HGNC Approved Gene Symbol: C7
Cytogenetic location: 5p13.1 Genomic coordinates (GRCh38): 5:40,909,497-40,984,643 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 5p13.1 | C7 deficiency | 610102 | 3 |
C7 is a single-chain plasma glycoprotein involved in the cytolytic phase of complement activation (Hobart et al., 1995). Mutations in the C7 gene cause C7 deficiency (610102), a defect associated with increased susceptibility to neisserial recurrent infections (Barroso et al., 2004).
By screening a liver cDNA library, DiScipio et al. (1988) obtained a full-length cDNA encoding C7. The deduced 843-amino acid protein has a 22-amino acid N-terminal leader sequence, 56 cysteines predicted to form 28 disulfide bonds, and 2 N-glycosylation sites.
Hobart et al. (1995) determined that the C7 gene contains 18 exons and spans 80 kb.
Hobart et al. (1978) identified 3 structural forms of C7, concluded they are the products of 3 codominant alleles at an autosomal locus, and found that the C6 and C7 loci are closely linked to each other but not to the HLA complex. By Southern blot analysis of hybrid cell DNAs using cDNA probes, Jeremiah et al. (1989, 1990) demonstrated that the human C6 and C7 genes are located on chromosome 5. See Coto et al. (1991) for linkage information indicating that C6, C7, and C9 are closely situated; C9 was mapped to 5p13.
Eldridge et al. (1983) found 2 closely linked C7 loci (7C1 and 7C2) in the dog. Both are closely linked to C6 and are not close to MHC. In the domestic cat, as in man, there is a single C7 locus.
Nakamura et al. (1984) identified common variants of C7 in Japanese. Washio et al. (1986) described polymorphism of C7 in Japanese and described a 'new' rare variant. No significant association was found between C6 and C7 alleles to suggest linkage disequilibrium. Washio et al. (1986) pointed out that Japanese show a higher degree of polymorphism of both C6 and C7 than do Caucasians.
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
Using an ELISA method with a monoclonal antibody, Wurzner et al. (1990) demonstrated a new C7 allele, which they referred to as C7*9. A gene frequency of 0.21 was estimated. With conventional techniques, C7*9 was included in the frequency of C7*1. Wurzner et al. (1992) described a new protein polymorphism detected by a monoclonal antibody.
Complement Component 7 Deficiency
Alvarez et al. (1995) described studies of 3 families segregating complement component 7 deficiency (C7D; 610102), in each of which 2 sibs suffered from recurrent Neisseria meningitidis infection and were demonstrably homozygous for a C7*Q0 'silent allele.' The haplotypes for RFLPs at the 3 closely linked C6, C7, and C9 genes were defined, allowing for the detection of carriers among asymptomatic relatives.
In patients with C7 deficiency, Nishizaka et al. (1996) identified homozygous mutations in the C7 gene (217070.0001-217070.0002).
In patients with C7 deficiency, Fernie and Hobart (1998) identified homozygous or compound heterozygous mutations in the C7 gene: 3 missense, 2 single-nucleotide deletions, and 2 defects of the 5-prime splice donor site (see, e.g., 217070.0003-217070.0006).
In patients with C7 deficiency, Barroso et al. (2006) identified homozygous or compound heterozygous mutations in the C7 gene (217070.0003 and 217070.0006-217070.0010).
Associations Pending Confirmation
For a discussion of a possible association between variation in the C7 gene and multiple sclerosis, see MS3 (612595).
In a Japanese patient with C7 deficiency (C7D; 610102), Nishizaka et al. (1996) identified a homozygous T-to-A transversion at nucleotide 2250 of the C7 gene, resulting in a cys-to-ter substitution at codon 728.
In a Japanese patient with C7 deficiency (C7D; 610102), Nishizaka et al. (1996) identified a homozygous 2-bp deletion in exon 15 of the C7 gene, denoted 2137delTG/2138delGT/2139delTG, that caused a frameshift and generated a premature termination codon 4 bp downstream.
In a patient with combined subtotal C7 and C6 deficiency, Fernie et al. (1996) identified a C-to-A transversion at position 72 of exon 11 of the C7 gene, resulting in the substitution of an arginine by a serine at codon 499. This mutation directs the synthesis of a protein of normal size, low circulating concentration, and with a different isoelectric focusing pattern than that produced by the common C7 allele. They found this mutation in homozygosity in individuals with combined subtotal deficiency of C6 (612446) and C7 (610102), together with a mutation in C6 (217050.0002, associated with C6 of low molecular weight and of low expressed concentration) on a characteristic haplotype. Fernie et al. (1996) also detected this mutation in isolation in one Russian family. Coupling of this chromosome with one carrying a defective (but still partially functional) C7 gene results in a profound deficiency of C7, because there is ample C6 to generate C56 and consume the already small amount of C7. Alternatively, coupling of this chromosome with another carrying a null C6 gene results in higher than expected C7 levels, because there is no C6 generating C56 to consume the C7.
In a 32-year-old Spanish woman with total deficiency of C7 and C4B (120820) associated with systemic lupus erythematosus (see 152700), Barroso et al. (2006) identified compound heterozygosity for mutations in the C7 gene: R499S and a T-to-A transversion at nucleotide 1458 in exon 10, resulting in a cys464-to-ter (C464X; 217070.0009) substitution and premature termination of the protein.
Fernie et al. (1997) described an Irish family with C7 deficiency (C7D; 610102) in which the affected individuals were compound heterozygous for a G-to-A transition at the -1 position of intron 1. The other allele carried a genomic deletion of exons 7 and 8 (see 217070.0005).
Fernie et al. (1997) described an Irish family in which an individual with C7 deficiency (C7D; 610102) was homozygous for a genomic deletion of exons 7 and 8. This defect is difficult to detect in heterozygosity.
Also see 217070.0004.
Fernie et al. (1997) described 2 families and 2 other unrelated individuals, all of Moroccan Sephardi Jewish ancestry, with C7 deficiency (C7D; 610102) due to a homozygous G-to-C transversion at nucleotide 1135, leading to a gly-to-arg substitution at codon 357. The glycine at position 357 is conserved in all 5 homologous members of the terminal complement family.
Barroso et al. (2004) reported a 17-year-old Spanish Gypsy girl with C7 deficiency who was compound heterozygous for the C357R mutation and a 1-bp deletion (1309A) in exon 10, resulting in premature termination at codon 419 (217070.0007).
Barroso et al. (2004) reported a 17-year-old Spanish Gypsy girl with C7 deficiency (C7D; 610102) who had suffered 2 meningococcal disease episodes. The patient and her father had a 1-bp deletion (1309A) in exon 10 of the C7 gene, resulting in premature termination at codon 419. The patient and her mother had the gly357-to-arg mutation (C357R; 217070.0006). Both parents were heterozygous for their mutations.
Barroso et al. (2004) reported a Spanish patient and her brother with C7 deficiency (C7D; 610102) who had suffered 1 and 3 episodes of meningococcal disease, respectively. Both patients were homozygous for a 2-bp deletion (1922delAG) in exon 14 of the C7 gene, resulting in a premature stop at codon 630. Of the patients' other sibs, 2 were heterozygous for the mutation and 2 had wildtype genotypes. The female patient's 3 daughters were all heterozygous for the mutation.
In a 23-year-old Swiss woman of Bolivian and Czech origin with C7 deficiency who presented with meningococcal meningitis with septic shock, Barroso et al. (2006) identified compound heterozygosity for mutations in the C7 gene: the 2-bp deletion in exon 14 and an 11-bp deletion of nucleotides 631 to 641 in exon 6 (217070.0010), leading to premature termination of the protein at residue 193.
For discussion of the 1561C-A transversion in exon 11 of the C7 gene that was found in compound heterozygous state in a 32-year-old Spanish woman with deficiency of C7 (610102) and C4B (120820) associated with systemic lupus erythematosus (see 152700) by Barroso et al. (2006), see 217070.0003.
For discussion of the 11-bp deletion (nucleotides 631-641) in exon 6 of the C7 gene that was found in compound heterozygous state in a 23-year-old Swiss woman of Bolivian and Czech origin with C7 deficiency (C7D; 610102) by Barroso et al. (2006), see 217070.0008.
Alvarez, V., Coto, E., Setien, F., Spath, P. J., Lopez-Larrea, C. Genetic detection of the silent allele (*Q0) in hereditary deficiencies of the human complement C6, C7, and C9 components. Am. J. Med. Genet. 55: 408-413, 1995. [PubMed: 7762578] [Full Text: https://doi.org/10.1002/ajmg.1320550405]
Barroso, S., Rieubland, C., Alvarez, A. J., Lopez-Trascasa, M., Bart, P.-A., Nunez-Roldan, A., Sanchez, B. Molecular defects of the C7 gene in two patients with complement C7 deficiency. Immunology 118: 257-260, 2006. [PubMed: 16771861] [Full Text: https://doi.org/10.1111/j.1365-2567.2006.02364.x]
Barroso, S., Sanchez, B., Alvarez, A. J., Lopez-Trascasa, M., Lanuza, A., Luque, R., Wichmann, I., Nunez-Roldan, A. Complement component C7 deficiency in two Spanish families. Immunology 113: 518-523, 2004. [PubMed: 15554930] [Full Text: https://doi.org/10.1111/j.1365-2567.2004.01997.x]
Coto, E., Martinez-Naves, E., Dominguez, O., DiScipio, R. G., Urra, J. M., Lopez-Larrea, C. DNA polymorphism and linkage relationship of the human complement component C6, C7, and C9 genes. Immunogenetics 33: 184-187, 1991. [PubMed: 1672663] [Full Text: https://doi.org/10.1007/BF01719238]
DiScipio, R. G., Chakravarti, D. N., Muller-Eberhard, H. J., Fey, G. H. The structure of human complement component C7 and the C5b-7 complex. J. Biol. Chem. 263: 549-560, 1988. [PubMed: 3335508]
Eldridge, P. R., Hobart, M. J., Lachmann, P. J. The genetics of the sixth and seventh components of complement in the dog: polymorphism, linkage, locus duplication, and silent alleles. Biochem. Genet. 21: 81-91, 1983. [PubMed: 6838492] [Full Text: https://doi.org/10.1007/BF02395393]
Fernie, B. A., Hobart, M. J. Complement C7 deficiency: seven further molecular defects and their associated marker haplotypes. Hum. Genet. 103: 513-519, 1998. [PubMed: 9856499] [Full Text: https://doi.org/10.1007/s004390050859]
Fernie, B. A., Orren, A., Sheehan, G., Schlesinger, M., Hobart, M. J. Molecular bases of C7 deficiency: three different defects. J. Immun. 159: 1019-1026, 1997. [PubMed: 9218625]
Fernie, B. A., Wurzner, R., Orren, A., Morgan, B. P., Potter, P. C., Platonov, A. E., Vershinina, I. V., Shipulin, G. A., Lachmann, P. J., Hobart, M. J. Molecular bases of combined subtotal deficiencies of C6 and C7: their effects in combination with other C6 and C7 deficiencies. J. Immun. 157: 3648-3657, 1996. [PubMed: 8871666]
Hobart, M. J., Fernie, B. A., DiScipio, R. G. Structure of the human C7 gene and comparison with the C6, C8A, C8B, and C9 genes. J. Immun. 154: 5188-5194, 1995. [PubMed: 7730625]
Hobart, M. J., Joysey, V., Lachmann, P. J. Inherited structural variation and linkage relationships of C7. J. Immunogenet. 5: 157-163, 1978. [PubMed: 690473] [Full Text: https://doi.org/10.1111/j.1744-313x.1978.tb00641.x]
Jeremiah, S. J., Abbott, C. M., Murad, Z., Povey, S., Thomas, H. J., Solomon, E., DiScipio, R. G., Fey, G. H. The assignment of the genes coding for human complement components C6 and C7 to chromosome 5. Ann. Hum. Genet. 54: 141-147, 1990. [PubMed: 2382968] [Full Text: https://doi.org/10.1111/j.1469-1809.1990.tb00370.x]
Jeremiah, S. J., West, L. F., Abbott, C. M., Murad, Z., Povey, S., Thomas, H. J., Solomon, E., Di Scipio, R., Fey, G. H. Three genes coding for late acting components of complement assigned to chromosome 5. (Abstract) Cytogenet. Cell Genet. 51: 1019 only, 1989.
Nakamura, S., Ooue, O., Abe, K. Genetic polymorphism of the seventh component of complement in a Japanese population. Hum. Genet. 66: 279-281, 1984. [PubMed: 6714987] [Full Text: https://doi.org/10.1007/BF00286617]
Nishimukai, H., Tamaki, Y. Genetic polymorphism of the seventh component of complement: a new variant. Vox Sang. 51: 60-62, 1986. [PubMed: 3526727] [Full Text: https://doi.org/10.1111/j.1423-0410.1986.tb00211.x]
Nishizaka, H., Horiuchi, T., Zhu, Z. B., Fukumori, Y., Volanakis, J. E. Genetic bases of human complement C7 deficiency. J. Immun. 157: 4239-4243, 1996. [PubMed: 8892662]
Roychoudhury, A. K., Nei, M. Human Polymorphic Genes: World Distribution. New York: Oxford Univ. Press (pub.) 1988.
Washio, K., Tokunaga, K., Omoto, K., Misawa, S. Human C7 polymorphism: classification and association analysis with C6. Jpn. J. Hum. Genet. 31: 345-352, 1986.
Whitehouse, D. B. Genetic polymorphism and linkage of the sixth and seventh complement components (C6 and C7) in the common marmoset. Biochem. Genet. 22: 51-63, 1984. [PubMed: 6424644] [Full Text: https://doi.org/10.1007/BF00499286]
Wurzner, R., Hobart, M. J., Orren, A., Tokunaga, K., Nitze, R., Gotze, O., Lachmann, P. J. A novel protein polymorphism of human complement C7 detected by a monoclonal antibody. Immunogenetics 35: 398-402, 1992. [PubMed: 1577506] [Full Text: https://doi.org/10.1007/BF00179797]
Wurzner, R., Nitze, R., Gotze, O. C7*9, a new frequent C7 allele detected by an allotype-specific monoclonal antibody. Complement Inflamm. 7: 290-297, 1990. [PubMed: 2088668] [Full Text: https://doi.org/10.1159/000463163]