properdin deficiency, X-linked

Summary

properdin deficiency, X-linked (MONDO:0010713) is a disease caused by CFP (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: CFP (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 11

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	properdin deficiency, X-linked
Mondo ID	MONDO:0010713
MeSH	C537241
OMIM	312060
Orphanet	2966
DOID	DOID:0111768
SNOMED CT	81166004
UMLS	C1839454
MedGen	333322
GARD	0004513
Is cancer (heuristic)	no

Also known as: CFPD · PFD · properdin deficiency, X-linked · properdin deficiency, X-linked, X-linked recessive

Data availability: 11 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › properdin deficiency, X-linked

Related subtypes (40): B cell deficiency, complement deficiency, phagocyte bactericidal dysfunction, trichohepatoenteric syndrome, hepatic veno-occlusive disease-immunodeficiency syndrome, immunodeficiency with defective T-cell response to interleukin 1, Say-Barber-Miller syndrome, familial isolated congenital asplenia, X-linked immunoneurologic disorder, ectodermal dysplasia and immune deficiency, immunodeficiency 33, immunodeficiency 47, combined immunodeficiency due to moesin deficiency, immunodeficiency, X-linked, with deficiency of 115,000 Dalton surface glycoprotein, combined immunodeficiency with faciooculoskeletal anomalies, recurrent infections associated with rare immunoglobulin isotypes deficiency, immunodeficiency 28, autosomal recessive primary immunodeficiency with defective spontaneous natural killer cell cytotoxicity, immunodeficiency 37, immunodeficiency 39, BENTA disease, primary immunodeficiency with post-measles-mumps-rubella vaccine viral infection, immunodeficiency 49, chronic mucocutaneous candidiasis, hereditary hemophagocytic lymphohistiocytosis, immunoglobulin heavy chain deficiency, immuno-osseous dysplasia, lymphoproliferative syndrome, IL10-related early-onset inflammatory bowel disease, T-cell immunodeficiency with epidermodysplasia verruciformis, Aicardi-Goutieres syndrome, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, inflammatory bowel disease-recurrent sinopulmonary infections syndrome, A20 haploinsufficiency, NK cell deficiency, T cell and NK cell immunodeficiency, dendritic cell deficiency, immunodysregulation with variable immunodeficiency and autoimmunity, immune dysregulation with immunodeficiency due to AIOLOS haploinsufficiency, STAT5 haploinsufficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 3 pathogenic, 2 conflicting classifications of pathogenicity, 1 benign/likely benign, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
11181	NM_001145252.3(CFP):c.481C>T (p.Arg161Ter)	CFP	Pathogenic	criteria provided, single submitter
11183	NM_001145252.3(CFP):c.893G>T (p.Gly298Val)	CFP	Pathogenic	no assertion criteria provided
11184	NM_001145252.3(CFP):c.617C>G (p.Ser206Ter)	CFP	Pathogenic	no assertion criteria provided
3065206	NM_001145252.3(CFP):c.767-2A>T	CFP	Likely pathogenic	criteria provided, single submitter
827996	NM_001145252.3(CFP):c.716C>T (p.Pro239Leu)	CFP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
973631	NM_001145252.3(CFP):c.476G>A (p.Arg159His)	CFP	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1019416	NM_001145252.3(CFP):c.470G>A (p.Arg157Gln)	CFP	Uncertain significance	criteria provided, multiple submitters, no conflicts
1177511	NM_001145252.3(CFP):c.643G>A (p.Glu215Lys)	CFP	Uncertain significance	criteria provided, multiple submitters, no conflicts
3767004	NM_001145252.3(CFP):c.724G>T (p.Ala242Ser)	CFP	Uncertain significance	criteria provided, single submitter
3779062	NM_001145252.3(CFP):c.400C>T (p.Pro134Ser)	CFP	Uncertain significance	criteria provided, single submitter
1166179	NM_001145252.3(CFP):c.121G>A (p.Gly41Ser)	CFP	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 2 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

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

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CFP	Orphanet:2966	Properdin deficiency

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CFP	HGNC:8864	ENSG00000126759	P27918	Properdin	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CFP	Properdin	A positive regulator of the alternate pathway (AP) of complement.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CFP	Other/Unknown	no		TSP1_rpt, TSP1_rpt_sf, CFP_TSR-0

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
granulocyte	1
leukocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CFP	136	broad	marker	granulocyte, monocyte, leukocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CFP	2,269

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CFP	P27918	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Alternative complement activation	1	2284.0×	0.002	CFP
Activation of C3 and C5	1	1268.9×	0.002	CFP
Defective B3GALTL causes PpS	1	308.6×	0.005	CFP
O-glycosylation of TSR domain-containing proteins	1	300.5×	0.005	CFP
Regulation of Complement cascade	1	233.1×	0.005	CFP
Neutrophil degranulation	1	23.1×	0.043	CFP

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
positive regulation of complement activation, alternative pathway	1	16852.0×	5e-04	CFP
positive regulation of opsonization	1	1685.2×	0.002	CFP
complement activation, alternative pathway	1	991.3×	0.003	CFP
complement activation	1	624.1×	0.003	CFP
positive regulation of immune response	1	481.5×	0.003	CFP
defense response to bacterium	1	108.0×	0.012	CFP
protein stabilization	1	66.9×	0.017	CFP
immune response	1	47.1×	0.021	CFP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CFP	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	CFP

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
CFP	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.