CFP

Summary

CFP (complement factor properdin, HGNC:8864) is a protein-coding gene on chromosome Xp11.23, encoding Properdin (P27918). A positive regulator of the alternate pathway (AP) of complement.

This gene encodes a plasma glycoprotein that positively regulates the alternative complement pathway of the innate immune system. This protein binds to many microbial surfaces and apoptotic cells and stabilizes the C3- and C5-convertase enzyme complexes in a feedback loop that ultimately leads to formation of the membrane attack complex and lysis of the target cell. Mutations in this gene result in two forms of properdin deficiency, which results in high susceptibility to meningococcal infections. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 5199 — RefSeq curated summary.

At a glance

• Gene–disease (curated): properdin deficiency, X-linked (Strong, GenCC)
• Clinical variants (ClinVar): 284 total — 7 pathogenic, 3 likely-pathogenic
• GTEx eGene: eQTL in 9 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 3
• MANE Select transcript: NM_001145252

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8864
Approved symbol	CFP
Name	complement factor properdin
Location	Xp11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000126759
Ensembl biotype	protein_coding
OMIM	300383
Entrez	5199

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 3 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000396992

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 4: 1, TSL 5: 3

ENST00000396992, ENST00000247153, ENST00000377005, ENST00000469388, ENST00000478222, ENST00000480317, ENST00000485991, ENST00000640573, ENST00000862734, ENST00000862735, ENST00000862736, ENST00000952425, ENST00001004728, ENST00001004733, ENST00001004734, ENST00001128771, ENST00001134965

RefSeq mRNA: 2 — MANE Select: NM_001145252 NM_001145252, NM_002621

CCDS: CCDS14282

Canonical transcript exons

ENST00000396992 — 9 exons

Exon	Start	End
ENSE00003460513	47626328	47626519
ENSE00003533834	47627141	47627332
ENSE00003563390	47627471	47627641
ENSE00003581396	47626773	47626946
ENSE00003621287	47629524	47629674
ENSE00003651877	47628102	47628277
ENSE00003688066	47626058	47626169
ENSE00003899736	47629769	47629930
ENSE00003903381	47623282	47624440

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 99.34.

FANTOM5 (CAGE): breadth broad, TPM avg 11.7414 / max 685.0209, expressed in 396 samples.

Highest expression (Bgee): granulocyte, monocyte, leukocyte, blood, spleen.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CFP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 9 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

12 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	sqtl	3.1e-08	+0.23	X:47628517:T:A
Whole Blood	eqtl	6.7e-08	+0.08	X:47628517:T:A
Brain Substantia nigra	eqtl	1.8e-02	+3.52	X:46695789:C:T
Breast Mammary Tissue	eqtl	1.8e-02	+0.28	X:47181235:T:C
Colon Sigmoid	sqtl	1.9e-02	-1.53	X:47271174:G:A
Vagina	eqtl	2.2e-02	+3.05	X:47552752:G:A
Cells Cultured fibroblasts	eqtl	2.2e-02	-0.59	X:47406476:C:A
Cells EBV-transformed lymphocytes	eqtl	2.4e-02	+0.43	X:47842281:G:A
Colon Transverse	eqtl	2.5e-02	-0.47	X:48567134:G:A
Brain Cerebellum	eqtl	3.8e-02	+0.34	X:47513933:C:G
Brain Putamen basal ganglia	eqtl	4.5e-02	+0.96	X:46753602:A:G
Minor Salivary Gland	sqtl	4.7e-02	-1.82	X:47280858:C:G

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
199134	11.7414	396

Top tissues by expression

showing 100 of 138 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.34	gold quality
monocyte	CL:0000576	99.27	gold quality
leukocyte	CL:0000738	99.27	gold quality
blood	UBERON:0000178	98.73	gold quality
spleen	UBERON:0002106	97.59	gold quality
bone element	UBERON:0001474	96.89	gold quality
bone marrow	UBERON:0002371	96.89	gold quality
bone marrow cell	CL:0002092	95.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.73	gold quality
vermiform appendix	UBERON:0001154	94.01	gold quality
lymph node	UBERON:0000029	88.82	gold quality
right lung	UBERON:0002167	88.64	gold quality
liver	UBERON:0002107	87.61	gold quality
right lobe of liver	UBERON:0001114	85.30	gold quality
upper lobe of left lung	UBERON:0008952	84.18	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.32	gold quality
lung	UBERON:0002048	81.04	gold quality
gall bladder	UBERON:0002110	79.30	gold quality
mucosa of stomach	UBERON:0001199	78.80	gold quality
omental fat pad	UBERON:0010414	78.80	gold quality
left uterine tube	UBERON:0001303	78.70	gold quality
adipose tissue	UBERON:0001013	77.90	gold quality
subcutaneous adipose tissue	UBERON:0002190	76.92	gold quality
mucosa of transverse colon	UBERON:0004991	76.04	gold quality
right coronary artery	UBERON:0001625	75.85	gold quality
right atrium auricular region	UBERON:0006631	75.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.96	gold quality
small intestine	UBERON:0002108	74.69	gold quality
smooth muscle tissue	UBERON:0001135	74.09	gold quality
cerebellum	UBERON:0002037	73.91	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.88	gold quality
cerebellar cortex	UBERON:0002129	73.85	gold quality
cerebellar hemisphere	UBERON:0002245	73.78	gold quality
duodenum	UBERON:0002114	73.75	gold quality
left coronary artery	UBERON:0001626	73.74	gold quality
left adrenal gland cortex	UBERON:0035825	73.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	73.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.39	gold quality
left adrenal gland	UBERON:0001234	73.06	gold quality
urinary bladder	UBERON:0001255	72.48	gold quality
right adrenal gland cortex	UBERON:0035827	72.10	gold quality
intestine	UBERON:0000160	71.84	gold quality
adrenal gland	UBERON:0002369	71.80	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	71.69	gold quality
placenta	UBERON:0001987	71.66	gold quality
right adrenal gland	UBERON:0001233	71.57	gold quality
rectum	UBERON:0001052	71.52	gold quality
heart	UBERON:0000948	71.46	gold quality
colon	UBERON:0001155	71.30	gold quality
transverse colon	UBERON:0001157	71.19	gold quality
material anatomical entity	UBERON:0000465	71.05	gold quality
multicellular organism	UBERON:0000468	71.05	gold quality
anatomical system	UBERON:0000467	71.00	gold quality
tonsil	UBERON:0002372	70.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	70.72	gold quality
lower esophagus muscularis layer	UBERON:0035833	70.71	gold quality
lower esophagus	UBERON:0013473	70.66	gold quality
fallopian tube	UBERON:0003889	70.50	gold quality
nucleus accumbens	UBERON:0001882	70.16	gold quality
putamen	UBERON:0001874	69.99	gold quality
descending thoracic aorta	UBERON:0002345	69.98	gold quality
heart left ventricle	UBERON:0002084	69.73	gold quality
skin of leg	UBERON:0001511	69.30	gold quality
amygdala	UBERON:0001876	69.07	gold quality
esophagus	UBERON:0001043	69.02	gold quality
thoracic aorta	UBERON:0001515	68.99	gold quality
temporal lobe	UBERON:0001871	68.94	gold quality
caudate nucleus	UBERON:0001873	68.93	gold quality
ascending aorta	UBERON:0001496	68.89	gold quality
zone of skin	UBERON:0000014	68.80	gold quality
thoracic mammary gland	UBERON:0005200	68.74	gold quality
apex of heart	UBERON:0002098	68.64	gold quality
muscle tissue	UBERON:0002385	68.63	gold quality
right frontal lobe	UBERON:0002810	68.62	gold quality
Ammon’s horn	UBERON:0001954	68.53	gold quality
anterior cingulate cortex	UBERON:0009835	68.50	gold quality
fundus of stomach	UBERON:0001160	68.38	gold quality
skin of abdomen	UBERON:0001416	68.27	gold quality
primary visual cortex	UBERON:0002436	68.23	gold quality
brain	UBERON:0000955	67.73	gold quality
right ovary	UBERON:0002118	67.53	gold quality
saliva-secreting gland	UBERON:0001044	67.51	gold quality
myometrium	UBERON:0001296	67.41	gold quality
body of stomach	UBERON:0001161	67.35	gold quality
esophagus mucosa	UBERON:0002469	67.32	gold quality
minor salivary gland	UBERON:0001830	67.24	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.77	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.72	gold quality
adenohypophysis	UBERON:0002196	66.70	gold quality
hypothalamus	UBERON:0001898	66.68	gold quality
pituitary gland	UBERON:0000007	66.62	gold quality
aorta	UBERON:0000947	66.46	gold quality
right lobe of thyroid gland	UBERON:0001119	66.30	gold quality
cerebral cortex	UBERON:0000956	66.20	gold quality
stomach	UBERON:0000945	66.12	gold quality
tibial nerve	UBERON:0001323	65.76	gold quality
colonic epithelium	UBERON:0000397	65.66	silver quality
muscle of leg	UBERON:0001383	65.41	gold quality
gastrocnemius	UBERON:0001388	65.27	gold quality
skeletal muscle tissue	UBERON:0001134	65.19	gold quality

Single-cell (SCXA)

Detected in 17 experiment(s), a significant marker in 16.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	714.79
E-HCAD-4	yes	178.79
E-CURD-122	yes	70.64
E-HCAD-1	yes	68.70
E-MTAB-6701	yes	39.36
E-HCAD-10	yes	34.95
E-MTAB-9221	yes	29.82
E-CURD-112	yes	29.42
E-MTAB-9467	yes	28.67
E-MTAB-10553	yes	24.95
E-HCAD-9	yes	15.66
E-CURD-88	yes	15.13
E-MTAB-9067	yes	14.50
E-MTAB-8410	yes	13.61
E-MTAB-9801	yes	7.14

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Bone marrow	tissue	79.3
Spleen	tissue	49.2
Appendix	tissue	19.4
Liver	tissue	11.2
Lymph node	tissue	11.0
Adipose tissue	tissue	5.6
Lung	tissue	5.0
Smooth muscle	tissue	4.9
Thymus	tissue	4.8
Urinary bladder	tissue	4.6
Tonsil	tissue	4.1
Small intestine	tissue	2.8
Cerebellum	tissue	2.3
Frontal cortex	tissue	2.2
Gallbladder	tissue	2.0
Adrenal gland	tissue	1.8
Esophagus	tissue	1.5
Colon	tissue	1.5
Olfactory bulb	tissue	1.5
Caudate putamen	tissue	1.3
Breast	tissue	1.2
Nucleus accumbens	tissue	1.2
Choroid plexus	tissue	1.2
Duodenum	tissue	1.2
Heart muscle	tissue	1.1
Cerebral cortex	tissue	1.1
Insular cortex	tissue	1.1
Skin 1	tissue	1.0
Stomach 1	tissue	1.0
Spinal cord	tissue	1.0
Hippocampus	tissue	1.0
Rectum	tissue	0.9
Skeletal muscle	tissue	0.9
Basal ganglia	tissue	0.9
Putamen	tissue	0.9
Hippocampal formation	tissue	0.9
Postcentral gyrus	tissue	0.9
Entorhinal cortex	tissue	0.9
Retrosplenial and cingulate cortex	tissue	0.9
Somatosensory cortex	tissue	0.9
Temporal cortex	tissue	0.9
Occipital cortex	tissue	0.9
Prefrontal cortex	tissue	0.8
Pancreas	tissue	0.8
Motor cortex	tissue	0.8
Amygdala	tissue	0.8
Hypothalamus	tissue	0.8
Placenta	tissue	0.8
Ventral forebrain	tissue	0.8
Retrosplenial cortex	tissue	0.8
Pituitary gland	tissue	0.7
Tongue	tissue	0.7
Periaqueductal gray	tissue	0.7
Septum	tissue	0.7
Vagina	tissue	0.6
Midbrain	tissue	0.6
Medulla oblongata	tissue	0.6
Superior colliculi	tissue	0.6
Substantia nigra	tissue	0.6
Locus coeruleus	tissue	0.6

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Blood vessel (2.2), Area parastriata, superior (2.1), Hippocampus, CA3 (1.6), Nucleus basalis of Meynert (1.6), Corticomedial amygdala (1.4).

Regulation

Is transcription factor: no

Functional genomics

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000396992 — one region, missense o/e 0.79.

Literature-anchored findings (GeneRIF, showing 35)

• A splice site mutation in exon 10 (c.1487-2A>G) was found in the properdin gene and co segregated with biochemically measured properdin deficiency. (PMID:16337490)
• study reports properdin binds predominantly to late apoptotic & necrotic cells but not to early apoptotic cells; binding occurs independently of C3b (PMID:18490764)
• The human complement protein properdin binds to early apoptotic T cells and initiates complement activation, leading to C3b opsonization and ingestion by phagocytic cells. (PMID:18579773)
• The contribution of properdin is pivotal in proteinuria-induced tubular complement activation and subsequent damage. Interference with properdin binding to tubular cells may provide an option for the treatment of proteinuric renal disease. (PMID:18753294)
• Properdin induces the formation of platelet-leukocyte aggregates via leukocyte activation, linking the complement system & platelet-leukocyte aggregates with potential significance in atherosclerotic vascular disease. (PMID:18791942)
• Significantly more transcripts encoding alternative pathway components factor B, C3 and properdin, and C3a receptor and C5a receptor were detected in grade 3 versus grade 0 or 1 biopsies of human cardiac allografts. (PMID:19005416)
• Factor P was expressed in 50% of choroidal neovascular membranes of patients with age-related macular degeneration(AMD). Additional studies need to investigate role of Factor P in development of AMD for potential therapeutic intervention. (PMID:19584655)
• Properdin presence is associated with increased SC5b-9 excretion and worse renal function. (PMID:19934084)
• CFP does not seem to confer any risk for age-related macular degeneration. (PMID:20122735)
• levels of properdin are not associated with childhood wheezing and atopy (PMID:20337960)
• Human properdin can selectively recognize surfaces and enhance or promote alternative pathway of complement activation. (PMID:20382442)
• The conventional mechanism of properdin function is to bind to and stabilize alternative pathway C3 convertases on the surface of Neisseria meningitidis and N. gonorrhoeae. (PMID:20530262)
• tubular HS as a novel docking platform for alternative pathway activation via properdin, which might play a role in proteinuric renal damage. (PMID:21135110)
• report a large Finnish family with a novel mutation in the properdin gene. The mutation is located in exon 9 and changes guanine to adenine at nucleotide 1164 (c.1164G>A) that causes tryptophan to change to a premature stop codon (W388X). (PMID:22229731)
• Properdin and SC5b-9 may be novel biomarkers for future risk of type 2 diabetes in this high-risk population and warrant further investigation. (PMID:22338105)
• Immune human serum that contained bactericidal Abs directed against the 2C7 lipooligosaccharide epitope required functional properdin to kill C4BP-binding strains, but not C4BP-nonbinding strains. (PMID:22368277)
• Factor h and properdin recognize different epitopes on renal tubular epithelial heparan sulfate. (PMID:22815489)
• Properdin released from human polymorphonuclear cells does not bind to zymosan or E. coli, but when incubated in properdin-depleted serum this form of properdin binds efficiently to both substrates in a strictly complement C3-dependent manner. (PMID:22851705)
• Our data show that physiological forms of human properdin bind directly to human platelets after activation by strong agonists in the absence of C3 (PMID:23677468)
• can directly interact with neutrophil myeloperoxidase resulting in activation of alternative pathway of complement (PMID:24355864)
• In the pathogenesis of renal tubular damage, P can directly bind to PTECs and may accelerate AP activation by surpassing fH regulation (PMID:24885016)
• P serum level expression could be a reliable clinical biomarker to identify patients with underlying surface alternative pathway C5 convertase dysregulation. (PMID:26660535)
• data indicate that properdin enhances platelet/granulocyte aggregates (PGAs) formation via increased production of C5a, and that inhibition of properdin function has therapeutic potential to limit thromboinflammation in diseases characterized by increased PGA formation (PMID:27183616)
• In conclusion, we challenge the view of properdin as a pattern recognition molecule by providing evidence that it binds to different exogenous and endogenous molecular patterns in only a C3-dependent manner. (PMID:28069958)
• this study shows that RNA interference of properdin in dendritic cells decreased alloantigen-specific T-cell proliferation (PMID:28105653)
• studies demonstrate an essential role of properdin oligomerization in vivo while our monomers enable detailed structural insight paving the way for novel modulators of complement. (PMID:28264884)
• Study identified 2 single nucleotide polymorphisms, 1 in the mannose-binding lectin 2 gene (p.Gly54Asp-MBL2) and 1 in the complement factor properdin gene (p.Asn428(p=)-CFP), that showed significant association with the absence and development of antibody-mediated cardiac allograft rejection, respectively. (PMID:28784323)
• Compound heterozygous mutations in IL10RA combined with a complement factor properdin mutation in infantile-onset inflammatory bowel disease. (PMID:30199474)
• TES-mediated upregulation of the transcription factor DDIT3 is involved in CFP suppression of breast cancer cell growth (PMID:30755730)
• Properdin Is a Key Player in Lysis of Red Blood Cells and Complement Activation on Endothelial Cells in Hemolytic Anemias Caused by Complement Dysregulation. (PMID:32793201)
• Soluble collectin-12 mediates C3-independent docking of properdin that activates the alternative pathway of complement. (PMID:32909942)
• The Role of Properdin in Killing of Non-Pathogenic Leptospira biflexa. (PMID:33240263)
• Properdin Is a Modulator of Tumour Immunity in a Syngeneic Mouse Melanoma Model. (PMID:33494138)
• Structure and function of a family of tick-derived complement inhibitors targeting properdin. (PMID:35031611)
• Properdin produced by dendritic cells contributes to the activation of T cells. (PMID:35843030)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch73-237c6.1	ENSDARG00000078114
danio_rerio	cfp	ENSDARG00000094451
mus_musculus	Cfp	ENSMUSG00000001128
rattus_norvegicus	Cfp	ENSRNOG00000025811
caenorhabditis_elegans		WBGENE00016468

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97545) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
impaired complement alternative pathway	2
abnormal cardiovascular system physiology	1
abnormal complement pathway	1
impaired complement classical pathway	1
decreased susceptibility to induced arthritis	1
sepsis	1
decreased susceptibility to injury	1
increased susceptibility to induced morbidity/mortality	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q9GLX9	97.5%	Diamond
Xenopus laevis	C5IAW9	96.9%	Diamond
Pongo abelii	Q5RBP8	95.9%	Diamond
Gallus gallus	Q7T2Z5	92.9%	Diamond
Oryctolagus cuniculus	P98137	83.2%	Diamond
Cavia porcellus	Q64181	73.9%	Diamond
Acropora millepora	B3EWZ3	58.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ELK1	protein-coding	2002
UXT	protein-coding	8409
ARAF	protein-coding	369
SYN1	protein-coding	6853
TIMP1	protein-coding	7076
UXT-AS1	ncRNA	100133957
MIR4769	ncRNA	100616147

Protein

Protein identifiers

Properdin — P27918 (reviewed: P27918)

Alternative names: Complement factor P

All UniProt accessions (4): A0A0S2Z4I5, C9J7V5, E9PAQ1, P27918

UniProt curated annotations — full annotation on UniProt →

Function. A positive regulator of the alternate pathway (AP) of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes. Inhibits CFI-CFH mediated degradation of Complement C3 beta chain (C3b).

Subunit / interactions. In plasma, properdin exists as dimers, trimers or tetramers in the relative proportions of 26:54:20. Interacts with the pro-C3-convertase enzyme complex (C3b-Bb) comprised of Complement C3 beta chain (C3b) and the Complement factor B Bb fragment (Bb), where it binds (via its TSP type-1 5 domain) with C3b and Bb. This interaction stabilizes the complex and allows it to become the active C3-convertase enzyme complex (C3b-Bb-FP). Interacts with C3b. Interacts with CFB.

Subcellular location. Secreted.

Disease relevance. Properdin deficiency (PFD) [MIM:312060] Results in higher susceptibility to bacterial infections; especially to meningococcal infections. Three phenotypes have been reported: complete deficiency (type I), incomplete deficiency (type II), and dysfunction of properdin (type III). The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. TSP type-1 domain 0 binds to TSP type-1 domain 4, and TSP type-1 domain 1 binds to TSP type-1 domain 6. These interactions mediate multimerization.

RefSeq proteins (2): NP_001138724, NP_002612 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000884	TSP1_rpt	Repeat
IPR036383	TSP1_rpt_sf	Homologous_superfamily
IPR049536	CFP_TSR-0	Repeat
IPR052065	Properdin-like	Family
IPR054019	CFP_TSR_C	Repeat

Pfam: PF00090, PF18487, PF22195

UniProt features (122 total): strand 31, disulfide bond 22, glycosylation site 20, helix 15, mutagenesis site 11, sequence variant 10, domain 7, region of interest 2, turn 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

14 structures by resolution:

PDB	Title	Method	Resolution (Å)
1W0R	Solution structure of dimeric form of properdin by X-ray solution scattering and …	SOLUTION SCATTERING	0
1W0S	Solution structure of trimeric form of properdin by X-ray solution scattering and …	SOLUTION SCATTERING	0
8Q6R	Structure of complement FP in complex with the TPP-3077 VHH	X-RAY DIFFRACTION	1.9
6S08	Crystal Structure of Properdin (TSR domains N1 & 456)	X-RAY DIFFRACTION	2.03
6S0B	Crystal Structure of Properdin in complex with the CTC domain of C3/C3b	X-RAY DIFFRACTION	2.31
6S0A	Crystal Structure of Properdin (TSR domains N12 & 456)	X-RAY DIFFRACTION	2.52
9U62	AP pathways C3 convertase C3bBbP and C3 complex	ELECTRON MICROSCOPY	2.7
6RUS	Structure of a functional properdin monomer	X-RAY DIFFRACTION	2.8
7B26	CirpA1 in complex with pseudo-monomeric Properdin lacking TSR2-3	X-RAY DIFFRACTION	3.4
6SEJ	Structure of a functional monomeric properdin lacking TSR3	X-RAY DIFFRACTION	3.5
6RV6	Structure of properdin lacking TSR3 based on anomalous data	X-RAY DIFFRACTION	3.51
7NOZ	Structure of the nanobody stablized properdin bound alternative pathway proconvertase …	X-RAY DIFFRACTION	3.9
6RUR	Structure of the SCIN stabilized C3bBb convertase bound to properdin	X-RAY DIFFRACTION	6
6RUV	Structure of the SCIN stabilized C3bBb convertase bound to Properdin and a the …	X-RAY DIFFRACTION	6.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P27918-F1	83.75	0.56

Antibody-complex structures (SAbDab)

4 antibodies co-crystallized with this protein: 6RUV, 7NOZ, 8Q6R, TARPERPRUMIG

Human Protein Atlas

Protein class: Predicted secreted proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles

Antibody reliability (HPA): IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (22)

Type	Positions
Disulfide bond	32–56, 43–72, 57–75, 89–127, 93–133, 104–111, 132–170, 148–184, 152–190, 163–174, 205–248, 209–254, 224–238, 269–306, 273–312, 284–296, 327–370, 337–376, 350–360, 391–455, 395–461, 407–439

Glycosylation sites (20)

Type	Positions
C-linked (man) tryptophan	83, 86, 139, 142, 145, 196, 199, 202, 260, 263, 321, 324, 382, 385, 388
O-linked (fuc…) threonine	92, 151, 272
O-linked (fuc…) serine	208
N-linked (glcnac…) (complex) asparagine	428

Mutagenesis-validated functional residues (11)

Position	Phenotype
47	inhibits oligomerization; when associated with a-58 and a-275.
58	inhibits oligomerization; when associated with a-47 and a-275.
244	inhibits oligomerization.
275	inhibits oligomerization; when associated with a-47 and a-58.
329	significantly decreases complement c3 beta chain binding.
330	slightly decreases complement c3 beta chain binding.
351	decreases complement c3 beta chain binding.
353	significantly decreases complement c3 beta chain binding.
359	significantly decreases complement c3 beta chain binding.
364–365	decreases complement c3 beta chain binding.
456	inhibits oligomerization; when associated with a-47 and a-58.

Function

Pathways and Gene Ontology

Reactome pathways

6 curated (TAS) of 17; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-5083635	Defective B3GALTL causes PpS ⚕	curated
R-HSA-174577	Activation of C3 and C5	curated
R-HSA-173736	Alternative complement activation	curated
R-HSA-6798695	Neutrophil degranulation	curated
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins	curated
R-HSA-977606	Regulation of Complement cascade	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-3906995	Diseases associated with O-glycosylation of proteins ⚕	—
R-HSA-3781865	Diseases of glycosylation ⚕	—
R-HSA-5668914	Diseases of metabolism ⚕	—
R-HSA-166658	Complement cascade	—
R-HSA-168256	Immune System	—
R-HSA-166663	Initial triggering of complement	—
R-HSA-168249	Innate Immune System	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-5173105	O-linked glycosylation	—
R-HSA-597592	Post-translational protein modification	—

MSigDB gene sets: 306 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOCC_SECRETORY_GRANULE, CHUNG_BLISTER_CYTOTOXICITY_DN, MODULE_45, RACCACAR_AML_Q6, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, MODULE_453, MODULE_16, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_IMMUNE_RESPONSE, MODULE_75, GOBP_COMPLEMENT_ACTIVATION

GO Biological Process (10): immune response (GO:0006955), complement activation (GO:0006956), complement activation, alternative pathway (GO:0006957), defense response to bacterium (GO:0042742), positive regulation of complement activation, alternative pathway (GO:0045958), positive regulation of immune response (GO:0050778), protein stabilization (GO:0050821), positive regulation of opsonization (GO:1903028), immune system process (GO:0002376), innate immune response (GO:0045087)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), endoplasmic reticulum lumen (GO:0005788), specific granule lumen (GO:0035580), cytoplasmic side of Golgi membrane (GO:0098548), tertiary granule lumen (GO:1904724), secretory granule (GO:0030141)

Reactome top-level categories

11 top-level categories:

Category	Pathways
Complement cascade	3
Innate Immune System	2
Initial triggering of complement	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Immune System	1
Diseases of metabolism	1
Diseases of glycosylation	1
Post-translational protein modification	1
Disease	1
Metabolism of proteins	1

GO top-level categories

36 GO namespaces:

Category	Terms
immune response	2
intracellular organelle lumen	2
immune system process	1
response to stimulus	1
immune effector process	1
activation of immune response	1
humoral immune response	1
protein activation cascade	1
complement activation	1
innate immune response	1
defense response	1
response to bacterium	1
complement activation, alternative pathway	1
regulation of complement activation, alternative pathway	1
positive regulation of innate immune response	1
positive regulation of complement activation	1
positive regulation of immune system process	1
positive regulation of response to stimulus	1
regulation of immune response	1
regulation of protein stability	1
positive regulation of immune effector process	1
opsonization	1
positive regulation of phagocytosis	1
regulation of opsonization	1
biological_process	1
defense response to symbiont	1
binding	1
cellular anatomical structure	1
endoplasmic reticulum	1
secretory granule lumen	1
specific granule	1
Golgi membrane	1
cytoplasmic side of membrane	1
tertiary granule	1
endomembrane system	1
secretory vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
positive regulation of complement activation, alternative pathway	BP	direct assay
protein stabilization	BP	direct assay
cytoplasmic side of Golgi membrane	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,244 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFP	C3	P01024	940
CFP	CFH	P08603	807
CFP	CFB	P00751	792
CFP	CFD	P00746	762
CFP	MBL2	P11226	759
CFP	C1S	P09871	756
CFP	C1R	P00736	734
CFP	CD55	P08174	726
CFP	C4A	P01028	717
CFP	CD59	P13987	703
CFP	F8W876	F8W876	702
CFP	SERPING1	P05155	700
CFP	CFI	P05156	682
CFP	CD46	P15529	682
CFP	C4A	P01028	678

IntAct

Human interaction partners of CFP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 42 partners by confidence:

Partner	Interaction type	MIscore	Records
ARMS2	direct interaction	0.660	8
CFHR4	physical association	0.610	3
FKBP6	physical association	0.600	4
SPAG8	physical association	0.600	4
KRTAP6-2	physical association	0.560	5
VENTX	physical association	0.560	5
BANF2	physical association	0.560	3
CFAP206	physical association	0.560	3
CYSRT1	physical association	0.560	3
FHL5	physical association	0.560	3
GEMIN4	physical association	0.560	3
GNE	physical association	0.560	3
HEXIM2	physical association	0.560	3
HOXA1	physical association	0.560	3
KCTD9	physical association	0.560	3
KLHL38	physical association	0.560	3
KRTAP11-1	physical association	0.560	3
KRTAP12-2	physical association	0.560	3
KRTAP3-1	physical association	0.560	3
LCE1A	physical association	0.560	3
LONRF1	physical association	0.560	3
MID2	physical association	0.560	3
NEK6	physical association	0.560	3
NOXA1	physical association	0.560	3
PRKAB2	physical association	0.560	3
RECK	physical association	0.560	3
SMARCC1	physical association	0.560	3
STK16	physical association	0.560	3
ZNF330	physical association	0.560	3
ZNF414	physical association	0.560	3

BioGRID (51 interactions; top human partners by supporting records): B3GALTL (Affinity Capture-MS; 2 records), C3 (Reconstituted Complex; 2 records), CRBN (Affinity Capture-MS; 2 records), CRTAC1 (Affinity Capture-MS; 2 records), DPY19L3 (Affinity Capture-MS; 2 records), BANF2 (Two-hybrid), C6orf165 (Two-hybrid), CFB (Reconstituted Complex), CYSRT1 (Two-hybrid), DDX58 (Affinity Capture-RNA), ELAVL1 (Affinity Capture-RNA), ESR2 (Affinity Capture-MS), FHL5 (Two-hybrid), FKBP6 (Two-hybrid), GEMIN4 (Two-hybrid)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
★ C3-convertase complex	3	C3, CFB, CFP

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 42 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	5	9.6×	6e-03
Neutrophil degranulation	7	5.6×	6e-03

Disease & clinical

Genetic variants

Variant evidence for CFP: 284 ClinVar records (10 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

284 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	3
Uncertain significance	151
Likely benign	88
Benign	2

Top pathogenic / likely-pathogenic (10)

Showing all 10 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
871201	NM_001145252.3(CFP):c.961T>G (p.Trp321Gly)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
11181	NM_001145252.3(CFP):c.481C>T (p.Arg161Ter)	Pathogenic	criteria provided, single submitter	2
4715864	NM_001145252.3(CFP):c.963G>A (p.Trp321Ter)	Pathogenic	criteria provided, single submitter	1
1497106	NM_001145252.3(CFP):c.227+2T>G	Likely pathogenic	criteria provided, single submitter	1
3065206	NM_001145252.3(CFP):c.767-2A>T	Likely pathogenic	criteria provided, single submitter	1
4950339	NM_001145252.3(CFP):c.321G>A (p.Trp107Ter)	Likely pathogenic	criteria provided, single submitter	1
2427222	NC_000023.10:g.(?46466387)(47489243_?)del	Pathogenic	criteria provided, single submitter	1
11183	NM_001145252.3(CFP):c.893G>T (p.Gly298Val)	Pathogenic	no assertion criteria provided	1
11184	NM_001145252.3(CFP):c.617C>G (p.Ser206Ter)	Pathogenic	no assertion criteria provided	1
11185	NM_001145252.3(CFP):c.1240T>G (p.Tyr414Asp)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore CFP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 20 predictions of 766):

Position(s)	Effect	Δscore	Sites
X:47629767–47629768	donor_loss	0.9900	5
X:47624282	donor_gain	0.9800
X:47626326–47626327	donor_loss	0.9800	3
X:47626520–47626521	acceptor_loss	0.9800	5
X:47627460	donor_gain	0.9800
X:47624449	acceptor_gain	0.9700
X:47626327	donor_loss	0.9700
X:47626520	acceptor_loss	0.9700
X:47628078	donor_gain	0.9700
X:47629552	donor_gain	0.9700

AlphaMissense

650 missense substitutions predicted likely pathogenic (of 3,002 scored), across 148 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
C327	7	0.980	0.989
C370	7	0.979	0.990
C407	7	0.974	0.989
C360	7	0.955	0.986
C391	7	0.953	0.973
C350	7	0.952	0.975
W324	7	0.950	0.996
C376	7	0.941	0.962
C439	7	0.940	0.977
C238	7	0.939	0.962
C455	7	0.938	0.969
C312	7	0.931	0.963
C296	7	0.929	0.961
C32	7	0.921	0.964
C284	7	0.920	0.955
W318	7	0.919	0.991
C224	7	0.918	0.968
C56	7	0.916	0.953
C174	7	0.916	0.955
C273	7	0.916	0.950

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Testicular Germ Cell Tumor)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.4e-06
Lung Adenocarcinoma (TCGA)	favorable	0.000715

Disease associations

OMIM: gene MIM:300383 | disease phenotypes: MIM:312060, MIM:300491

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
properdin deficiency, X-linked	Strong	X-linked	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (2 panels, 2 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

2 panels:

Panel	Rating
COVID-19 research	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green

Mondo (2): properdin deficiency, X-linked (MONDO:0010713), epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (MONDO:0010339)

Orphanet (2): Properdin deficiency (Orphanet:2966), X-linked epilepsy-learning disabilities-behavior disorders syndrome (Orphanet:85294)

HPO phenotypes

3 phenotypes (HPO-id order):

HPO	Term
HP:0001419	X-linked recessive inheritance
HP:0005423	Dysfunctional alternative complement pathway
HP:0031300	Abnormal circulating properdin concentration

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C564505	Epilepsy, X-Linked, with Variable Learning Disabilities and Behavior Disorders *(supp.)*
C537241	Properdin deficiency, X-linked *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression, increases mutagenesis	3
Cisplatin	decreases expression, increases expression, affects cotreatment	2
Nickel	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases methylation	1
sulforaphane	increases expression	1
sodium arsenite	decreases expression	1
versicolorin A	increases expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	decreases expression, increases abundance	1
Arsenicals	increases expression	1
Niclosamide	increases expression	1
Testosterone	increases expression	1
Tretinoin	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1
Copper Sulfate	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.