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): 266 total — 7 pathogenic, 2 likely-pathogenic
• 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: 12 — 8 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000247153, ENST00000377005, ENST00000396992, ENST00000469388, ENST00000478222, ENST00000480317, ENST00000485991, ENST00000640573, ENST00000862734, ENST00000862735, ENST00000862736, ENST00000952425

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.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199134	11.7414	396

Top tissues by expression

138 total, 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

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

Regulation

Is transcription factor: no

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

Protein

Protein identifiers

Properdin — P27918 (reviewed: P27918)

Alternative names: Complement factor P

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

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	Compl_asym_regulator	Family
IPR054019	CFP_TSR_C	Repeat

Pfam: PF00090, PF18487, PF22195

UniProt features (108 total): strand 31, disulfide bond 22, glycosylation site 20, mutagenesis site 11, sequence variant 10, domain 7, region of interest 2, turn 2, signal peptide 1, chain 1, helix 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
1W0R	SOLUTION SCATTERING	0
1W0S	SOLUTION SCATTERING	0
8Q6R	X-RAY DIFFRACTION	1.9
6S08	X-RAY DIFFRACTION	2.03
6S0B	X-RAY DIFFRACTION	2.31
6S0A	X-RAY DIFFRACTION	2.52
9U62	ELECTRON MICROSCOPY	2.7
6RUS	X-RAY DIFFRACTION	2.8
7B26	X-RAY DIFFRACTION	3.4
6SEJ	X-RAY DIFFRACTION	3.5
6RV6	X-RAY DIFFRACTION	3.51
7NOZ	X-RAY DIFFRACTION	3.9
6RUR	X-RAY DIFFRACTION	6
6RUV	X-RAY DIFFRACTION	6.15

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab): 3 — 6RUV, 7NOZ, 8Q6R

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): 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 …

Glycosylation sites (20): 83, 86, 92, 139, 142, 145, 151, 196, 199, 202, 208, 260, 263, 272, 321, 324, 382, 385, 388, 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 pathways

ID	Pathway
R-HSA-173736	Alternative complement activation
R-HSA-174577	Activation of C3 and C5
R-HSA-5083635	Defective B3GALTL causes PpS
R-HSA-5173214	O-glycosylation of TSR domain-containing proteins
R-HSA-6798695	Neutrophil degranulation
R-HSA-977606	Regulation of Complement cascade

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 (7): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), 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

Rollup of top-5 pathways:

Category	Pathways
Complement cascade	2
Initial triggering of complement	1
Diseases associated with O-glycosylation of proteins	1
O-linked glycosylation	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

2094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CFP	C3	P01024	999
CFP	NCR1	O76036	958
CFP	CFB	P00751	891
CFP	CFH	P08603	873
CFP	CFD	P00746	793
CFP	MBL2	P11226	776
CFP	SERPING1	P05155	770
CFP	C1S	P09871	747
CFP	C1R	P00736	740
CFP	COMP	P49747	724
CFP	C4A	P01028	718
CFP	CD55	P08174	709
CFP	CD59	P13987	702
CFP	CFI	P05156	695
CFP	C4A	P01028	693

IntAct

124 interactions, top by confidence:

A	B	Type	Score
PTX3	CFH	psi-mi:“MI:0914”(association)	0.820
CFP	ARMS2	psi-mi:“MI:0407”(direct interaction)	0.660
ARMS2	CFP	psi-mi:“MI:0915”(physical association)	0.660
CFP	ARMS2	psi-mi:“MI:0403”(colocalization)	0.660
CFP	ARMS2	psi-mi:“MI:0915”(physical association)	0.660
CFHR4	CFP	psi-mi:“MI:0915”(physical association)	0.610
CFP	CFHR4	psi-mi:“MI:0407”(direct interaction)	0.610
FKBP6	CFP	psi-mi:“MI:0915”(physical association)	0.600
CFP	SPAG8	psi-mi:“MI:0915”(physical association)	0.600
CFP	FKBP6	psi-mi:“MI:0915”(physical association)	0.600
CFAP206	CFP	psi-mi:“MI:0915”(physical association)	0.560
CFP	HOXA1	psi-mi:“MI:0915”(physical association)	0.560
CFP	GEMIN4	psi-mi:“MI:0915”(physical association)	0.560
CFP	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	CFP	psi-mi:“MI:0915”(physical association)	0.560
CFP	KRTAP3-1	psi-mi:“MI:0915”(physical association)	0.560
CFP	KLHL38	psi-mi:“MI:0915”(physical association)	0.560
CFP	ZNF414	psi-mi:“MI:0915”(physical association)	0.560
CFP	HEXIM2	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	CFP	psi-mi:“MI:0915”(physical association)	0.560
CFP	KRTAP6-2	psi-mi:“MI:0915”(physical association)	0.560
CFP	SMARCC1	psi-mi:“MI:0915”(physical association)	0.560
CFP	FHL5	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (51): B3GALTL (Affinity Capture-MS), DPY19L3 (Affinity Capture-MS), CRTAC1 (Affinity Capture-MS), CRBN (Affinity Capture-MS), TRIP13 (Two-hybrid), CFP (Affinity Capture-MS), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid), CFP (Two-hybrid)

ESM2 similar proteins: A7MBS7, D3YXF5, F1LW30, O89103, P10643, P11680, P27918, P35446, P82987, P90884, Q29RQ1, Q2I0M5, Q2MKA7, Q3UPR9, Q3UTY6, Q4R7Z5, Q5M7L6, Q5RAD0, Q5RBP1, Q5RBP8, Q5UE90, Q64181, Q66PY1, Q69ZU6, Q6NZL8, Q6P4U0, Q6UXX9, Q6ZMP0, Q7T3Q2, Q7TSK7, Q80YN4, Q86TH1, Q8BFU0, Q8BJ73, Q8BLI0, Q8IUX8, Q8IWY4, Q8IX30, Q8N6G6, Q8VCC9

Diamond homologs: A2VEC9, A6QNY1, B3EWZ3, B3EWZ8, C0HL12, C5IAW9, D3YXG0, D3ZTD8, F1LW30, O08721, O08722, O08747, O14514, O15072, O55225, O60241, O60242, O75173, O88783, O95185, O95450, P04275, P07358, P07996, P27918, P35441, P35442, P35448, P55314, P57110, P58397, P58459, P59384, P79331, P80012, P97857, P98088, P98092, P98160, P98164

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 47 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
Regulation of Complement cascade	6	42.4×	6e-07
Keratinization	5	8.4×	7e-03
Neutrophil degranulation	9	6.3×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
complement activation	6	93.6×	9e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	2
Uncertain significance	143
Likely benign	83
Benign	12

Top pathogenic / likely-pathogenic (9)

Variant ID	HGVS	Classification
11181	NM_001145252.3(CFP):c.481C>T (p.Arg161Ter)	Pathogenic
11183	NM_001145252.3(CFP):c.893G>T (p.Gly298Val)	Pathogenic
11184	NM_001145252.3(CFP):c.617C>G (p.Ser206Ter)	Pathogenic
11185	NM_001145252.3(CFP):c.1240T>G (p.Tyr414Asp)	Pathogenic
2427222	NC_000023.10:g.(?46466387)(47489243_?)del	Pathogenic
4715864	NM_001145252.3(CFP):c.963G>A (p.Trp321Ter)	Pathogenic
871201	NM_001145252.3(CFP):c.961T>G (p.Trp321Gly)	Pathogenic
1497106	NM_001145252.3(CFP):c.227+2T>G	Likely pathogenic
3065206	NM_001145252.3(CFP):c.767-2A>T	Likely pathogenic

SpliceAI

1338 predictions. Top by Δscore:

Variant	Effect	Δscore
X:47626516:TCCA:T	acceptor_gain	1.0000
X:47626517:CCA:C	acceptor_gain	1.0000
X:47626517:CCAC:C	acceptor_gain	1.0000
X:47626518:CAC:C	acceptor_gain	1.0000
X:47626520:C:CC	acceptor_gain	1.0000
X:47624449:T:TC	acceptor_gain	0.9900
X:47626320:ACACT:A	donor_loss	0.9900
X:47626321:CACTC:C	donor_loss	0.9900
X:47626322:ACTCA:A	donor_loss	0.9900
X:47626323:CTCA:C	donor_loss	0.9900
X:47626324:T:TC	donor_loss	0.9900
X:47626325:CACA:C	donor_loss	0.9900
X:47626326:A:AC	donor_gain	0.9900
X:47626326:ACA:A	donor_loss	0.9900
X:47626327:C:A	donor_loss	0.9900
X:47626327:C:CC	donor_gain	0.9900
X:47626327:CAGG:C	donor_gain	0.9900
X:47626515:ATCCA:A	acceptor_gain	0.9900
X:47626518:CA:C	acceptor_gain	0.9900
X:47626519:ACTG:A	acceptor_loss	0.9900
X:47626520:C:CA	acceptor_loss	0.9900
X:47626521:T:A	acceptor_loss	0.9900
X:47627460:C:A	donor_gain	0.9900
X:47628091:AT:A	donor_gain	0.9900
X:47629763:CCTCA:C	donor_loss	0.9900
X:47629764:CTCA:C	donor_loss	0.9900
X:47629765:TCA:T	donor_loss	0.9900
X:47629768:C:A	donor_loss	0.9900
X:47624447:CAT:C	acceptor_gain	0.9800
X:47624449:T:C	acceptor_gain	0.9800

AlphaMissense

3002 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:47626488:C:A	W324C	0.996
X:47626488:C:G	W324C	0.996
X:47626147:C:A	W385C	0.993
X:47626147:C:G	W385C	0.993
X:47626497:C:A	W321C	0.991
X:47626497:C:G	W321C	0.991
X:47626506:C:A	W318C	0.991
X:47626506:C:G	W318C	0.991
X:47626351:C:G	C370S	0.990
X:47626352:A:T	C370S	0.990
X:47627310:C:A	W199C	0.990
X:47627310:C:G	W199C	0.990
X:47626082:C:G	C407S	0.989
X:47626083:A:T	C407S	0.989
X:47626350:G:C	C370W	0.989
X:47626480:C:G	C327S	0.989
X:47626481:A:T	C327S	0.989
X:47626138:C:A	W388C	0.988
X:47626138:C:G	W388C	0.988
X:47626490:A:G	W324R	0.988
X:47626490:A:T	W324R	0.988
X:47626924:C:A	W263C	0.988
X:47626924:C:G	W263C	0.988
X:47626479:A:C	C327W	0.987
X:47626381:C:G	C360S	0.986
X:47626382:A:T	C360S	0.986
X:47626480:C:T	C327Y	0.986
X:47627619:C:A	W142C	0.986
X:47627619:C:G	W142C	0.986
X:47626156:C:A	W382C	0.983

dbSNP variants (sampled 300 via entrez): RS1000238234 (X:47623233 G>A), RS1000427520 (X:47625047 T>C), RS1000460105 (X:47624616 A>C), RS1001427977 (X:47627205 A>C,G), RS1002427330 (X:47629274 G>T), RS1002578452 (X:47630005 T>C), RS1002918695 (X:47622803 A>C), RS1003430241 (X:47631456 G>A), RS1003461980 (X:47630980 G>A,C), RS1003815247 (X:47627987 T>C,G), RS1004329991 (X:47624518 C>G), RS1004423889 (X:47623846 A>G,T), RS1005287791 (X:47631691 T>G), RS1005879662 (X:47628911 C>A), RS1005900530 (X:47628706 A>C,G)

Disease associations

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

GenCC curated gene-disease

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

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 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0001419	X-linked recessive inheritance
HP:0001939	Abnormality of metabolism/homeostasis
HP:0005423	Dysfunctional alternative complement pathway

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

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 (VIP=true, CPIC=false)

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	affects cotreatment, decreases expression, increases expression	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)

0 trials via MONDO — disease-level, not drug-specific.