Full text data of AAGAB
AAGAB
[Confidence: low (only semi-automatic identification from reviews)]
Alpha- and gamma-adaptin-binding protein p34
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Alpha- and gamma-adaptin-binding protein p34
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q6PD74
ID AAGAB_HUMAN Reviewed; 315 AA.
AC Q6PD74; Q6FI86; Q7Z5X9; Q9H0P1; Q9HAK0;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 85.
DE RecName: Full=Alpha- and gamma-adaptin-binding protein p34;
GN Name=AAGAB;
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 [LARGE SCALE MRNA], AND VARIANT LEU-132.
RC TISSUE=Embryo;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-132.
RC TISSUE=Fetal kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-132.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP INVOLVEMENT IN PPKP1A, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23000146; DOI=10.1016/j.ajhg.2012.08.024;
RA Giehl K.A., Eckstein G.N., Pasternack S.M., Praetzel-Wunder S.,
RA Ruzicka T., Lichtner P., Seidl K., Rogers M., Graf E., Langbein L.,
RA Braun-Falco M., Betz R.C., Strom T.M.;
RT "Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma
RT type Buschke-Fischer-Brauer.";
RL Am. J. Hum. Genet. 91:754-759(2012).
RN [11]
RP INVOLVEMENT IN PPKP1A, FUNCTION, IDENTIFICATION IN AP-1 AND AP-2
RP COMPLEXES, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23064416; DOI=10.1038/ng.2444;
RA Pohler E., Mamai O., Hirst J., Zamiri M., Horn H., Nomura T.,
RA Irvine A.D., Moran B., Wilson N.J., Smith F.J., Goh C.S.,
RA Sandilands A., Cole C., Barton G.J., Evans A.T., Shimizu H.,
RA Akiyama M., Suehiro M., Konohana I., Shboul M., Teissier S.,
RA Boussofara L., Denguezli M., Saad A., Gribaa M.,
RA Dopping-Hepenstal P.J., McGrath J.A., Brown S.J., Goudie D.R.,
RA Reversade B., Munro C.S., McLean W.H.;
RT "Haploinsufficiency for AAGAB causes clinically heterogeneous forms of
RT punctate palmoplantar keratoderma.";
RL Nat. Genet. 44:1272-1276(2012).
CC -!- FUNCTION: May be involved in endocytic recycling of growth factor
CC receptors such as EGFR.
CC -!- SUBUNIT: Associated with AP-1 and AP-2 complexes.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- TISSUE SPECIFICITY: Widely expressed, including in skin and
CC keratinocytes, with highest levels in adrenal gland, rectum and
CC thymus.
CC -!- DISEASE: Keratoderma, palmoplantar, punctate 1A (PPKP1A)
CC [MIM:148600]: An autosomal dominant dermatological disorder
CC characterized by multiple hyperkeratotic, centrally indented,
CC papules that develop in early adolescence, or later, and are
CC irregularly distributed on the palms and soles (other palmoplantar
CC keratoses have mostly diffuse hyperkeratinization). In
CC mechanically irritated areas, confluent plaques can be found.
CC Interfamilial and intrafamilial severity shows broad variation. In
CC some cases, PPKP1 is associated with the development of early- and
CC late-onset malignancies, including squamous cell carcinoma.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
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DR EMBL; AK021568; BAB13845.1; -; mRNA.
DR EMBL; AL136715; CAB66649.1; -; mRNA.
DR EMBL; CR533540; CAG38571.1; -; mRNA.
DR EMBL; BC001975; AAH01975.1; -; mRNA.
DR EMBL; BC047026; AAH47026.1; -; mRNA.
DR EMBL; BC058886; AAH58886.1; -; mRNA.
DR RefSeq; NP_001258814.1; NM_001271885.1.
DR RefSeq; NP_001258815.1; NM_001271886.1.
DR RefSeq; NP_078942.3; NM_024666.4.
DR UniGene; Hs.254642; -.
DR UniGene; Hs.602761; -.
DR ProteinModelPortal; Q6PD74; -.
DR IntAct; Q6PD74; 2.
DR MINT; MINT-1373784; -.
DR STRING; 9606.ENSP00000261880; -.
DR PhosphoSite; Q6PD74; -.
DR DMDM; 62286981; -.
DR PaxDb; Q6PD74; -.
DR PeptideAtlas; Q6PD74; -.
DR PRIDE; Q6PD74; -.
DR DNASU; 79719; -.
DR Ensembl; ENST00000261880; ENSP00000261880; ENSG00000103591.
DR GeneID; 79719; -.
DR KEGG; hsa:79719; -.
DR UCSC; uc002aqk.5; human.
DR CTD; 79719; -.
DR GeneCards; GC15M067493; -.
DR HGNC; HGNC:25662; AAGAB.
DR HPA; HPA039371; -.
DR HPA; HPA040174; -.
DR MIM; 148600; phenotype.
DR MIM; 614888; gene.
DR neXtProt; NX_Q6PD74; -.
DR Orphanet; 79501; Punctate palmoplantar keratoderma type 1.
DR PharmGKB; PA165478457; -.
DR eggNOG; NOG271587; -.
DR HOGENOM; HOG000115322; -.
DR InParanoid; Q6PD74; -.
DR OMA; VMKNDRN; -.
DR OrthoDB; EOG7DZ8PB; -.
DR PhylomeDB; Q6PD74; -.
DR ChiTaRS; AAGAB; human.
DR GeneWiki; FLJ11506; -.
DR GenomeRNAi; 79719; -.
DR NextBio; 69069; -.
DR PRO; PR:Q6PD74; -.
DR ArrayExpress; Q6PD74; -.
DR Bgee; Q6PD74; -.
DR Genevestigator; Q6PD74; -.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR019341; Alpha/Gamma-adaptin-bd_p34.
DR Pfam; PF10199; Adaptin_binding; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Palmoplantar keratoderma;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 315 Alpha- and gamma-adaptin-binding protein
FT p34.
FT /FTId=PRO_0000058134.
FT MOD_RES 310 310 Phosphoserine.
FT MOD_RES 311 311 Phosphoserine.
FT VARIANT 132 132 I -> L (in dbSNP:rs7173826).
FT /FTId=VAR_021533.
FT CONFLICT 26 26 I -> T (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 77 77 V -> A (in Ref. 3; CAG38571).
FT CONFLICT 88 88 Q -> R (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 131 131 C -> S (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 265 265 L -> P (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 313 313 E -> G (in Ref. 2; CAB66649 and 3;
FT CAG38571).
SQ SEQUENCE 315 AA; 34594 MW; C1C765B4F9717E0B CRC64;
MAAGVPCALV TSCSSVFSGD QLVQHILGTE DLIVEVTSND AVRFYPWTID NKYYSADINL
CVVPNKFLVT AEIAESVQAF VVYFDSTQKS GLDSVSSWLP LAKAWLPEVM ILVCDRVSED
GINRQKAQEW CIKHGFELVE LSPEELPEED DDFPESTGVK RIVQALNANV WSNVVMKNDR
NQGFSLLNSL TGTNHSIGSA DPCHPEQPHL PAADSTESLS DHRGGASNTT DAQVDSIVDP
MLDLDIQELA SLTTGGGDVE NFERLFSKLK EMKDKAATLP HEQRKVHAEK VAKAFWMAIG
GDRDEIEGLS SDEEH
//
ID AAGAB_HUMAN Reviewed; 315 AA.
AC Q6PD74; Q6FI86; Q7Z5X9; Q9H0P1; Q9HAK0;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
read moreDT 05-JUL-2004, sequence version 1.
DT 22-JAN-2014, entry version 85.
DE RecName: Full=Alpha- and gamma-adaptin-binding protein p34;
GN Name=AAGAB;
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 [LARGE SCALE MRNA], AND VARIANT LEU-132.
RC TISSUE=Embryo;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-132.
RC TISSUE=Fetal kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-132.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and 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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT the kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-310 AND SER-311, AND
RP MASS SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP INVOLVEMENT IN PPKP1A, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23000146; DOI=10.1016/j.ajhg.2012.08.024;
RA Giehl K.A., Eckstein G.N., Pasternack S.M., Praetzel-Wunder S.,
RA Ruzicka T., Lichtner P., Seidl K., Rogers M., Graf E., Langbein L.,
RA Braun-Falco M., Betz R.C., Strom T.M.;
RT "Nonsense mutations in AAGAB cause punctate palmoplantar keratoderma
RT type Buschke-Fischer-Brauer.";
RL Am. J. Hum. Genet. 91:754-759(2012).
RN [11]
RP INVOLVEMENT IN PPKP1A, FUNCTION, IDENTIFICATION IN AP-1 AND AP-2
RP COMPLEXES, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23064416; DOI=10.1038/ng.2444;
RA Pohler E., Mamai O., Hirst J., Zamiri M., Horn H., Nomura T.,
RA Irvine A.D., Moran B., Wilson N.J., Smith F.J., Goh C.S.,
RA Sandilands A., Cole C., Barton G.J., Evans A.T., Shimizu H.,
RA Akiyama M., Suehiro M., Konohana I., Shboul M., Teissier S.,
RA Boussofara L., Denguezli M., Saad A., Gribaa M.,
RA Dopping-Hepenstal P.J., McGrath J.A., Brown S.J., Goudie D.R.,
RA Reversade B., Munro C.S., McLean W.H.;
RT "Haploinsufficiency for AAGAB causes clinically heterogeneous forms of
RT punctate palmoplantar keratoderma.";
RL Nat. Genet. 44:1272-1276(2012).
CC -!- FUNCTION: May be involved in endocytic recycling of growth factor
CC receptors such as EGFR.
CC -!- SUBUNIT: Associated with AP-1 and AP-2 complexes.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol.
CC -!- TISSUE SPECIFICITY: Widely expressed, including in skin and
CC keratinocytes, with highest levels in adrenal gland, rectum and
CC thymus.
CC -!- DISEASE: Keratoderma, palmoplantar, punctate 1A (PPKP1A)
CC [MIM:148600]: An autosomal dominant dermatological disorder
CC characterized by multiple hyperkeratotic, centrally indented,
CC papules that develop in early adolescence, or later, and are
CC irregularly distributed on the palms and soles (other palmoplantar
CC keratoses have mostly diffuse hyperkeratinization). In
CC mechanically irritated areas, confluent plaques can be found.
CC Interfamilial and intrafamilial severity shows broad variation. In
CC some cases, PPKP1 is associated with the development of early- and
CC late-onset malignancies, including squamous cell carcinoma.
CC Note=The disease is caused by mutations affecting the gene
CC represented in this entry.
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; AK021568; BAB13845.1; -; mRNA.
DR EMBL; AL136715; CAB66649.1; -; mRNA.
DR EMBL; CR533540; CAG38571.1; -; mRNA.
DR EMBL; BC001975; AAH01975.1; -; mRNA.
DR EMBL; BC047026; AAH47026.1; -; mRNA.
DR EMBL; BC058886; AAH58886.1; -; mRNA.
DR RefSeq; NP_001258814.1; NM_001271885.1.
DR RefSeq; NP_001258815.1; NM_001271886.1.
DR RefSeq; NP_078942.3; NM_024666.4.
DR UniGene; Hs.254642; -.
DR UniGene; Hs.602761; -.
DR ProteinModelPortal; Q6PD74; -.
DR IntAct; Q6PD74; 2.
DR MINT; MINT-1373784; -.
DR STRING; 9606.ENSP00000261880; -.
DR PhosphoSite; Q6PD74; -.
DR DMDM; 62286981; -.
DR PaxDb; Q6PD74; -.
DR PeptideAtlas; Q6PD74; -.
DR PRIDE; Q6PD74; -.
DR DNASU; 79719; -.
DR Ensembl; ENST00000261880; ENSP00000261880; ENSG00000103591.
DR GeneID; 79719; -.
DR KEGG; hsa:79719; -.
DR UCSC; uc002aqk.5; human.
DR CTD; 79719; -.
DR GeneCards; GC15M067493; -.
DR HGNC; HGNC:25662; AAGAB.
DR HPA; HPA039371; -.
DR HPA; HPA040174; -.
DR MIM; 148600; phenotype.
DR MIM; 614888; gene.
DR neXtProt; NX_Q6PD74; -.
DR Orphanet; 79501; Punctate palmoplantar keratoderma type 1.
DR PharmGKB; PA165478457; -.
DR eggNOG; NOG271587; -.
DR HOGENOM; HOG000115322; -.
DR InParanoid; Q6PD74; -.
DR OMA; VMKNDRN; -.
DR OrthoDB; EOG7DZ8PB; -.
DR PhylomeDB; Q6PD74; -.
DR ChiTaRS; AAGAB; human.
DR GeneWiki; FLJ11506; -.
DR GenomeRNAi; 79719; -.
DR NextBio; 69069; -.
DR PRO; PR:Q6PD74; -.
DR ArrayExpress; Q6PD74; -.
DR Bgee; Q6PD74; -.
DR Genevestigator; Q6PD74; -.
DR GO; GO:0005737; C:cytoplasm; IDA:LIFEdb.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR InterPro; IPR019341; Alpha/Gamma-adaptin-bd_p34.
DR Pfam; PF10199; Adaptin_binding; 1.
PE 1: Evidence at protein level;
KW Complete proteome; Cytoplasm; Palmoplantar keratoderma;
KW Phosphoprotein; Polymorphism; Protein transport; Reference proteome;
KW Transport.
FT CHAIN 1 315 Alpha- and gamma-adaptin-binding protein
FT p34.
FT /FTId=PRO_0000058134.
FT MOD_RES 310 310 Phosphoserine.
FT MOD_RES 311 311 Phosphoserine.
FT VARIANT 132 132 I -> L (in dbSNP:rs7173826).
FT /FTId=VAR_021533.
FT CONFLICT 26 26 I -> T (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 77 77 V -> A (in Ref. 3; CAG38571).
FT CONFLICT 88 88 Q -> R (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 131 131 C -> S (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 265 265 L -> P (in Ref. 2; CAB66649 and 3;
FT CAG38571).
FT CONFLICT 313 313 E -> G (in Ref. 2; CAB66649 and 3;
FT CAG38571).
SQ SEQUENCE 315 AA; 34594 MW; C1C765B4F9717E0B CRC64;
MAAGVPCALV TSCSSVFSGD QLVQHILGTE DLIVEVTSND AVRFYPWTID NKYYSADINL
CVVPNKFLVT AEIAESVQAF VVYFDSTQKS GLDSVSSWLP LAKAWLPEVM ILVCDRVSED
GINRQKAQEW CIKHGFELVE LSPEELPEED DDFPESTGVK RIVQALNANV WSNVVMKNDR
NQGFSLLNSL TGTNHSIGSA DPCHPEQPHL PAADSTESLS DHRGGASNTT DAQVDSIVDP
MLDLDIQELA SLTTGGGDVE NFERLFSKLK EMKDKAATLP HEQRKVHAEK VAKAFWMAIG
GDRDEIEGLS SDEEH
//
MIM
148600
*RECORD*
*FIELD* NO
148600
*FIELD* TI
#148600 KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA; PPKP1A
;;KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE I; PPKP1;;
read moreKPPP1;;
KERATODERMIA PALMOPLANTARIS PAPULOSA, BUSCHKE-FISCHER-BRAUER TYPE;;
KERATOSIS PALMOPLANTARIS PAPULOSA
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
punctate palmoplantar keratoderma type IA (PPKP1A) is caused by
heterozygous mutation in the AAGAB gene (614888) on chromosome 15q22.
DESCRIPTION
Punctate palmoplantar keratoderma type I, also called keratosis punctate
palmoplantaris type Buschke-Fisher-Brauer, is a rare autosomal dominant
hereditary skin disease characterized by multiple hyperkeratotic
centrally indented papules that develop in early adolescence or later
and are irregularly distributed on the palms and soles. In mechanically
irritated areas, confluent plaques can be found. Interfamilial and
intrafamilial severity shows broad variation. There have been reports of
an association between PPKP and the development of early- and late-onset
malignancies, including squamous cell carcinoma (summary by Giehl et
al., 2012).
Another form of PPKP type I has been mapped to chromosome 8q24 (PPKP1B;
614936).
Other forms of punctate palmoplantar keratoderma include a porokeratotic
type (PPKP2; 175860) and focal acrohyperkeratosis (PPKP3; 101850).
For a general phenotypic description and a discussion of genetic
heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK
(144200).
CLINICAL FEATURES
In 14 families with keratosis palmoplantaris papulosa reported by
Schirren and Dinger (1965), direct transmission was observed. Females
were less severely affected. Salamon et al. (1982) studied a family with
8 cases including instances of male-to-male transmission. Onset in the
proband was at age 20 years. Useful clinical photographs were provided.
Comparison of the histologic findings with those reported by others
suggested to Salamon et al. (1982) that keratodermia palmoplantaris
papulosa is genetically heterogeneous.
Stevens et al. (1994, 1996) reported a large family in which 38 persons
in 4 generations had keratosis punctata. Ten of 34 affected adults
developed different malignancies (Hodgkin disease and renal, breast,
pancreatic, and colonic adenocarcinomas). In 5 persons malignancies
developed before the age of 50. Stevens et al. (1994) proposed that in
this family mutation in the type I acidic keratin gene cluster at
17q12-q21 (see, e.g., KRT9, 607606) might be related to pathology of
tumor suppressor gene(s) in the region of 17q21 (see, e.g., BRCA1,
113705). In a Table, Stevens et al. (1996) stated that the
characteristics in this family were onset between ages 12 and 30 years,
multiple tiny punctate keratoses over the entire palmoplantar surfaces,
coalescence of the punctate keratoses into a more diffuse pattern over
the pressure points of the soles, and variable nail changes.
In 3 ethnically diverse, 4-generation families segregating punctate
palmoplantar keratoderma type I (PPKP1), Martinez-Mir et al. (2003)
found that all affected family members had typical features without nail
involvement. No increased prevalence of cancer was found in the
families.
Giehl et al. (2012) studied 3 families with PPKP, 2 of Croatian origin
and 1 of German origin. In the 14 affected individuals, keratoses on the
soles were more severe than those on the palms, especially over pressure
points. Histology showed marked hyperkeratosis with focal parakeratosis
and prominent hypergranulosis, consistent with PPKP1. Phenotypic
variability was observed between as well as within the families.
Pohler et al. (2012) studied a collection of 18 PPKP1 kindreds from
Scotland, Ireland, Japan, and Tunisia, 11 of which had a family history
consistent with autosomal dominant inheritance. In all families the
onset was typically in the first to second decades of life, with the
appearance of small circumscribed lesions on the palms and soles that
consistently increased in number with advancing age and later coalesced
to form larger lesions. However, there was considerable phenotypic
variation between families, with lesions remaining subtle in some,
whereas in others the phenotype resembled human papillomavirus
(HPV)-induced lesions and was much more severe, painful, and
debilitating. Histology of affected palmar epidermis from 3 unrelated
kindreds of different ethnicities showed very similar findings,
involving a well-defined central epidermal depression associated with
hypergranulosis and a prominent layer of overlying orthokeratosis.
Immunohistochemical staining for the cell proliferation marker Ki67
showed continuous staining of the proliferative basal cell compartment
of the epidermis beneath the hyperkeratotic lesions, indicative of a
hyperproliferative form of hyperkeratosis rather than a retention
hyperkeratosis due to defective desquamation. Ultrastructural analysis
of affected plantar skin showed mild acanthosis, a reduction in the
granular cell layer, and compact orthokeratosis. In basal keratinocytes,
there was a large increase in the number of small vesicles close to the
cell membrane and prominent dilatation of the Golgi apparatus in
affected epidermis compared to control skin. Pohler et al. (2012) noted
that the ultrastructural findings were compatible with a defect in
vesicle transport.
MAPPING
In 3 ethnically diverse, 4-generation families segregating punctate
palmoplantar keratoderma type I, Martinez-Mir et al. (2003) found
linkage of the disorder to a 9.98-cM interval flanked by markers D15S534
and D15S818 on chromosome 15q22-q24 (maximum 2-point lod score of 4.93
at theta = 0.0 for D15S988).
In a large 7-generation Tunisian PPKP kindred that originated from Saudi
Arabia and was previously reported by El Amri et al. (2010), Pohler et
al. (2012) found linkage to the previously reported 15q22 locus,
obtaining a maximum 2-point lod score of 8.18 at theta = 0.0 for the
marker D15S983. A 6.24-Mb critical interval was defined by recombination
events.
- Exclusion Studies
Kelsell et al. (1995) excluded linkage of a form of PPKP to the keratin
gene clusters on 12q and 17q.
MOLECULAR GENETICS
In 2 Croatian families and a German family with PPKP1, Giehl et al.
(2012) performed whole-exome sequencing followed by filtering and
identified 2 heterozygous nonsense mutations in the AAGAB gene, R161X
(614888.0001) and R124X (614888.0002), that segregated fully with
disease in the respective families. Haplotype analysis of the 2 Croatian
families indicated that the R161X mutation was inherited by descent from
a common ancestor.
By whole-exome sequencing in the proband from a 4-generation Scottish
family with PPKP1, Pohler et al. (2012) identified heterozygosity for
the R161X mutation in the AAGAB gene, which was confirmed by
conventional sequencing to segregate with disease in the family and was
not found in the current dbSNP or 1000 Genomes databases. Sequencing of
AAGAB in a large 7-generation Tunisian pedigree with PPKP mapping to
15q22 revealed a heterozygous 2-bp deletion (614888.0003) that
segregated with disease in the family, as well as in 2 additional
Tunisian families. Sequencing of another 14 PPKP kindreds of Scottish,
Irish, Japanese, and Tunisian backgrounds, respectively, revealed
another 6 mutations in the AAGAB gene, including 1 splice site, 1
nonsense, and 4 frameshift mutations (see, e.g.,
614888.0004-614888.0006).
*FIELD* RF
1. El Amri, I.; Mamai, O.; Ghariani, N.; Denquezli, M.; Sriha, B.;
Adala, L.; Saad, A.; Gribaa, M.; Nouira, R.: Clinical and genetic
characteristics of Buschke-Fischer-Brauer's disease in a Tunisian
family. Ann. Derm. Venerol. 137: 269-275, 2010.
2. Giehl, K. A.; Eckstein, G. N.; Pasternack, S. M.; Praetzel-Wunder,
S.; Ruzicka, T.; Lichtner, P.; Seidl, K.; Rogers, M.; Graf, E.; Langbein,
L.; Braun-Falco, M.; Betz, R. C.; Strom, T. M.: Nonsense mutations
in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am.
J. Hum. Genet. 91: 754-759, 2012.
3. Kelsell, D. P.; Stevens, H. P.; Ratnavel, R.; Bryant, S. P.; Bishop,
D. T.; Leigh, I. M.; Spurr, N. K.: Genetic linkage studies in non-epidermolytic
palmoplantar keratoderma: evidence for heterogeneity. Hum. Molec.
Genet. 4: 1021-1025, 1995.
4. Martinez-Mir, A.; Zlotogorski, A.; Londono, D.; Gordon, D.; Grunn,
A.; Uribe, E.; Horev, L.; Ruiz, I. M.; Davalos, N. O.; Alayan, O.;
Liu, J.; Gilliam, T. C.; Salas-Alanis, J. C.; Christiano, A. M.:
Identification of a locus for type I punctate palmoplantar keratoderma
on chromosome 15q22-q24. J. Med. Genet. 40: 872-878, 2003.
5. Pohler, E.; Mamai, O.; Hirst, J.; Zamiri, M.; Horn, H.; Nomura,
T.; Irvine, A. D.; Moran, B.; Wilson, N. J.; Smith, F. J. D.; Goh,
C. S. M.; Sandilands, A.; and 20 others: Haploinsufficiency for
AAGAB causes clinically heterogenous forms of punctate palmoplantar
keratoderma. Nature Genet. 44: 1272-1276, 2012.
6. Salamon, T.; Stolic, V.; Lazovic-Tepavac, O.; Bosnjak, D.: Peculiar
findings in a family with keratodermia palmo-plantaris papulosa Buschke-Fischer-Brauer. Hum.
Genet. 60: 314-319, 1982.
7. Schirren, V.; Dinger, R.: Untersuchungen bei Keratosis palmo-plantaris
papulosa. Arch. Klin. Exp. Derm. 221: 481-495, 1965.
8. Stevens, H. P.; Kelsell, D. P.; Bryant, S. P.; Bishop, D. T.; Spurr,
N. K.; Weissenbach, J.; Marger, D.; Marger, R. S.; Leigh, I. M.:
Linkage of an American pedigree with palmoplantar keratoderma and
malignancy (palmoplantar ectodermal dysplasia type III) to 17q24:
literature survey and proposed updated classification of the keratodermas. Arch.
Derm. 132: 640-651, 1996.
9. Stevens, H. P.; Kelsell, D. P.; Leigh, I. M.; Ostlere, L. S.; MacDermot,
K. D.; Rustin, M. H. A.: Punctate palmoplantar keratoderma and malignancy
in a four-generation family. Brit. J. Derm. 134: 720-726, 1996.
10. Stevens, H. P.; Rustin, M. H. A.; MacDermot, K.: Keratosis punctata
palmaris et plantaris: an autosomal dominantly inherited keratoderma
associated with malignancy. (Abstract) J. Med. Genet. 31: 168 only,
1994.
*FIELD* CS
Skin:
Keratodermia palmoplantaris papulosa
Misc:
Late onset;
Females less severely affected
Inheritance:
Autosomal dominant;
heterogeneous
*FIELD* CN
Marla J. F. O'Neill - updated: 11/15/2012
Marla J. F. O'Neill - updated: 11/6/2012
Marla J. F. O'Neill - updated: 7/10/2009
Natalie E. Krasikov - updated: 3/30/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 11/15/2012
terry: 11/15/2012
carol: 11/8/2012
carol: 11/7/2012
terry: 11/6/2012
carol: 5/20/2010
carol: 7/27/2009
carol: 7/10/2009
joanna: 4/2/2009
carol: 4/2/2009
carol: 4/7/2004
terry: 3/30/2004
carol: 3/18/2004
alopez: 3/11/2004
jamie: 12/4/1996
terry: 12/3/1996
terry: 11/8/1996
mimadm: 11/5/1994
carol: 11/12/1993
supermim: 3/16/1992
carol: 3/4/1992
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
148600
*FIELD* TI
#148600 KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA; PPKP1A
;;KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE I; PPKP1;;
read moreKPPP1;;
KERATODERMIA PALMOPLANTARIS PAPULOSA, BUSCHKE-FISCHER-BRAUER TYPE;;
KERATOSIS PALMOPLANTARIS PAPULOSA
*FIELD* TX
A number sign (#) is used with this entry because of evidence that
punctate palmoplantar keratoderma type IA (PPKP1A) is caused by
heterozygous mutation in the AAGAB gene (614888) on chromosome 15q22.
DESCRIPTION
Punctate palmoplantar keratoderma type I, also called keratosis punctate
palmoplantaris type Buschke-Fisher-Brauer, is a rare autosomal dominant
hereditary skin disease characterized by multiple hyperkeratotic
centrally indented papules that develop in early adolescence or later
and are irregularly distributed on the palms and soles. In mechanically
irritated areas, confluent plaques can be found. Interfamilial and
intrafamilial severity shows broad variation. There have been reports of
an association between PPKP and the development of early- and late-onset
malignancies, including squamous cell carcinoma (summary by Giehl et
al., 2012).
Another form of PPKP type I has been mapped to chromosome 8q24 (PPKP1B;
614936).
Other forms of punctate palmoplantar keratoderma include a porokeratotic
type (PPKP2; 175860) and focal acrohyperkeratosis (PPKP3; 101850).
For a general phenotypic description and a discussion of genetic
heterogeneity of palmoplantar keratoderma (PPK), see epidermolytic PPK
(144200).
CLINICAL FEATURES
In 14 families with keratosis palmoplantaris papulosa reported by
Schirren and Dinger (1965), direct transmission was observed. Females
were less severely affected. Salamon et al. (1982) studied a family with
8 cases including instances of male-to-male transmission. Onset in the
proband was at age 20 years. Useful clinical photographs were provided.
Comparison of the histologic findings with those reported by others
suggested to Salamon et al. (1982) that keratodermia palmoplantaris
papulosa is genetically heterogeneous.
Stevens et al. (1994, 1996) reported a large family in which 38 persons
in 4 generations had keratosis punctata. Ten of 34 affected adults
developed different malignancies (Hodgkin disease and renal, breast,
pancreatic, and colonic adenocarcinomas). In 5 persons malignancies
developed before the age of 50. Stevens et al. (1994) proposed that in
this family mutation in the type I acidic keratin gene cluster at
17q12-q21 (see, e.g., KRT9, 607606) might be related to pathology of
tumor suppressor gene(s) in the region of 17q21 (see, e.g., BRCA1,
113705). In a Table, Stevens et al. (1996) stated that the
characteristics in this family were onset between ages 12 and 30 years,
multiple tiny punctate keratoses over the entire palmoplantar surfaces,
coalescence of the punctate keratoses into a more diffuse pattern over
the pressure points of the soles, and variable nail changes.
In 3 ethnically diverse, 4-generation families segregating punctate
palmoplantar keratoderma type I (PPKP1), Martinez-Mir et al. (2003)
found that all affected family members had typical features without nail
involvement. No increased prevalence of cancer was found in the
families.
Giehl et al. (2012) studied 3 families with PPKP, 2 of Croatian origin
and 1 of German origin. In the 14 affected individuals, keratoses on the
soles were more severe than those on the palms, especially over pressure
points. Histology showed marked hyperkeratosis with focal parakeratosis
and prominent hypergranulosis, consistent with PPKP1. Phenotypic
variability was observed between as well as within the families.
Pohler et al. (2012) studied a collection of 18 PPKP1 kindreds from
Scotland, Ireland, Japan, and Tunisia, 11 of which had a family history
consistent with autosomal dominant inheritance. In all families the
onset was typically in the first to second decades of life, with the
appearance of small circumscribed lesions on the palms and soles that
consistently increased in number with advancing age and later coalesced
to form larger lesions. However, there was considerable phenotypic
variation between families, with lesions remaining subtle in some,
whereas in others the phenotype resembled human papillomavirus
(HPV)-induced lesions and was much more severe, painful, and
debilitating. Histology of affected palmar epidermis from 3 unrelated
kindreds of different ethnicities showed very similar findings,
involving a well-defined central epidermal depression associated with
hypergranulosis and a prominent layer of overlying orthokeratosis.
Immunohistochemical staining for the cell proliferation marker Ki67
showed continuous staining of the proliferative basal cell compartment
of the epidermis beneath the hyperkeratotic lesions, indicative of a
hyperproliferative form of hyperkeratosis rather than a retention
hyperkeratosis due to defective desquamation. Ultrastructural analysis
of affected plantar skin showed mild acanthosis, a reduction in the
granular cell layer, and compact orthokeratosis. In basal keratinocytes,
there was a large increase in the number of small vesicles close to the
cell membrane and prominent dilatation of the Golgi apparatus in
affected epidermis compared to control skin. Pohler et al. (2012) noted
that the ultrastructural findings were compatible with a defect in
vesicle transport.
MAPPING
In 3 ethnically diverse, 4-generation families segregating punctate
palmoplantar keratoderma type I, Martinez-Mir et al. (2003) found
linkage of the disorder to a 9.98-cM interval flanked by markers D15S534
and D15S818 on chromosome 15q22-q24 (maximum 2-point lod score of 4.93
at theta = 0.0 for D15S988).
In a large 7-generation Tunisian PPKP kindred that originated from Saudi
Arabia and was previously reported by El Amri et al. (2010), Pohler et
al. (2012) found linkage to the previously reported 15q22 locus,
obtaining a maximum 2-point lod score of 8.18 at theta = 0.0 for the
marker D15S983. A 6.24-Mb critical interval was defined by recombination
events.
- Exclusion Studies
Kelsell et al. (1995) excluded linkage of a form of PPKP to the keratin
gene clusters on 12q and 17q.
MOLECULAR GENETICS
In 2 Croatian families and a German family with PPKP1, Giehl et al.
(2012) performed whole-exome sequencing followed by filtering and
identified 2 heterozygous nonsense mutations in the AAGAB gene, R161X
(614888.0001) and R124X (614888.0002), that segregated fully with
disease in the respective families. Haplotype analysis of the 2 Croatian
families indicated that the R161X mutation was inherited by descent from
a common ancestor.
By whole-exome sequencing in the proband from a 4-generation Scottish
family with PPKP1, Pohler et al. (2012) identified heterozygosity for
the R161X mutation in the AAGAB gene, which was confirmed by
conventional sequencing to segregate with disease in the family and was
not found in the current dbSNP or 1000 Genomes databases. Sequencing of
AAGAB in a large 7-generation Tunisian pedigree with PPKP mapping to
15q22 revealed a heterozygous 2-bp deletion (614888.0003) that
segregated with disease in the family, as well as in 2 additional
Tunisian families. Sequencing of another 14 PPKP kindreds of Scottish,
Irish, Japanese, and Tunisian backgrounds, respectively, revealed
another 6 mutations in the AAGAB gene, including 1 splice site, 1
nonsense, and 4 frameshift mutations (see, e.g.,
614888.0004-614888.0006).
*FIELD* RF
1. El Amri, I.; Mamai, O.; Ghariani, N.; Denquezli, M.; Sriha, B.;
Adala, L.; Saad, A.; Gribaa, M.; Nouira, R.: Clinical and genetic
characteristics of Buschke-Fischer-Brauer's disease in a Tunisian
family. Ann. Derm. Venerol. 137: 269-275, 2010.
2. Giehl, K. A.; Eckstein, G. N.; Pasternack, S. M.; Praetzel-Wunder,
S.; Ruzicka, T.; Lichtner, P.; Seidl, K.; Rogers, M.; Graf, E.; Langbein,
L.; Braun-Falco, M.; Betz, R. C.; Strom, T. M.: Nonsense mutations
in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am.
J. Hum. Genet. 91: 754-759, 2012.
3. Kelsell, D. P.; Stevens, H. P.; Ratnavel, R.; Bryant, S. P.; Bishop,
D. T.; Leigh, I. M.; Spurr, N. K.: Genetic linkage studies in non-epidermolytic
palmoplantar keratoderma: evidence for heterogeneity. Hum. Molec.
Genet. 4: 1021-1025, 1995.
4. Martinez-Mir, A.; Zlotogorski, A.; Londono, D.; Gordon, D.; Grunn,
A.; Uribe, E.; Horev, L.; Ruiz, I. M.; Davalos, N. O.; Alayan, O.;
Liu, J.; Gilliam, T. C.; Salas-Alanis, J. C.; Christiano, A. M.:
Identification of a locus for type I punctate palmoplantar keratoderma
on chromosome 15q22-q24. J. Med. Genet. 40: 872-878, 2003.
5. Pohler, E.; Mamai, O.; Hirst, J.; Zamiri, M.; Horn, H.; Nomura,
T.; Irvine, A. D.; Moran, B.; Wilson, N. J.; Smith, F. J. D.; Goh,
C. S. M.; Sandilands, A.; and 20 others: Haploinsufficiency for
AAGAB causes clinically heterogenous forms of punctate palmoplantar
keratoderma. Nature Genet. 44: 1272-1276, 2012.
6. Salamon, T.; Stolic, V.; Lazovic-Tepavac, O.; Bosnjak, D.: Peculiar
findings in a family with keratodermia palmo-plantaris papulosa Buschke-Fischer-Brauer. Hum.
Genet. 60: 314-319, 1982.
7. Schirren, V.; Dinger, R.: Untersuchungen bei Keratosis palmo-plantaris
papulosa. Arch. Klin. Exp. Derm. 221: 481-495, 1965.
8. Stevens, H. P.; Kelsell, D. P.; Bryant, S. P.; Bishop, D. T.; Spurr,
N. K.; Weissenbach, J.; Marger, D.; Marger, R. S.; Leigh, I. M.:
Linkage of an American pedigree with palmoplantar keratoderma and
malignancy (palmoplantar ectodermal dysplasia type III) to 17q24:
literature survey and proposed updated classification of the keratodermas. Arch.
Derm. 132: 640-651, 1996.
9. Stevens, H. P.; Kelsell, D. P.; Leigh, I. M.; Ostlere, L. S.; MacDermot,
K. D.; Rustin, M. H. A.: Punctate palmoplantar keratoderma and malignancy
in a four-generation family. Brit. J. Derm. 134: 720-726, 1996.
10. Stevens, H. P.; Rustin, M. H. A.; MacDermot, K.: Keratosis punctata
palmaris et plantaris: an autosomal dominantly inherited keratoderma
associated with malignancy. (Abstract) J. Med. Genet. 31: 168 only,
1994.
*FIELD* CS
Skin:
Keratodermia palmoplantaris papulosa
Misc:
Late onset;
Females less severely affected
Inheritance:
Autosomal dominant;
heterogeneous
*FIELD* CN
Marla J. F. O'Neill - updated: 11/15/2012
Marla J. F. O'Neill - updated: 11/6/2012
Marla J. F. O'Neill - updated: 7/10/2009
Natalie E. Krasikov - updated: 3/30/2004
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
carol: 11/15/2012
terry: 11/15/2012
carol: 11/8/2012
carol: 11/7/2012
terry: 11/6/2012
carol: 5/20/2010
carol: 7/27/2009
carol: 7/10/2009
joanna: 4/2/2009
carol: 4/2/2009
carol: 4/7/2004
terry: 3/30/2004
carol: 3/18/2004
alopez: 3/11/2004
jamie: 12/4/1996
terry: 12/3/1996
terry: 11/8/1996
mimadm: 11/5/1994
carol: 11/12/1993
supermim: 3/16/1992
carol: 3/4/1992
supermim: 3/20/1990
ddp: 10/27/1989
MIM
614888
*RECORD*
*FIELD* NO
614888
*FIELD* TI
*614888 ALPHA- AND GAMMA-ADAPTIN-BINDING PROTEIN; AAGAB
;;p34
*FIELD* TX
DESCRIPTION
read more
AP1 and AP2 are heterotetrameric complexes involved in clathrin-coated
vesicle trafficking that associate with the trans-Golgi network (TGN)
and plasma membrane, respectively. AAGAB, or p34, interacts with the
gamma-adaptin (AP1G1; 603533) subunit of AP1 and with the alpha-adaptin
(AP2A1; 601026) subunit of AP2 (Page et al., 1999).
CLONING
Using mouse gamma-adaptin in a yeast 2-hybrid screen of a rat brain cDNA
library, Page et al. (1999) cloned Aagab, which they called p34. The
deduced protein contains 315 amino acids. Northern blot analysis
detected variable Aagab expression in all rat tissues examined.
By searching for genes in a region of chromosome 15 linked to punctate
palmoplantar keratoderma type I (PPKP1A; 148600), followed by PCR of a
human keratinocyte cDNA library, Giehl et al. (2012) cloned full-length
AAGAB. RT-PCR analysis detected AAGAB expression in hair follicle cells,
skin, HaCaT keratinocytes, and lymphocytes, with highest relative
expression in HaCaT cells. Database analysis suggested ubiquitous AAGAB
expression. Immunohistochemical analysis of normal palmoplantar skin
detected granular cytoplasmic AAGAB staining, particularly in the
stratum basale and the first suprabasal cell layers of the stratum
spinosum. Much weaker staining was detected in upper layers of the
stratum spinosum, where it localized only around nuclei in a few
keratinocytes. Dermal vessels were also AAGAB positive.
Independently, Pohler et al. (2012) cloned AAGAB by RT-PCR of HaCaT cell
total RNA. The deduced 315-amino acid protein contains a RAB (see
179508)-like GTPase domain in its N-terminal half and an adaptin-binding
domain in its C-terminal half. Quantitative RT-PCR analysis revealed
AAGAB expression in all 48 human tissues examined, with highest
expression in rectum and thymus, followed by adrenal gland, spleen,
uterus, and vagina. Lowest expression was detected in mammary gland.
Fluorescence-tagged AAGAB was expressed in cytosol, but not in membrane
or clathrin-coated vesicle fractions, of HaCaT and HeLa cells.
GENE STRUCTURE
Independently, Giehl et al. (2012) and Pohler et al. (2012) determined
that the AAGAB gene contains 10 exons. Pohler et al. (2012) reported
that the AAGAB gene spans 53.7 kb.
MAPPING
By genomic sequence analysis, Giehl et al. (2012) mapped the AAGAB gene
to chromosome 15q22.33-q23.
GENE FUNCTION
Using yeast 2-hybrid analysis, Page et al. (1999) found that rat p34
interacted with mouse gamma-adaptin and alpha-adaptin.
Using immunoprecipitation analysis and Western blot analysis, Pohler et
al. (2012) confirmed that p34 interacted with both AP1 and AP2
complexes. Knockdown of p34 did not alter the TNG or plasma membrane
localization of AP1 or AP2, respectively. In HaCaT cells, knockdown of
AAGAB increased EGFR (131550) mRNA levels and EGFR tyrosine
phosphorylation, indicative of active EGFR signaling. Pohler et al.
(2012) concluded that AAGAB may have a role in regulating EGFR turnover,
possibly via ATPase activity.
MOLECULAR GENETICS
In 3 families with type I punctate palmoplantar keratoderma (PPKP1;
148600), Giehl et al. (2012) identified 2 heterozygous nonsense
mutations in the AAGAB gene, R161X (614888.0001) and R124X
(614888.0002), that segregated fully with disease in the respective
families. Immunofluorescence analyses of skin from the palms and soles
of affected individuals revealed that the amount of granular staining in
keratinocytes was lower in the cytoplasm but higher around the nucleus
than in keratinocytes from controls, suggesting clumping of defective
keratin molecules.
In a collection of 18 PPKP1 kindreds from Scotland, Ireland, Japan, and
Tunisia, 11 of which had a family history consistent with autosomal
dominant inheritance, Pohler et al. (2012) identified heterozygous
mutations in the AAGAB gene (see, e.g., 614888.0001 and
614888.0003-614888.0006).
*FIELD* AV
.0001
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, ARG161TER
In affected members of 2 Croatian families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Giehl et al. (2012)
identified heterozygosity for a 481C-T transition in exon 5 of the AAGAB
gene, resulting in an arg161-to-ter (R161X) substitution. The mutation
was not found in unaffected family members. Genotyping of 21 individuals
from the 2 families revealed a 1.2-Mb common haplotype between markers
SNP15-67469128 and SNP15-68728632, indicating that the affected
individuals inherited the mutation by descent from a common ancestor.
Immunoblot analysis confirmed the predicted truncated size of
approximately 24 kD for R161X and showed a strong band, suggesting that
the protein is stable and not degraded. Allele-specific PCR
amplification yielded only a very small peak for the 481C-T allele.
In a 4-generation Scottish family with PPKP, Pohler et al. (2012)
identified heterozygosity for the R161X mutation, which segregated with
disease in the family and was not found in the dbSNP or 1000 Genomes
databases.
.0002
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, ARG124TER
In affected members of a German family with type I punctate palmoplantar
keratoderma (PPKP1A; 148600), Giehl et al. (2012) identified
heterozygosity for a 370C-T transition in exon 4 of the AAGAB gene,
resulting in an arg124-to-ter (R124X) substitution. The mutation was not
found in unaffected family members. Immunoblot analysis confirmed the
predicted truncated size of approximately 18 kD for R124X but showed
only a faint band, suggesting that the corresponding mRNA is prone to
decay. Allele-specific PCR amplification yielded undetectable results
for the 370C-T allele, indicating loss of the protein.
.0003
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 2-BP DEL, 348AG
In affected members of 3 Tunisian families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), 1 of which was originally
reported by El Amri et al. (2010), Pohler et al. (2012) identified
heterozygosity for a 2-bp deletion (348_349delAG) in the AAGAB gene,
predicted to cause a frameshift within the GTPase domain resulting in a
premature termination codon (R116Sfs*1).
.0004
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 1-BP DEL, NT473
In affected members of 5 Scottish families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a 1-bp deletion (473del) in the AAGAB
gene, predicted to cause a frameshift resulting in a premature
termination codon (Gly158Glufs*0).
.0005
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 4-BP DEL, NT200
In affected members of 2 Japanese families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a 4-bp deletion (200_203del) in the AAGAB
gene, predicted to cause a frameshift resulting in a premature
termination codon (Phe67Leufs*41).
.0006
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, IVS, G-A, +1
In affected members of 2 Scottish families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a splice site mutation (870+1G-A) in the
AAGAB gene.
*FIELD* RF
1. El Amri, I.; Mamai, O.; Ghariani, N.; Denquezli, M.; Sriha, B.;
Adala, L.; Saad, A.; Gribaa, M.; Nouira, R.: Clinical and genetic
characteristics of Buschke-Fischer-Brauer's disease in a Tunisian
family. Ann. Derm. Venerol. 137: 269-275, 2010.
2. Giehl, K. A.; Eckstein, G. N.; Pasternack, S. M.; Praetzel-Wunder,
S.; Ruzicka, T.; Lichtner, P.; Seidl, K.; Rogers, M.; Graf, E.; Langbein,
L.; Braun-Falco, M.; Betz, R. C.; Strom, T. M.: Nonsense mutations
in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am.
J. Hum. Genet. 91: 754-759, 2012.
3. Page, L. J.; Sowerby, P. J.; Lui, W. W. Y.; Robinson, M. S.: Gamma-synergin:
an EH domain-containing protein that interacts with gamma-adaptin. J.
Cell Biol. 146: 993-1004, 1999.
4. Pohler, E.; Mamai, O.; Hirst, J.; Zamiri, M.; Horn, H.; Nomura,
T.; Irvine, A. D.; Moran, B.; Wilson, N. J.; Smith, F. J. D.; Goh,
C. S. M.; Sandilands, A.; and 20 others: Haploinsufficiency for
AAGAB causes clinically heterogeneous forms of punctate palmoplantar
keratoderma. Nature Genet. 44: 1272-1276, 2012.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/15/2012
Marla J. F. O'Neill - updated: 11/6/2012
*FIELD* CD
Patricia A. Hartz: 10/26/2012
*FIELD* ED
carol: 11/28/2012
terry: 11/15/2012
carol: 11/8/2012
carol: 11/7/2012
terry: 11/6/2012
mgross: 10/26/2012
*RECORD*
*FIELD* NO
614888
*FIELD* TI
*614888 ALPHA- AND GAMMA-ADAPTIN-BINDING PROTEIN; AAGAB
;;p34
*FIELD* TX
DESCRIPTION
read more
AP1 and AP2 are heterotetrameric complexes involved in clathrin-coated
vesicle trafficking that associate with the trans-Golgi network (TGN)
and plasma membrane, respectively. AAGAB, or p34, interacts with the
gamma-adaptin (AP1G1; 603533) subunit of AP1 and with the alpha-adaptin
(AP2A1; 601026) subunit of AP2 (Page et al., 1999).
CLONING
Using mouse gamma-adaptin in a yeast 2-hybrid screen of a rat brain cDNA
library, Page et al. (1999) cloned Aagab, which they called p34. The
deduced protein contains 315 amino acids. Northern blot analysis
detected variable Aagab expression in all rat tissues examined.
By searching for genes in a region of chromosome 15 linked to punctate
palmoplantar keratoderma type I (PPKP1A; 148600), followed by PCR of a
human keratinocyte cDNA library, Giehl et al. (2012) cloned full-length
AAGAB. RT-PCR analysis detected AAGAB expression in hair follicle cells,
skin, HaCaT keratinocytes, and lymphocytes, with highest relative
expression in HaCaT cells. Database analysis suggested ubiquitous AAGAB
expression. Immunohistochemical analysis of normal palmoplantar skin
detected granular cytoplasmic AAGAB staining, particularly in the
stratum basale and the first suprabasal cell layers of the stratum
spinosum. Much weaker staining was detected in upper layers of the
stratum spinosum, where it localized only around nuclei in a few
keratinocytes. Dermal vessels were also AAGAB positive.
Independently, Pohler et al. (2012) cloned AAGAB by RT-PCR of HaCaT cell
total RNA. The deduced 315-amino acid protein contains a RAB (see
179508)-like GTPase domain in its N-terminal half and an adaptin-binding
domain in its C-terminal half. Quantitative RT-PCR analysis revealed
AAGAB expression in all 48 human tissues examined, with highest
expression in rectum and thymus, followed by adrenal gland, spleen,
uterus, and vagina. Lowest expression was detected in mammary gland.
Fluorescence-tagged AAGAB was expressed in cytosol, but not in membrane
or clathrin-coated vesicle fractions, of HaCaT and HeLa cells.
GENE STRUCTURE
Independently, Giehl et al. (2012) and Pohler et al. (2012) determined
that the AAGAB gene contains 10 exons. Pohler et al. (2012) reported
that the AAGAB gene spans 53.7 kb.
MAPPING
By genomic sequence analysis, Giehl et al. (2012) mapped the AAGAB gene
to chromosome 15q22.33-q23.
GENE FUNCTION
Using yeast 2-hybrid analysis, Page et al. (1999) found that rat p34
interacted with mouse gamma-adaptin and alpha-adaptin.
Using immunoprecipitation analysis and Western blot analysis, Pohler et
al. (2012) confirmed that p34 interacted with both AP1 and AP2
complexes. Knockdown of p34 did not alter the TNG or plasma membrane
localization of AP1 or AP2, respectively. In HaCaT cells, knockdown of
AAGAB increased EGFR (131550) mRNA levels and EGFR tyrosine
phosphorylation, indicative of active EGFR signaling. Pohler et al.
(2012) concluded that AAGAB may have a role in regulating EGFR turnover,
possibly via ATPase activity.
MOLECULAR GENETICS
In 3 families with type I punctate palmoplantar keratoderma (PPKP1;
148600), Giehl et al. (2012) identified 2 heterozygous nonsense
mutations in the AAGAB gene, R161X (614888.0001) and R124X
(614888.0002), that segregated fully with disease in the respective
families. Immunofluorescence analyses of skin from the palms and soles
of affected individuals revealed that the amount of granular staining in
keratinocytes was lower in the cytoplasm but higher around the nucleus
than in keratinocytes from controls, suggesting clumping of defective
keratin molecules.
In a collection of 18 PPKP1 kindreds from Scotland, Ireland, Japan, and
Tunisia, 11 of which had a family history consistent with autosomal
dominant inheritance, Pohler et al. (2012) identified heterozygous
mutations in the AAGAB gene (see, e.g., 614888.0001 and
614888.0003-614888.0006).
*FIELD* AV
.0001
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, ARG161TER
In affected members of 2 Croatian families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Giehl et al. (2012)
identified heterozygosity for a 481C-T transition in exon 5 of the AAGAB
gene, resulting in an arg161-to-ter (R161X) substitution. The mutation
was not found in unaffected family members. Genotyping of 21 individuals
from the 2 families revealed a 1.2-Mb common haplotype between markers
SNP15-67469128 and SNP15-68728632, indicating that the affected
individuals inherited the mutation by descent from a common ancestor.
Immunoblot analysis confirmed the predicted truncated size of
approximately 24 kD for R161X and showed a strong band, suggesting that
the protein is stable and not degraded. Allele-specific PCR
amplification yielded only a very small peak for the 481C-T allele.
In a 4-generation Scottish family with PPKP, Pohler et al. (2012)
identified heterozygosity for the R161X mutation, which segregated with
disease in the family and was not found in the dbSNP or 1000 Genomes
databases.
.0002
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, ARG124TER
In affected members of a German family with type I punctate palmoplantar
keratoderma (PPKP1A; 148600), Giehl et al. (2012) identified
heterozygosity for a 370C-T transition in exon 4 of the AAGAB gene,
resulting in an arg124-to-ter (R124X) substitution. The mutation was not
found in unaffected family members. Immunoblot analysis confirmed the
predicted truncated size of approximately 18 kD for R124X but showed
only a faint band, suggesting that the corresponding mRNA is prone to
decay. Allele-specific PCR amplification yielded undetectable results
for the 370C-T allele, indicating loss of the protein.
.0003
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 2-BP DEL, 348AG
In affected members of 3 Tunisian families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), 1 of which was originally
reported by El Amri et al. (2010), Pohler et al. (2012) identified
heterozygosity for a 2-bp deletion (348_349delAG) in the AAGAB gene,
predicted to cause a frameshift within the GTPase domain resulting in a
premature termination codon (R116Sfs*1).
.0004
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 1-BP DEL, NT473
In affected members of 5 Scottish families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a 1-bp deletion (473del) in the AAGAB
gene, predicted to cause a frameshift resulting in a premature
termination codon (Gly158Glufs*0).
.0005
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, 4-BP DEL, NT200
In affected members of 2 Japanese families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a 4-bp deletion (200_203del) in the AAGAB
gene, predicted to cause a frameshift resulting in a premature
termination codon (Phe67Leufs*41).
.0006
KERATODERMA, PALMOPLANTAR, PUNCTATE TYPE IA
AAGAB, IVS, G-A, +1
In affected members of 2 Scottish families with type I punctate
palmoplantar keratoderma (PPKP1A; 148600), Pohler et al. (2012)
identified heterozygosity for a splice site mutation (870+1G-A) in the
AAGAB gene.
*FIELD* RF
1. El Amri, I.; Mamai, O.; Ghariani, N.; Denquezli, M.; Sriha, B.;
Adala, L.; Saad, A.; Gribaa, M.; Nouira, R.: Clinical and genetic
characteristics of Buschke-Fischer-Brauer's disease in a Tunisian
family. Ann. Derm. Venerol. 137: 269-275, 2010.
2. Giehl, K. A.; Eckstein, G. N.; Pasternack, S. M.; Praetzel-Wunder,
S.; Ruzicka, T.; Lichtner, P.; Seidl, K.; Rogers, M.; Graf, E.; Langbein,
L.; Braun-Falco, M.; Betz, R. C.; Strom, T. M.: Nonsense mutations
in AAGAB cause punctate palmoplantar keratoderma type Buschke-Fischer-Brauer. Am.
J. Hum. Genet. 91: 754-759, 2012.
3. Page, L. J.; Sowerby, P. J.; Lui, W. W. Y.; Robinson, M. S.: Gamma-synergin:
an EH domain-containing protein that interacts with gamma-adaptin. J.
Cell Biol. 146: 993-1004, 1999.
4. Pohler, E.; Mamai, O.; Hirst, J.; Zamiri, M.; Horn, H.; Nomura,
T.; Irvine, A. D.; Moran, B.; Wilson, N. J.; Smith, F. J. D.; Goh,
C. S. M.; Sandilands, A.; and 20 others: Haploinsufficiency for
AAGAB causes clinically heterogeneous forms of punctate palmoplantar
keratoderma. Nature Genet. 44: 1272-1276, 2012.
*FIELD* CN
Marla J. F. O'Neill - updated: 11/15/2012
Marla J. F. O'Neill - updated: 11/6/2012
*FIELD* CD
Patricia A. Hartz: 10/26/2012
*FIELD* ED
carol: 11/28/2012
terry: 11/15/2012
carol: 11/8/2012
carol: 11/7/2012
terry: 11/6/2012
mgross: 10/26/2012