Calcium-dependent lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:11907111, PubMed:15804047, PubMed:17215869, PubMed:26133042). Specifically recognizes and binds carbohydrates on the pathogen surface, activating the MASP1 serine protease and initiating the proteolytic cascade of the lectin co

SecretedCell surface

Ficolin 3 deficiency

A disorder characterized by immunodeficiency, recurrent infections, brain abscesses and recurrent warts on the fingers. Affected individuals have normal levels of lymphocytes, normal T-cell responses, and normal antibodies, but a selective deficient antibody response to pneumococcal polysaccharide vaccine.

Calcium-dependent lectin, which acts as a pattern recognition receptor that initiates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:14515269, PubMed:22966085, PubMed:7634089, PubMed:9087411). Specifically recognizes and binds the mannose moiety of carbohydrates on the pathogen surface, activating the MASP1 serine protease and initiating the proteolytic casc

SecretedCell surface

Precursor of the catalytic component of the C3 and C5 convertase complexes of the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:3638964, PubMed:624565, PubMed:6554279, PubMed:6919543, PubMed:9748277). The alternative complement pathway acts as an amplification loop that enhances other complement pathways (classical, lectin and GZMK) by promoting formation

SecretedCell surface

Macular degeneration, age-related, 14

A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.

Glycoprotein that plays an essential role in maintaining a well-balanced immune response by modulating complement activation. Acts as a soluble inhibitor of complement, where its binding to self markers such as glycan structures prevents complement activation and amplification on cell surfaces (PubMed:21285368, PubMed:21317894, PubMed:25402769). Accelerates the decay of the complement alternative pathway (AP) C3 convertase C3bBb, thus preventing local formation of more C3b, the central player of

Secreted

Basal laminar drusen

Drusen are extracellular deposits that accumulate below the retinal pigment epithelium on Bruch membrane. Basal laminar drusen refers to an early adult-onset drusen phenotype that shows a pattern of uniform small, slightly raised yellow subretinal nodules randomly scattered in the macula. In later stages, these drusen often become more numerous, with clustered groups of drusen scattered throughout the retina. In time these small basal laminar drusen may expand and ultimately lead to a serous pigment epithelial detachment of the macula that may result in vision loss.

Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:26841837, PubMed:27052168, PubMed:30552328). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:30552328, PubMed:39914456, PubMed:39814882). The complement pathwa

SecretedTarget cell membrane

Membrane-bound diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:15544348, PubMed:19744926, PubMed:21477596, PubMed:22108654, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (PubMed:15544348, PubMed:8626589). Also plays an

MembraneCytoplasm

Nephrotic syndrome 7

A form of nephrotic syndrome, a renal disease clinically characterized by severe proteinuria, resulting in complications such as hypoalbuminemia, hyperlipidemia and edema. NPHS7 is an autosomal recessive form characterized by onset of proteinuria usually in the first decade of life. The disorder is progressive, and some patients develop end-stage renal disease within several years. Renal biopsy typically shows membranoproliferative glomerulonephritis.

Serine protease component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:17996945, PubMed:19473974, PubMed:29449492). C1R catalyzes the first enzymatic step in the classical complement pathway: it is activated by the C1Q subcomplex of the C1 complex, which associates with IgG or IgM immun

SecretedCell surface

Ehlers-Danlos syndrome, periodontal type, 1

A form of Ehlers-Danlos syndrome, a connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. EDSPD1 is characterized by the association of typical features of Ehlers-Danlos syndrome with gingival recession and severe early-onset periodontal disease, leading to premature loss of permanent teeth. EDSPD1 inheritance is autosomal dominant.

Acts as a cofactor for complement factor I, a serine protease which protects autologous cells against complement-mediated injury by cleaving C3b and C4b deposited on host tissue. May be involved in the fusion of the spermatozoa with the oocyte during fertilization. Also acts as a costimulatory factor for T-cells which induces the differentiation of CD4+ into T-regulatory 1 cells. T-regulatory 1 cells suppress immune responses by secreting interleukin-10, and therefore are thought to prevent auto

Cytoplasmic vesicle, secretory vesicle, acrosome inner membrane

Hemolytic uremic syndrome, atypical, 2

An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.

Endothelial cell receptor that plays a critical role in regulating several physiological processes including hemostasis, coagulation, fibrinolysis, inflammation, and angiogenesis (PubMed:10761923). Acts as a cofactor for thrombin activation of protein C/PROC on the surface of vascular endothelial cells leading to initiation of the activated protein C anticoagulant pathway (PubMed:29323190, PubMed:33836597, PubMed:9395524). Also accelerates the activation of the plasma carboxypeptidase B2/CPB2, w

Membrane

Thrombophilia due to thrombomodulin defect

A hemostatic disorder characterized by a tendency to thrombosis.

Pore-forming component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22832194, PubMed:26841837, PubMed:26841934, PubMed:27052168, PubMed:30552328, PubMed:6177822, PubMed:9212048, PubMed:9634479). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK

SecretedTarget cell membrane

Complement component 9 deficiency

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections predominantly by Neisseria gonorrhoeae or Neisseria meningitidis. Some patients may develop dermatomyositis.

Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22267737, PubMed:22832194, PubMed:26841837, PubMed:27052168, PubMed:30552328). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:30552328, PubMed:39914456, PubMe

SecretedTarget cell membrane

Complement component 6 deficiency

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12847249, PubMed:19006321, PubMed:24626930, PubMed:29449492, PubMed:3258649, PubMed:34155115, PubMed:6249812, PubMed:6776418). The classical complement pathway is initiated by the C1Q subcomplex of the C1 complex, which specifi

SecretedCell surface

C1q deficiency 3

An autosomal recessive disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease characterized by recurrent skin lesions, chronic infections, an increased risk of systemic lupus erythematosus, and glomerulonephritis.

Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22832194, PubMed:26841837, PubMed:27052168, PubMed:30552328, PubMed:7440581). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:30552328, PubMed:39914456, PubMed

SecretedTarget cell membrane

Complement component 8 deficiency, 2

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Trypsin-like serine protease that plays an essential role in regulating the immune response by controlling all complement pathways. Inhibits these pathways by cleaving three peptide bonds in the alpha-chain of C3b and two bonds in the alpha-chain of C4b thereby inactivating these proteins (PubMed:17320177, PubMed:7360115). Essential cofactors for these reactions include factor H and C4BP in the fluid phase and membrane cofactor protein/CD46 and CR1 on cell surfaces (PubMed:12055245, PubMed:21418

Secreted, extracellular spaceSecreted

Hemolytic uremic syndrome, atypical, 3

An atypical form of hemolytic uremic syndrome. It is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.

Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12847249, PubMed:19006321, PubMed:24626930, PubMed:29449492, PubMed:3258649, PubMed:34155115, PubMed:6249812, PubMed:6776418). The classical complement pathway is initiated by the C1Q subcomplex of the C1 complex, which specifi

SecretedCell surface

C1q deficiency 1

An autosomal recessive disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease characterized by recurrent skin lesions, chronic infections, an increased risk of systemic lupus erythematosus, and glomerulonephritis.

Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:17872444, PubMed:22832194, PubMed:26841837, PubMed:27052168, PubMed:30552328, PubMed:7440581). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:17872444, PubMed

SecretedTarget cell membrane

Complement component 8 deficiency, 1

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system Non-enzymatic component of C3 and C5 convertases (PubMed:8538770). Generated following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway), it covalently attaches to the surface of pathogens, where it acts as an opson

SecretedSynapseCell projection, axonCell projection, dendriteCell surface

Complement component 4A deficiency

A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.

Component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:11445589, PubMed:16169853, PubMed:417728, PubMed:467643, PubMed:6271784, PubMed:6282646, PubMed:6319179, PubMed:70787, PubMed:9422791). C1S is activated following association of the C1 complex with immunoglobulins (IgG or IgM) compl

SecretedCell surface

Complement component C1s deficiency

A rare defect resulting in C1 deficiency and impaired activation of the complement classical pathway. C1 deficiency generally leads to severe immune complex disease with features of systemic lupus erythematosus and glomerulonephritis.

Serine protease that initiates the alternative pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:21205667, PubMed:22362762, PubMed:6769474, PubMed:874324, PubMed:9748277). In contrast to other complement pathways (classical, lectin and GZMK) that are directly activated by pathogens or antigen-antibody complexes, the alternative complement pathway is initiated by the spont

Secreted

Complement factor D deficiency

An immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway.

Serine protease inhibitor, which acrs as a regulator of the classical complement pathway (PubMed:10946292, PubMed:11527969, PubMed:3458172, PubMed:6416294). Forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases (PubMed:10946292, PubMed:3458172, PubMed:6416294). May also regulate blood coagulation, fibrinolysis and the generation of kinins (PubMed:8495195). Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein (PubMed:8495195)

Secreted

Angioedema, hereditary, 1

An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional.

Component of the membrane attack complex (MAC), a multiprotein complex activated by the complement cascade, which inserts into a target cell membrane and forms a pore, leading to target cell membrane rupture and cell lysis (PubMed:22832194, PubMed:26841837, PubMed:27052168, PubMed:30552328, PubMed:3335508). The MAC is initiated by proteolytic cleavage of C5 into complement C5b in response to the classical, alternative, lectin and GZMK complement pathways (PubMed:22832194, PubMed:30552328, PubMed

SecretedTarget cell membrane

Complement component 7 deficiency

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Precursor of non-enzymatic components of the classical, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system Non-enzymatic component of C3 and C5 convertases (By similarity). Generated following cleavage by complement proteases (C1S, MASP2 or GZMK, depending on the complement pathway), it covalently attaches to the surface of pathogens, where it acts as an opsoni

SecretedSynapseCell projection, axonCell projection, dendriteCell surface

Systemic lupus erythematosus

A chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. It is of unknown etiology, but is thought to represent a failure of the regulatory mechanisms of the autoimmune system. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow.

Core component of the complement C1 complex, a multiprotein complex that initiates the classical pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12847249, PubMed:19006321, PubMed:24626930, PubMed:29449492, PubMed:3258649, PubMed:34155115, PubMed:6249812, PubMed:6776418). The classical complement pathway is initiated by the C1Q subcomplex of the C1 complex, which specifi

SecretedCell surface

C1q deficiency 2

An autosomal recessive disorder caused by impaired activation of the complement classical pathway. It generally leads to severe immune complex disease characterized by recurrent skin lesions, chronic infections, an increased risk of systemic lupus erythematosus, and glomerulonephritis.

Precursor of non-enzymatic components of the classical, alternative, lectin and GZMK complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system Non-enzymatic component of C5 convertase (PubMed:28264884, PubMed:31507604, PubMed:3653927, PubMed:3897448). Generated following cleavage by C3 convertase, it covalently attaches to the surface of pathogens, where it acts as an opsonin that ma

SecretedCell surface

Complement component 3 deficiency

A rare defect of the complement classical pathway. Patients develop recurrent, severe, pyogenic infections because of ineffective opsonization of pathogens. Some patients may also develop autoimmune disorders, such as arthralgia and vasculitic rashes, lupus-like syndrome and membranoproliferative glomerulonephritis.

Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12878586, PubMed:18204047, PubMed:30643019, PubMed:6554279). Activated downstream of classical, alternative, lectin and GZMK complement pathways (PubMed:12878586, PubMed:18204047, PubMed:30643019, PubMed:39914456, PubMed:39814882, PubMed:6554279) C

SecretedTarget cell membrane

Complement component 5 deficiency

A rare defect of the complement classical pathway associated with susceptibility to severe recurrent infections, predominantly by Neisseria gonorrhoeae or Neisseria meningitidis.

Precursor of the catalytic component of the C3 and C5 convertase complexes, which are part of the complement pathway, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:12878586, PubMed:17027507, PubMed:18204047, PubMed:39914456, PubMed:39814882). Component C2 is part of the classical, lectin and GZMK complement systems (PubMed:12878586, PubMed:17027507, PubMed:18204047, PubMed:22691502, PubMed:39914456) C

SecretedCell surface

Macular degeneration, age-related, 14

A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane.

Precursor of a serum protease that activates the lectin pathway of the complement system, a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune system (PubMed:11527969, PubMed:22691502). The lectin complement system is activated following association of lectins, such as MBL2, FCN1, FCN2 or FCN3, to carbohydrates on the pathogen surface (PubMed:22691502, PubMed:22966085). MASP2 is cleaved and activated by MASP1 in response t

SecretedCell surface

MASP2 deficiency

A disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.