Details of Disease

General Information of Disease (ID: DISGN469)

• Disease Name: Complement deficiency
• Synonyms: immunodeficiency due to a complement cascade component deficiency; disorder of complement activation; complement deficiency disease; complement deficiency; complement activation disease
• Definition: A genetic deficiency of any of the component of the complement system (including the classical, alternative, and terminal pathway components), that can either be acquired or inherited.
• Disease Hierarchy:
  DISWD40R: Disease
  DISNGCMN: Inborn error of immunity
  DIS093I0: Immunodeficiency
  DISGN469: Complement deficiency
• Disease Identifiers:
  MONDO ID: MONDO_0003832
  MESH ID: D000081208
  UMLS CUI: C0272242
  MedGen ID: 82898
  HPO ID: HP:0004431
  Orphanet ID: 459345
  SNOMED CT ID: 24743004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 13 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
MASP2	TTR01E9	Limited	Biomarker	[1]
CFB	TTA0P7K	moderate	Biomarker	[2]
C1QB	TT8A9DM	Strong	Biomarker	[3]
C1S	TT7LRQH	Strong	Biomarker	[4]
C3	TTJGY7A	Strong	Biomarker	[5]
C5	TTKANGO	Strong	Biomarker	[6]
CD46	TTMS7DF	Strong	Biomarker	[7]
CD55	TT5Z9WY	Strong	Biomarker	[8]
CD59	TTBGTEJ	Strong	Biomarker	[9]
CFD	TT8D13I	Strong	Biomarker	[10]
CFH	TTUW6OP	Strong	Biomarker	[11]
CFP	TTLA0VS	Strong	Biomarker	[12]
SERPING1	TTVQ6R9	Strong	Biomarker	[13]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
FCN3	OTPRENLS	Limited	Biomarker	[14]
MTA2	OTCCYIQJ	Limited	Biomarker	[15]
CFHR5	OT7BMOYE	moderate	Biomarker	[16]
C1QA	OT6XKVVA	Strong	Biomarker	[17]
C1QC	OTLE5U1P	Strong	Biomarker	[18]
C1R	OTA0ZNIU	Strong	Biomarker	[19]
C2	OTHMF4YM	Strong	Biomarker	[4]
C4A	OTXMOYXU	Strong	Biomarker	[20]
C6	OTCKR304	Strong	Biomarker	[21]
C7	OTZ27VJN	Strong	Biomarker	[22]
C8A	OTIJ65J4	Strong	Biomarker	[23]
C8B	OTGDJJOK	Strong	Biomarker	[24]
C9	OT7I5FDX	Strong	Genetic Variation	[25]

References

• [1] Mannan-binding lectin-associated serine protease-2 (MASP-2) deficiency in two patients with pulmonary tuberculosis and one healthy control.Cell Mol Immunol. 2015 Jan;12(1):119-21. doi: 10.1038/cmi.2014.19. Epub 2014 Mar 24.
• [2] Genetic polymorphism in human glycine-rich beta-glycoprotein.J Exp Med. 1972 Jan;135(1):68-80. doi: 10.1084/jem.135.1.68.
• [3] C1q regulatory region polymorphism down-regulating murine c1q protein levels with linkage to lupus nephritis.J Immunol. 2002 Aug 1;169(3):1334-9. doi: 10.4049/jimmunol.169.3.1334.
• [4] Recombinant human complement component C2 produced in a human cell line restores the classical complement pathway activity in-vitro: an alternative treatment for C2 deficiency diseases.BMC Immunol. 2010 Aug 20;11:43. doi: 10.1186/1471-2172-11-43.
• [5] Homozygous deficiency of C3 in a patient with repeated infections.Lancet. 1972 Dec 2;2(7788):1179-81. doi: 10.1016/s0140-6736(72)92598-6.
• [6] A complement C5 gene mutation, c.754G>A:p.A252T, is common in the Western Cape, South Africa and found to be homozygous in seven percent of Black African meningococcal disease cases.Mol Immunol. 2015 Mar;64(1):170-6. doi: 10.1016/j.molimm.2014.11.010. Epub 2014 Dec 19.
• [7] Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood. 2006 Aug 15;108(4):1267-79. doi: 10.1182/blood-2005-10-007252. Epub 2006 Apr 18.
• [8] CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med. 2017 Jul 6;377(1):52-61. doi: 10.1056/NEJMoa1615887. Epub 2017 Jun 28.
• [9] Early-onset chronic axonal neuropathy, strokes, and hemolysis: inherited CD59 deficiency.Neurology. 2015 Mar 24;84(12):1220-4. doi: 10.1212/WNL.0000000000001391. Epub 2015 Feb 25.
• [10] A type III complement factor D deficiency: Structural insights for inhibition of the alternative pathway.J Allergy Clin Immunol. 2018 Jul;142(1):311-314.e6. doi: 10.1016/j.jaci.2018.01.048. Epub 2018 Mar 6.
• [11] Characterization of a factor H mutation that perturbs the alternative pathway of complement in a family with membranoproliferative GN.J Am Soc Nephrol. 2014 Nov;25(11):2425-33. doi: 10.1681/ASN.2013070732. Epub 2014 Apr 10.
• [12] Partial properdin deficiency.J Lab Clin Med. 1980 Oct;96(4):633-9.
• [13] Interpretation of Serological Complement Biomarkers in Disease.Front Immunol. 2018 Oct 24;9:2237. doi: 10.3389/fimmu.2018.02237. eCollection 2018.
• [14] Primary Ficolin-3 deficiency--Is it associated with increased susceptibility to infections?.Immunobiology. 2015 Jun;220(6):711-3. doi: 10.1016/j.imbio.2015.01.003. Epub 2015 Jan 19.
• [15] The Kuwait National Primary Immunodeficiency Registry 2004-2018.Front Immunol. 2019 Jul 24;10:1754. doi: 10.3389/fimmu.2019.01754. eCollection 2019.
• [16] Circulating complement factor H-related proteins 1and 5 correlate with disease activity in IgA nephropathy.Kidney Int. 2017 Oct;92(4):942-952. doi: 10.1016/j.kint.2017.03.043. Epub 2017 Jun 30.
• [17] C1q: A fresh look upon an old molecule.Mol Immunol. 2017 Sep;89:73-83. doi: 10.1016/j.molimm.2017.05.025. Epub 2017 Jun 7.
• [18] Homozygous hereditary C1q deficiency and systemic lupus erythematosus. A new family and the molecular basis of C1q deficiency in three families.Arthritis Rheum. 1996 Apr;39(4):663-70. doi: 10.1002/art.1780390419.
• [19] Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease. Arthritis Rheumatol. 2017 Sep;69(9):1832-1839. doi: 10.1002/art.40158. Epub 2017 Jul 10.
• [20] Complement-4 deficiency in a child with systemic lupus erythematosus presenting with standard treatment-resistant severe skin lesion.ISRN Rheumatol. 2011;2011:917673. doi: 10.5402/2011/917673. Epub 2011 Feb 10.
• [21] Restricted genetic defects underlie human complement C6 deficiency.Clin Exp Immunol. 2003 Apr;132(1):87-91. doi: 10.1046/j.1365-2249.2003.02099.x.
• [22] Complement component C7 deficiency in two Spanish families. Immunology. 2004 Dec;113(4):518-23. doi: 10.1111/j.1365-2567.2004.01997.x.
• [23] Genetic basis of human complement C8 alpha-gamma deficiency.J Immunol. 1998 Oct 1;161(7):3762-6.
• [24] A novel mutation in a patient with a deficiency of the eighth component of complement associated with recurrent meningococcal meningitis. J Clin Immunol. 2009 Sep;29(5):691-5. doi: 10.1007/s10875-009-9295-7. Epub 2009 May 12.
• [25] Molecular epidemiology of C9 deficiency heterozygotes with an Arg95Stop mutation of the C9 gene in Japan.J Hum Genet. 1999;44(2):109-11. doi: 10.1007/s100380050119.