RBCC Red Blood Cell Collection

HLA-B (HLAB) [Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
HLA class I histocompatibility antigen, B-7 alpha chain (MHC class I antigen B*7; Flags: Precursor)

UniProt P01889
ID 1B07_HUMAN Reviewed; 362 AA.
AC P01889; Q29638; Q29681; Q29854; Q29861; Q31613; Q5SRJ2; Q9GIX1;
read moreAC Q9TP95;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1991, sequence version 3.
DT 22-JAN-2014, entry version 146.
DE RecName: Full=HLA class I histocompatibility antigen, B-7 alpha chain;
DE AltName: Full=MHC class I antigen B*7;
DE Flags: Precursor;
GN Name=HLA-B; Synonyms=HLAB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:02).
RX PubMed=2320591; DOI=10.1073/pnas.87.7.2833;
RA Ennis P.D., Zemmour J., Salter R.D., Parham P.;
RT "Rapid cloning of HLA-A,B cDNA by using the polymerase chain reaction:
RT frequency and nature of errors produced in amplification.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:2833-2837(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE (ALLELE B*07:02).
RX PubMed=2700944;
RA Parham P., Benjamin R.J., Chen B.P., Clayberger C., Ennis P.D.,
RA Krensky A.M., Lawlor D.A., Littman D.R., Norment A.M., Orr H.T.,
RA Salter R.D., Zemmour J.;
RT "Diversity of class I HLA molecules: functional and evolutionary
RT interactions with T cells.";
RL Cold Spring Harb. Symp. Quant. Biol. 54:529-543(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:02).
RX PubMed=2993161; DOI=10.1007/BF00563508;
RA Sood A.K., Pan J., Biro P.A., Pereira D., Srivastava R., Reddy V.B.,
RA Duceman B.W., Weissman S.M.;
RT "Structure and polymorphism of class I MHC antigen mRNA.";
RL Immunogenetics 22:101-121(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE (ALLELE B*07:02).
RA Ellexson M.E., Zhang L., Hildebrand W.H.;
RL Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:03).
RX PubMed=8106270; DOI=10.1016/0198-8859(93)90533-7;
RA Bergmans A., Tijssen H., Lardy J., Reekers P.;
RT "Complete nucleotide sequence of HLA-B*0703, a B7-variant (BPOT).";
RL Hum. Immunol. 38:159-162(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:04).
RX PubMed=7652739; DOI=10.1111/j.1399-0039.1995.tb02461.x;
RA Kubens B.S., Arnett K.L., Adams E.J., Parham P., Grosse-Wilde H.;
RT "Definition of a new HLA-B7 subtype (B*0704) by isoelectric focusing,
RT family studies and DNA sequence analysis.";
RL Tissue Antigens 45:322-327(1995).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:05).
RX PubMed=7878658; DOI=10.1111/j.1399-0039.1994.tb02402.x;
RA Arnett K.L., Adams E.J., Domena J.D., Parham P.;
RT "Structure of a novel subtype of B7 (B*0705) isolated from a Chinese
RT individual.";
RL Tissue Antigens 44:318-321(1994).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELES B*07:03 AND B*07:05).
RX PubMed=8537119;
RA Smith K.D., Epperson D.F., Lutz C.T.;
RT "Alloreactive cytotoxic T-lymphocyte-defined HLA-B7 subtypes differ in
RT peptide antigen presentation.";
RL Immunogenetics 43:27-37(1996).
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] (ALLELE B*07:06).
RX PubMed=8773323; DOI=10.1111/j.1399-0039.1996.tb02561.x;
RA Sanz L., Vilches C., de Pablo R., Bunce M., Moreno M.E., Kreisler M.;
RT "Haplotypic association of two new HLA class I alleles: Cw*15052 and
RT B*0706: evolutionary relationships of HLA-Cw*15 alleles.";
RL Tissue Antigens 47:329-332(1996).
RN [10]
RP NUCLEOTIDE SEQUENCE (ALLELE B*07:18).
RA Bettinotti M.P., Hadzikadic L., Dhillon G., Barracchini K.,
RA Marincola F.M.;
RT "A new HLA-B allele.";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE (ALLELE B*07:02).
RA Marsh S.G.E.;
RT "Intron sequences of HLA class I.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [12]
RP NUCLEOTIDE SEQUENCE (ALLELE B*07:02).
RC TISSUE=Blood;
RX PubMed=12622774; DOI=10.1034/j.1399-0039.2003.610103.x;
RA Cox S.T., McWhinnie A.J., Robinson J., Marsh S.G.E., Parham P.,
RA Madrigal J.A., Little A.-M.;
RT "Cloning and sequencing full-length HLA-B and -C genes.";
RL Tissue Antigens 61:20-48(2003).
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Subthalamic nucleus;
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 [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E.,
RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S.,
RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J.,
RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P.,
RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E.,
RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A.,
RA Frankland J., French L., Garner P., Garnett J., Ghori M.J.,
RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M.,
RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S.,
RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R.,
RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E.,
RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A.,
RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C.,
RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M.,
RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K.,
RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T.,
RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R.,
RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W.,
RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M.,
RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L.,
RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J.,
RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B.,
RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L.,
RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W.,
RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A.,
RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [15]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 26-206 (ALLELE B*07:24).
RC TISSUE=Peripheral blood;
RX PubMed=11556973; DOI=10.1034/j.1399-0039.2001.057005471.x;
RA Middleton D., Curran M.D., Anholts J.D., Reilly E.R., Schreuder G.M.;
RT "Characterisation of a new HLA-B allele, HLA-B*0724.";
RL Tissue Antigens 57:471-473(2001).
RN [16]
RP PROTEIN SEQUENCE OF 25-295 (B*07:02).
RX PubMed=518865; DOI=10.1021/bi00592a030;
RA Orr H.T., Lopez de Castro J.A., Lancet D., Strominger J.L.;
RT "Complete amino acid sequence of a papain-solubilized human
RT histocompatibility antigen, HLA-B7. 2. Sequence determination and
RT search for homologies.";
RL Biochemistry 18:5711-5720(1979).
RN [17]
RP INTERACTION WITH HTLV-1 ACCESSORY PROTEIN P12I.
RX PubMed=11390610; DOI=10.1128/JVI.75.13.6086-6094.2001;
RA Johnson J.M., Nicot C., Fullen J., Ciminale V., Casareto L.,
RA Mulloy J.C., Jacobson S., Franchini G.;
RT "Free major histocompatibility complex class I heavy chain is
RT preferentially targeted for degradation by human T-cell
RT leukemia/lymphotropic virus type 1 p12(I) protein.";
RL J. Virol. 75:6086-6094(2001).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-110, AND MASS
RP SPECTROMETRY.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of
RT multiple enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [19]
RP VARIANT [LARGE SCALE ANALYSIS] THR-65, AND MASS SPECTROMETRY.
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).
CC -!- FUNCTION: Involved in the presentation of foreign antigens to the
CC immune system.
CC -!- SUBUNIT: Heterodimer of an alpha chain and a beta chain (beta-2-
CC microglobulin). Interacts with human herpesvirus 8 MIR1 protein
CC (By similarity). Interacts with HTLV-1 accessory protein p12I.
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein.
CC -!- PTM: Polyubiquitinated in a post ER compartment by interaction
CC with human herpesvirus 8 MIR1 protein. This targets the protein
CC for rapid degradation via the ubiquitin system (By similarity).
CC -!- POLYMORPHISM: The following alleles of B-7 are known: B*07:02
CC (B7.2), B*07:03 (BPOT), B*07:04, B*07:05, B*07:06 (B7_L79),
CC B*07:18 and B*07:24. The sequence shown is B*07:02.
CC -!- SIMILARITY: Belongs to the MHC class I family.
CC -!- SIMILARITY: Contains 1 Ig-like C1-type (immunoglobulin-like)
CC domain.
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DR EMBL; M32317; AAA36230.1; -; mRNA.
DR EMBL; M16102; AAA59622.1; ALT_SEQ; mRNA.
DR EMBL; U29057; AAA91229.1; -; mRNA.
DR EMBL; X64454; CAA45785.1; -; mRNA.
DR EMBL; U04245; AAA87398.1; -; mRNA.
DR EMBL; L33922; AAA65639.1; -; mRNA.
DR EMBL; U21052; AAA92563.1; -; mRNA.
DR EMBL; U21053; AAA92564.1; -; mRNA.
DR EMBL; X91749; CAA62864.1; -; mRNA.
DR EMBL; AF189017; AAF01052.1; -; mRNA.
DR EMBL; AJ309047; CAC35468.1; -; Genomic_DNA.
DR EMBL; AJ292075; CAC33440.1; -; Genomic_DNA.
DR EMBL; AL671883; CAI18148.1; -; Genomic_DNA.
DR EMBL; AK313911; BAG36634.1; -; mRNA.
DR EMBL; AJ401222; CAC10402.1; -; Genomic_DNA.
DR PIR; B35997; HLHUB7.
DR PIR; I54418; I54418.
DR PIR; I59651; I59651.
DR PIR; S60601; S60601.
DR RefSeq; NP_005505.2; NM_005514.6.
DR UniGene; Hs.654404; -.
DR UniGene; Hs.77961; -.
DR PDB; 3VCL; X-ray; 1.70 A; A=25-299.
DR PDBsum; 3VCL; -.
DR ProteinModelPortal; P01889; -.
DR SMR; P01889; 25-299.
DR IntAct; P01889; 4.
DR DMDM; 122162; -.
DR PaxDb; P01889; -.
DR PRIDE; P01889; -.
DR Ensembl; ENST00000412585; ENSP00000399168; ENSG00000234745.
DR GeneID; 3106; -.
DR KEGG; hsa:3106; -.
DR UCSC; uc003ntg.1; human.
DR CTD; 3106; -.
DR GeneCards; GC06M031321; -.
DR HGNC; HGNC:4932; HLA-B.
DR HPA; CAB015418; -.
DR MIM; 142830; gene.
DR neXtProt; NX_P01889; -.
DR PharmGKB; PA35056; -.
DR eggNOG; NOG42056; -.
DR HOVERGEN; HBG016709; -.
DR KO; K06751; -.
DR OMA; KANTRIY; -.
DR OrthoDB; EOG7JT6WQ; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; HLA-B; human.
DR GeneWiki; HLA-B; -.
DR GenomeRNAi; 3106; -.
DR NextBio; 12323; -.
DR PRO; PR:P01889; -.
DR ArrayExpress; P01889; -.
DR Bgee; P01889; -.
DR CleanEx; HS_HLA-B; -.
DR Genevestigator; P01889; -.
DR GO; GO:0031901; C:early endosome membrane; TAS:Reactome.
DR GO; GO:0012507; C:ER to Golgi transport vesicle membrane; TAS:Reactome.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0071556; C:integral to lumenal side of endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
DR GO; GO:0042612; C:MHC class I protein complex; IEA:UniProtKB-KW.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0042605; F:peptide antigen binding; IBA:RefGenome.
DR GO; GO:0002479; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent; TAS:Reactome.
DR GO; GO:0002480; P:antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-independent; TAS:Reactome.
DR GO; GO:0060333; P:interferon-gamma-mediated signaling pathway; TAS:Reactome.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0001916; P:positive regulation of T cell mediated cytotoxicity; IEA:InterPro.
DR GO; GO:2001198; P:regulation of dendritic cell differentiation; IMP:BHF-UCL.
DR GO; GO:0050776; P:regulation of immune response; TAS:Reactome.
DR GO; GO:0032655; P:regulation of interleukin-12 production; IMP:BHF-UCL.
DR GO; GO:0032675; P:regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0002667; P:regulation of T cell anergy; IMP:BHF-UCL.
DR GO; GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 3.30.500.10; -; 1.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003006; Ig/MHC_CS.
DR InterPro; IPR003597; Ig_C1-set.
DR InterPro; IPR011161; MHC_I-like_Ag-recog.
DR InterPro; IPR011162; MHC_I/II-like_Ag-recog.
DR InterPro; IPR027648; MHC_I_a.
DR InterPro; IPR001039; MHC_I_a_a1/a2.
DR InterPro; IPR010579; MHC_I_a_C.
DR Pfam; PF07654; C1-set; 1.
DR Pfam; PF00129; MHC_I; 1.
DR Pfam; PF06623; MHC_I_C; 1.
DR PRINTS; PR01638; MHCCLASSI.
DR SMART; SM00407; IGc1; 1.
DR SUPFAM; SSF54452; SSF54452; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
DR PROSITE; PS00290; IG_MHC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Host-virus interaction; Immunity;
KW Membrane; MHC I; Polymorphism; Reference proteome; Signal;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1 24
FT CHAIN 25 362 HLA class I histocompatibility antigen,
FT B-7 alpha chain.
FT /FTId=PRO_0000018833.
FT TOPO_DOM 25 309 Extracellular (Potential).
FT TRANSMEM 310 333 Helical; (Potential).
FT TOPO_DOM 334 362 Cytoplasmic (Potential).
FT DOMAIN 209 295 Ig-like C1-type.
FT REGION 25 114 Alpha-1.
FT REGION 115 206 Alpha-2.
FT REGION 207 298 Alpha-3.
FT REGION 299 309 Connecting peptide.
FT CARBOHYD 110 110 N-linked (GlcNAc...).
FT DISULFID 125 188
FT DISULFID 227 283
FT VARIANT 4 4 M -> T (in dbSNP:rs1050458).
FT /FTId=VAR_050332.
FT VARIANT 9 9 V -> L (in dbSNP:rs1050462).
FT /FTId=VAR_050333.
FT VARIANT 17 17 L -> V (in dbSNP:rs1131165).
FT /FTId=VAR_050334.
FT VARIANT 35 35 S -> A (in dbSNP:rs1131170).
FT /FTId=VAR_050335.
FT VARIANT 36 36 V -> M (in dbSNP:rs1050486).
FT /FTId=VAR_050336.
FT VARIANT 48 48 S -> A (in dbSNP:rs713031).
FT /FTId=VAR_061386.
FT VARIANT 48 48 S -> P (in dbSNP:rs713031).
FT /FTId=VAR_061387.
FT VARIANT 48 48 S -> T (in dbSNP:rs713031).
FT /FTId=VAR_061388.
FT VARIANT 65 65 A -> T (in dbSNP:rs1050529).
FT /FTId=VAR_050337.
FT VARIANT 87 87 N -> D (in dbSNP:rs1050570).
FT /FTId=VAR_050338.
FT VARIANT 87 87 N -> K (in dbSNP:rs1065386).
FT /FTId=VAR_059467.
FT VARIANT 93 95 AQA -> TNT (in allele B*07:03).
FT /FTId=VAR_016351.
FT VARIANT 97 97 T -> A (in dbSNP:rs1050393).
FT /FTId=VAR_050339.
FT VARIANT 98 98 D -> Y (in dbSNP:rs1131215).
FT /FTId=VAR_059468.
FT VARIANT 101 101 S -> N (in dbSNP:rs1050388).
FT /FTId=VAR_050340.
FT VARIANT 118 119 TL -> II (in allele B*07:18).
FT /FTId=VAR_016352.
FT VARIANT 121 121 S -> R (in allele B*07:18).
FT /FTId=VAR_016353.
FT VARIANT 137 137 H -> Y (in dbSNP:rs1050379).
FT /FTId=VAR_050341.
FT VARIANT 138 138 D -> H (in dbSNP:rs709055).
FT /FTId=VAR_061389.
FT VARIANT 138 138 D -> N (in allele B*07:05 and allele
FT B*07:06; dbSNP:rs709055).
FT /FTId=VAR_016354.
FT VARIANT 155 155 R -> S (in dbSNP:rs1050654).
FT /FTId=VAR_050342.
FT VARIANT 180 180 R -> D (in allele B*07:04; requires 2
FT nucleotide substitutions).
FT /FTId=VAR_016355.
FT VARIANT 187 187 E -> A (in dbSNP:rs2308466).
FT /FTId=VAR_059469.
FT VARIANT 187 187 E -> G (in dbSNP:rs2308466).
FT /FTId=VAR_059470.
FT VARIANT 187 187 E -> K (in dbSNP:rs2523600).
FT /FTId=VAR_059471.
FT VARIANT 187 187 E -> L (in allele B*07:24; requires 2
FT nucleotide substitutions).
FT /FTId=VAR_016616.
FT VARIANT 187 187 E -> Q (in dbSNP:rs2523600).
FT /FTId=VAR_059472.
FT VARIANT 187 187 E -> V (in dbSNP:rs2308466).
FT /FTId=VAR_059473.
FT VARIANT 195 195 Y -> H (in dbSNP:rs1050696).
FT /FTId=VAR_050343.
FT VARIANT 306 306 V -> I (in allele B*07:05;
FT dbSNP:rs1131500).
FT /FTId=VAR_016356.
FT VARIANT 329 329 A -> T (in dbSNP:rs1051488).
FT /FTId=VAR_050344.
FT VARIANT 349 349 C -> S (in dbSNP:rs2308655).
FT /FTId=VAR_061390.
FT VARIANT 349 349 C -> Y (in dbSNP:rs2308655).
FT /FTId=VAR_061391.
FT CONFLICT 15 18 AALA -> GPW (in Ref. 3; AAA59622).
FT CONFLICT 266 266 Q -> E (in Ref. 16; AA sequence).
FT CONFLICT 268 268 W -> S (in Ref. 3; AAA59622).
FT CONFLICT 297 297 R -> G (in Ref. 3; AAA59622).
FT CONFLICT 314 315 GL -> RP (in Ref. 3; AAA59622).
FT STRAND 27 36
FT STRAND 45 52
FT STRAND 55 61
FT STRAND 64 66
FT HELIX 74 76
FT HELIX 81 108
FT STRAND 118 127
FT STRAND 133 142
FT STRAND 145 150
FT STRAND 157 161
FT HELIX 162 173
FT HELIX 176 185
FT HELIX 187 198
FT HELIX 200 203
FT STRAND 210 235
FT STRAND 238 243
FT HELIX 249 251
FT STRAND 252 254
FT STRAND 261 263
FT STRAND 265 274
FT HELIX 278 280
FT STRAND 281 286
FT STRAND 290 292
FT STRAND 294 296
SQ SEQUENCE 362 AA; 40460 MW; 5E5A7BDE031403D6 CRC64;
MLVMAPRTVL LLLSAALALT ETWAGSHSMR YFYTSVSRPG RGEPRFISVG YVDDTQFVRF
DSDAASPREE PRAPWIEQEG PEYWDRNTQI YKAQAQTDRE SLRNLRGYYN QSEAGSHTLQ
SMYGCDVGPD GRLLRGHDQY AYDGKDYIAL NEDLRSWTAA DTAAQITQRK WEAAREAEQR
RAYLEGECVE WLRRYLENGK DKLERADPPK THVTHHPISD HEATLRCWAL GFYPAEITLT
WQRDGEDQTQ DTELVETRPA GDRTFQKWAA VVVPSGEEQR YTCHVQHEGL PKPLTLRWEP
SSQSTVPIVG IVAGLAVLAV VVIGAVVAAV MCRRKSSGGK GGSYSQAACS DSAQGSDVSL
TA
//

MIM 142830
*RECORD*
*FIELD* NO
142830
*FIELD* TI
+142830 MAJOR HISTOCOMPATIBILITY COMPLEX, CLASS I, B; HLA-B
;;HLA-B HISTOCOMPATIBILITY TYPE
read moreABACAVIR HYPERSENSITIVITY, SUSCEPTIBILITY TO, INCLUDED;;
SYNOVITIS, CHRONIC, SUSCEPTIBILITY TO, INCLUDED;;
DRUG-INDUCED LIVER INJURY DUE TO FLUCLOXACILLIN, INCLUDED
*FIELD* TX
For background information on the major histocompatibility complex (MHC)
and human leukocyte antigens (HLAs), see HLA-A (142800).

MAPPING

Cann et al. (1983) found a restriction fragment that segregated with
HLA-B8. Either the fragment carried the B8 specificity or represented
another class I gene (or pseudogene) in linkage disequilibrium with
HLA-B8.

Dunham et al. (1987) used pulsed-field gel electrophoresis and 'cosmid
walking' to establish a molecular map of the MHC region. They concluded
that the MHC spans 3,800 kb. The HLA-B locus lies about 250 kb on the
telomeric side of the tumor necrosis factor genes (see TNFA; 191160).

Spies et al. (1989) found that the HLA-B gene is 210 kb from the TNFA
and TNFB (153440) genes. The class III gene C2 is separated from the
HLA-B gene by 600 kb.

Spies et al. (1989) concluded that a 600-kb DNA segment between C2 and
HLA-B contains a minimum of 19 genes. In addition to BAT1 (142560)
through BAT5 (142620), which had been localized to the vicinity of the
TNFA and TNFB genes, 4 genes, called BAT6 through BAT9, were mapped near
C2 within a 120-kb region that also includes a pair of heat-shock
protein genes (see 140550). A large number of BssHII and SacII
restriction sites, known to indicate the presence of multiple islands of
CPG-rich sequences and in turn the association of expressed genes,
occurred within 140 kb of DNA upstream from C2. In contrast, no gene was
found within the 175-kb interval between BAT1 and HLA-B, which is
relatively devoid of CPG-rich sequences.

Bronson et al. (1991) isolated yeast artificial chromosome (YAC) clones
carrying the HLA-B and HLA-C (142840) genes. The loci were found to be
located about 85 kb apart, each in close association with a CpG island.

GENE FUNCTION

Fleischhauer et al. (1990) demonstrated that a single amino acid
difference in the HLA-B molecule is sufficient for the development of
alloreactivity in vivo. They reported the case of a 29-year-old man with
chronic myelogenous leukemia who received a bone marrow transplant from
an unrelated female donor who was serologically HLA identical and
compatible in mixed lymphocyte culture. However, they differed with
respect to HLA-B44 subtypes B44.1 and B44.2, which were distinguishable
by their characteristic band patterns in isoelectric-focusing (IEF) gel
electrophoresis. The IEF difference, based on differences in charged
amino acids, was found to be due to leucine versus aspartic acid at
position 156.

Leinders-Zufall et al. (2004) showed that small peptides that serve as
ligands for MHC class I molecules function also as sensory stimuli for a
subset of vomeronasal sensory neurons located in the basal G-alpha-o-
(139311) and V2R receptor (see 605234)-expressing zone of the
vomeronasal epithelium. In behaving mice, the same peptides function as
individuality signals underlying mate recognition in the context of
pregnancy block. MHC peptides constitute a previously unknown family of
chemosensory stimuli by which MHC genotypic diversity can influence
social behavior.

MOLECULAR GENETICS

- Association With Protection From Severe Malaria

By means of a large case-controlled study of malaria (see 611162) in
West African children, Hill et al. (1991) showed that HLA-Bw53 and the
HLA class II haplotype, DRB1*1302/DQB1*0501, (see HLA-DRB1, 142857) are
independently associated with protection from severe malaria. The
antigens listed are common in West Africans but rare in other racial
groups. In this population, they account for as great a reduction in
disease incidence as the sickle-cell hemoglobin variant. Although the
relative strength of the protection is less than that of the sickle-cell
variant, the greater frequency of the DQB1 (see HLA-DQB1, 604305)
polymorphism makes the net effect on resistance to malaria comparable.
The findings support the hypothesis that the extraordinary polymorphism
of major histocompatibility complex genes has evolved primarily through
natural selection by infectious pathogens.

Hill et al. (1992) further investigated the protective association
between HLA-B53 and severe malaria by sequencing peptides eluted from
this molecule followed by screening of candidate epitopes from
pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical
and cellular assays. Among malaria-immune Africans, they found that
HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved
nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no
HLA-B53-restricted epitopes were identified in other malaria antigens.
The findings of this 'reverse immunogenetic' approach indicated a
possible molecular basis for this HLA-disease association and supported
the candidacy of LSA-1 as a component for a malaria vaccine.

- Association With HIV-1 Disease Progression

Carrington et al. (1999) reported that the extended survival of 28 to
40% of HIV-1-infected Caucasian patients who avoided AIDS for 10 or more
years (see 609423) could be attributed to their being fully heterozygous
at HLA class I loci, to lacking the AIDS-associated alleles B*35 and
Cw*04, or to both.

Gao et al. (2001) examined subtypes of HLA-B*35 in 5 cohorts and
analyzed the relation of structural differences between subtypes to the
risk of progression to AIDS. Two subtypes were identified according to
peptide-binding specificity: the HLA-B*35-PY group, which consists
primarily of HLA-B*3501 and binds epitopes with proline in position 2
and tyrosine in position 9; and the more broadly reactive HLA-B*35-Px
group, which also binds epitopes with proline in position 2 but combines
several different amino acids (not including tyrosine) in position 9.
The influence of HLA-B*35 in accelerating progression to AIDS was
completely attributable to HLA-B*35-Px alleles, some of which differ
from HLA-B*35-Py alleles by only 1 amino acid residue. Gao et al. (2001)
concluded that the previously observed association of HLA-Cw*04 with
progression to AIDS was due to its linkage disequilibrium with
HLA-B*35-Px alleles. The fact that the association with B*35-Px was
observed in both blacks and whites supported the hypothesis that these
HLA-B alleles exert an effect on the immune response to HIV-1 infection.

Gao et al. (2005) found that HLA-B alleles acted during distinct
intervals after HIV infection. HLA-B35-Px and HLA-B57 were associated
with rate of progression to 4 outcomes: (1) progression to CD4+ T cells
less than 200 (CD4 less than 200), (2) CD4 less than 200 and/or an
AIDS-defining illness, (3) an AIDS-defining illness, and (4) death.
HLA-B27 (142830.0001), on the other hand, was only associated with the
last 3 outcomes. Protection mediated by HLA-B57 occurred early after
infection, whereas HLA-B27-mediated protection instead delayed
progression to an AIDS-defining illness after the decline in CD4 counts.
HLA-B35-Px showed an early susceptibility effect associated with rapid
progression from seroconversion to CD4 less than 200. Gao et al. (2005)
proposed that the presence of the various HLA-B alleles may lead to
different scenarios for viral escape from cytotoxic T-lymphocyte
pressure and virus subtypes with different fitnesses.

Martin et al. (2002) reported that the activating KIR allele KIR3DS1
(604946), in combination with HLA-B alleles that encode molecules with
isoleucine at position 80 (HLA-B Bw4-80Ile), is associated with delayed
progression to AIDS in individuals infected with HIV-1 (604946.0001). In
the absence of KIR3DS1, the HLA-B Bw4-80Ile allele was not associated
with any of the AIDS outcomes measured. By contrast, in the absence of
HLA-B Bw4-80Ile alleles, KIR3DS1 was significantly associated with more
rapid progression to AIDS. These observations strongly suggested a model
involving an epistatic interaction between the 2 loci. The strongest
synergistic effect of these loci was on progression to depletion of CD4+
T cells, which suggested that a protective response of NK cells
involving KIR3DS1 and its HLA class I ligands begins soon after HIV-1
infection.

Kiepiela et al. (2004) performed a comprehensive analysis of class I
restricted CD8+ T cell responses against HIV-1, immune control of which
depended upon virus-specific CD8+ T cell activity. In 375 HIV-1 infected
study subjects from southern Africa, a significantly greater number of
CD8+ T cell responses were HLA-B restricted compared to HLA-A (142800)
(2.5-fold; P = 0.0033). Kiepiela et al. (2004) showed that variation in
viral set point, in absolute CD4 count and, by inference, in rate of
disease progression in the cohort, was strongly associated with
particular HLA-B but not HLA-A allele expression (P less than 0.0001 and
P = 0.91, respectively). Moreover, substantially greater selection
pressure was imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold,
P = 0.0003). Kiepiela et al. (2004) concluded that their data indicated
that the principal focus of HIV-specific activity is at the HLA-B locus.
Furthermore, HLA-B gene frequencies in the population are those likely
to be most influenced by HIV disease, consistent with the observation
that B alleles evolve more rapidly than A alleles.

By testing the effects on HIV disease progression and viral load of
inhibitory KIR3DL1 subtypes in combination with HLA-B allelic groups,
Martin et al. (2007) determined that highly expressed, highly inhibitory
KIR3DL1*h alleles strongly enhance protection conferred by HLA-Bw4-80Ile
alleles, including HLA-B*57. Martin et al. (2007) proposed that greater
dependency on the expression of specific KIR3DL1-Bw4 receptor-ligand
pairs for NK cell inhibition in the resting state results in more
pronounced NK cell responses when the inhibition is abrogated in the
face of infection.

To define host genetic effects on the outcome of a chronic viral
infection, The International HIV Controllers Study (2010) performed
genomewide association analysis in a multiethnic cohort of HIV-1
controllers and progressors, and analyzed the effects of individual
amino acids within the classical human leukocyte antigen (HLA) proteins.
The International HIV Controllers Study (2010) identified more than 300
genomewide significant SNPs within the MHC and none elsewhere. Specific
amino acids in the HLA-B peptide binding groove, at positions 62, 63,
67, 70, and 97, as well as an independent HLA-C effect, explained the
SNP associations and reconciled both protective and risk HLA alleles.
The International HIV Controllers Study (2010) concluded that their
results implicated the nature of the HLA-viral peptide interaction as
the major factor modulating durable control of HIV infection.

- Association With Abacavir Hypersensitivity

Abacavir is a commonly used nucleoside analog with potent antiviral
activity against HIV-1. Approximately 5 to 9% of patients treated with
abacavir develop a hypersensitivity reaction characterized by
multisystem involvement that can be fatal in rare cases (Mallal et al.,
2002; Hetherington et al., 2002). Symptoms usually appear within the
first 6 weeks of treatment and include fever, rash, gastrointestinal
symptoms, and lethargy or malaise. Symptoms related to the
hypersensitivity reaction worsen with continued therapy and improve
within 72 hours of discontinuation of abacavir. Rechallenging with
abacavir after a hypersensitivity reaction typically results in
recurrence of symptoms within hours. Genetic predisposition for this
idiosyncratic hypersensitivity syndrome was suggested by its occurrence
in a small percentage of abacavir recipients during a short period of
drug exposure, and familial occurrence and decreased incidence in
individuals of African American origin (Symonds et al., 2002).
Consistent with these clinical observations, a strong predictive
association of HLA-B*5701 (142830.0003) was demonstrated, with further
evidence from recombinant haplotype mapping that the susceptibility
locus or loci reside specifically with the 57.1 ancestral haplotype,
identified by the haplospecific alleles HLA-B*5701 and C4A6 (see 120810)
and the HLA-DRB1*0701, HLA-DQ3 combination (Mallal et al., 2002). Martin
et al. (2004) reported that the combination of HLA-B*5701 and a
haplotypic M493T polymorphism of HSP70-HOM (140559) is highly predictive
of abacavir hypersensitivity.

- Association With Ankylosing Spondylitis

In a study of 15 multiplex families with ankylosing spondylitis
(106300), Rubin et al. (1992, 1994) found that 13 of 15 affected females
and 46 of 49 affected males were HLA-B27 (142830.0001) positive, as
compared with 22 of 43 unaffected females and 16 of 40 unaffected males.
The risk of ankylosing spondylitis for homozygotes was placed at 99.5%
and for heterozygotes at 43% with a sporadic risk of 0.1%. The B27
haplotype did not consistently segregate with disease in 2 families, but
both families still supported linkage to the major histocompatibility
complex. Identity-by-descent analyses showed a significant departure
from random segregation among affected avuncular (uncle/nephew-niece)
and cousin pairs. The presence of HLA-B40 in HLA-B27 positive
individuals increased the risk for disease more than 3-fold, confirming
previous reports. Disease susceptibility modeling suggested an autosomal
dominant pattern of inheritance with penetrance of approximately 20%. In
this study, which involved families from Toronto and Newfoundland, B27
alleles were detected by hybridization with sequence-specific
oligonucleotide probes after amplification of genomic DNA by PCR.

- Association With Age-Related Macular Degeneration

Goverdhan et al. (2005) investigated whether HLA genotypes were
associated with age-related macular degeneration (ARMD; see 603075).
They genotyped class I HLA-A, -B, and -Cw (see 142840) and class II DRB1
(142857) and DQB1 (604305) in 200 patients with ARMD, as well as in
controls. Allele Cw*0701 correlated positively with ARMD, whereas
alleles B*4001 and DRB1*1301 were negatively associated. These HLA
associations were independent of any linkage disequilibrium. Goverdhan
et al. (2005) concluded that HLA polymorphisms influenced the
development of ARMD and proposed modulation of choroidal immune function
as a possible mechanism for this effect.

- Association With Type I Diabetes

Nejentsev et al. (2007) used several large type I diabetes data sets to
analyze a combined total of 1,729 polymorphisms, and applied statistical
methods--recursive partitioning and regression--to pinpoint disease
susceptibility to the MHC class I genes HLA-B and HLA-A (142800) (risk
ratios greater than 1.5; P(combined) = 2.01 x 10(-19) and 2.35 x
10(-13), respectively) in addition to the established associations of
the MHC class II genes HLA-DQB1 (604305) and HLA-DRB1 (142857).
Nejentsev et al. (2007) suggested that other loci with smaller and/or
rarer effects might also be involved, but to find these future searches
must take into account both the HLA class II and class I genes and use
even larger samples. Taken together with previous studies, Nejentsev et
al. (2007) concluded that MHC class I-mediated events, principally
involving HLA-B*39, contribute to the etiology of type I diabetes.

- Association With Chronic Synovitis

Chronic synovitis occurs in about 10% of Indian patients with severe
hemophilia (HEMA, 306700; HEMB, 306900). Ghosh et al. (2003) reported an
association between the development of chronic synovitis in patients
with hemophilia and the HLA-B27 allele (142830.0001). Twenty-one (64%)
of 33 patients with both disorders had HLA-B27, compared to 23 (5%) of
440 with severe hemophilia without synovitis (odds ratio of 31.6). There
were 3 sib pairs with hemophilia in whom only 1 sib had synovitis; all
the affected sibs had the HLA-B27 allele, whereas the unaffected sibs
did not. Chronic synovitis presented as swelling of the joint with heat
and redness and absence of response to treatment with factor
concentrate. Ghosh et al. (2003) suggested that patients with HLA-B27
may ot be able to easily downregulate inflammatory mediators after
bleeding in the joints, leading to chronic synovitis.

- Association With Severe Cutaneous Adverse Reaction

Chung et al. (2004) studied 44 patients with carbamazepine-induced
Stevens-Johnson syndrome (608579), including 5 with overlapping toxic
epidermal necrolysis, in whom the clinical morphology fulfilled
Roujeau's diagnostic criteria (Roujeau, 1994). Controls included 101
patients who had been treated with carbamazepine for at least 3 months
without adverse reaction and 93 normal individuals. All participants
were Han Chinese residing in Taiwan. One hundred percent of the patients
who developed Stevens-Johnson syndrome carried the HLA-B*1502 allele
(142830.0002), while only 3% of the carbamazepine-tolerant individuals
and 8.6% of the normal controls carried this allele. When the
carbamazepine-tolerant group was used as the control, the presence of
HLA-B*1502 had a 93.6% positive predictive value for developing
carbamazepine-induced Stevens-Johnson syndrome, whereas its absence had
a negative prediction value of 100%.

To identify genetic markers for allopurinol-induced severe cutaneous
adverse reaction (SCAR; 608579), Hung et al. (2005) genotyped 51
patients with allopurinol-SCAR and 228 controls (135
allopurinol-tolerant patients and 93 healthy individuals) for 823 SNPs
in genes related to drug metabolism and immune response. All
participants were unrelated Han Chinese residing in Taiwan. The
HLA-B*5801 allele (142830.0004) was present in all 51 of the patients
with allopurinol-SCAR, but in only 15% of allopurinol-tolerant controls
and 20% of healthy controls (p = 4.7 x 10(-24) and p = 8.1 x 10(-18),
respectively). Hung et al. (2005) concluded that the HLA-B*5801 allele
is an important genetic risk factor for severe cutaneous adverse
reactions to allopurinol in the Han Chinese population.

- Association With Drug-Induced Liver Injury Due To Flucloxacillin

In a genomewide association study of 51 patients with
flucloxacillin-induced liver injury and 282 controls, Daly et al. (2009)
found an association with dbSNP rs2395029 in the HCP5 gene (604676) in
the MHC region (p = 8.7 x 10(-33)). The SNP is in complete linkage
disequilibrium with HLA-B*5701 (142830.0003). Further MHC genotyping of
64 flucloxacillin-tolerant controls confirmed the association with
HLA-B*5701 (odds ratio of 80.6; p = 9.0 x 10(-19)). The association was
replicated in a second cohort of 23 patients. In HLA-B*5701 carriers,
dbSNP rs10937275 in the ST6GAL1 (109675) gene on chromosome 3q also
showed genomewide significance (odds ratio of 4.1; p = 1.4 x 10(-8)).

- Association With Chronic Thromboembolic Pulmonary Hypertension
Without Deep Vein Thrombosis

For a discussion of a possible association between variation in the
HLA-B gene and chronic thromboembolic pulmonary hypertension (CTEPH)
without deep vein thrombosis, see 612862.

- Reviews

Cooke and Hill (2001) reviewed the genetics of susceptibility to human
infectious disease. Association with class I HLA alleles and infectious
disease have been demonstrated mainly with HLA-B: B8 with susceptibility
to pulmonary tuberculosis, B35 with susceptibility to AIDS, B53 with
resistance to severe malaria, and B57 with resistance to AIDS (see Table
3 of Cooke and Hill, 2001).

EVOLUTION

All Amerindian groups show limited HLA polymorphism which probably
reflects the small founder populations that colonized America by
overland migration from Asia 11,000 to 40,000 years ago. Belich et al.
(1992) found that the nucleotide sequences of HLA-B alleles from 2
culturally and linguistically distinct tribes of Southern Brazil are
distinct from those in Caucasian, Oriental, and other populations. By
comparison, the HLA-A (142800) and HLA-C alleles are similar. These
results and those reported by Watkins et al. (1992) from studies of a
tribe in Ecuador showed that a marked evolution of HLA-B occurred after
humans first entered South America. New alleles were formed through
recombination between preexisting alleles, not by point mutation, giving
rise to distinctive diversification of HLA-B in different South American
Indian tribes. Segmental exchanges of this type, even if they occur at a
lower frequency than point mutations, could be useful in the development
of resistance to infectious disease, for example, inasmuch as the
probability of an adaptively useful variant is much higher when there is
segmental exchange of already structurally valid coding sequence rather
than random point mutation.

Although most of the human MHC loci are relatively stable, the HLA-B
locus appears to be capable of rapid changes, especially in isolated
populations. To investigate the mechanisms of HLA-B evolution, McAdam et
al. (1994) compared the sequences of 19 HLA-B homologs from chimpanzees
(Pan troglodytes) and bonobos (Pan paniscus) to 65 HLA-B sequences.
Despite obvious similarities between chimpanzee and human alleles in
exon 2, there was little conservation of exon 3 between human and the 2
chimpanzee species. This finding suggested to McAdam et al. (1994) that,
unlike all other HLA loci, recombination has characterized the HLA-B
locus and its homologs for over 5 million years.

By genotyping individuals from 30 distinct populations, Single et al.
(2007) detected strong negative correlations between the presence of
activating KIR genes and their corresponding HLA ligand groups across
populations, particularly for KIR3DS1 (604946) and its putative HLA-B
Bw4-80Ile ligands. Weak positive relationships, on the other hand, were
found between inhibitory KIR genes and their HLA ligands. A negative
correlation was observed between distance from East Africa and the
frequency of activating KIR genes and their corresponding ligands.
Single et al. (2007) concluded that activating, rather than inhibitory,
receptor-ligand pairs show the strongest signature of coevolution
between the complex KIR and HLA genetic systems.

*FIELD* AV
.0001
ANKYLOSING SPONDYLITIS, SUSCEPTIBILITY TO, 1
SYNOVITIS, CHRONIC, SUSCEPTIBILITY TO, INCLUDED
HLA-B, HLA-B27

In a study of 15 multiplex families with ankylosing spondylitis
(106300), Rubin et al. (1992, 1994) found that 13 of 15 affected females
and 46 of 49 affected males were HLA-B27 positive, as compared with 22
of 43 unaffected females and 16 of 40 unaffected males. The risk of
ankylosing spondylitis for homozygotes was placed at 99.5% and for
heterozygotes at 43% with a sporadic risk of 0.1%. The B27 haplotype did
not consistently segregate with disease in 2 families, but both families
still supported linkage to the major histocompatibility complex.
Identity-by-descent analyses showed a significant departure from random
segregation among affected avuncular (uncle/nephew-niece) and cousin
pairs. The presence of HLA-B40 in HLA-B27 positive individuals increased
the risk for disease more than 3-fold, confirming previous reports.
Disease susceptibility modeling suggested an autosomal dominant pattern
of inheritance with penetrance of approximately 20%. In this study,
which involved families from Toronto and Newfoundland, B27 alleles were
detected by hybridization with sequence-specific oligonucleotide probes
after amplification of genomic DNA by PCR.

Chronic synovitis occurs in about 10% of Indian patients with severe
hemophilia (HEMA, 306700; HEMB, 306900). Ghosh et al. (2003) reported an
association between the development of chronic synovitis in patients
with hemophilia and the HLA-B27 allele. Twenty-one (64%) of 33 patients
with both disorders had HLA-B27, compared to 23 (5%) of 440 with severe
hemophilia without synovitis (odds ratio of 31.6). There were 3 sib
pairs with hemophilia in whom only 1 sib had synovitis; all the affected
sibs had the HLA-B27 allele, whereas the unaffected sibs did not.
Chronic synovitis presented as swelling of the joint with heat and
redness and absence of response to treatment with factor concentrate.
Ghosh et al. (2003) suggested that patients with HLA-B27 may ot be able
to easily downregulate inflammatory mediators after bleeding in the
joints, leading to chronic synovitis.

.0002
SEVERE CUTANEOUS ADVERSE REACTION, SUSCEPTIBILITY TO
STEVENS-JOHNSON SYNDROME, SUSCEPTIBILITY TO, INCLUDED;;
TOXIC EPIDERMAL NECROLYSIS, SUSCEPTIBILITY TO, INCLUDED
HLA-B, HLA-B*1502

Chung et al. (2004) studied 44 patients with carbamazepine-induced
Stevens-Johnson syndrome (608579), including 5 with overlapping toxic
epidermal necrolysis, in whom the clinical morphology fulfilled
Roujeau's diagnostic criteria (Roujeau, 1994). Controls included 101
patients who had been treated with carbamazepine for at least 3 months
without adverse reaction and 93 normal individuals. All participants
were Han Chinese residing in Taiwan. One hundred percent of the patients
who developed Stevens-Johnson syndrome carried the HLA-B*1502 allele,
while only 3% of the carbamazepine-tolerant individuals and 8.6% of the
normal controls carried this allele. When the carbamazepine-tolerant
group was used as the control, the presence of HLA-B*1502 had a 93.6%
positive predictive value for developing carbamazepine-induced
Stevens-Johnson syndrome, whereas its absence had a negative prediction
value of 100%.

In an expanded study of 60 Chinese patients with carbamazepine-induced
Stevens-Johnson syndrome or toxic epidermal necrolysis, including the 44
patients reported by Chung et al. (2004), Hung et al. (2006) confirmed
the association between drug reaction and the HLA-B*1502 allele (p = 1.6
x 10(-41), odds ratio of 1,357). Fifty-nine of the 60 patients had the
susceptibility allele compared to 6 (4.2%) of 144 tolerant controls.
There was no association between HLA-B*1502 and 31 patients with
nonbullous adverse drug reactions, suggesting that HLA-B*1502 is
specific for bullous phenotypes.

Chen et al. (2011) recruited 4,877 candidate subjects from 23 hospitals
in Taiwan who had not taken carbamazepine. All were genotyped to
determine whether they carried the HLA-B*1502 allele. Those testing
positive (7.7% of the total) were advised not to take carbamazepine.
None of the 92.3% who were advised to take carbamazepine developed
Stevens-Johnson syndrome or toxic epidermal necrolysis. The estimated
historical incidence of carbamazepine-induced SJS-TEN (0.23%) would
translate into approximately 10 cases among study subjects (P less than
0.001).

.0003
ABACAVIR HYPERSENSITIVITY, SUSCEPTIBILITY TO
DRUG-INDUCED LIVER INJURY DUE TO FLUCLOXACILLIN, INCLUDED
HLA-B, HLA-B*5701

Abacavir is an HIV reverse transcriptase inhibitor used in combination
with other antivirals in the treatment of HIV infection. Its efficacy is
equivalent to other HIV drugs, such as HIV protease inhibitors, and
different combinations of drugs are used in clinical practice depending
on patient response, side effects, and drug resistance profiles.
Hypersensitivity reactions occur in approximately 5% of abacavir
patients and are characterized by symptoms such as fever, rash, and
acute respiratory symptoms, and can lead to potentially life-threatening
hypotension if drug therapy is not discontinued (Clay, 2002). Veenstra
(2004) noted that 2 studies had shown that patients with the HLA-B*5701
genotype are at greater risk of a hypersensitivity reaction, with an
odds ratio of 117 (95% CI = 29-481) in 1 study (Mallal et al., 2002) and
23.6 (95% CI = 8-70) in another (Hetherington et al., 2002). Hughes et
al. (2004) presented a cost-effectiveness analysis of HLA-B*5701
genotyping in preventing abacavir hypersensitivity.

Martin et al. (2004) reported that the combination of HLA-B*5701 and a
haplotypic M493T polymorphism of HSP70-HOM (140559) is highly predictive
of abacavir hypersensitivity.

Mallal et al. (2008) found that HLA-B*5701 screening reduced the risk of
hypersensitivity reaction to abacavir used in the treatment of HIV
infection.

In a genomewide association study of 51 patients with
flucloxacillin-induced liver injury and 282 controls, Daly et al. (2009)
found an association with dbSNP rs2395029 in the MHC region (p = 8.7 x
10(-33)). The SNP is in complete linkage disequilibrium with HLA-B*5701.
Further MHC genotyping of 64 flucloxacillin-tolerant controls confirmed
the association with HLA-B*5701 (odds ratio of 80.6; p = 9.0 x 10(-19)).
The association was replicated in a second cohort of 23 patients. In
HLA-B*5701 carriers, dbSNP rs10937275 in the ST6GAL1 (109675) gene on
chromosome 3q also showed genomewide significance (odds ratio of 4.1; p
= 1.4 x 10(-8)).

.0004
SEVERE CUTANEOUS ADVERSE REACTION, SUSCEPTIBILITY TO
STEVENS-JOHNSON SYNDROME, SUSCEPTIBILITY TO, INCLUDED;;
TOXIC EPIDERMAL NECROLYSIS, SUSCEPTIBILITY TO, INCLUDED
HLA-B, HLA-B*5801

To identify genetic markers for allopurinol-induced severe cutaneous
adverse reaction (SCAR; 608579), Hung et al. (2005) genotyped 51
patients with allopurinol-SCAR and 228 controls (135
allopurinol-tolerant patients and 93 healthy individuals) for 823 SNPs
in genes related to drug metabolism and immune response. All
participants were unrelated Han Chinese residing in Taiwan. The
HLA-B*5801 allele was present in all 51 of the patients with
allopurinol-SCAR, but in only 15% of allopurinol-tolerant controls and
20% of healthy controls (p = 4.7 x 10(-24) and p = 8.1 x 10(-18),
respectively). Hung et al. (2005) concluded that the HLA-B*5801 allele
is an important genetic risk factor for severe cutaneous adverse
reactions to allopurinol in the Han Chinese population.

*FIELD* SA
Coppin et al. (1985); Mickelson et al. (1976)
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*FIELD* CN
Ada Hamosh - updated: 6/7/2011
Ada Hamosh - updated: 1/19/2011
Cassandra L. Kniffin - updated: 8/5/2009
Cassandra L. Kniffin - updated: 6/22/2009
Ada Hamosh - updated: 4/24/2008
Victor A. McKusick - updated: 3/10/2008
Paul J. Converse - updated: 12/6/2007
Cassandra L. Kniffin - updated: 11/13/2007
Cassandra L. Kniffin - updated: 10/30/2007
Paul J. Converse - updated: 3/31/2006
Jane Kelly - updated: 11/21/2005
Ada Hamosh - updated: 7/20/2005
Marla J. F. O'Neill - updated: 4/29/2005
Ada Hamosh - updated: 3/3/2005
Ada Hamosh - updated: 1/19/2005
Victor A. McKusick - updated: 10/4/2004
Victor A. McKusick - updated: 4/28/2004
Ada Hamosh - updated: 4/7/2004
Anne M. Stumpf - updated: 4/23/2003
Victor A. McKusick - updated: 2/14/2002
Victor A. McKusick - updated: 6/25/2001
Ada Hamosh - updated: 3/24/1999

*FIELD* CD
Victor A. McKusick: 6/4/1986

*FIELD* ED
terry: 12/20/2012
alopez: 6/13/2011
terry: 6/7/2011
carol: 5/23/2011
alopez: 1/19/2011
terry: 1/19/2011
carol: 7/27/2010
wwang: 4/13/2010
mgross: 3/29/2010
mgross: 3/25/2010
wwang: 8/18/2009
ckniffin: 8/5/2009
wwang: 6/26/2009
ckniffin: 6/22/2009
alopez: 5/8/2008
terry: 4/24/2008
terry: 3/10/2008
alopez: 12/6/2007
wwang: 11/20/2007
ckniffin: 11/13/2007
wwang: 11/12/2007
ckniffin: 10/30/2007
mgross: 7/5/2007
carol: 2/28/2007
alopez: 1/17/2007
mgross: 3/31/2006
alopez: 11/21/2005
alopez: 7/20/2005
terry: 7/20/2005
mgross: 6/16/2005
carol: 5/18/2005
wwang: 5/12/2005
wwang: 5/5/2005
terry: 4/29/2005
alopez: 3/4/2005
terry: 3/3/2005
tkritzer: 2/4/2005
wwang: 2/3/2005
wwang: 2/1/2005
wwang: 1/27/2005
terry: 1/19/2005
carol: 1/18/2005
tkritzer: 1/18/2005
terry: 10/4/2004
tkritzer: 5/5/2004
terry: 4/28/2004
alopez: 4/13/2004
terry: 4/7/2004
carol: 4/6/2004
alopez: 4/23/2003
cwells: 2/21/2002
cwells: 2/15/2002
terry: 2/14/2002
terry: 6/25/2001
carol: 2/24/2000
alopez: 12/3/1999
alopez: 3/24/1999
alopez: 5/29/1998
psherman: 5/4/1998
jason: 7/12/1994
carol: 1/7/1993
carol: 1/6/1993
carol: 6/26/1992
carol: 6/23/1992
supermim: 3/16/1992