and painful
plantar keratoderma. Prospective evaluation of 57 PC patients from 41
families revealed variable clinical findings: hyperhidrosis (79%), oral
leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma
(60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%),
coarse or twisted hair (26%), early primary tooth loss (14%), and
presence of natal or prenatal teeth (2%). Stratification of these data
by keratin mutation confirmed the increased incidence of cyst formation
and natal teeth among PC2 patients, although cysts were more commonly
seen in PC1 patients than had previously reported (25-33%). Previously
unreported clinical features of PC included development of painful oral
and nipple lesions during breastfeeding, copious production of waxy
material in ears, and inability to walk without an ambulatory aid (50%).
- Pachyonychia Congenita Tarda, Type 1
Pachyonychia congenita with late onset of symptoms has been described by
several authors (Paller et al., 1991; Iraci et al., 1993; Lucker and
Steijlen, 1995; Mouaci-Midoun et al., 1996; Hannaford and Stapleton,
2000) and has been referred to as pachyonychia congenita tarda. There
has been some debate as to whether these late-onset cases represent a
separate genetic syndrome or a variant form of PC1. Connors et al.
(2001) described a young girl with clinical features of pachyonychia
congenita type 1 that was unusual in that the typical skin and nail
changes were not noted until the age of 6 years. Direct sequencing of
the KRT16 gene revealed a novel lys354 to asn mutation (K354N;
148067.0008) in the central 2B domain of the KRT16 polypeptide.
Mutations in this region of KRT16 had not been described, but had been
described in homologous regions of KRT14 (148066) in the milder Koebner
(131900) and Weber-Cockayne (131800) variants of epidermolysis simplex.
It was unclear whether the position of the mutation was sufficient to
explain the late-onset phenotype.
DIAGNOSIS
- Prenatal Diagnosis
Using a genomic PCR system, Smith et al. (1999) carried out the first
prenatal diagnosis of Jadassohn-Lewandowsky syndrome using CVS material
and correctly predicted a normal fetus.
MOLECULAR GENETICS
In a sporadic case of pachyonychia congenita type 1, Smith et al. (1999)
identified heterozygosity for a 3-bp deletion (148067.0001) in the KRT16
gene.
In affected members of a Slovenian family segregating PC1, Bowden et al.
(1995) identified heterozygosity for a 3-bp deletion in the KRT6A gene
(148041.0001).
*FIELD* SA
Akesson (1967); Cohn et al. (1976); Franzot et al. (1981); Jadassohn
and Lewandowsky (1906); Joseph (1964); Witkop and Gorlin (1961)
*FIELD* RF
1. Akesson, H. O.: Pachyonychia congenita in six generations. Hereditas 58:
103-110, 1967.
2. Bowden, P. E.; Haley, J. L.; Kansky, A.; Rothnagel, J. A.; Jones,
D. O.; Turner, R. J.: Mutation of a type II keratin gene (K6a) in
pachyonychia congenita. Nature Genet. 10: 363-365, 1995.
3. Cohn, A. M.; McFarlane, J. F.; Knox, J.: Pachyonychia congenita
with involvement of the larynx. Arch. Otolaryng. 102: 233-235, 1976.
4. Connors, J. B.; Rahil, A. K.; Smith, F. J. D.; McLean, W. H. I.;
Milstone, L. M.: Delayed-onset pachyonychia congenita associated
with a novel mutation in the central 2B domain of keratin 16. Brit.
J. Derm. 144: 1058-1062, 2001.
5. Feinstein, A.; Friedman, J.; Schewach-Millet, M.: Pachyonychia
congenita. J. Am. Acad. Derm. 19: 705-711, 1988.
6. Franzot, J.; Kansky, A.; Kavcic, S.: Pachyonychia congenita (Jadassohn-Lewandowsky
syndrome): a review of 14 cases in Slovenia. Dermatologica 160:
462-472, 1981.
7. Gorlin, R. J.; Pindborg, J. J.; Cohen, M. M., Jr.: Syndromes of
the Head and Neck. New York: McGraw-Hill (pub.) (2nd ed.): 1976.
Pp. 600-603.
8. Hannaford, R. S.; Stapleton, K.: Pachyonychia congenita tarda. Australas.
J. Derm. 41: 175-177, 2000.
9. Iraci, S.; Bianchi, L.; Gatti, S.; Carrozzo, A. M.; Bettini, D.;
Nini, G.: Pachyonychia congenita with late onset of nail dystrophy--a
new clinical entity? Clin. Exp. Derm. 18: 478-480, 1993.
10. Jadassohn, J.; Lewandowsky, F.: Pachyonychia congenita.In: Jacobs
Ikonographia Dermatologica. Berlin: Urban and Schwarzenberg (pub.)
1: 1906. P. 29.
11. Joseph, H. L.: Pachyonychia congenita. Arch. Derm. 90: 594-603,
1964.
12. Kumer, L.; Loos, H. O.: Ueber Pachyonychia congenita (Typus Riehl). Wien.
Klin. Wschr. 48: 174-178, 1935.
13. Leachman, S. A.; Kaspar, R. L.; Fleckman, P.; Florell, S. R.;
Smith, F. J. D.; McLean, W. H. I.; Lunny, D. P.; Milstone, L. M.;
van Steensel, M. A. M.; Munro, C. S.; O'Toole, E. A.; Celebi, J. T.;
Kansky, A.; Lane, E. B.: Clinical and pathological features of pachyonychia
congenita. J. Invest. Derm. Symp. Proc. 10: 3-17, 2005.
14. Lucker, G. P. H.; Steijlen, P. M.: Pachyonychia congenita tarda. Clin.
Exp. Derm. 20: 226-229, 1995.
15. McKusick, V. A.: Pachyonychia congenita in father and son. Birth
Defects Orig. Art. Ser. VII(8): 274-275, 1971.
16. Mouaci-Midoun, N.; Cambiaghi, S.; Abimelec, P.: Pachyonychia
congenita tarda. J. Am. Acad. Derm. 35: 334-335, 1996.
17. Murray, F. A.: Congenital anomalies of the nails. Four cases
of hereditary hypertrophy of the nail bed associated with a history
of erupted teeth at birth. Brit. J. Derm. 33: 409-412, 1921.
18. Paller, A. S.; Moore, J. A.; Scher, R.: Pachyonychia congenita
tarda: a late-onset form of pachyonychia congenita. Arch. Derm. 127:
701-703, 1991.
19. Smith, F. J. D.; McKusick, V. A.; Nielsen, K.; Pfendner, E.; Uitto,
J.; McLean, W. H. I.: Cloning of multiple keratin 16 genes facilitates
prenatal diagnosis of pachyonychia congenita type 1. Prenatal Diag. 19:
941-946, 1999.
20. Stieglitz, J. B.; Centerwall, W. R.: Pachyonychia congenita (Jadassohn-Lewandowsky
syndrome): a seventeen-member, four-generation pedigree with unusual
respiratory and dental involvement. Am. J. Med. Genet. 14: 21-28,
1983.
21. Terrinoni, A.; Smith, F. J. D.; Didona, B.; Canzona, F.; Paradisi,
M.; Huber, M.; Hohl, D.; David, A.; Verloes, A.; Leigh, I. M.; Munro,
C. S.; Melino, G.; McLean, W. H. I.: Novel and recurrent mutations
in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia
congenita. J. Invest. Derm. 117: 1391-1396, 2001.
22. Witkop, C. J., Jr.; Gorlin, R. J.: Four hereditary mucosal syndromes. Arch.
Derm. 84: 762-771, 1961.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Mouth];
Oral leukokeratosis
SKIN, NAILS, HAIR:
[Skin];
Palmoplantar hyperkeratosis;
Follicular hyperkeratosis;
[Nails];
Onychogryposis
MISCELLANEOUS:
Genetic heterogeneity
MOLECULAR BASIS:
Caused by mutation in the keratin 16 gene (KRT16, 148067.0001);
Caused by mutation in the keratin 6A gene (KRT6A, 148041.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 03/08/2008
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 03/08/2008
*FIELD* CN
Victor A. McKusick - updated: 1/17/2006
Gary A. Bellus - updated: 4/23/2003
Victor A. McKusick - updated: 3/13/1998
Victor A. McKusick - updated: 3/25/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 01/10/2014
carol: 7/8/2013
alopez: 7/3/2013
terry: 4/30/2010
terry: 12/16/2009
carol: 2/11/2009
carol: 4/18/2006
carol: 1/17/2006
terry: 1/17/2006
carol: 6/23/2005
cwells: 11/7/2003
tkritzer: 9/29/2003
alopez: 4/23/2003
alopez: 4/12/2000
carol: 1/28/2000
carol: 7/29/1998
alopez: 5/5/1998
alopez: 3/13/1998
terry: 3/10/1998
alopez: 3/25/1997
terry: 3/18/1997
terry: 6/30/1995
carol: 3/15/1995
mimadm: 1/14/1995
pfoster: 4/1/1994
warfield: 3/3/1994
supermim: 3/16/1992
*RECORD*
*FIELD* NO
167200
*FIELD* TI
#167200 PACHYONYCHIA CONGENITA, TYPE 1; PC1
;;PACHYONYCHIA CONGENITA, JADASSOHN-LEWANDOWSKY TYPE;;
read moreJADASSOHN-LEWANDOWSKY SYNDROME
PACHYONYCHIA CONGENITA TARDA, TYPE 1, INCLUDED
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
pachyonychia congenita type 1 (PC1) can be caused by heterozygous
mutation in the keratin-16 gene (KRT16; 148067) on chromosome 17 or in
the keratin-6A gene (KRT6A; 148041) on chromosome 12.
Pachyonychia congenita type 2, or the Jackson-Lawler (PC2; 167210), can
be caused by mutation in the KRT17 gene (148069) on chromosome 17 or in
the KRT6B gene (148042) on chromosome 12.
See 260130 for a possible autosomal recessive form of pachyonychia
congenita.
CLINICAL FEATURES
Pachyonychia congenita is characterized by onychogryposis,
hyperkeratosis of the palms, soles, knees and elbows, tiny cutaneous
horns in many areas, and leukoplakia of the oral mucous membranes.
Hyperhidrosis of the hands and feet is usually present. Murray (1921)
found 7 affected in 3 generations. Kumer and Loos (1935) found 24
affected in 5 generations. McKusick (1971) observed an apparent new
mutation with transmission from father to son in a Jewish family.
Laryngeal changes requiring tracheostomy for respiratory distress during
childhood were reported by Stieglitz and Centerwall (1983) in father and
son. Feinstein et al. (1988) classified 168 reported cases into 4 types,
of which type IV, present in 7.2% of the cases, had laryngeal lesions,
hoarseness, mental retardation, hair anomalies, and alopecia. Paller et
al. (1991) described a late-onset form in which typical subungual
hyperkeratoses began during the teenage years. Leukokeratosis and
keratoderma of the palms and soles were associated. The family history
of 3 of the 5 patients was consistent with autosomal dominant
inheritance.
Gorlin et al. (1976) suggested that 2 distinct syndromes are subsumed
under the designation pachyonychia congenita. PC1, the
Jadassohn-Lewandowsky type, shows oral leukokeratosis. PC2, the Jackson
and Lawler type, has natal teeth and epidermoid cysts (cylindromas), but
no oral leukoplakia. Corneal dystrophy may be a feature exclusively of
the Jackson-Lawler type. Both disorders are clearly autosomal dominant.
On the basis of a study of 13 patients with PC1 or PC2, Terrinoni et al.
(2001) concluded that the presence of pilosebaceous cysts following
puberty is the best indicator of PC2; prepubescent patients are more
difficult to classify due to the lack of cysts. Natal teeth are
indicative of PC2, although their absence does not preclude the PC2
diagnosis.
Leachman et al. (2005) analyzed clinical, pathologic, and genetic data
from the literature in 2 research registries. They found that more than
97% of PC cases exhibited fingernail and toenail thickening, and painful
plantar keratoderma. Prospective evaluation of 57 PC patients from 41
families revealed variable clinical findings: hyperhidrosis (79%), oral
leukokeratosis (75%), follicular keratosis (65%), palmar keratoderma
(60%), cutaneous cysts (35%), hoarseness or laryngeal involvement (16%),
coarse or twisted hair (26%), early primary tooth loss (14%), and
presence of natal or prenatal teeth (2%). Stratification of these data
by keratin mutation confirmed the increased incidence of cyst formation
and natal teeth among PC2 patients, although cysts were more commonly
seen in PC1 patients than had previously reported (25-33%). Previously
unreported clinical features of PC included development of painful oral
and nipple lesions during breastfeeding, copious production of waxy
material in ears, and inability to walk without an ambulatory aid (50%).
- Pachyonychia Congenita Tarda, Type 1
Pachyonychia congenita with late onset of symptoms has been described by
several authors (Paller et al., 1991; Iraci et al., 1993; Lucker and
Steijlen, 1995; Mouaci-Midoun et al., 1996; Hannaford and Stapleton,
2000) and has been referred to as pachyonychia congenita tarda. There
has been some debate as to whether these late-onset cases represent a
separate genetic syndrome or a variant form of PC1. Connors et al.
(2001) described a young girl with clinical features of pachyonychia
congenita type 1 that was unusual in that the typical skin and nail
changes were not noted until the age of 6 years. Direct sequencing of
the KRT16 gene revealed a novel lys354 to asn mutation (K354N;
148067.0008) in the central 2B domain of the KRT16 polypeptide.
Mutations in this region of KRT16 had not been described, but had been
described in homologous regions of KRT14 (148066) in the milder Koebner
(131900) and Weber-Cockayne (131800) variants of epidermolysis simplex.
It was unclear whether the position of the mutation was sufficient to
explain the late-onset phenotype.
DIAGNOSIS
- Prenatal Diagnosis
Using a genomic PCR system, Smith et al. (1999) carried out the first
prenatal diagnosis of Jadassohn-Lewandowsky syndrome using CVS material
and correctly predicted a normal fetus.
MOLECULAR GENETICS
In a sporadic case of pachyonychia congenita type 1, Smith et al. (1999)
identified heterozygosity for a 3-bp deletion (148067.0001) in the KRT16
gene.
In affected members of a Slovenian family segregating PC1, Bowden et al.
(1995) identified heterozygosity for a 3-bp deletion in the KRT6A gene
(148041.0001).
*FIELD* SA
Akesson (1967); Cohn et al. (1976); Franzot et al. (1981); Jadassohn
and Lewandowsky (1906); Joseph (1964); Witkop and Gorlin (1961)
*FIELD* RF
1. Akesson, H. O.: Pachyonychia congenita in six generations. Hereditas 58:
103-110, 1967.
2. Bowden, P. E.; Haley, J. L.; Kansky, A.; Rothnagel, J. A.; Jones,
D. O.; Turner, R. J.: Mutation of a type II keratin gene (K6a) in
pachyonychia congenita. Nature Genet. 10: 363-365, 1995.
3. Cohn, A. M.; McFarlane, J. F.; Knox, J.: Pachyonychia congenita
with involvement of the larynx. Arch. Otolaryng. 102: 233-235, 1976.
4. Connors, J. B.; Rahil, A. K.; Smith, F. J. D.; McLean, W. H. I.;
Milstone, L. M.: Delayed-onset pachyonychia congenita associated
with a novel mutation in the central 2B domain of keratin 16. Brit.
J. Derm. 144: 1058-1062, 2001.
5. Feinstein, A.; Friedman, J.; Schewach-Millet, M.: Pachyonychia
congenita. J. Am. Acad. Derm. 19: 705-711, 1988.
6. Franzot, J.; Kansky, A.; Kavcic, S.: Pachyonychia congenita (Jadassohn-Lewandowsky
syndrome): a review of 14 cases in Slovenia. Dermatologica 160:
462-472, 1981.
7. Gorlin, R. J.; Pindborg, J. J.; Cohen, M. M., Jr.: Syndromes of
the Head and Neck. New York: McGraw-Hill (pub.) (2nd ed.): 1976.
Pp. 600-603.
8. Hannaford, R. S.; Stapleton, K.: Pachyonychia congenita tarda. Australas.
J. Derm. 41: 175-177, 2000.
9. Iraci, S.; Bianchi, L.; Gatti, S.; Carrozzo, A. M.; Bettini, D.;
Nini, G.: Pachyonychia congenita with late onset of nail dystrophy--a
new clinical entity? Clin. Exp. Derm. 18: 478-480, 1993.
10. Jadassohn, J.; Lewandowsky, F.: Pachyonychia congenita.In: Jacobs
Ikonographia Dermatologica. Berlin: Urban and Schwarzenberg (pub.)
1: 1906. P. 29.
11. Joseph, H. L.: Pachyonychia congenita. Arch. Derm. 90: 594-603,
1964.
12. Kumer, L.; Loos, H. O.: Ueber Pachyonychia congenita (Typus Riehl). Wien.
Klin. Wschr. 48: 174-178, 1935.
13. Leachman, S. A.; Kaspar, R. L.; Fleckman, P.; Florell, S. R.;
Smith, F. J. D.; McLean, W. H. I.; Lunny, D. P.; Milstone, L. M.;
van Steensel, M. A. M.; Munro, C. S.; O'Toole, E. A.; Celebi, J. T.;
Kansky, A.; Lane, E. B.: Clinical and pathological features of pachyonychia
congenita. J. Invest. Derm. Symp. Proc. 10: 3-17, 2005.
14. Lucker, G. P. H.; Steijlen, P. M.: Pachyonychia congenita tarda. Clin.
Exp. Derm. 20: 226-229, 1995.
15. McKusick, V. A.: Pachyonychia congenita in father and son. Birth
Defects Orig. Art. Ser. VII(8): 274-275, 1971.
16. Mouaci-Midoun, N.; Cambiaghi, S.; Abimelec, P.: Pachyonychia
congenita tarda. J. Am. Acad. Derm. 35: 334-335, 1996.
17. Murray, F. A.: Congenital anomalies of the nails. Four cases
of hereditary hypertrophy of the nail bed associated with a history
of erupted teeth at birth. Brit. J. Derm. 33: 409-412, 1921.
18. Paller, A. S.; Moore, J. A.; Scher, R.: Pachyonychia congenita
tarda: a late-onset form of pachyonychia congenita. Arch. Derm. 127:
701-703, 1991.
19. Smith, F. J. D.; McKusick, V. A.; Nielsen, K.; Pfendner, E.; Uitto,
J.; McLean, W. H. I.: Cloning of multiple keratin 16 genes facilitates
prenatal diagnosis of pachyonychia congenita type 1. Prenatal Diag. 19:
941-946, 1999.
20. Stieglitz, J. B.; Centerwall, W. R.: Pachyonychia congenita (Jadassohn-Lewandowsky
syndrome): a seventeen-member, four-generation pedigree with unusual
respiratory and dental involvement. Am. J. Med. Genet. 14: 21-28,
1983.
21. Terrinoni, A.; Smith, F. J. D.; Didona, B.; Canzona, F.; Paradisi,
M.; Huber, M.; Hohl, D.; David, A.; Verloes, A.; Leigh, I. M.; Munro,
C. S.; Melino, G.; McLean, W. H. I.: Novel and recurrent mutations
in the genes encoding keratins K6a, K16 and K17 in 13 cases of pachyonychia
congenita. J. Invest. Derm. 117: 1391-1396, 2001.
22. Witkop, C. J., Jr.; Gorlin, R. J.: Four hereditary mucosal syndromes. Arch.
Derm. 84: 762-771, 1961.
*FIELD* CS
INHERITANCE:
Autosomal dominant
HEAD AND NECK:
[Mouth];
Oral leukokeratosis
SKIN, NAILS, HAIR:
[Skin];
Palmoplantar hyperkeratosis;
Follicular hyperkeratosis;
[Nails];
Onychogryposis
MISCELLANEOUS:
Genetic heterogeneity
MOLECULAR BASIS:
Caused by mutation in the keratin 16 gene (KRT16, 148067.0001);
Caused by mutation in the keratin 6A gene (KRT6A, 148041.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 03/08/2008
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 03/08/2008
*FIELD* CN
Victor A. McKusick - updated: 1/17/2006
Gary A. Bellus - updated: 4/23/2003
Victor A. McKusick - updated: 3/13/1998
Victor A. McKusick - updated: 3/25/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 01/10/2014
carol: 7/8/2013
alopez: 7/3/2013
terry: 4/30/2010
terry: 12/16/2009
carol: 2/11/2009
carol: 4/18/2006
carol: 1/17/2006
terry: 1/17/2006
carol: 6/23/2005
cwells: 11/7/2003
tkritzer: 9/29/2003
alopez: 4/23/2003
alopez: 4/12/2000
carol: 1/28/2000
carol: 7/29/1998
alopez: 5/5/1998
alopez: 3/13/1998
terry: 3/10/1998
alopez: 3/25/1997
terry: 3/18/1997
terry: 6/30/1995
carol: 3/15/1995
mimadm: 1/14/1995
pfoster: 4/1/1994
warfield: 3/3/1994
supermim: 3/16/1992