Full text data of IGKC
IGKC
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Ig kappa chain C region
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Ig kappa chain C region
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P01834
ID IGKC_HUMAN Reviewed; 106 AA.
AC P01834;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Ig kappa chain C region;
GN Name=IGKC;
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 PROTEIN SEQUENCE (MYELOMA PROTEIN EU).
RX PubMed=5489770; DOI=10.1021/bi00818a007;
RA Gottlieb P.D., Cunningham B.A., Rutishauser U., Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. VI. Amino
RT acid sequence of the light chain.";
RL Biochemistry 9:3155-3161(1970).
RN [2]
RP DISULFIDE BONDS.
RX PubMed=4923144; DOI=10.1021/bi00818a011;
RA Gall W.E., Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. X.
RT Intrachain disulfide bonds.";
RL Biochemistry 9:3188-3196(1970).
RN [3]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN TI).
RX PubMed=5027703;
RA Suter L., Barnikol H.U., Watanabe S., Hilschmann N.;
RT "Rule of antibody structure. The primary structure of a monoclonal
RT immunoglobulin L-chain of kappa-type, subgroup 3 (Bence-Jones protein
RT Ti). IV. The complete amino acid sequence and its significance for the
RT mechanism of antibody production.";
RL Hoppe-Seyler's Z. Physiol. Chem. 353:189-208(1972).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6775818; DOI=10.1016/0092-8674(80)90168-3;
RA Hieter P.A., Max E.E., Seidman J.G., Maizel J.V. Jr., Leder P.;
RT "Cloned human and mouse kappa immunoglobulin constant and J region
RT genes conserve homology in functional segments.";
RL Cell 22:197-207(1980).
RN [5]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN ROY).
RA Hilschmann N., Barnikol H.U., Hess M., Langer B., Ponstingl H.,
RA Steinmetz-Kayne M., Suter L., Watanabe S.;
RL (In) Franek F., Shugar D. (eds.);
RL Gamma globulins: structure and function, pp.57-74, Academic Press, New
RL York (1969).
RN [6]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN CUM).
RX PubMed=5586923;
RA Hilschmann N.;
RT "The complete amino acid sequence of Bence Jones protein Cum (kappa-
RT type).";
RL Hoppe-Seyler's Z. Physiol. Chem. 348:1718-1722(1967).
RN [7]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN AG).
RX PubMed=4893682;
RA Titani K., Shinoda T., Putnam F.W.;
RT "The amino acid sequence of a kappa type Bence-Jones protein. 3. The
RT complete sequence and the location of the disulfide bridges.";
RL J. Biol. Chem. 244:3550-3560(1969).
RN [8]
RP PROTEIN SEQUENCE (WALDENSTROM'S MACROGLOBULIN OU).
RX PubMed=5447531; DOI=10.1126/science.169.3940.56;
RA Kohler H., Shimizu A., Paul C., Putnam F.W.;
RT "Macroglobulin structure: variable sequence of light and heavy
RT chains.";
RL Science 169:56-59(1970).
RN [9]
RP PROTEIN SEQUENCE OF 1-33; 38-41 AND 62-80.
RC TISSUE=Abdominal adipose tissue;
RX PubMed=9588180; DOI=10.1006/bbrc.1998.8515;
RA Olsen K.E., Sletten K., Westermark P.;
RT "Extended analysis of AL-amyloid protein from abdominal wall
RT subcutaneous fat biopsy: kappa IV immunoglobulin light chain.";
RL Biochem. Biophys. Res. Commun. 245:713-716(1998).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP VARIANT IGKCD ARG-40.
RX PubMed=3931219; DOI=10.1126/science.3931219;
RA Stavnezer-Nordgren J., Kekish O., Zegers B.J.;
RT "Molecular defects in a human immunoglobulin kappa chain deficiency.";
RL Science 230:458-461(1985).
CC -!- DISEASE: Immunoglobulin kappa light chain deficiency (IGKCD)
CC [MIM:614102]: A disease characterized by the complete absence of
CC immunoglobulin kappa chains. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The EU sequence has the INV (3) allotypic marker,
CC Ala-45 and Val-83. The ROY sequence has the INV (1,2) allotypic
CC marker, Ala-45 and Leu-83.
CC -!- SIMILARITY: Contains 1 Ig-like (immunoglobulin-like) domain.
CC -!- WEB RESOURCE: Name=IMGT/GENE-DB;
CC URL="http://www.imgt.org/IMGT_GENE-DB/GENElect?query=2+IGKC&species;=Homo+sapiens";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; J00241; AAA58989.1; -; Genomic_DNA.
DR PIR; B90562; K3HU.
DR UniGene; Hs.449609; -.
DR PDB; 1A4J; X-ray; 2.10 A; A/L=1-104.
DR PDB; 1A4K; X-ray; 2.40 A; A/L=1-104.
DR PDB; 1D5B; X-ray; 2.80 A; A/L=1-103.
DR PDB; 1D5I; X-ray; 2.00 A; L=1-103.
DR PDB; 1D6V; X-ray; 2.00 A; L=1-103.
DR PDB; 1DFB; X-ray; 2.70 A; L=1-106.
DR PDB; 1HEZ; X-ray; 2.70 A; A/C=1-106.
DR PDB; 1HKL; X-ray; 2.68 A; L=1-106.
DR PDB; 1HZH; X-ray; 2.70 A; L/M=2-106.
DR PDB; 1I7Z; X-ray; 2.30 A; A/C=1-106.
DR PDB; 1MIM; X-ray; 2.60 A; L=1-105.
DR PDB; 1OP3; X-ray; 1.75 A; K/L=1-105.
DR PDB; 1UCB; X-ray; 2.50 A; L=1-106.
DR PDB; 2O5X; X-ray; 2.05 A; L=1-106.
DR PDB; 2O5Y; X-ray; 2.85 A; L=1-106.
DR PDB; 2O5Z; X-ray; 2.40 A; L=1-106.
DR PDB; 2QQK; X-ray; 2.75 A; L=1-106.
DR PDB; 2QQL; X-ray; 3.10 A; L=1-106.
DR PDB; 2QQN; X-ray; 2.20 A; L=1-106.
DR PDB; 2QSC; X-ray; 2.80 A; L=1-106.
DR PDB; 2R56; X-ray; 2.80 A; L/M=1-103.
DR PDB; 2VXQ; X-ray; 1.90 A; L=1-106.
DR PDB; 3B2U; X-ray; 2.58 A; D/G/K/L/O/R/U/X=1-104.
DR PDB; 3B2V; X-ray; 3.30 A; L=1-104.
DR PDB; 3BDY; X-ray; 2.60 A; L=1-106.
DR PDB; 3BE1; X-ray; 2.90 A; L=1-106.
DR PDB; 3BKY; X-ray; 2.61 A; L=1-106.
DR PDB; 3BN9; X-ray; 2.17 A; C/E=1-106.
DR PDB; 3BQU; X-ray; 3.00 A; A=1-106.
DR PDB; 3C08; X-ray; 2.15 A; L=1-105.
DR PDB; 3C09; X-ray; 3.20 A; B/L=1-105.
DR PDB; 3CFJ; X-ray; 2.60 A; A/C/E/L=1-106.
DR PDB; 3CFK; X-ray; 2.60 A; A/C/E/G/J/L/M/O=1-106.
DR PDB; 3CSY; X-ray; 3.40 A; B/D/F/H=1-103.
DR PDB; 3D0L; X-ray; 2.35 A; A=1-105.
DR PDB; 3D85; X-ray; 1.90 A; A=1-106.
DR PDB; 3DVG; X-ray; 2.60 A; A=1-106.
DR PDB; 3DVN; X-ray; 2.70 A; A/L=1-106.
DR PDB; 3EYF; X-ray; 2.30 A; A/C=1-106.
DR PDB; 3EYO; X-ray; 2.50 A; A/C=1-106.
DR PDB; 3EYQ; X-ray; 2.40 A; C=1-106.
DR PDB; 3O11; X-ray; 2.80 A; A/L=2-106.
DR PDB; 3QCT; X-ray; 2.15 A; L=2-105.
DR PDB; 3QCU; X-ray; 1.98 A; L/M=2-105.
DR PDB; 3QCV; X-ray; 2.51 A; L/M=2-105.
DR PDB; 3U0W; X-ray; 2.00 A; L=1-106.
DR PDB; 3U7W; X-ray; 2.60 A; L=1-106.
DR PDB; 3U7Y; X-ray; 2.45 A; L=1-106.
DR PDB; 3VH8; X-ray; 1.80 A; C/F=93-101.
DR PDB; 4D9R; X-ray; 2.42 A; D/L=2-106.
DR PDB; 4HIX; X-ray; 2.20 A; L=1-106.
DR PDBsum; 1A4J; -.
DR PDBsum; 1A4K; -.
DR PDBsum; 1D5B; -.
DR PDBsum; 1D5I; -.
DR PDBsum; 1D6V; -.
DR PDBsum; 1DFB; -.
DR PDBsum; 1HEZ; -.
DR PDBsum; 1HKL; -.
DR PDBsum; 1HZH; -.
DR PDBsum; 1I7Z; -.
DR PDBsum; 1MIM; -.
DR PDBsum; 1OP3; -.
DR PDBsum; 1UCB; -.
DR PDBsum; 2O5X; -.
DR PDBsum; 2O5Y; -.
DR PDBsum; 2O5Z; -.
DR PDBsum; 2QQK; -.
DR PDBsum; 2QQL; -.
DR PDBsum; 2QQN; -.
DR PDBsum; 2QSC; -.
DR PDBsum; 2R56; -.
DR PDBsum; 2VXQ; -.
DR PDBsum; 3B2U; -.
DR PDBsum; 3B2V; -.
DR PDBsum; 3BDY; -.
DR PDBsum; 3BE1; -.
DR PDBsum; 3BKY; -.
DR PDBsum; 3BN9; -.
DR PDBsum; 3BQU; -.
DR PDBsum; 3C08; -.
DR PDBsum; 3C09; -.
DR PDBsum; 3CFJ; -.
DR PDBsum; 3CFK; -.
DR PDBsum; 3CSY; -.
DR PDBsum; 3D0L; -.
DR PDBsum; 3D85; -.
DR PDBsum; 3DVG; -.
DR PDBsum; 3DVN; -.
DR PDBsum; 3EYF; -.
DR PDBsum; 3EYO; -.
DR PDBsum; 3EYQ; -.
DR PDBsum; 3O11; -.
DR PDBsum; 3QCT; -.
DR PDBsum; 3QCU; -.
DR PDBsum; 3QCV; -.
DR PDBsum; 3U0W; -.
DR PDBsum; 3U7W; -.
DR PDBsum; 3U7Y; -.
DR PDBsum; 3VH8; -.
DR PDBsum; 4D9R; -.
DR PDBsum; 4HIX; -.
DR ProteinModelPortal; P01834; -.
DR SMR; P01834; 1-105.
DR IntAct; P01834; 36.
DR MINT; MINT-159227; -.
DR STRING; 9606.ENSP00000374777; -.
DR PhosphoSite; P01834; -.
DR DMDM; 125145; -.
DR UCD-2DPAGE; P01834; -.
DR PaxDb; P01834; -.
DR PRIDE; P01834; -.
DR GeneCards; GC02M089156; -.
DR H-InvDB; HIX0161619; -.
DR HGNC; HGNC:5716; IGKC.
DR MIM; 147200; gene.
DR MIM; 614102; phenotype.
DR neXtProt; NX_P01834; -.
DR Orphanet; 183675; Recurrent infections associated with rare immunoglobulin isotypes deficiency.
DR eggNOG; NOG116969; -.
DR HOGENOM; HOG000059537; -.
DR HOVERGEN; HBG039526; -.
DR InParanoid; P01834; -.
DR OMA; SFNRNEC; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; P01834; -.
DR PRO; PR:P01834; -.
DR Bgee; P01834; -.
DR CleanEx; HS_IGKC; -.
DR Genevestigator; P01834; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0003823; F:antigen binding; NAS:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 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 Pfam; PF07654; C1-set; 1.
DR SMART; SM00407; IGc1; 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 Disease mutation; Disulfide bond; Immunoglobulin C region;
KW Immunoglobulin domain; Reference proteome.
FT CHAIN <1 106 Ig kappa chain C region.
FT /FTId=PRO_0000153596.
FT DOMAIN 5 102 Ig-like.
FT DISULFID 26 86
FT DISULFID 106 106 Interchain (with a heavy chain).
FT VARIANT 40 40 W -> R (in IGKCD).
FT /FTId=VAR_066403.
FT VARIANT 83 83 V -> L (in INV(1,2) marker).
FT /FTId=VAR_003897.
FT CONFLICT 14 14 D -> N (in Ref. 7; AA sequence and 8; AA
FT sequence).
FT CONFLICT 57 57 E -> Q (in Ref. 5; AA sequence and 6; AA
FT sequence).
FT NON_TER 1 1
FT STRAND 6 10
FT HELIX 14 17
FT TURN 18 20
FT STRAND 21 34
FT STRAND 36 44
FT STRAND 49 55
FT TURN 60 62
FT STRAND 65 74
FT HELIX 75 78
FT STRAND 82 90
FT STRAND 93 95
FT STRAND 97 102
FT TURN 103 105
SQ SEQUENCE 106 AA; 11609 MW; 51984D1FDD372CE8 CRC64;
TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS
KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC
//
ID IGKC_HUMAN Reviewed; 106 AA.
AC P01834;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 21-JUL-1986, sequence version 1.
DT 22-JAN-2014, entry version 136.
DE RecName: Full=Ig kappa chain C region;
GN Name=IGKC;
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 PROTEIN SEQUENCE (MYELOMA PROTEIN EU).
RX PubMed=5489770; DOI=10.1021/bi00818a007;
RA Gottlieb P.D., Cunningham B.A., Rutishauser U., Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. VI. Amino
RT acid sequence of the light chain.";
RL Biochemistry 9:3155-3161(1970).
RN [2]
RP DISULFIDE BONDS.
RX PubMed=4923144; DOI=10.1021/bi00818a011;
RA Gall W.E., Edelman G.M.;
RT "The covalent structure of a human gamma G-immunoglobulin. X.
RT Intrachain disulfide bonds.";
RL Biochemistry 9:3188-3196(1970).
RN [3]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN TI).
RX PubMed=5027703;
RA Suter L., Barnikol H.U., Watanabe S., Hilschmann N.;
RT "Rule of antibody structure. The primary structure of a monoclonal
RT immunoglobulin L-chain of kappa-type, subgroup 3 (Bence-Jones protein
RT Ti). IV. The complete amino acid sequence and its significance for the
RT mechanism of antibody production.";
RL Hoppe-Seyler's Z. Physiol. Chem. 353:189-208(1972).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6775818; DOI=10.1016/0092-8674(80)90168-3;
RA Hieter P.A., Max E.E., Seidman J.G., Maizel J.V. Jr., Leder P.;
RT "Cloned human and mouse kappa immunoglobulin constant and J region
RT genes conserve homology in functional segments.";
RL Cell 22:197-207(1980).
RN [5]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN ROY).
RA Hilschmann N., Barnikol H.U., Hess M., Langer B., Ponstingl H.,
RA Steinmetz-Kayne M., Suter L., Watanabe S.;
RL (In) Franek F., Shugar D. (eds.);
RL Gamma globulins: structure and function, pp.57-74, Academic Press, New
RL York (1969).
RN [6]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN CUM).
RX PubMed=5586923;
RA Hilschmann N.;
RT "The complete amino acid sequence of Bence Jones protein Cum (kappa-
RT type).";
RL Hoppe-Seyler's Z. Physiol. Chem. 348:1718-1722(1967).
RN [7]
RP PROTEIN SEQUENCE (BENCE-JONES PROTEIN AG).
RX PubMed=4893682;
RA Titani K., Shinoda T., Putnam F.W.;
RT "The amino acid sequence of a kappa type Bence-Jones protein. 3. The
RT complete sequence and the location of the disulfide bridges.";
RL J. Biol. Chem. 244:3550-3560(1969).
RN [8]
RP PROTEIN SEQUENCE (WALDENSTROM'S MACROGLOBULIN OU).
RX PubMed=5447531; DOI=10.1126/science.169.3940.56;
RA Kohler H., Shimizu A., Paul C., Putnam F.W.;
RT "Macroglobulin structure: variable sequence of light and heavy
RT chains.";
RL Science 169:56-59(1970).
RN [9]
RP PROTEIN SEQUENCE OF 1-33; 38-41 AND 62-80.
RC TISSUE=Abdominal adipose tissue;
RX PubMed=9588180; DOI=10.1006/bbrc.1998.8515;
RA Olsen K.E., Sletten K., Westermark P.;
RT "Extended analysis of AL-amyloid protein from abdominal wall
RT subcutaneous fat biopsy: kappa IV immunoglobulin light chain.";
RL Biochem. Biophys. Res. Commun. 245:713-716(1998).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP VARIANT IGKCD ARG-40.
RX PubMed=3931219; DOI=10.1126/science.3931219;
RA Stavnezer-Nordgren J., Kekish O., Zegers B.J.;
RT "Molecular defects in a human immunoglobulin kappa chain deficiency.";
RL Science 230:458-461(1985).
CC -!- DISEASE: Immunoglobulin kappa light chain deficiency (IGKCD)
CC [MIM:614102]: A disease characterized by the complete absence of
CC immunoglobulin kappa chains. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: The EU sequence has the INV (3) allotypic marker,
CC Ala-45 and Val-83. The ROY sequence has the INV (1,2) allotypic
CC marker, Ala-45 and Leu-83.
CC -!- SIMILARITY: Contains 1 Ig-like (immunoglobulin-like) domain.
CC -!- WEB RESOURCE: Name=IMGT/GENE-DB;
CC URL="http://www.imgt.org/IMGT_GENE-DB/GENElect?query=2+IGKC&species;=Homo+sapiens";
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; J00241; AAA58989.1; -; Genomic_DNA.
DR PIR; B90562; K3HU.
DR UniGene; Hs.449609; -.
DR PDB; 1A4J; X-ray; 2.10 A; A/L=1-104.
DR PDB; 1A4K; X-ray; 2.40 A; A/L=1-104.
DR PDB; 1D5B; X-ray; 2.80 A; A/L=1-103.
DR PDB; 1D5I; X-ray; 2.00 A; L=1-103.
DR PDB; 1D6V; X-ray; 2.00 A; L=1-103.
DR PDB; 1DFB; X-ray; 2.70 A; L=1-106.
DR PDB; 1HEZ; X-ray; 2.70 A; A/C=1-106.
DR PDB; 1HKL; X-ray; 2.68 A; L=1-106.
DR PDB; 1HZH; X-ray; 2.70 A; L/M=2-106.
DR PDB; 1I7Z; X-ray; 2.30 A; A/C=1-106.
DR PDB; 1MIM; X-ray; 2.60 A; L=1-105.
DR PDB; 1OP3; X-ray; 1.75 A; K/L=1-105.
DR PDB; 1UCB; X-ray; 2.50 A; L=1-106.
DR PDB; 2O5X; X-ray; 2.05 A; L=1-106.
DR PDB; 2O5Y; X-ray; 2.85 A; L=1-106.
DR PDB; 2O5Z; X-ray; 2.40 A; L=1-106.
DR PDB; 2QQK; X-ray; 2.75 A; L=1-106.
DR PDB; 2QQL; X-ray; 3.10 A; L=1-106.
DR PDB; 2QQN; X-ray; 2.20 A; L=1-106.
DR PDB; 2QSC; X-ray; 2.80 A; L=1-106.
DR PDB; 2R56; X-ray; 2.80 A; L/M=1-103.
DR PDB; 2VXQ; X-ray; 1.90 A; L=1-106.
DR PDB; 3B2U; X-ray; 2.58 A; D/G/K/L/O/R/U/X=1-104.
DR PDB; 3B2V; X-ray; 3.30 A; L=1-104.
DR PDB; 3BDY; X-ray; 2.60 A; L=1-106.
DR PDB; 3BE1; X-ray; 2.90 A; L=1-106.
DR PDB; 3BKY; X-ray; 2.61 A; L=1-106.
DR PDB; 3BN9; X-ray; 2.17 A; C/E=1-106.
DR PDB; 3BQU; X-ray; 3.00 A; A=1-106.
DR PDB; 3C08; X-ray; 2.15 A; L=1-105.
DR PDB; 3C09; X-ray; 3.20 A; B/L=1-105.
DR PDB; 3CFJ; X-ray; 2.60 A; A/C/E/L=1-106.
DR PDB; 3CFK; X-ray; 2.60 A; A/C/E/G/J/L/M/O=1-106.
DR PDB; 3CSY; X-ray; 3.40 A; B/D/F/H=1-103.
DR PDB; 3D0L; X-ray; 2.35 A; A=1-105.
DR PDB; 3D85; X-ray; 1.90 A; A=1-106.
DR PDB; 3DVG; X-ray; 2.60 A; A=1-106.
DR PDB; 3DVN; X-ray; 2.70 A; A/L=1-106.
DR PDB; 3EYF; X-ray; 2.30 A; A/C=1-106.
DR PDB; 3EYO; X-ray; 2.50 A; A/C=1-106.
DR PDB; 3EYQ; X-ray; 2.40 A; C=1-106.
DR PDB; 3O11; X-ray; 2.80 A; A/L=2-106.
DR PDB; 3QCT; X-ray; 2.15 A; L=2-105.
DR PDB; 3QCU; X-ray; 1.98 A; L/M=2-105.
DR PDB; 3QCV; X-ray; 2.51 A; L/M=2-105.
DR PDB; 3U0W; X-ray; 2.00 A; L=1-106.
DR PDB; 3U7W; X-ray; 2.60 A; L=1-106.
DR PDB; 3U7Y; X-ray; 2.45 A; L=1-106.
DR PDB; 3VH8; X-ray; 1.80 A; C/F=93-101.
DR PDB; 4D9R; X-ray; 2.42 A; D/L=2-106.
DR PDB; 4HIX; X-ray; 2.20 A; L=1-106.
DR PDBsum; 1A4J; -.
DR PDBsum; 1A4K; -.
DR PDBsum; 1D5B; -.
DR PDBsum; 1D5I; -.
DR PDBsum; 1D6V; -.
DR PDBsum; 1DFB; -.
DR PDBsum; 1HEZ; -.
DR PDBsum; 1HKL; -.
DR PDBsum; 1HZH; -.
DR PDBsum; 1I7Z; -.
DR PDBsum; 1MIM; -.
DR PDBsum; 1OP3; -.
DR PDBsum; 1UCB; -.
DR PDBsum; 2O5X; -.
DR PDBsum; 2O5Y; -.
DR PDBsum; 2O5Z; -.
DR PDBsum; 2QQK; -.
DR PDBsum; 2QQL; -.
DR PDBsum; 2QQN; -.
DR PDBsum; 2QSC; -.
DR PDBsum; 2R56; -.
DR PDBsum; 2VXQ; -.
DR PDBsum; 3B2U; -.
DR PDBsum; 3B2V; -.
DR PDBsum; 3BDY; -.
DR PDBsum; 3BE1; -.
DR PDBsum; 3BKY; -.
DR PDBsum; 3BN9; -.
DR PDBsum; 3BQU; -.
DR PDBsum; 3C08; -.
DR PDBsum; 3C09; -.
DR PDBsum; 3CFJ; -.
DR PDBsum; 3CFK; -.
DR PDBsum; 3CSY; -.
DR PDBsum; 3D0L; -.
DR PDBsum; 3D85; -.
DR PDBsum; 3DVG; -.
DR PDBsum; 3DVN; -.
DR PDBsum; 3EYF; -.
DR PDBsum; 3EYO; -.
DR PDBsum; 3EYQ; -.
DR PDBsum; 3O11; -.
DR PDBsum; 3QCT; -.
DR PDBsum; 3QCU; -.
DR PDBsum; 3QCV; -.
DR PDBsum; 3U0W; -.
DR PDBsum; 3U7W; -.
DR PDBsum; 3U7Y; -.
DR PDBsum; 3VH8; -.
DR PDBsum; 4D9R; -.
DR PDBsum; 4HIX; -.
DR ProteinModelPortal; P01834; -.
DR SMR; P01834; 1-105.
DR IntAct; P01834; 36.
DR MINT; MINT-159227; -.
DR STRING; 9606.ENSP00000374777; -.
DR PhosphoSite; P01834; -.
DR DMDM; 125145; -.
DR UCD-2DPAGE; P01834; -.
DR PaxDb; P01834; -.
DR PRIDE; P01834; -.
DR GeneCards; GC02M089156; -.
DR H-InvDB; HIX0161619; -.
DR HGNC; HGNC:5716; IGKC.
DR MIM; 147200; gene.
DR MIM; 614102; phenotype.
DR neXtProt; NX_P01834; -.
DR Orphanet; 183675; Recurrent infections associated with rare immunoglobulin isotypes deficiency.
DR eggNOG; NOG116969; -.
DR HOGENOM; HOG000059537; -.
DR HOVERGEN; HBG039526; -.
DR InParanoid; P01834; -.
DR OMA; SFNRNEC; -.
DR Reactome; REACT_160300; Binding and Uptake of Ligands by Scavenger Receptors.
DR Reactome; REACT_6900; Immune System.
DR EvolutionaryTrace; P01834; -.
DR PRO; PR:P01834; -.
DR Bgee; P01834; -.
DR CleanEx; HS_IGKC; -.
DR Genevestigator; P01834; -.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0003823; F:antigen binding; NAS:UniProtKB.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome.
DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR Gene3D; 2.60.40.10; -; 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 Pfam; PF07654; C1-set; 1.
DR SMART; SM00407; IGc1; 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 Disease mutation; Disulfide bond; Immunoglobulin C region;
KW Immunoglobulin domain; Reference proteome.
FT CHAIN <1 106 Ig kappa chain C region.
FT /FTId=PRO_0000153596.
FT DOMAIN 5 102 Ig-like.
FT DISULFID 26 86
FT DISULFID 106 106 Interchain (with a heavy chain).
FT VARIANT 40 40 W -> R (in IGKCD).
FT /FTId=VAR_066403.
FT VARIANT 83 83 V -> L (in INV(1,2) marker).
FT /FTId=VAR_003897.
FT CONFLICT 14 14 D -> N (in Ref. 7; AA sequence and 8; AA
FT sequence).
FT CONFLICT 57 57 E -> Q (in Ref. 5; AA sequence and 6; AA
FT sequence).
FT NON_TER 1 1
FT STRAND 6 10
FT HELIX 14 17
FT TURN 18 20
FT STRAND 21 34
FT STRAND 36 44
FT STRAND 49 55
FT TURN 60 62
FT STRAND 65 74
FT HELIX 75 78
FT STRAND 82 90
FT STRAND 93 95
FT STRAND 97 102
FT TURN 103 105
SQ SEQUENCE 106 AA; 11609 MW; 51984D1FDD372CE8 CRC64;
TVAAPSVFIF PPSDEQLKSG TASVVCLLNN FYPREAKVQW KVDNALQSGN SQESVTEQDS
KDSTYSLSST LTLSKADYEK HKVYACEVTH QGLSSPVTKS FNRGEC
//
MIM
147200
*RECORD*
*FIELD* NO
147200
*FIELD* TI
*147200 IMMUNOGLOBULIN KAPPA LIGHT CHAIN CONSTANT REGION; IGKC
;;IMMUNOGLOBULIN KM;;
read moreIMMUNOGLOBULIN InV
*FIELD* TX
DESCRIPTION
Immunoglobulins (Ig) are the antigen recognition molecules of B cells.
An Ig molecule is made up of 2 identical heavy chains (see 147100) and 2
identical light chains, either kappa or lambda (see 147220), joined by
disulfide bonds so that each heavy chain is linked to a light chain and
the 2 heavy chains are linked together. The kappa and lambda light
chains have no apparent functional differences. Each Ig kappa light
chain has an N-terminal variable (V) region containing the
antigen-binding site and a C-terminal constant (C) region, encoded by
the C region gene (IGKC), that provides signaling functions. The kappa
light chain V region is encoded by 2 types of genes: V genes (see
146980) and joining (J) genes (see 146970). Random selection of just 1
gene of each type to assemble a V region accounts for the great
diversity of V regions among Ig molecules. The kappa light chain locus
on chromosome 2 contains approximately 40 functional V genes, followed
by approximately 5 functional J genes. Due to polymorphism, the numbers
of functional V and J genes differ among individuals (Janeway et al.,
2005).
GENE STRUCTURE
Liu et al. (2005) analyzed the putative promoter regions (PPRs) of 333
Ig genes to determine their CpG island content. CpG islands are regions
of about 200 bp rich in CpG dinucleotides that are typically associated
with housekeeping genes. Liu et al. (2005) noted that IGK light chain
genes are located on the plus and minus strands of chromosome 2, IGH
heavy chain genes are located on the minus strand only of chromosome 14,
and IGL light chain genes are located on the plus strand only of
chromosome 22. They found that none of the joining region genes have CpG
islands in their PPRs. While IGKC and 6 of 11 IGHC constant region genes
have CpG islands, none of the 7 IGLC constant region genes have CpG
islands. Among Ig variable region genes, the frequency of CpG islands is
somewhat greater for the heavy chain genes on chromosome 14 than for the
light chain genes on chromosomes 2 and 22. Compared with non-Ig genes on
chromosome 22, a CpG-rich chromosome, Ig genes are significantly less
likely to have CpG islands and significantly more likely to have
less-dense CpG islands. Liu et al. (2005) concluded that the occurrence
of CpG islands in the PPRs of human and mouse Ig genes is nonrandom and
nonneutral.
MAPPING
Malcolm et al. (1982) assigned the kappa light chain gene cluster to
chromosome 2cen-p13 by in situ hybridization. They used a probe for the
variable genes of the kappa chain. Using nucleic acid probes prepared
from the cloned kappa constant gene in Southern blots of DNA from
somatic cell hybrids, McBride et al. (1982) assigned the human kappa
constant gene to chromosome 2.
Gross (2011) mapped the IGKC gene to chromosome 2p11.2 based on an
alignment of the IGKC sequence (GenBank GENBANK AF113887) with the
genomic sequence (GRCh37).
From study of somatic cell hybrids, Hengartner et al. (1978) concluded
that the locus for the kappa light chain genes is on chromosome 6 in the
mouse. The kappa light chain genes were assigned to mouse chromosome 6
by Swan et al. (1979). The genes for at least 1 variable region subgroup
are also on 6. Swan et al. (1979) used nucleic acid probes for nucleic
acid hybridization in mouse-hamster hybrids with a variable number of
mouse chromosomes.
GENE FUNCTION
Allelic exclusion ensures monoallelic expression of Ig genes by each B
cell to maintain single receptor specificity. Using FISH analysis for
DNA replication timing in mouse spleen cells, Mostoslavsky et al. (2001)
showed that IGKC, IGKV (146980), and IGHM (147020), as well as TCRB (see
186930), replicate asynchronously, indicated by a high frequency of
single (pre-replication) and double (after replication) hybridization
signals in the loci of interphase nuclei, in a manner analogous to the
process of X chromosome inactivation. Mostoslavsky et al. (2001)
concluded that monoallelic inactivation is not unique to the X
chromosome, but can also take place, in a regional manner, on autosomes
as well. They noted that asynchronous replication also occurs at the
loci for olfactory receptors (see OR2H3, 600578), IL2 (147680), and IL4
(147780).
Skok et al. (2001) used FISH analysis and multicolor fluorescence
microscopy to demonstrate that after activation of mature B cells, a
single endogenous IGHM allele, as well as 3 IGL (see IGLC1, 147220)
alleles, are recruited to centromeric heterochromatin containing Ikaros
(603023), a protein required for B and T lymphocyte development and
implicated in the silencing of specific target genes, whereas the other
IGHM and IGK alleles are localized away from centromeric
heterochromatin. Skok et al. (2001) concluded that epigenetic factors
may have a role in maintaining the monoallelic expression of Ig in
normal B cells.
Using FISH, Kosak et al. (2002) demonstrated that the IgH and Ig-kappa
loci, but not the smaller Ig-lambda locus, which has only 3 V gene
segments, have an inverse nuclear distribution in mouse hemopoietic
progenitors and pro-T lymphocytes compared with pro-B lymphocytes. In
pro-T cells, in which these large multisegmented loci are inactive, they
are preferentially positioned at the nuclear periphery, whereas in pro-B
cells, which actively express Ig loci, they have a central configuration
and undergo large-scale IL7R (146661)-dependent compaction. Kosak et al.
(2002) proposed that a peripheral positioning of these loci inhibits
their transcription and rearrangement by being sequestered away from the
transcription and recombination apparatus and/or by the assembly of a
refractory structure. In addition, the large-scale central compaction
may function to facilitate long-range V(D)J rearrangement.
The immunoglobulin genes are members of a class of autosomal genes
subject to random monoallelic expression, a class thought to comprise
isolated examples of genes involved in the immune or nervous systems.
Gimelbrant et al. (2007) developed a method for genomewide
identification of such genes and found that more than 5% of assessed
genes were subject to random monoallelic expression, a fraction much
higher than had been anticipated.
MOLECULAR GENETICS
- Immunoglobulin Kappa Light Chain Polymorphisms
Terry et al. (1969) investigated the relationship between Inv phenotype
and the amino acid at position 191 in immunoglobulin kappa light
polypeptide chains from 10 normal human sera. In each case, the amino
acid present at position 191 correlated with the Inv phenotype of the
individual. Kappa chains of 7 Inv(-1,3) homozygotes had valine, while
those of 3 Inv(1,3) heterozygotes had some chains with leucine and some
with valine at this position. Terry et al. (1969) concluded that the
valine-leucine interchange is encoded by 2 allelic forms of a single
kappa chain common region gene.
Polymorphism in the single constant gene for the kappa light chain was
first defined with 3 alleles by means of antisera (Terry et al., 1965).
The single amino acid changes at positions 153 and 191 underlying these
allotypes were defined by Milstein et al. (1974) and Steinberg et al.
(1974). Leucine at position 191 (147200.0001) confers so-called Inv1
activity, i.e., reactivity to antiserum-1. Alanine at position 153 with
retention of leucine at 191 (147200.0002) confers Inv2 activity, i.e.,
reactivity to antiserum-2. Inv2 reactivity is not observed in the
absence of Inv1 reactivity. Valine at position 191 and alanine at
position 153 (147200.0003) results in loss of Inv1 and Inv2 reactivity
and confers Inv3 reactivity, i.e., reactivity to antiserum-3. Thus, the
3 alleles were named Inv1, Inv1,2, and Inv3. These allele names were
subsequently changed to Km1, Km1,2, and Km3, respectively, to conform to
the system of nomenclature used for other allotypes (Steinberg and Cook,
1981).
Guillain-Barre syndrome (139393) is associated with antecedent
Campylobacter jejuni infection. Only a minority of the infected
individuals, however, develop the disease, implying a role for genetic
factors in conferring susceptibility. To determine the role of
immunoglobulin KM genes (genetic markers of the constant region of kappa
chains) in the etiology of this syndrome, Pandey and Vedeler (2003)
genotyped 83 patients and 196 healthy controls from Norway for KM1 and
KM3 alleles by PCR-RFLP. The frequency of KM3 homozygotes was
significantly increased in patients compared with controls. Conversely,
the frequency of KM1/KM3 heterozygotes was significantly decreased in
patients compared with controls. The results suggested that KM genes may
be relevant to the etiology of Guillain-Barre syndrome.
By sequence analysis of monoclonal kappa light chain constant region
fragments obtained from a patient with rapidly progressive AL
amyloidosis (see 254500), Wally et al. (1999) identified a ser177-to-asn
substitution. Cloning and sequencing of cDNA from premortem bone marrow
cells detected an AGC-to-AAC nucleotide substitution that accounted for
the protein variant. Wally et al. (1999) proposed that polymorphisms in
light chain constant regions may contribute to amyloidogenesis.
Data on gene frequencies of allelic variants at the kappa light chain
locus were tabulated by Roychoudhury and Nei (1988).
- Immunoglobulin Kappa Light Chain Deficiency
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency (IGKCD; 614102) in a patient reported by Zegers
et al. (1976). They identified compound heterozygosity for 2 point
mutations in the IGKC gene, resulting in loss of an invariant tryptophan
in one allele (W148R; 147200.0004) and an invariant cysteine in the
other allele (C194G; 147200.0005). Both mutations were predicted to
abolish formation of stable intradomain disulfide bonds.
CYTOGENETICS
Klein (1981) found that B cell-derived tumors (mouse myeloma and human
Burkitt lymphoma and B-cell acute lymphoblastic leukemia) had anomalous
patterns of immunoglobulin synthesis that correlated with the type of
chromosomal aberration. Similar observations were made by Lenoir et al.
(1982), who had collected the largest number of variant Burkitt lymphoma
translocations. Of 10 tested, all agreed with the hypothesis as to light
chain expression: all the 8;22 translocation cells produced lambda as
the only light chain; all the 2;8 translocation cells produced only
kappa; and 8;14 translocation cells produced either kappa or lambda,
with an approximate ratio of 2:1. In the mouse, trisomy 15 is regularly
associated with mouse T-cell leukemias, even if they are induced by
different agents, including various leukemia viruses, x-rays, and
chemical carcinogens. On the other hand, all mouse plasmacytomas show a
consistent translocation of the distal part of chromosome 15 to either
chromosome 6 or chromosome 12 (Ohno et al., 1979), both of which are
immunoglobulin genes in the mouse. The parallelism with the situation in
human Burkitt tumors is evident.
EVOLUTION
By physical mapping methods, Weichhold et al. (1993) developed a
detailed map of the kappa locus. They concluded that the kappa locus
comprises 2 copies showing opposite 5-prime/3-prime polarity. Several
immunoglobulin kappa-related sequences were transposed in evolution from
the short arm to the long arm of chromosome 2. By in situ hybridization
and by pulsed field gel electrophoresis experiments with hybridization
probes from both arms of chromosome 2 (i.e., from 2cen-p12 and
2cen-q11), Lautner-Rieske et al. (1993) demonstrated that the common
pericentric inversion of chromosome 2 found in the present-day
populations results in an apparent reinversion of these sequences to the
short arm and the transposition of the kappa and CD8-alpha (CD8A;
186910) loci to the long arm. The fusion between 2 ape chromosomes to
form the human chromosome 2 has been well documented (Yunis and Prakash,
1982), and interstitial telomere-like repeat stretches in this region
have been discussed in relation to possible breakage, fragility, and
recombination (Hastie and Allshire, 1989). The sites of fusion and
fragility at 2q13 were studied in molecular detail by IJdo et al. (1991,
1992).
ANIMAL MODEL
Redegeld et al. (2002) noted that light chains not associated with
immunoglobulin (IgLC) are present in serum and are produced at augmented
levels by plasma cells in rheumatoid arthritis (180300) and multiple
sclerosis (126200). Although IgE (see 147180) has a central role in
eliciting immediate hypersensitivity reactions, studies in IgE-deficient
mice showed that active anaphylaxis can be induced by IgG (see 147100)
triggering of FCGR3 (146740) (Miyajima et al., 1997). Redegeld et al.
(2002) showed that allergen-specific IgLC, but not heavy chains or
intact IgG, are capable of transferring stable hypersensitivity to
normal or, at a reduced level, B cell-deficient or Fc-epsilon-RI (see
147140) -/- naive mice. Hypersensitivity cannot be transferred, however,
to mast cell-deficient mice. Histologic analysis of mast
cell-replenished mice showed that IgLC induced mast cell degranulation,
plasma leakage, and histamine release through crosslinking of mast cell
surface 45-kD proteins. Immunoblot and sequence analysis confirmed that
the 27-kD IgLC factor consists of Igkc. Furthermore, Igkc-deficient mice
could not produce the sensitizing factor, and a 9-residue peptide, F991,
from Tamm-Horsfall protein (UMOD; 191845) specifically bound to and
inhibited both early and late swelling induced by IgLC sensitization in
a dose-dependent manner. Redegeld et al. (2002) concluded that IgLC can
elicit immediate hypersensitivity-like responses.
Using homologous recombination in ES cells, Liang et al. (2004)
generated knockin mice expressing a GFP cDNA from an unrearranged
immunoglobulin kappa light chain allele. They found that only a small
fraction of kappa alleles were highly transcribed in a population of
pre-B cells, that such transcription was monoallelic, and that these
highly transcribed alleles accounted for the vast majority of kappa
light chain gene rearrangements. These data suggested that probabilistic
enhancer activation and allelic competition are part of the mechanism of
kappa locus allelic exclusion and may be a general mechanism
contributing to cellular differentiation during development.
HISTORY
Keats et al. (1977, 1978) suggested that the Km gene and the Kidd blood
group (JK; 111000) are linked, with a lod score of 3.4 at theta 0.23.
The Lu (111200)-Se (FUT2; 182100)-DM (160900) linkage group and the
Km-Jk-Co (110450) linkage group were tentatively tied together by a
family with myotonic dystrophy reported by Larsen et al. (1979).
Harrington et al. (1997) created de novo human artificial chromosomes
(HACs) by combining long synthetic arrays of alpha satellite DNA with
telomeric DNA and genomic DNA. The resulting linear microchromosomes
were mitotically and cytogenetically stable in the absence of selection
for up to 6 months in culture, bound centromere proteins specific for
active centromeres, and were estimated to be 6 to 10 Mb in size. They
suggested that this first-generation system for the construction of HACs
should be suitable for dissecting the sequence requirements of human
centromeres, as well as developing constructs useful for therapeutic
applications. The next step, the introduction of chromosome fragments
into the mouse germline, was achieved by Tomizuka et al. (1997). They
used microcell-mediated chromosome transfer (MMCT) to introduce human
chromosomes or chromosome fragments derived from normal fibroblasts into
mouse embryonic stem (ES) cells and succeeded in producing viable
chimeric mice. Transferred chromosomes were stably retained and human
genes, including immunoglobulin genes, were expressed in proper
tissue-specific manner in adult chimeric tissues. Tomizuka et al. (1997)
found that a human chromosome 2-derived fragment was transmitted to the
offspring of chimeric mice through the germline. The chimeric
transchromosomic mice were found to produce functional human sequences
composed of rearranged human V, J, and D segments of human mu, kappa,
and lambda immunoglobulin chains. Immunization with human serum albumin
(HSA) resulted in production of HSA-specific antibodies, indicating the
usefulness of this system for the production of monoclonal antibodies.
The investigators suspected that passage through the male germline might
be a stumbling block and therefore used both male and female ES cells as
recipients in the microcell fusions. They were unable to transmit
fragments of human chromosomes 14 or 22 (containing the heavy chain and
lambda light chain genes) through the germline of the chimeric mice. In
2 cases, however, they documented transmission of a fragment of human
chromosome 2 through the germline, producing offspring that carried
copies of this fragment, which appeared to be structurally and
functionally unchanged. Transmission of the human fragment from 4 female
chimeras and 1 male chimera was achieved. Rastan (1997) reviewed the
findings, noting that the fact that the transferred chromosomal
fragments were visible cytogenetically means that they were probably of
the order of 5 to 20 Mb and would carry hundreds if not thousands of
genes.
*FIELD* AV
.0001
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv1
IGKC, LEU191/VAL153
Polymorphism in the single constant gene for the kappa light chain was
first defined with 3 alleles by means of antisera (Terry et al., 1965).
The single amino acid changes at positions 153 and 191 underlying these
allotypes were defined by Milstein et al. (1974) and Steinberg et al.
(1974). Leucine at position 191 confers so-called Inv1 activity, i.e.,
reactivity to antiserum-1. Alanine at position 153 with retention of
leucine at 191 (147200.0002) confers Inv2 activity, i.e., reactivity to
antiserum-2. Inv2 reactivity is not observed in the absence of Inv1
reactivity. Valine at position 191 and alanine at position 153
(147200.0003) results in loss of Inv1 and Inv2 reactivity and confers
Inv3 reactivity, i.e., reactivity to antiserum-3. Thus, the 3 alleles
were named Inv1, Inv1,2, and Inv3. These allele names were subsequently
changed to Km1, Km1,2, and Km3, respectively, to conform to the system
of nomenclature used for other allotypes (Steinberg and Cook, 1981). The
sequence of the Km2 C-kappa sequence was published by Hieter et al.
(1980). Km1 has the sequence GTC-153/CTC-191. Km1,2 has codon structure
GCC-153/CTC-191. Km3 has codon structure GCC-153/GTC-191. Kurth et al.
(1991) used PCR for amplification and an allele-specific oligonucleotide
for screening for allotype, a PCR/ASO method of Km typing, for
population screening.
.0002
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv2
IGKC, ALA153/LEU191
See 147200.0001.
.0003
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv3
IGKC, VAL191/ALA153
See 147200.0001.
.0004
IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY
IGKC, TRP148ARG
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency (614102) in a male patient reported by Zegers et
al. (1976). They identified compound heterozygosity for 2 point
mutations in the IGKC gene. A T-to-C transition in one allele resulted
in replacement of an invariant tryptophan at position 148 with arginine
(W148R). A T-to-G transversion in the other allele resulted in
replacement of an invariant cysteine at position 194 with glycine
(C194G; 147200.0005). Both mutations were predicted to abolish formation
of stable intradomain disulfide bonds. The patient's sister showed
partial deficiency of kappa chains, suggesting that the patient's
mutations were inherited from his parents. However, sera from the
patient's parents and another sib had approximately normal amounts of
kappa chains, suggesting that addition genes or environmental factors
may influence kappa light chain gene expression in this family.
.0005
IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY
IGKC, CYS194GLY
See 147200.0004 and Stavnezer-Nordgren et al. (1985).
*FIELD* SA
Ambrosino et al. (1986); Weigert et al. (1980)
*FIELD* RF
1. Ambrosino, D. M.; Barrus, V. A.; DeLange, G. G.; Siber, G. R.:
Correlation of the Km(1) immunoglobulin allotype with anti-polysaccharide
antibodies in Caucasian adults. J. Clin. Invest. 78: 361-365, 1986.
2. Gimelbrant, A.; Hutchinson, J. N.; Thompson, B. R.; Chess, A.:
Widespread monoallelic expression on human autosomes. Science 318:
1136-1140, 2007.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 7/19/2011.
4. Harrington, J. J.; Van Bokkelen, G.; Mays, R. W.; Gustashaw, K.;
Willard, H. F.: Formation of de novo centromeres and construction
of first-generation human artificial microchromosomes. Nature Genet. 15:
345-355, 1997.
5. Hastie, N. D.; Allshire, R. C.: Human telomeres: fusion and interstitial
sites. Trends Genet. 5: 326-331, 1989.
6. Hengartner, H.; Meo, T.; Muller, E.: Assignment of genes for immunoglobulin
kappa and heavy chains to chromosomes 6 and 12 in mouse. Proc. Nat.
Acad. Sci. 75: 4494-4498, 1978.
7. Hieter, P. A.; Max, E. E.; Seidman, J. G.; Maizel, J. V., Jr.;
Leder, P.: Cloned human and mouse kappa immunoglobulin constant and
J region genes conserve homology in functional segments. Cell 22:
197-207, 1980.
8. IJdo, J. W.; Baldini, A.; Ward, D. C.; Reeders, S. T.; Wells, R.
A.: Origin of human chromosome 2: an ancestral telomere-telomere
fusion. Proc. Nat. Acad. Sci. 88: 9051-9055, 1991.
9. IJdo, J. W.; Baldini, A.; Wells, R. A.; Ward, D. C.; Reeders, S.
T.: FRA2B is distinct from inverted telomere repeat arrays at 2q13. Genomics 12:
833-835, 1992.
10. Janeway, C. A., Jr.; Travers, P.; Walport, M.; Shlomchik, M. J.
: Immunobiology: The Immune System in Health and Disease. New York:
Garland Science Publishing (6th ed.) , 2005. Pp. 103-106, 135-139.
11. Keats, B. J. B.; Morton, N. E.; Rao, D. C.: Possible linkages
(lod score over 1.5) and a tentative map of the Jk-Km linkage group. Cytogenet.
Cell Genet. 22: 304-308, 1978.
12. Keats, B. J. B.; Morton, N. E.; Rao, D. C.: Likely linkage: InV
with Jk. Hum. Genet. 39: 157-159, 1977.
13. Klein, G.: Personal Communication. Stockholm, Sweden 11/4/1981.
14. Kosak, S. T.; Skok, J. A.; Medina, K. L.; Riblet, R.; Le Beau,
M. M.; Fisher, A. G.; Singh, H.: Subnuclear compartmentalization
of immunoglobulin loci during lymphocyte development. Science 296:
158-162, 2002.
15. Kurth, J. H.; Bowcock, A. M.; Erlich, H. A.; Nevo, S.; Cavalli-Sforza,
L. L.: Km typing with PCR: application to population screening. Am.
J. Hum. Genet. 48: 613-620, 1991.
16. Larsen, B.; Johnson, G.; van Loghem, E.; Newton, R. M.; Pryse-Phillips,
W.: Additions to the myotonic dystrophy linkage group. Clin. Genet. 15:
513-517, 1979.
17. Lautner-Rieske, A.; Hameister, H.; Barbi, G.; Zachau, H. G.:
Mapping immunoglobulin gene-related DNA probes to the central region
of normal and pericentrically inverted human chromosome 2. Genomics 16:
497-502, 1993.
18. Lenoir, G. M.; Preud'homme, J. L.; Bernheim, A.; Berger, R.:
Correlation between immunoglobulin light chain expression and variant
translocation in Burkitt's lymphoma. Nature 298: 474-476, 1982.
19. Liang, H.-E.; Hsu, L.-Y.; Cado, D.; Schlissel, M. S.: Variegated
transcriptional activation of the immunoglobulin kappa locus in pre-B
cells contributes to the allelic exclusion of light-chain expression. Cell 118:
19-29, 2004.
20. Liu, G. B.; Yan, H.; Jiang, Y. F.; Chen, R.; Pettigrew, J. D.;
Zhao, K.-N.: The properties of CpG islands in the putative promoter
regions of human immunoglobulin (Ig) genes. Gene 358: 127-138, 2005.
21. Malcolm, S.; Barton, P.; Bentley, D. L.; Ferguson-Smith, M. A.;
Murphy, C. S.; Rabbitts, T. H.: Assignment of a IGKV locus for immunoglobulin
light chains to the short arm of chromosome 2 (2p13-cen) by in situ
hybridisation using a cRNA probe of H(kappa)101(lambda)Ch4A. (Abstract) Cytogenet.
Cell Genet. 32: 296 only, 1982.
22. McBride, O. W.; Hieter, P. A.; Hollis, G. F.; Swan, D.; Otey,
M. C.; Leder, P.: Chromosomal location of human kappa and lambda
immunoglobulin light chain constant region genes. J. Exp. Med. 155:
1480-1490, 1982.
23. Milstein, C. P.; Steinberg, A. G.; McLaughlin, C. L.; Solomon,
A.: Amino acid sequence change associated with genetic marker Inv(2)
of human immunoglobulin. Nature 248: 160-161, 1974.
24. Miyajima, I.; Dombrowicz, D.; Martin, T. R.; Ravetch, J. V.; Kinet,
J.-P.; Galli, S. J.: Systemic anaphylaxis in the mouse can be mediated
largely through IgG1 and Fc-gamma-RIII: assessment of the cardiopulmonary
changes, mast cell degranulation, and death associated with active
or IgE- or IgG1-dependent passive anaphylaxis. J. Clin. Invest. 99:
901-914, 1997.
25. Mostoslavsky, R.; Singh, N.; Tenzen, T.; Goldmit, M.; Gabay, C.;
Elizur, S.; Qi, P.; Reubinoff, B. E.; Chess, A.; Cedar, H.; Bergman,
Y.: Asynchronous replication and allelic exclusion in the immune
system. Nature 414: 221-225, 2001.
26. Ohno, S.; Babonits, M.; Wiener, F.; Spira, J.; Klein, G.; Potter,
M.: Nonrandom chromosome changes involving the Ig gene-carrying chromosomes
12 and 6 in pristane-induced mouse plasmacytomas. Cell 18: 1001-1007,
1979.
27. Pandey, J. P.; Vedeler, C. A.: Immunoglobulin KM genes in Guillain-Barre
syndrome. Neurogenetics 4: 147-149, 2003.
28. Rastan, S.: Of men in mice. Nature Genet. 16: 113-114, 1997.
29. Redegeld, F. A.; van der Heijden, M. W.; Kool, M.; Heijdra, B.
M.; Garssen, J.; Kraneveld, A. D.; Van Loveren, H.; Roholl, P.; Saito,
T.; Verbeek, J. S.; Claassens, J.; Koster, A. S.; Nijkamp, F. P.:
Immunoglobulin-free light chains elicit immediate hypersensitivity-like
responses. Nature Med. 8: 694-701, 2002.
30. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
31. Skok, J. A.; Brown, K. E.; Azuara, V.; Caparros, M. L.; Baxter,
J.; Takacs, K.; Dillon, N.; Gray, D.; Perry, R. P.; Merkenschlager,
M.; Fisher, A. G.: Nonequivalent nuclear location of immunoglobulin
alleles in B lymphocytes. Nature Immun. 2: 848-54, 2001.
32. Stavnezer-Nordgren, J.; Kekish, O.; Zegers, B. J. M.: Molecular
defects in a human immunoglobulin kappa chain deficiency. Science 230:
458-461, 1985.
33. Steinberg, A. G.; Cook, C. E.: The Distribution of the Human
Immunoglobulin Allotypes. Oxford: Oxford Univ. Press (pub.) 1981.
34. Steinberg, A. G.; Milstein, C. P.; McLaughlin, C. L.; Solomon,
A.: Structural studies of an Inv(1,-2) kappa light chain. Immunogenetics 1:
108-117, 1974.
35. Swan, D.; D'Eustachio, P. D.; Leinwand, L.; Seidman, J.; Keithley,
D.; Ruddle, F. H.: Chromosomal assignment of the mouse kappa light
chain genes. Proc. Nat. Acad. Sci. 76: 2735-2739, 1979.
36. Terry, W. D.; Fahey, J. L.; Steinberg, A. G.: Gm and Inv factors
in subclasses of human IgG. J. Exp. Med. 122: 1087-1102, 1965.
37. Terry, W. D.; Hood, L. E.; Steinberg, A. G.: Genetics of immunoglobulin
kappa chains: chemical analysis of normal human light chains of differing
Inv types. Proc. Nat. Acad. Sci. 63: 71-77, 1969.
38. Tomizuka, K.; Yoshida, H.; Uejima, H.; Kugoh, H.; Sato, K.; Ohguma,
A.; Hayasaka, M.; Hanaoka, K.; Oshimura, M.; Ishida, I.: Functional
expression and germline transmission of a human chromosome fragment
in chimaeric mice. Nature Genet. 16: 133-143, 1997.
39. Wally, J.; Kica, G.; Zhang, Y.; Ericsson, T.; Connors, L. H.;
Benson, M. D.; Liepnieks, J. J.; Murray, J.; Skinner, M.; Comenzo,
R. L.: Identification of a novel substitution in the constant region
of a gene coding for an amyloidogenic kappa-1 light chain. Biochim.
Biophys. Acta 1454: 49-56, 1999.
40. Weichhold, G. M.; Ohnheiser, R.; Zachau, H. G.: The human immunoglobulin
kappa locus consists of two copies that are organized in opposite
polarity. Genomics 16: 503-511, 1993.
41. Weigert, M.; Perry, R.; Kelley, D.; Hunkapiller, T.; Schilling,
J.; Hood, L.: The joining of V and J gene segments creates antibody
diversity. Nature 283: 497-499, 1980.
42. Yunis, J. J.; Prakash, O.: The origin of man: a chromosomal pictorial
legacy. Science 215: 1525-1530, 1982.
43. Zegers, B. J. M.; Maertzdorf, W. J.; van Loghem, E.; Mul, N. A.
J.; Stoop, J. W.; van der Laag, J.; Vossen, J. J.; Ballieux, R. E.
: Kappa-chain deficiency: an immunoglobulin disorder. New Eng. J.
Med. 294: 1026-1030, 1976.
*FIELD* CN
Paul J. Converse - updated: 9/15/2011
Matthew B. Gross - updated: 7/19/2011
Ada Hamosh - updated: 2/18/2008
Paul J. Converse - updated: 8/30/2006
Stylianos E. Antonarakis - updated: 8/3/2004
Victor A. McKusick - updated: 7/14/2003
Paul J. Converse - updated: 6/17/2002
Paul J. Converse - updated: 4/9/2002
Paul J. Converse - updated: 11/7/2001
Victor A. McKusick - updated: 5/29/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
mgross: 10/07/2013
carol: 1/18/2012
carol: 12/15/2011
mgross: 9/15/2011
mgross: 7/19/2011
alopez: 2/18/2008
mgross: 8/30/2006
mgross: 8/3/2004
mgross: 3/17/2004
carol: 7/15/2003
terry: 7/14/2003
terry: 1/6/2003
alopez: 7/25/2002
alopez: 6/17/2002
mgross: 4/9/2002
alopez: 11/7/2001
carol: 4/14/2000
dkim: 12/15/1998
jenny: 7/2/1997
mark: 5/29/1997
terry: 5/28/1997
mark: 12/20/1995
mimadm: 11/5/1994
davew: 6/28/1994
warfield: 4/21/1994
carol: 11/11/1993
carol: 5/26/1993
supermim: 3/16/1992
*RECORD*
*FIELD* NO
147200
*FIELD* TI
*147200 IMMUNOGLOBULIN KAPPA LIGHT CHAIN CONSTANT REGION; IGKC
;;IMMUNOGLOBULIN KM;;
read moreIMMUNOGLOBULIN InV
*FIELD* TX
DESCRIPTION
Immunoglobulins (Ig) are the antigen recognition molecules of B cells.
An Ig molecule is made up of 2 identical heavy chains (see 147100) and 2
identical light chains, either kappa or lambda (see 147220), joined by
disulfide bonds so that each heavy chain is linked to a light chain and
the 2 heavy chains are linked together. The kappa and lambda light
chains have no apparent functional differences. Each Ig kappa light
chain has an N-terminal variable (V) region containing the
antigen-binding site and a C-terminal constant (C) region, encoded by
the C region gene (IGKC), that provides signaling functions. The kappa
light chain V region is encoded by 2 types of genes: V genes (see
146980) and joining (J) genes (see 146970). Random selection of just 1
gene of each type to assemble a V region accounts for the great
diversity of V regions among Ig molecules. The kappa light chain locus
on chromosome 2 contains approximately 40 functional V genes, followed
by approximately 5 functional J genes. Due to polymorphism, the numbers
of functional V and J genes differ among individuals (Janeway et al.,
2005).
GENE STRUCTURE
Liu et al. (2005) analyzed the putative promoter regions (PPRs) of 333
Ig genes to determine their CpG island content. CpG islands are regions
of about 200 bp rich in CpG dinucleotides that are typically associated
with housekeeping genes. Liu et al. (2005) noted that IGK light chain
genes are located on the plus and minus strands of chromosome 2, IGH
heavy chain genes are located on the minus strand only of chromosome 14,
and IGL light chain genes are located on the plus strand only of
chromosome 22. They found that none of the joining region genes have CpG
islands in their PPRs. While IGKC and 6 of 11 IGHC constant region genes
have CpG islands, none of the 7 IGLC constant region genes have CpG
islands. Among Ig variable region genes, the frequency of CpG islands is
somewhat greater for the heavy chain genes on chromosome 14 than for the
light chain genes on chromosomes 2 and 22. Compared with non-Ig genes on
chromosome 22, a CpG-rich chromosome, Ig genes are significantly less
likely to have CpG islands and significantly more likely to have
less-dense CpG islands. Liu et al. (2005) concluded that the occurrence
of CpG islands in the PPRs of human and mouse Ig genes is nonrandom and
nonneutral.
MAPPING
Malcolm et al. (1982) assigned the kappa light chain gene cluster to
chromosome 2cen-p13 by in situ hybridization. They used a probe for the
variable genes of the kappa chain. Using nucleic acid probes prepared
from the cloned kappa constant gene in Southern blots of DNA from
somatic cell hybrids, McBride et al. (1982) assigned the human kappa
constant gene to chromosome 2.
Gross (2011) mapped the IGKC gene to chromosome 2p11.2 based on an
alignment of the IGKC sequence (GenBank GENBANK AF113887) with the
genomic sequence (GRCh37).
From study of somatic cell hybrids, Hengartner et al. (1978) concluded
that the locus for the kappa light chain genes is on chromosome 6 in the
mouse. The kappa light chain genes were assigned to mouse chromosome 6
by Swan et al. (1979). The genes for at least 1 variable region subgroup
are also on 6. Swan et al. (1979) used nucleic acid probes for nucleic
acid hybridization in mouse-hamster hybrids with a variable number of
mouse chromosomes.
GENE FUNCTION
Allelic exclusion ensures monoallelic expression of Ig genes by each B
cell to maintain single receptor specificity. Using FISH analysis for
DNA replication timing in mouse spleen cells, Mostoslavsky et al. (2001)
showed that IGKC, IGKV (146980), and IGHM (147020), as well as TCRB (see
186930), replicate asynchronously, indicated by a high frequency of
single (pre-replication) and double (after replication) hybridization
signals in the loci of interphase nuclei, in a manner analogous to the
process of X chromosome inactivation. Mostoslavsky et al. (2001)
concluded that monoallelic inactivation is not unique to the X
chromosome, but can also take place, in a regional manner, on autosomes
as well. They noted that asynchronous replication also occurs at the
loci for olfactory receptors (see OR2H3, 600578), IL2 (147680), and IL4
(147780).
Skok et al. (2001) used FISH analysis and multicolor fluorescence
microscopy to demonstrate that after activation of mature B cells, a
single endogenous IGHM allele, as well as 3 IGL (see IGLC1, 147220)
alleles, are recruited to centromeric heterochromatin containing Ikaros
(603023), a protein required for B and T lymphocyte development and
implicated in the silencing of specific target genes, whereas the other
IGHM and IGK alleles are localized away from centromeric
heterochromatin. Skok et al. (2001) concluded that epigenetic factors
may have a role in maintaining the monoallelic expression of Ig in
normal B cells.
Using FISH, Kosak et al. (2002) demonstrated that the IgH and Ig-kappa
loci, but not the smaller Ig-lambda locus, which has only 3 V gene
segments, have an inverse nuclear distribution in mouse hemopoietic
progenitors and pro-T lymphocytes compared with pro-B lymphocytes. In
pro-T cells, in which these large multisegmented loci are inactive, they
are preferentially positioned at the nuclear periphery, whereas in pro-B
cells, which actively express Ig loci, they have a central configuration
and undergo large-scale IL7R (146661)-dependent compaction. Kosak et al.
(2002) proposed that a peripheral positioning of these loci inhibits
their transcription and rearrangement by being sequestered away from the
transcription and recombination apparatus and/or by the assembly of a
refractory structure. In addition, the large-scale central compaction
may function to facilitate long-range V(D)J rearrangement.
The immunoglobulin genes are members of a class of autosomal genes
subject to random monoallelic expression, a class thought to comprise
isolated examples of genes involved in the immune or nervous systems.
Gimelbrant et al. (2007) developed a method for genomewide
identification of such genes and found that more than 5% of assessed
genes were subject to random monoallelic expression, a fraction much
higher than had been anticipated.
MOLECULAR GENETICS
- Immunoglobulin Kappa Light Chain Polymorphisms
Terry et al. (1969) investigated the relationship between Inv phenotype
and the amino acid at position 191 in immunoglobulin kappa light
polypeptide chains from 10 normal human sera. In each case, the amino
acid present at position 191 correlated with the Inv phenotype of the
individual. Kappa chains of 7 Inv(-1,3) homozygotes had valine, while
those of 3 Inv(1,3) heterozygotes had some chains with leucine and some
with valine at this position. Terry et al. (1969) concluded that the
valine-leucine interchange is encoded by 2 allelic forms of a single
kappa chain common region gene.
Polymorphism in the single constant gene for the kappa light chain was
first defined with 3 alleles by means of antisera (Terry et al., 1965).
The single amino acid changes at positions 153 and 191 underlying these
allotypes were defined by Milstein et al. (1974) and Steinberg et al.
(1974). Leucine at position 191 (147200.0001) confers so-called Inv1
activity, i.e., reactivity to antiserum-1. Alanine at position 153 with
retention of leucine at 191 (147200.0002) confers Inv2 activity, i.e.,
reactivity to antiserum-2. Inv2 reactivity is not observed in the
absence of Inv1 reactivity. Valine at position 191 and alanine at
position 153 (147200.0003) results in loss of Inv1 and Inv2 reactivity
and confers Inv3 reactivity, i.e., reactivity to antiserum-3. Thus, the
3 alleles were named Inv1, Inv1,2, and Inv3. These allele names were
subsequently changed to Km1, Km1,2, and Km3, respectively, to conform to
the system of nomenclature used for other allotypes (Steinberg and Cook,
1981).
Guillain-Barre syndrome (139393) is associated with antecedent
Campylobacter jejuni infection. Only a minority of the infected
individuals, however, develop the disease, implying a role for genetic
factors in conferring susceptibility. To determine the role of
immunoglobulin KM genes (genetic markers of the constant region of kappa
chains) in the etiology of this syndrome, Pandey and Vedeler (2003)
genotyped 83 patients and 196 healthy controls from Norway for KM1 and
KM3 alleles by PCR-RFLP. The frequency of KM3 homozygotes was
significantly increased in patients compared with controls. Conversely,
the frequency of KM1/KM3 heterozygotes was significantly decreased in
patients compared with controls. The results suggested that KM genes may
be relevant to the etiology of Guillain-Barre syndrome.
By sequence analysis of monoclonal kappa light chain constant region
fragments obtained from a patient with rapidly progressive AL
amyloidosis (see 254500), Wally et al. (1999) identified a ser177-to-asn
substitution. Cloning and sequencing of cDNA from premortem bone marrow
cells detected an AGC-to-AAC nucleotide substitution that accounted for
the protein variant. Wally et al. (1999) proposed that polymorphisms in
light chain constant regions may contribute to amyloidogenesis.
Data on gene frequencies of allelic variants at the kappa light chain
locus were tabulated by Roychoudhury and Nei (1988).
- Immunoglobulin Kappa Light Chain Deficiency
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency (IGKCD; 614102) in a patient reported by Zegers
et al. (1976). They identified compound heterozygosity for 2 point
mutations in the IGKC gene, resulting in loss of an invariant tryptophan
in one allele (W148R; 147200.0004) and an invariant cysteine in the
other allele (C194G; 147200.0005). Both mutations were predicted to
abolish formation of stable intradomain disulfide bonds.
CYTOGENETICS
Klein (1981) found that B cell-derived tumors (mouse myeloma and human
Burkitt lymphoma and B-cell acute lymphoblastic leukemia) had anomalous
patterns of immunoglobulin synthesis that correlated with the type of
chromosomal aberration. Similar observations were made by Lenoir et al.
(1982), who had collected the largest number of variant Burkitt lymphoma
translocations. Of 10 tested, all agreed with the hypothesis as to light
chain expression: all the 8;22 translocation cells produced lambda as
the only light chain; all the 2;8 translocation cells produced only
kappa; and 8;14 translocation cells produced either kappa or lambda,
with an approximate ratio of 2:1. In the mouse, trisomy 15 is regularly
associated with mouse T-cell leukemias, even if they are induced by
different agents, including various leukemia viruses, x-rays, and
chemical carcinogens. On the other hand, all mouse plasmacytomas show a
consistent translocation of the distal part of chromosome 15 to either
chromosome 6 or chromosome 12 (Ohno et al., 1979), both of which are
immunoglobulin genes in the mouse. The parallelism with the situation in
human Burkitt tumors is evident.
EVOLUTION
By physical mapping methods, Weichhold et al. (1993) developed a
detailed map of the kappa locus. They concluded that the kappa locus
comprises 2 copies showing opposite 5-prime/3-prime polarity. Several
immunoglobulin kappa-related sequences were transposed in evolution from
the short arm to the long arm of chromosome 2. By in situ hybridization
and by pulsed field gel electrophoresis experiments with hybridization
probes from both arms of chromosome 2 (i.e., from 2cen-p12 and
2cen-q11), Lautner-Rieske et al. (1993) demonstrated that the common
pericentric inversion of chromosome 2 found in the present-day
populations results in an apparent reinversion of these sequences to the
short arm and the transposition of the kappa and CD8-alpha (CD8A;
186910) loci to the long arm. The fusion between 2 ape chromosomes to
form the human chromosome 2 has been well documented (Yunis and Prakash,
1982), and interstitial telomere-like repeat stretches in this region
have been discussed in relation to possible breakage, fragility, and
recombination (Hastie and Allshire, 1989). The sites of fusion and
fragility at 2q13 were studied in molecular detail by IJdo et al. (1991,
1992).
ANIMAL MODEL
Redegeld et al. (2002) noted that light chains not associated with
immunoglobulin (IgLC) are present in serum and are produced at augmented
levels by plasma cells in rheumatoid arthritis (180300) and multiple
sclerosis (126200). Although IgE (see 147180) has a central role in
eliciting immediate hypersensitivity reactions, studies in IgE-deficient
mice showed that active anaphylaxis can be induced by IgG (see 147100)
triggering of FCGR3 (146740) (Miyajima et al., 1997). Redegeld et al.
(2002) showed that allergen-specific IgLC, but not heavy chains or
intact IgG, are capable of transferring stable hypersensitivity to
normal or, at a reduced level, B cell-deficient or Fc-epsilon-RI (see
147140) -/- naive mice. Hypersensitivity cannot be transferred, however,
to mast cell-deficient mice. Histologic analysis of mast
cell-replenished mice showed that IgLC induced mast cell degranulation,
plasma leakage, and histamine release through crosslinking of mast cell
surface 45-kD proteins. Immunoblot and sequence analysis confirmed that
the 27-kD IgLC factor consists of Igkc. Furthermore, Igkc-deficient mice
could not produce the sensitizing factor, and a 9-residue peptide, F991,
from Tamm-Horsfall protein (UMOD; 191845) specifically bound to and
inhibited both early and late swelling induced by IgLC sensitization in
a dose-dependent manner. Redegeld et al. (2002) concluded that IgLC can
elicit immediate hypersensitivity-like responses.
Using homologous recombination in ES cells, Liang et al. (2004)
generated knockin mice expressing a GFP cDNA from an unrearranged
immunoglobulin kappa light chain allele. They found that only a small
fraction of kappa alleles were highly transcribed in a population of
pre-B cells, that such transcription was monoallelic, and that these
highly transcribed alleles accounted for the vast majority of kappa
light chain gene rearrangements. These data suggested that probabilistic
enhancer activation and allelic competition are part of the mechanism of
kappa locus allelic exclusion and may be a general mechanism
contributing to cellular differentiation during development.
HISTORY
Keats et al. (1977, 1978) suggested that the Km gene and the Kidd blood
group (JK; 111000) are linked, with a lod score of 3.4 at theta 0.23.
The Lu (111200)-Se (FUT2; 182100)-DM (160900) linkage group and the
Km-Jk-Co (110450) linkage group were tentatively tied together by a
family with myotonic dystrophy reported by Larsen et al. (1979).
Harrington et al. (1997) created de novo human artificial chromosomes
(HACs) by combining long synthetic arrays of alpha satellite DNA with
telomeric DNA and genomic DNA. The resulting linear microchromosomes
were mitotically and cytogenetically stable in the absence of selection
for up to 6 months in culture, bound centromere proteins specific for
active centromeres, and were estimated to be 6 to 10 Mb in size. They
suggested that this first-generation system for the construction of HACs
should be suitable for dissecting the sequence requirements of human
centromeres, as well as developing constructs useful for therapeutic
applications. The next step, the introduction of chromosome fragments
into the mouse germline, was achieved by Tomizuka et al. (1997). They
used microcell-mediated chromosome transfer (MMCT) to introduce human
chromosomes or chromosome fragments derived from normal fibroblasts into
mouse embryonic stem (ES) cells and succeeded in producing viable
chimeric mice. Transferred chromosomes were stably retained and human
genes, including immunoglobulin genes, were expressed in proper
tissue-specific manner in adult chimeric tissues. Tomizuka et al. (1997)
found that a human chromosome 2-derived fragment was transmitted to the
offspring of chimeric mice through the germline. The chimeric
transchromosomic mice were found to produce functional human sequences
composed of rearranged human V, J, and D segments of human mu, kappa,
and lambda immunoglobulin chains. Immunization with human serum albumin
(HSA) resulted in production of HSA-specific antibodies, indicating the
usefulness of this system for the production of monoclonal antibodies.
The investigators suspected that passage through the male germline might
be a stumbling block and therefore used both male and female ES cells as
recipients in the microcell fusions. They were unable to transmit
fragments of human chromosomes 14 or 22 (containing the heavy chain and
lambda light chain genes) through the germline of the chimeric mice. In
2 cases, however, they documented transmission of a fragment of human
chromosome 2 through the germline, producing offspring that carried
copies of this fragment, which appeared to be structurally and
functionally unchanged. Transmission of the human fragment from 4 female
chimeras and 1 male chimera was achieved. Rastan (1997) reviewed the
findings, noting that the fact that the transferred chromosomal
fragments were visible cytogenetically means that they were probably of
the order of 5 to 20 Mb and would carry hundreds if not thousands of
genes.
*FIELD* AV
.0001
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv1
IGKC, LEU191/VAL153
Polymorphism in the single constant gene for the kappa light chain was
first defined with 3 alleles by means of antisera (Terry et al., 1965).
The single amino acid changes at positions 153 and 191 underlying these
allotypes were defined by Milstein et al. (1974) and Steinberg et al.
(1974). Leucine at position 191 confers so-called Inv1 activity, i.e.,
reactivity to antiserum-1. Alanine at position 153 with retention of
leucine at 191 (147200.0002) confers Inv2 activity, i.e., reactivity to
antiserum-2. Inv2 reactivity is not observed in the absence of Inv1
reactivity. Valine at position 191 and alanine at position 153
(147200.0003) results in loss of Inv1 and Inv2 reactivity and confers
Inv3 reactivity, i.e., reactivity to antiserum-3. Thus, the 3 alleles
were named Inv1, Inv1,2, and Inv3. These allele names were subsequently
changed to Km1, Km1,2, and Km3, respectively, to conform to the system
of nomenclature used for other allotypes (Steinberg and Cook, 1981). The
sequence of the Km2 C-kappa sequence was published by Hieter et al.
(1980). Km1 has the sequence GTC-153/CTC-191. Km1,2 has codon structure
GCC-153/CTC-191. Km3 has codon structure GCC-153/GTC-191. Kurth et al.
(1991) used PCR for amplification and an allele-specific oligonucleotide
for screening for allotype, a PCR/ASO method of Km typing, for
population screening.
.0002
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv2
IGKC, ALA153/LEU191
See 147200.0001.
.0003
IMMUNOGLOBULIN KAPPA LIGHT CHAIN POLYMORPHISM Inv3
IGKC, VAL191/ALA153
See 147200.0001.
.0004
IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY
IGKC, TRP148ARG
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency (614102) in a male patient reported by Zegers et
al. (1976). They identified compound heterozygosity for 2 point
mutations in the IGKC gene. A T-to-C transition in one allele resulted
in replacement of an invariant tryptophan at position 148 with arginine
(W148R). A T-to-G transversion in the other allele resulted in
replacement of an invariant cysteine at position 194 with glycine
(C194G; 147200.0005). Both mutations were predicted to abolish formation
of stable intradomain disulfide bonds. The patient's sister showed
partial deficiency of kappa chains, suggesting that the patient's
mutations were inherited from his parents. However, sera from the
patient's parents and another sib had approximately normal amounts of
kappa chains, suggesting that addition genes or environmental factors
may influence kappa light chain gene expression in this family.
.0005
IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY
IGKC, CYS194GLY
See 147200.0004 and Stavnezer-Nordgren et al. (1985).
*FIELD* SA
Ambrosino et al. (1986); Weigert et al. (1980)
*FIELD* RF
1. Ambrosino, D. M.; Barrus, V. A.; DeLange, G. G.; Siber, G. R.:
Correlation of the Km(1) immunoglobulin allotype with anti-polysaccharide
antibodies in Caucasian adults. J. Clin. Invest. 78: 361-365, 1986.
2. Gimelbrant, A.; Hutchinson, J. N.; Thompson, B. R.; Chess, A.:
Widespread monoallelic expression on human autosomes. Science 318:
1136-1140, 2007.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 7/19/2011.
4. Harrington, J. J.; Van Bokkelen, G.; Mays, R. W.; Gustashaw, K.;
Willard, H. F.: Formation of de novo centromeres and construction
of first-generation human artificial microchromosomes. Nature Genet. 15:
345-355, 1997.
5. Hastie, N. D.; Allshire, R. C.: Human telomeres: fusion and interstitial
sites. Trends Genet. 5: 326-331, 1989.
6. Hengartner, H.; Meo, T.; Muller, E.: Assignment of genes for immunoglobulin
kappa and heavy chains to chromosomes 6 and 12 in mouse. Proc. Nat.
Acad. Sci. 75: 4494-4498, 1978.
7. Hieter, P. A.; Max, E. E.; Seidman, J. G.; Maizel, J. V., Jr.;
Leder, P.: Cloned human and mouse kappa immunoglobulin constant and
J region genes conserve homology in functional segments. Cell 22:
197-207, 1980.
8. IJdo, J. W.; Baldini, A.; Ward, D. C.; Reeders, S. T.; Wells, R.
A.: Origin of human chromosome 2: an ancestral telomere-telomere
fusion. Proc. Nat. Acad. Sci. 88: 9051-9055, 1991.
9. IJdo, J. W.; Baldini, A.; Wells, R. A.; Ward, D. C.; Reeders, S.
T.: FRA2B is distinct from inverted telomere repeat arrays at 2q13. Genomics 12:
833-835, 1992.
10. Janeway, C. A., Jr.; Travers, P.; Walport, M.; Shlomchik, M. J.
: Immunobiology: The Immune System in Health and Disease. New York:
Garland Science Publishing (6th ed.) , 2005. Pp. 103-106, 135-139.
11. Keats, B. J. B.; Morton, N. E.; Rao, D. C.: Possible linkages
(lod score over 1.5) and a tentative map of the Jk-Km linkage group. Cytogenet.
Cell Genet. 22: 304-308, 1978.
12. Keats, B. J. B.; Morton, N. E.; Rao, D. C.: Likely linkage: InV
with Jk. Hum. Genet. 39: 157-159, 1977.
13. Klein, G.: Personal Communication. Stockholm, Sweden 11/4/1981.
14. Kosak, S. T.; Skok, J. A.; Medina, K. L.; Riblet, R.; Le Beau,
M. M.; Fisher, A. G.; Singh, H.: Subnuclear compartmentalization
of immunoglobulin loci during lymphocyte development. Science 296:
158-162, 2002.
15. Kurth, J. H.; Bowcock, A. M.; Erlich, H. A.; Nevo, S.; Cavalli-Sforza,
L. L.: Km typing with PCR: application to population screening. Am.
J. Hum. Genet. 48: 613-620, 1991.
16. Larsen, B.; Johnson, G.; van Loghem, E.; Newton, R. M.; Pryse-Phillips,
W.: Additions to the myotonic dystrophy linkage group. Clin. Genet. 15:
513-517, 1979.
17. Lautner-Rieske, A.; Hameister, H.; Barbi, G.; Zachau, H. G.:
Mapping immunoglobulin gene-related DNA probes to the central region
of normal and pericentrically inverted human chromosome 2. Genomics 16:
497-502, 1993.
18. Lenoir, G. M.; Preud'homme, J. L.; Bernheim, A.; Berger, R.:
Correlation between immunoglobulin light chain expression and variant
translocation in Burkitt's lymphoma. Nature 298: 474-476, 1982.
19. Liang, H.-E.; Hsu, L.-Y.; Cado, D.; Schlissel, M. S.: Variegated
transcriptional activation of the immunoglobulin kappa locus in pre-B
cells contributes to the allelic exclusion of light-chain expression. Cell 118:
19-29, 2004.
20. Liu, G. B.; Yan, H.; Jiang, Y. F.; Chen, R.; Pettigrew, J. D.;
Zhao, K.-N.: The properties of CpG islands in the putative promoter
regions of human immunoglobulin (Ig) genes. Gene 358: 127-138, 2005.
21. Malcolm, S.; Barton, P.; Bentley, D. L.; Ferguson-Smith, M. A.;
Murphy, C. S.; Rabbitts, T. H.: Assignment of a IGKV locus for immunoglobulin
light chains to the short arm of chromosome 2 (2p13-cen) by in situ
hybridisation using a cRNA probe of H(kappa)101(lambda)Ch4A. (Abstract) Cytogenet.
Cell Genet. 32: 296 only, 1982.
22. McBride, O. W.; Hieter, P. A.; Hollis, G. F.; Swan, D.; Otey,
M. C.; Leder, P.: Chromosomal location of human kappa and lambda
immunoglobulin light chain constant region genes. J. Exp. Med. 155:
1480-1490, 1982.
23. Milstein, C. P.; Steinberg, A. G.; McLaughlin, C. L.; Solomon,
A.: Amino acid sequence change associated with genetic marker Inv(2)
of human immunoglobulin. Nature 248: 160-161, 1974.
24. Miyajima, I.; Dombrowicz, D.; Martin, T. R.; Ravetch, J. V.; Kinet,
J.-P.; Galli, S. J.: Systemic anaphylaxis in the mouse can be mediated
largely through IgG1 and Fc-gamma-RIII: assessment of the cardiopulmonary
changes, mast cell degranulation, and death associated with active
or IgE- or IgG1-dependent passive anaphylaxis. J. Clin. Invest. 99:
901-914, 1997.
25. Mostoslavsky, R.; Singh, N.; Tenzen, T.; Goldmit, M.; Gabay, C.;
Elizur, S.; Qi, P.; Reubinoff, B. E.; Chess, A.; Cedar, H.; Bergman,
Y.: Asynchronous replication and allelic exclusion in the immune
system. Nature 414: 221-225, 2001.
26. Ohno, S.; Babonits, M.; Wiener, F.; Spira, J.; Klein, G.; Potter,
M.: Nonrandom chromosome changes involving the Ig gene-carrying chromosomes
12 and 6 in pristane-induced mouse plasmacytomas. Cell 18: 1001-1007,
1979.
27. Pandey, J. P.; Vedeler, C. A.: Immunoglobulin KM genes in Guillain-Barre
syndrome. Neurogenetics 4: 147-149, 2003.
28. Rastan, S.: Of men in mice. Nature Genet. 16: 113-114, 1997.
29. Redegeld, F. A.; van der Heijden, M. W.; Kool, M.; Heijdra, B.
M.; Garssen, J.; Kraneveld, A. D.; Van Loveren, H.; Roholl, P.; Saito,
T.; Verbeek, J. S.; Claassens, J.; Koster, A. S.; Nijkamp, F. P.:
Immunoglobulin-free light chains elicit immediate hypersensitivity-like
responses. Nature Med. 8: 694-701, 2002.
30. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
31. Skok, J. A.; Brown, K. E.; Azuara, V.; Caparros, M. L.; Baxter,
J.; Takacs, K.; Dillon, N.; Gray, D.; Perry, R. P.; Merkenschlager,
M.; Fisher, A. G.: Nonequivalent nuclear location of immunoglobulin
alleles in B lymphocytes. Nature Immun. 2: 848-54, 2001.
32. Stavnezer-Nordgren, J.; Kekish, O.; Zegers, B. J. M.: Molecular
defects in a human immunoglobulin kappa chain deficiency. Science 230:
458-461, 1985.
33. Steinberg, A. G.; Cook, C. E.: The Distribution of the Human
Immunoglobulin Allotypes. Oxford: Oxford Univ. Press (pub.) 1981.
34. Steinberg, A. G.; Milstein, C. P.; McLaughlin, C. L.; Solomon,
A.: Structural studies of an Inv(1,-2) kappa light chain. Immunogenetics 1:
108-117, 1974.
35. Swan, D.; D'Eustachio, P. D.; Leinwand, L.; Seidman, J.; Keithley,
D.; Ruddle, F. H.: Chromosomal assignment of the mouse kappa light
chain genes. Proc. Nat. Acad. Sci. 76: 2735-2739, 1979.
36. Terry, W. D.; Fahey, J. L.; Steinberg, A. G.: Gm and Inv factors
in subclasses of human IgG. J. Exp. Med. 122: 1087-1102, 1965.
37. Terry, W. D.; Hood, L. E.; Steinberg, A. G.: Genetics of immunoglobulin
kappa chains: chemical analysis of normal human light chains of differing
Inv types. Proc. Nat. Acad. Sci. 63: 71-77, 1969.
38. Tomizuka, K.; Yoshida, H.; Uejima, H.; Kugoh, H.; Sato, K.; Ohguma,
A.; Hayasaka, M.; Hanaoka, K.; Oshimura, M.; Ishida, I.: Functional
expression and germline transmission of a human chromosome fragment
in chimaeric mice. Nature Genet. 16: 133-143, 1997.
39. Wally, J.; Kica, G.; Zhang, Y.; Ericsson, T.; Connors, L. H.;
Benson, M. D.; Liepnieks, J. J.; Murray, J.; Skinner, M.; Comenzo,
R. L.: Identification of a novel substitution in the constant region
of a gene coding for an amyloidogenic kappa-1 light chain. Biochim.
Biophys. Acta 1454: 49-56, 1999.
40. Weichhold, G. M.; Ohnheiser, R.; Zachau, H. G.: The human immunoglobulin
kappa locus consists of two copies that are organized in opposite
polarity. Genomics 16: 503-511, 1993.
41. Weigert, M.; Perry, R.; Kelley, D.; Hunkapiller, T.; Schilling,
J.; Hood, L.: The joining of V and J gene segments creates antibody
diversity. Nature 283: 497-499, 1980.
42. Yunis, J. J.; Prakash, O.: The origin of man: a chromosomal pictorial
legacy. Science 215: 1525-1530, 1982.
43. Zegers, B. J. M.; Maertzdorf, W. J.; van Loghem, E.; Mul, N. A.
J.; Stoop, J. W.; van der Laag, J.; Vossen, J. J.; Ballieux, R. E.
: Kappa-chain deficiency: an immunoglobulin disorder. New Eng. J.
Med. 294: 1026-1030, 1976.
*FIELD* CN
Paul J. Converse - updated: 9/15/2011
Matthew B. Gross - updated: 7/19/2011
Ada Hamosh - updated: 2/18/2008
Paul J. Converse - updated: 8/30/2006
Stylianos E. Antonarakis - updated: 8/3/2004
Victor A. McKusick - updated: 7/14/2003
Paul J. Converse - updated: 6/17/2002
Paul J. Converse - updated: 4/9/2002
Paul J. Converse - updated: 11/7/2001
Victor A. McKusick - updated: 5/29/1997
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
mgross: 10/07/2013
carol: 1/18/2012
carol: 12/15/2011
mgross: 9/15/2011
mgross: 7/19/2011
alopez: 2/18/2008
mgross: 8/30/2006
mgross: 8/3/2004
mgross: 3/17/2004
carol: 7/15/2003
terry: 7/14/2003
terry: 1/6/2003
alopez: 7/25/2002
alopez: 6/17/2002
mgross: 4/9/2002
alopez: 11/7/2001
carol: 4/14/2000
dkim: 12/15/1998
jenny: 7/2/1997
mark: 5/29/1997
terry: 5/28/1997
mark: 12/20/1995
mimadm: 11/5/1994
davew: 6/28/1994
warfield: 4/21/1994
carol: 11/11/1993
carol: 5/26/1993
supermim: 3/16/1992
MIM
614102
*RECORD*
*FIELD* NO
614102
*FIELD* TI
#614102 IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY; IGKCD
;;KAPPA CHAIN DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because immunoglobulin kappa
light chain deficiency (IGKCD) can be caused by compound heterozygous
mutation in the immunoglobulin kappa constant region gene (IGKC; 147200)
on chromosome 2p11.
CLINICAL FEATURES
In a female offspring of an uncle-niece marriage, Bernier et al. (1972)
observed deficient synthesis of kappa chain-bearing immunoglobulins. She
also had recurrent respiratory infections and diarrhea.
Zegers et al. (1976) observed complete absence of immunoglobulin kappa
chains in a male patient with cystic fibrosis (219700) in whom kappa
chains were absent in serum immunoglobulins and in blood and bone marrow
lymphocytes. Lymphocytes stimulated by pokeweed mitogen produced no
kappa chains. A sister, who also had cystic fibrosis, showed partial
deficiency of kappa chains. Sera from the patient's parents and another
sib had approximately normal amounts of kappa chains. The patient's
immune responses to a variety of antigens were normal, suggesting that
kappa deficiency has little effect on health. Zegers et al. (1976) noted
that a few individuals with reduced kappa chains had been described
(Bernier et al., 1972; Barandun et al., 1976).
MAPPING
Kappa light chain deficiency results from mutation in the IGKC gene,
which Gross (2011) mapped to chromosome 2p11.2.
MOLECULAR GENETICS
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency in the patient reported by Zegers et al. (1976).
They identified compound heterozygosity for 2 point mutations in the
IGKC gene, resulting in loss of an invariant tryptophan in one allele
(W148R; 147200.0004) and an invariant cysteine in the other allele
(C194G; 147200.0005). Both mutations were predicted to abolish formation
of stable intradomain disulfide bonds.
*FIELD* RF
1. Barandun, S.; Morell, A.; Skvaril, F.; Oberdorfer, A.: Deficiency
of kappa- or lambda-type immunoglobulins. Blood 47: 79-89, 1976.
2. Bernier, G. M.; Gunderman, J. R.; Ruymann, F. B.: Kappa-chain
deficiency. Blood 40: 795-805, 1972.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 7/19/2011.
4. Stavnezer-Nordgren, J.; Kekish, O.; Zegers, B. J. M.: Molecular
defects in a human immunoglobulin kappa chain deficiency. Science 230:
458-461, 1985.
5. Zegers, B. J. M.; Maertzdorf, W. J.; van Loghem, E.; Mul, N. A.
J.; Stoop, J. W.; van der Laag, J.; Vossen, J. J.; Ballieux, R. E.
: Kappa-chain deficiency: an immunoglobulin disorder. New Eng. J.
Med. 294: 1026-1030, 1976.
*FIELD* CS
INHERITANCE:
Autosomal recessive
RESPIRATORY:
Recurrent infections (in 1 patient)
ABDOMEN:
[Gastrointestinal];
Diarrhea (in 1 patient)
IMMUNOLOGY:
Immunoglobulin kappa light chain deficiency
MISCELLANEOUS:
Very few patients reported;
One patient studied at molecular level (as of July 2011)
MOLECULAR BASIS:
Caused by mutation in the immunoglobulin kappa constant region gene
(IGKC, 147200.0004)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CD
Matthew B. Gross: 7/19/2011
*FIELD* ED
carol: 12/15/2011
carol: 7/20/2011
mgross: 7/19/2011
*RECORD*
*FIELD* NO
614102
*FIELD* TI
#614102 IMMUNOGLOBULIN KAPPA LIGHT CHAIN DEFICIENCY; IGKCD
;;KAPPA CHAIN DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because immunoglobulin kappa
light chain deficiency (IGKCD) can be caused by compound heterozygous
mutation in the immunoglobulin kappa constant region gene (IGKC; 147200)
on chromosome 2p11.
CLINICAL FEATURES
In a female offspring of an uncle-niece marriage, Bernier et al. (1972)
observed deficient synthesis of kappa chain-bearing immunoglobulins. She
also had recurrent respiratory infections and diarrhea.
Zegers et al. (1976) observed complete absence of immunoglobulin kappa
chains in a male patient with cystic fibrosis (219700) in whom kappa
chains were absent in serum immunoglobulins and in blood and bone marrow
lymphocytes. Lymphocytes stimulated by pokeweed mitogen produced no
kappa chains. A sister, who also had cystic fibrosis, showed partial
deficiency of kappa chains. Sera from the patient's parents and another
sib had approximately normal amounts of kappa chains. The patient's
immune responses to a variety of antigens were normal, suggesting that
kappa deficiency has little effect on health. Zegers et al. (1976) noted
that a few individuals with reduced kappa chains had been described
(Bernier et al., 1972; Barandun et al., 1976).
MAPPING
Kappa light chain deficiency results from mutation in the IGKC gene,
which Gross (2011) mapped to chromosome 2p11.2.
MOLECULAR GENETICS
Stavnezer-Nordgren et al. (1985) studied the molecular basis of complete
kappa chain deficiency in the patient reported by Zegers et al. (1976).
They identified compound heterozygosity for 2 point mutations in the
IGKC gene, resulting in loss of an invariant tryptophan in one allele
(W148R; 147200.0004) and an invariant cysteine in the other allele
(C194G; 147200.0005). Both mutations were predicted to abolish formation
of stable intradomain disulfide bonds.
*FIELD* RF
1. Barandun, S.; Morell, A.; Skvaril, F.; Oberdorfer, A.: Deficiency
of kappa- or lambda-type immunoglobulins. Blood 47: 79-89, 1976.
2. Bernier, G. M.; Gunderman, J. R.; Ruymann, F. B.: Kappa-chain
deficiency. Blood 40: 795-805, 1972.
3. Gross, M. B.: Personal Communication. Baltimore, Md. 7/19/2011.
4. Stavnezer-Nordgren, J.; Kekish, O.; Zegers, B. J. M.: Molecular
defects in a human immunoglobulin kappa chain deficiency. Science 230:
458-461, 1985.
5. Zegers, B. J. M.; Maertzdorf, W. J.; van Loghem, E.; Mul, N. A.
J.; Stoop, J. W.; van der Laag, J.; Vossen, J. J.; Ballieux, R. E.
: Kappa-chain deficiency: an immunoglobulin disorder. New Eng. J.
Med. 294: 1026-1030, 1976.
*FIELD* CS
INHERITANCE:
Autosomal recessive
RESPIRATORY:
Recurrent infections (in 1 patient)
ABDOMEN:
[Gastrointestinal];
Diarrhea (in 1 patient)
IMMUNOLOGY:
Immunoglobulin kappa light chain deficiency
MISCELLANEOUS:
Very few patients reported;
One patient studied at molecular level (as of July 2011)
MOLECULAR BASIS:
Caused by mutation in the immunoglobulin kappa constant region gene
(IGKC, 147200.0004)
*FIELD* CD
Joanna S. Amberger: 3/5/2012
*FIELD* ED
joanna: 03/05/2012
*FIELD* CD
Matthew B. Gross: 7/19/2011
*FIELD* ED
carol: 12/15/2011
carol: 7/20/2011
mgross: 7/19/2011