RBCC Red Blood Cell Collection

C1QB [Confidence: low (only semi-automatic identification from reviews)]
Complement C1q subcomponent subunit B; Flags: Precursor
Note: presumably soluble (membrane word is not in UniProt keywords or features)

UniProt P02746
ID C1QB_HUMAN Reviewed; 253 AA.
AC P02746; Q5T959; Q96H17;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUN-2010, sequence version 3.
DT 22-JAN-2014, entry version 156.
DE RecName: Full=Complement C1q subcomponent subunit B;
DE Flags: Precursor;
GN Name=C1QB;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 26-253.
RX PubMed=3000358;
RA Reid K.B.M.;
RT "Molecular cloning and characterization of the complementary DNA and
RT gene coding for the B-chain of subcomponent C1q of the human
RT complement system.";
RL Biochem. J. 231:729-735(1985).
RN [4]
RP PROTEIN SEQUENCE OF 28-195, GLYCOSYLATION, PYROGLUTAMATE FORMATION AT
RP GLU-28, DISULFIDE BOND, AND HYDROXYLATION.
RX PubMed=708376;
RA Reid K.B.M., Thompson E.O.P.;
RT "Amino acid sequence of the N-terminal 108 amino acid residues of the
RT B chain of subcomponent C1q of the first component of human
RT complement.";
RL Biochem. J. 173:863-868(1978).
RN [5]
RP PROTEIN SEQUENCE OF 28-135.
RX PubMed=486087;
RA Reid K.B.M.;
RT "Complete amino acid sequences of the three collagen-like regions
RT present in subcomponent C1q of the first component of human
RT complement.";
RL Biochem. J. 179:367-371(1979).
RN [6]
RP PROTEIN SEQUENCE OF 136-253.
RX PubMed=6981411;
RA Reid K.B.M., Gagnon J., Frampton J.;
RT "Completion of the amino acid sequences of the A and B chains of
RT subcomponent C1q of the first component of human complement.";
RL Biochem. J. 203:559-569(1982).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-253.
RC TISSUE=Liver;
RX PubMed=6208566;
RA Reid K.B.M., Bentley D.R., Wood K.J.;
RT "Cloning and characterization of the complementary DNA for the B chain
RT of normal human serum C1q.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 306:345-354(1984).
RN [8]
RP GLYCOSYLATION ON HYDROXYLYSINES.
RX PubMed=6286235;
RA Yonemasu K., Shinkai H., Sasaki T.;
RT "Comparable content of hydroxylysine-linked glycosides in
RT subcomponents C1q of the first component of human, bovine and mouse
RT complement.";
RL Coll. Relat. Res. 1:385-390(1981).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 119-250.
RX PubMed=12960167; DOI=10.1074/jbc.M307764200;
RA Gaboriaud C., Juanhuix J., Gruez A., Lacroix M., Darnault C.,
RA Pignol D., Verger D., Fontecilla-Camps J.-C., Arlaud G.J.;
RT "The crystal structure of the globular head of complement protein C1q
RT provides a basis for its versatile recognition properties.";
RL J. Biol. Chem. 278:46974-46982(2003).
RN [10]
RP REVIEW ON C1Q DEFICIENCY.
RX PubMed=9777412;
RA Petry F.;
RT "Molecular basis of hereditary C1q deficiency.";
RL Immunobiology 199:286-294(1998).
RN [11]
RP VARIANT C1QD ASP-42.
RX PubMed=9476130; DOI=10.1016/S0162-3109(97)00065-9;
RA Petry F., Hauptmann G., Goetz J., Grosshans E., Loos M.;
RT "Molecular basis of a new type of C1q-deficiency associated with a
RT non-functional low molecular weight (LMW) C1q: parallels and
RT differences to other known genetic C1q-defects.";
RL Immunopharmacology 38:189-201(1997).
RN [12]
RP VARIANT [LARGE SCALE ANALYSIS] THR-123.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: C1q associates with the proenzymes C1r and C1s to yield
CC C1, the first component of the serum complement system. The
CC collagen-like regions of C1q interact with the Ca(2+)-dependent
CC C1r(2)C1s(2) proenzyme complex, and efficient activation of C1
CC takes place on interaction of the globular heads of C1q with the
CC Fc regions of IgG or IgM antibody present in immune complexes.
CC -!- SUBUNIT: C1 is a calcium-dependent trimolecular complex of C1q,
CC c1r and C1s in the molar ration of 1:2:2. C1q subcomponent is
CC composed of nine subunits, six of which are disulfide-linked
CC dimers of the A and B chains, and three of which are disulfide-
CC linked dimers of the C chain.
CC -!- INTERACTION:
CC P02745:C1QA; NbExp=4; IntAct=EBI-2813376, EBI-1220209;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: Hydroxylated on lysine and proline residues. Hydroxylated
CC lysine residues can be glycosylated. Human C1Q contains up to 68.3
CC hydroxylysine-galactosylglucose residues and up to 2.5
CC hydroxylysine-galactose per molecule. Total percentage
CC hydroxylysine residues glycosylated is 86.4%.
CC -!- DISEASE: Complement component C1q deficiency (C1QD) [MIM:613652]:
CC A disorder caused by impaired activation of the complement
CC classical pathway. It generally leads to severe immune complex
CC disease with features of systemic lupus erythematosus and
CC glomerulonephritis. Note=The disease is caused by mutations
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Contains 1 C1q domain.
CC -!- SIMILARITY: Contains 2 collagen-like domains.
CC -!- WEB RESOURCE: Name=C1QBbase; Note=C1QB mutation db;
CC URL="http://bioinf.uta.fi/C1QBbase/";
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; AL158086; CAI22896.1; -; Genomic_DNA.
DR EMBL; BC008983; AAH08983.1; -; mRNA.
DR EMBL; X03084; CAA26880.1; -; mRNA.
DR EMBL; M36278; AAC41692.1; -; mRNA.
DR PIR; B23422; C1HUQB.
DR RefSeq; NP_000482.3; NM_000491.3.
DR RefSeq; XP_005246039.1; XM_005245982.1.
DR UniGene; Hs.8986; -.
DR PDB; 1PK6; X-ray; 1.85 A; B=119-250.
DR PDB; 2JG8; X-ray; 2.05 A; B/E=118-251.
DR PDB; 2JG9; X-ray; 1.90 A; B/E=118-251.
DR PDB; 2WNU; X-ray; 2.30 A; B/E=118-253.
DR PDB; 2WNV; X-ray; 1.25 A; B/E=118-253.
DR PDBsum; 1PK6; -.
DR PDBsum; 2JG8; -.
DR PDBsum; 2JG9; -.
DR PDBsum; 2WNU; -.
DR PDBsum; 2WNV; -.
DR ProteinModelPortal; P02746; -.
DR SMR; P02746; 80-105, 119-250.
DR IntAct; P02746; 7.
DR MINT; MINT-6629999; -.
DR STRING; 9606.ENSP00000313967; -.
DR DrugBank; DB00054; Abciximab.
DR DrugBank; DB00051; Adalimumab.
DR DrugBank; DB00092; Alefacept.
DR DrugBank; DB00087; Alemtuzumab.
DR DrugBank; DB00074; Basiliximab.
DR DrugBank; DB00112; Bevacizumab.
DR DrugBank; DB00002; Cetuximab.
DR DrugBank; DB00111; Daclizumab.
DR DrugBank; DB00095; Efalizumab.
DR DrugBank; DB00005; Etanercept.
DR DrugBank; DB00056; Gemtuzumab ozogamicin.
DR DrugBank; DB00078; Ibritumomab.
DR DrugBank; DB00028; Immune globulin.
DR DrugBank; DB00075; Muromonab.
DR DrugBank; DB00108; Natalizumab.
DR DrugBank; DB00110; Palivizumab.
DR DrugBank; DB00073; Rituximab.
DR DrugBank; DB00081; Tositumomab.
DR DrugBank; DB00072; Trastuzumab.
DR PhosphoSite; P02746; -.
DR DMDM; 298286922; -.
DR PaxDb; P02746; -.
DR PRIDE; P02746; -.
DR DNASU; 713; -.
DR Ensembl; ENST00000314933; ENSP00000313967; ENSG00000173369.
DR GeneID; 713; -.
DR KEGG; hsa:713; -.
DR UCSC; uc001bgd.3; human.
DR CTD; 713; -.
DR GeneCards; GC01P022979; -.
DR HGNC; HGNC:1242; C1QB.
DR HPA; HPA052116; -.
DR MIM; 120570; gene.
DR MIM; 613652; phenotype.
DR neXtProt; NX_P02746; -.
DR Orphanet; 169147; Immunodeficiency due to an early component of complement deficiency.
DR PharmGKB; PA25623; -.
DR eggNOG; NOG115400; -.
DR HOGENOM; HOG000085653; -.
DR HOVERGEN; HBG108220; -.
DR InParanoid; P02746; -.
DR KO; K03987; -.
DR OMA; ENRNYEP; -.
DR PhylomeDB; P02746; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; C1QB; human.
DR EvolutionaryTrace; P02746; -.
DR GenomeRNAi; 713; -.
DR NextBio; 2898; -.
DR PRO; PR:P02746; -.
DR ArrayExpress; P02746; -.
DR Bgee; P02746; -.
DR CleanEx; HS_C1QB; -.
DR Genevestigator; P02746; -.
DR GO; GO:0005581; C:collagen; IEA:UniProtKB-KW.
DR GO; GO:0005602; C:complement component C1 complex; TAS:ProtInc.
DR GO; GO:0006958; P:complement activation, classical pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR Gene3D; 2.60.120.40; -; 1.
DR InterPro; IPR001073; C1q.
DR InterPro; IPR008160; Collagen.
DR InterPro; IPR008983; Tumour_necrosis_fac-like_dom.
DR Pfam; PF00386; C1q; 1.
DR Pfam; PF01391; Collagen; 2.
DR PRINTS; PR00007; COMPLEMNTC1Q.
DR SMART; SM00110; C1Q; 1.
DR SUPFAM; SSF49842; SSF49842; 1.
DR PROSITE; PS50871; C1Q; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Collagen; Complement pathway; Complete proteome;
KW Direct protein sequencing; Disease mutation; Disulfide bond;
KW Glycoprotein; Hydroxylation; Immunity; Innate immunity; Polymorphism;
KW Pyrrolidone carboxylic acid; Reference proteome; Repeat; Secreted;
KW Signal.
FT SIGNAL 1 27
FT CHAIN 28 253 Complement C1q subcomponent subunit B.
FT /FTId=PRO_0000003521.
FT DOMAIN 37 86 Collagen-like 1.
FT DOMAIN 60 114 Collagen-like 2.
FT DOMAIN 117 253 C1q.
FT MOD_RES 28 28 Pyrrolidone carboxylic acid.
FT DISULFID 31 31 Interchain (with C-26 in chain A).
FT VARIANT 42 42 G -> D (in C1QD).
FT /FTId=VAR_008541.
FT VARIANT 123 123 A -> T (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_035551.
FT CONFLICT 28 28 Q -> E (in Ref. 4; AA sequence).
FT CONFLICT 85 85 N -> D (in Ref. 4; AA sequence).
FT CONFLICT 100 100 G -> P (in Ref. 4; AA sequence and 5; AA
FT sequence).
FT STRAND 123 127
FT STRAND 144 149
FT TURN 155 157
FT STRAND 159 161
FT STRAND 166 178
FT STRAND 180 190
FT STRAND 192 199
FT STRAND 202 204
FT STRAND 206 216
FT STRAND 221 230
FT STRAND 241 249
SQ SEQUENCE 253 AA; 26722 MW; D80C753C0D430EDC CRC64;
MMMKIPWGSI PVLMLLLLLG LIDISQAQLS CTGPPAIPGI PGIPGTPGPD GQPGTPGIKG
EKGLPGLAGD HGEFGEKGDP GIPGNPGKVG PKGPMGPKGG PGAPGAPGPK GESGDYKATQ
KIAFSATRTI NVPLRRDQTI RFDHVITNMN NNYEPRSGKF TCKVPGLYYF TYHASSRGNL
CVNLMRGRER AQKVVTFCDY AYNTFQVTTG GMVLKLEQGE NVFLQATDKN SLLGMEGANS
IFSGFLLFPD MEA
//

MIM 120570
*RECORD*
*FIELD* NO
120570
*FIELD* TI
*120570 COMPLEMENT COMPONENT 1, q SUBCOMPONENT, B CHAIN; C1QB
;;COMPLEMENT COMPONENT 1, q SUBCOMPONENT, BETA POLYPEPTIDE;;
read moreCOMPLEMENT COMPONENT C1q, B CHAIN
*FIELD* TX

CLONING

C1q, the first subcomponent of C1, has a complicated 18-chain structure:
6 A, 6 B, and 6 C chains. Each chain has a stretch of about 80 amino
acids with the collagenous triplet Gly-X-Y where X and Y can include
hydroxyproline and hydroxylysine. The A (120550), B, and C (120575)
chains combine to form 6 heteromeric triple helices in the collagenous
regions of the chains (Sellar et al., 1991).

MAPPING

Using a cDNA probe to the B chain of C1q, Solomon et al. (1985) assigned
the gene to chromosome 1 in somatic cell hybrids. A hybrid containing
1p, but no 1q, allowed them to localize the gene to 1p.

The genes for the A, B, and C chains of C1q are tandemly arranged
5-prime to 3-prime in the order A-C-B on a 24-kb stretch of DNA (Sellar
et al., 1991). A and C are separated by 4 kb and B and C are separated
by 11 kb. Hybridization of cDNA probes to a hybrid cell line containing
the derived X chromosome from an X;1(q21.2;p34) translocation described
in a female patient with Duchenne muscular dystrophy (Lindenbaum et al.,
1979; Boyd et al., 1988) showed that the A and B genes are located in
the region 1p36.3-p34.1 (Sellar et al., 1992).

GENE FUNCTION

Querec et al. (2009) noted that a major challenge of vaccinology is to
prospectively determine efficacy. They applied a systems biology
approach, including multiplex cytokine analysis, flow cytometry, and
microarray transcriptional profiling, to identify early gene signatures
predicting immune responses in humans immunized with YF-17D, the
well-established and successful vaccine for yellow fever. Computational
analysis identified a gene signature that included C1QB and EIF2AK4
(609280), a part of the integrated stress response, that correlated with
and predicted CD8 (see 186910)-positive T-cell responses to the vaccine.
Neutralizing antibody responses completely correlated with induction of
TNFRSF17 (109545), the B-cell maturation factor. Querec et al. (2009)
concluded that systems biology approaches can identify correlates of
innate immunity and subsequent adaptive immune responses.

MOLECULAR GENETICS

The first molecular lesion in C1q deficiency (613652) was reported by
McAdam et al. (1988). A homozygous G-to-A transition at nucleotide 150
in the B-chain (120570.0001) resulted in a premature stop codon. The
patient had no antigenetically detectable C1q.

*FIELD* AV
.0001
C1Q DEFICIENCY
C1QB, 150G-A

The first molecular lesion in C1q deficiency (613652) was reported by
McAdam et al. (1988). A homozygous G-to-A transition at nucleotide 150
in the B-chain resulted in a premature stop codon. The patient had no
antigenetically detectable C1q.

*FIELD* RF
1. Boyd, Y.; Cockburn, D.; Holt, S.; Munro, E.; van Ommen, G. J.;
Gillard, B.; Affara, N.; Ferguson-Smith, M.; Craig, I.: Mapping of
12 translocation breakpoints in the Xp21 region with respect to the
locus for Duchenne muscular dystrophy. Cytogenet. Cell Genet. 48:
28-34, 1988.

2. Lindenbaum, R. H.; Clarke, G.; Patel, C.; Moncrieff, M.; Hughes,
J. T.: Muscular dystrophy in an X;1 translocation female suggests
that Duchenne locus is on X chromosome short arm. J. Med. Genet. 16:
389-392, 1979.

3. McAdam, R. A.; Goundis, D.; Reid, K. B. M.: A homozygous point
mutation results in a stop codon in the C1q B-chain of a C1q-deficient
individual. Immunogenetics 27: 259-264, 1988.

4. Querec, T. D.; Akondy, R. S.; Lee, E. K.; Cao, W.; Nakaya, H. I.;
Teuwen, D.; Pirani, A.; Gernert, K.; Deng, J.; Marzolf, B.; Kennedy,
K.; Wu, H.; Bennouna, S.; Oluoch, H.; Miller, J.; Vencio, R. Z.; Mulligan,
M.; Aderem, A.; Ahmed, R.; Pulendran, B.: Systems biology approach
predicts immunogenicity of the yellow fever vaccine in humans. Nature
Immun. 10: 116-125, 2009.

5. Sellar, G. C.; Blake, D. J.; Reid, K. B.: Characterization and
organization of the genes encoding the A-, B-, and C-chains of human
complement subcomponent C1q: the complete derived amino acid sequence
of human C1q. Biochem. J. 274: 481-490, 1991.

6. Sellar, G. C.; Cockburn, D.; Reid, K. B. M.: Localization of the
gene cluster encoding the A, B, and C chains of human C1q to 1p34.1-1p36.3. Immunogenetics 35:
214-216, 1992.

7. Solomon, E.; Skok, J.; Griffin, J.; Reid, K. B. M.: Human C1q
B chain (C1QB) is on chromosome 1p. (Abstract) Cytogenet. Cell Genet. 40:
749 only, 1985.

*FIELD* CN
Paul J. Converse - updated: 01/30/2014

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

*FIELD* ED
mgross: 01/30/2014
terry: 2/18/2011
carol: 2/17/2011
mgross: 3/14/2008
mgross: 3/17/2004
carol: 4/21/1999
terry: 11/14/1996
terry: 11/11/1996
jason: 6/29/1994
carol: 10/13/1992
carol: 5/12/1992
supermim: 3/16/1992
carol: 9/9/1991
carol: 3/14/1991

MIM 613652
*RECORD*
*FIELD* NO
613652
*FIELD* TI
#613652 C1q DEFICIENCY; C1QD
*FIELD* TX
A number sign (#) is used with this entry because C1q deficiency can be
read morecaused by homozygous mutation in the C1QA (120550), C1QB (120570), or
C1QC (120575) gene, all of which are located on chromosome 1p36.

DESCRIPTION

C1q deficiency is a rare autosomal recessive disorder associated with
recurrent skin lesions, chronic infections, systemic lupus erythematosis
(SLE; see 152700) or SLE-like diseases. It has also been associated with
mesangial proliferative glomerulonephritis. C1q deficiency presents in 2
different forms, absent C1q protein or presence of a dysfunctional
molecule (summary by Topaloglu et al., 1996).

CLINICAL FEATURES

Thompson et al. (1980) reported C1q deficiency in a 4-year-old son of
first-cousin Pakistani parents, who presented with a lupus-like illness
and later developed glomerulonephritis. A younger sister, as yet
clinically unaffected, had the same complement profile and a younger
brother had half-normal functional C1 levels. The heterozygous status of
both parents, the younger brother, and an older sister was suggested by
the presence of double lines on immunochemical analysis of serum from
these persons using anti-C1q antiserum; one line showed a reaction of
identity with the abnormal C1q of the proband, whereas the other showed
a reaction of identity with normal C1q.

Hannema et al. (1984) found deficiency of C1q in 2 sisters and a
brother. In these persons a dysfunctional C1q molecule was characterized
by low molecular weight and antigenic deficiency. In the 2 sisters a
systemic lupus erythematosus-like disease began at ages 20 and 23,
respectively, resulting in death of 1 of them. All 3 sibs suffered from
glomerulonephritis during childhood. The brother was apparently healthy
but showed membranous glomerulopathy, stage 1, on renal biopsy.

Topaloglu et al. (1996) described 2 sibs with C1q deficiency. Both
presented with a photosensitive rash and during follow-up 1 developed
SLE with proteinuria in the nephrotic range. The other sib had
microscopic hematuria with a history of macroscopic hematuria. Renal
biopsies revealed mesangioproliferative glomerulonephritis in 1 and IgA
nephropathy in the other. Antibody response to hepatitis B vaccine was
normal in affected and unaffected members of the family.

Topaloglu et al. (1996) stated that of the 34 reported patients with C1q
deficiency, all but one had SLE or an SLE-like illness.

MOLECULAR GENETICS

The first molecular lesion in C1q deficiency was reported by McAdam et
al. (1988). A homozygous G-to-A transition at nucleotide 150 in the C1QB
gene (120570.0001) resulted in a premature stop codon.

In 2 sibs with C1q deficiency, Topaloglu et al. (1996) identified
homozygosity for a C-T transition in codon 186 of the C1QA gene
(120550.0001) that resulted in a gln-to-stop (Q186X) substitution. The
mutation was present in heterozygous state in both parents and in 2
unaffected sibs. Topaloglu et al. (1996) stated that the same mutation
had been described in an affected member of a Slovakian family with C1q
deficiency by Petry et al. (1995).

Petry et al. (1997) identified homozygosity for the Q186X mutation in
affected members of 3 Turkish families. In 1 family, an asymptomatic
sister of the proband was also found to be homozygous for the mutation.
Petry et al. (1997) hypothesized that this defective allele is present
in the population of southeast Europe and Turkey.

In patients with C1q deficiency, Slingsby et al. (1996) identified
homozygous mutations in the C1QC gene (120575.0001-120575.0003).

- Reviews

Rother (1986) gave a summary of reported deficiencies of components of
complement. Many examples of deficiencies of C1q were listed, most of
them associated with systemic lupus erythematosus or glomerulonephritis.

ANIMAL MODEL

The complement system plays a paradoxical role in development and
expression of autoimmunity in humans. The activation of complement in
SLE contributes to tissue injury. In contrast, inherited deficiency of
classic pathway components, particularly C1q, is probably associated
with development of SLE. This leads to the hypothesis that a physiologic
action of the early part of the classic pathway protects against
development of SLE and implies that C1q may play a key role in this
respect. Botto et al. (1998) generated C1q-deficient (C1qa -/-) mice by
gene targeting and monitored them for 8 months. C1qa -/- mice had
increased mortality and higher titers of autoantibodies, compared with
strain-matched controls. Of the C1qa -/- mice, 25% had
glomerulonephritis with immune deposits and multiple apoptotic cell
bodies. Among mice without glomerulonephritis, there were significantly
greater numbers of glomerular apoptotic bodies in C1q-deficient mice
compared with controls. The phenotype associated with C1q deficiency was
modified by background genes. These findings are compatible with the
hypothesis that C1q deficiency causes autoimmunity by impairment of the
clearance of apoptotic cells.

Garlanda et al. (2002) found that C1q-deficient mice were highly
susceptible to invasive pulmonary aspergillus infection, which could be
reversed by administration of pentraxin-3 (PTX3; 602492).

*FIELD* RF
1. Botto, M.; Dell'Agnola, C.; Bygrave, A. E.; Thompson, E. M.; Cook,
H. T.; Petry, F.; Loos, M.; Pandolfi, P. P.; Walport, M. J.: Homozygous
C1q deficiency causes glomerulonephritis associated with multiple
apoptotic bodies. Nature Genet. 19: 56-59, 1998.

2. Garlanda, C.; Hirsch, E.; Bozza, S.; Salustri, A.; De Acetis, M.;
Nota, R.; Maccagno, A.; Riva, F.; Bottazzi, B.; Peri, G.; Doni, A.;
Vago, L.; Botto, M.; De Santis, R.; Carminati, P.; Siracusa, G.; Altruda,
F.; Vecchi, A.; Romani, L.; Mantovani, A.: Non-redundant role of
the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420:
182-186, 2002.

3. Hannema, A. J.; Kluin-Nelemans, J. C.; Hack, C. E.; Eerenberg-Belmer,
A. J. M.; Mallee, C.; van Helden, H. P. T.: SLE like syndrome and
functional deficiency of C1q in members of a large family. Clin.
Exp. Immun. 55: 106-114, 1984.

4. McAdam, R. A.; Goundis, D.; Reid, K. B. M.: A homozygous point
mutation results in a stop codon in the C1q B-chain of a C1q-deficient
individual. Immunogenetics 27: 259-264, 1988.

5. Petry, F.; Berkel, A. I.; Loos, M.: Multiple identification of
a particular type of hereditary C1q deficiency in the Turkish population:
review of the cases and additional genetic and functional analysis. Hum.
Genet. 100: 51-56, 1997.

6. Petry, F.; Le, D. T.; Kirschfink, M.; Loos, M.: Non-sense and
missense mutations in the structural genes of complement component
C1qA and C chains are linked with two different types of complete
selective C1q deficiencies. J. Immun. 155: 4735-4738, 1995.

7. Rother, K.: Hereditary deficiencies in man: summary of reported
deficiencies. Prog. Allergy 39: 202-211, 1986.

8. Slingsby, J. H.; Norsworthy, P.; Pearce, G.; Vaishnaw, A. K.; Issler,
H.; Morley, B. J.; Walport, M. J.: Homozygous hereditary C1q deficiency
and systemic lupus erythematosus: a new family and the molecular basis
of C1q deficiency in three families. Arthritis Rheum. 39: 663-670,
1996.

9. Thompson, R. A.; Haeney, M.; Reid, K. B. M.; Davis, J. G.; White,
R. H.; Cameron, A. H.: A genetic defect of the C1q subcomponent of
complement associated with childhood (immune complex) nephritis. New
Eng. J. Med. 303: 22-24, 1980.

10. Topaloglu, R.; Bakkaloglu, A.; Slingsby, J. H.; Mihatsch, M. J.;
Pascual, M.; Norsworthy, P.; Morley, B. J.; Saatci, U.; Schifferli,
J. A.; Walport, M. J.: Molecular basis of hereditary C1q deficiency
associated with SLE and IgA nephropathy in a Turkish family. Kidney
Int. 50: 635-642, 1996.

*FIELD* CS
INHERITANCE:
Autosomal recessive

GENITOURINARY:
[Kidneys];
Mesangial proliferative glomerulonephritis (in some patients)

IMMUNOLOGY:
Systemic lupus erythematosis (in some patients);
Autoimmune disease;
C1q deficiency;
C1q molecule present, but dysfunctional

MOLECULAR BASIS:
Caused by mutation in the complement component 1, q subcomponent,
A chain gene (C1QA, 120550.0001);
Caused by mutation in the complement component 1, q subcomponent,
B chain gene (C1QB, 120570.0001);
Caused by mutation in the complement component 1, q subcomponent,
C chain gene (C1QC, 120575.0001)

*FIELD* CD
Joanna S. Amberger: 3/5/2012

*FIELD* ED
joanna: 03/05/2012

*FIELD* CD
Carol A. Bocchini: 11/19/2010

*FIELD* ED
carol: 04/27/2012
terry: 3/27/2012
carol: 4/22/2011
terry: 2/18/2011
carol: 2/17/2011