Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1

Summary

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 (MONDO:0009309) is a disease caused by NCF1 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: NCF1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 18

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1
Mondo ID	MONDO:0009309
MeSH	C565532
OMIM	233700
DOID	DOID:0070192
UMLS	C1856251
MedGen	341102
GARD	0015176
Is cancer (heuristic)	no

Also known as: CDG1 · chronic granulomatous disease 1, autosomal recessive · chronic granulomatous disease caused by mutation in NCF1 · granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1 · NCF1 chronic granulomatous disease

Data availability: 18 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › chronic granulomatous disease › granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1

Related subtypes (6): granulomatous disease with defect in neutrophil chemotaxis, granulomatous disease, chronic, autosomal recessive, cytochrome b-negative, granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2, granulomatous disease, chronic, X-linked, granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 3, granulomatous disease, chronic, autosomal recessive, 5

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

18 retrieved; paginated sample, class counts are floors:

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

ClinVar	Variant (HGVS)	Gene	Classification	Review
2249	NM_000265.7(NCF1):c.75_76del (p.Tyr26fs)	LOC106029312	Pathogenic	criteria provided, multiple submitters, no conflicts
2255	NM_000265.7(NCF1):c.574G>A (p.Gly192Ser)	LOC106029312	Pathogenic	no assertion criteria provided
426990	NM_000265.7(NCF1):c.579G>A (p.Trp193Ter)	LOC106029312	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
636577	NM_000265.7(NCF1):c.124C>T (p.Arg42Trp)	LOC106029312	Pathogenic	criteria provided, single submitter
2250	NM_000265.7(NCF1):c.502del (p.Glu168fs)	NCF1	Pathogenic	no assertion criteria provided
2251	NM_000265.7(NCF1):c.125G>A (p.Arg42Gln)	NCF1	Pathogenic	criteria provided, multiple submitters, no conflicts
2252	NM_000265.7(NCF1):c.811del (p.Val271fs)	NCF1	Pathogenic	no assertion criteria provided
2253	NM_000265.7(NCF1):c.271C>T (p.Gln91Ter)	NCF1	Pathogenic	no assertion criteria provided
2254	NM_000265.7(NCF1):c.333T>A (p.Cys111Ter)	NCF1	Pathogenic	no assertion criteria provided
4820136	NC_000007.14:g.(74774103_74777267)_(74779422_74782939)del	LOC106029312	Likely pathogenic	criteria provided, single submitter
4845844	NM_000265.7(NCF1):c.144delinsTGT (p.Glu49fs)	LOC106029312	Likely pathogenic	criteria provided, single submitter
636728	NM_000265.7(NCF1):c.285_288dup (p.Tyr97fs)	LOC106029312	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1175021	NM_000265.7(NCF1):c.292T>G (p.Cys98Gly)	LOC106029312	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1297511	NM_000265.7(NCF1):c.269G>A (p.Arg90His)	LOC106029312	Uncertain significance	criteria provided, multiple submitters, no conflicts
2434075	NM_000265.7(NCF1):c.575-6G>A	LOC106029312	Uncertain significance	criteria provided, single submitter
625985	NM_000265.7(NCF1):c.108G>A (p.Ser36=)	LOC106029312	Uncertain significance	criteria provided, single submitter
3235028	NM_000265.7(NCF1):c.682+5C>T	NCF1	Uncertain significance	criteria provided, single submitter
973652	NM_000265.7(NCF1):c.923C>T (p.Ala308Val)	NCF1	Likely benign	no assertion criteria provided

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 2 · 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
NCF1	Strong	Autosomal recessive	granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 1	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NCF1	Orphanet:379	Chronic granulomatous disease
NCF1	Orphanet:904	Williams syndrome

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
NCF1	HGNC:7660	ENSG00000158517	P14598	Neutrophil cytosol factor 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NCF1	Neutrophil cytosol factor 1	Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)).

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · 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
Scaffold/PPI	1	17.3×	0.058

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NCF1	Scaffold/PPI	no		SH3_domain, P47PHOX, PX_dom

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
blood	1
granulocyte	1
monocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NCF1	136		marker	granulocyte, blood, monocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCF1	3,403

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NCF1	P14598	11

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 23. 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
Cross-presentation of particulate exogenous antigens (phagosomes)	1	1427.5×	0.015	NCF1
RHO GTPases Activate NADPH Oxidases	1	456.8×	0.015	NCF1
ROS and RNS production in phagocytes	1	335.9×	0.015	NCF1
Antigen processing-Cross presentation	1	317.2×	0.015	NCF1
Detoxification of Reactive Oxygen Species	1	300.5×	0.015	NCF1
Signaling by VEGF	1	219.6×	0.017	NCF1
Cellular response to chemical stress	1	142.8×	0.019	NCF1
VEGFA-VEGFR2 Pathway	1	139.3×	0.019	NCF1
RAC2 GTPase cycle	1	126.9×	0.019	NCF1
RAC3 GTPase cycle	1	119.0×	0.019	NCF1
Class I MHC mediated antigen processing & presentation	1	70.1×	0.027	NCF1
RHO GTPase Effectors	1	68.0×	0.027	NCF1
RAC1 GTPase cycle	1	61.1×	0.027	NCF1
RHO GTPase cycle	1	60.1×	0.027	NCF1
Signaling by Receptor Tyrosine Kinases	1	51.7×	0.030	NCF1
Cellular responses to stress	1	36.8×	0.038	NCF1
Signaling by Rho GTPases	1	34.2×	0.038	NCF1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	33.5×	0.038	NCF1
Cellular responses to stimuli	1	31.5×	0.038	NCF1
Adaptive Immune System	1	29.8×	0.039	NCF1
Innate Immune System	1	25.5×	0.043	NCF1
Immune System	1	13.0×	0.081	NCF1
Signal Transduction	1	10.2×	0.098	NCF1

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
neutrophil-mediated killing of fungus	1	8426.0×	0.001	NCF1
regulation of respiratory burst involved in inflammatory response	1	5617.3×	0.001	NCF1
respiratory burst involved in defense response	1	4213.0×	0.001	NCF1
neutrophil-mediated killing of gram-positive bacterium	1	4213.0×	0.001	NCF1
cellular response to testosterone stimulus	1	2407.4×	0.001	NCF1
response to yeast	1	2106.5×	0.001	NCF1
hydrogen peroxide biosynthetic process	1	1404.3×	0.001	NCF1
leukotriene metabolic process	1	1296.3×	0.001	NCF1
respiratory burst	1	1296.3×	0.001	NCF1
superoxide metabolic process	1	991.3×	0.002	NCF1
superoxide anion generation	1	674.1×	0.002	NCF1
cellular defense response	1	318.0×	0.004	NCF1
epithelial cell proliferation	1	312.1×	0.004	NCF1
protein targeting to membrane	1	295.6×	0.004	NCF1
cellular response to glucose stimulus	1	267.5×	0.004	NCF1
inflammatory response	1	37.7×	0.028	NCF1
innate immune response	1	33.6×	0.030	NCF1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
NCF1	1	3

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
EBSELEN	3	NCF1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
NCF1	49	Binding:49

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

1 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.

Compound	Max phase	Cohort target (bioactivity)
EBSELEN	3	NCF1

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	1	NCF1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 0.