CFP

protein-coding

complement factor properdin, the group of Complement system activation components

Gene summary

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.[provided by RefSeq, Feb 2009]

Previous symbols:

MANE transcript

NM_001145252.3

Inheritance

ClinVar variants

P:10U:147B:78

Top phenotype

Properdin deficiency, X-linked

gnomAD constraint

pLI —, LoF o/e 0.19

Max pathogenic AF

—

Genomic locus

chrX:47,623,172-47,630,305

External References & Databases

Ensembl (ENSG00000126759)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

properdin deficiency, X-linkedSTRONG

Inheritance Pattern: XL

Disease ID:MONDO:0010713

Submitter: Labcorp Genetics (formerly Invitae)

properdin deficiency, X-linkedSUPPORTIVE

Inheritance Pattern: XL

Disease ID:MONDO:0010713

Submitter: Orphanet

Clinical Genomic Database (CGD)

Properdin deficiency, X-linkedXL

Manifestation: Allergy/Immunology/Infectious

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals are especially susceptible to Neisseria infections, warranting infectious prophylaxis and early and aggressive treatment of infections

Refs: 8530058; 8871668; 10909851; 22229731

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CFP variants in ClinVar

7 Conditions Cataloged

not providedTotal: 243

not specifiedTotal: 36

Inborn genetic diseasesTotal: 27

CFP-related disorderTotal: 13

Properdin deficiency, X-linkedTotal: 11

Properdin deficiency, type IITotal: 1

Properdin deficiency, type IIITotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001145252.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	61 clinvar	1 clinvar	65
missense	3 clinvar		140 clinvar	16 clinvar		159
nonsense	3 clinvar	2 clinvar				5
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)		2 clinvar	3 clinvar			5
Total	6	4	147	77	1	235

Highest pathogenic variant AF is 0.0000063750767

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001145252.3	RefSeq	NP_001138724.1	9	MANE Select
ENST00000396992.8	Ensembl	ENSP00000380189.3	9	MANE Select
NM_002621.2	RefSeq	NP_002612.1	9	Standard
ENST00000247153.7	Ensembl	ENSP00000247153.3	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Herpes simplex infection - Homo sapiens (human)
Human Complement System
Complement Activation
Neutrophil degranulation
alternative complement pathway

Biological Process

proteolysis
immune response
complement activation
complement activation, alternative pathway
regulation of complement activation

Molecular Function

serine-type endopeptidase activity
protein binding

Cellular Component

extracellular region
extracellular space
endoplasmic reticulum lumen
specific granule lumen
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000247153
Coding exons: 9
Length: 6093
Individuals with no LoFs: 125592
Homozygous LoFs: 3
Heterozygous LoFs: 1
Defined: 125596
p: 0.0000159

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.17	115	202	0.571	0.0000173	2952
Missense (PolyPhen)		36	84.21	0.4275		1144
Synonymous	0.988	68	79.2	0.859	0.00000666	931
Loss of Function	3.47	4	21.3	0.188	0.00000172	286

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000049	0.000035	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: A positive regulator of the alternate pathway of complement. It binds to and stabilizes the C3- and C5-convertase enzyme complexes. {ECO:0000269|PubMed:20382442}.;
Disease: DISEASE: 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). {ECO:0000269|PubMed:10909851, ECO:0000269|PubMed:8871668, ECO:0000269|PubMed:9710744}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.268

Intolerance Scores

LoFtool: 0.330
RVIS EVS: 0.35
RVIS percentile EVS: 74.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.662

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium