Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2

Summary

Granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 (MONDO:0009310) is a disease caused by NCF2 (GenCC Definitive), with 2 cohort genes.

At a glance

• Causal gene: NCF2 (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 593

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 2
Mondo ID	MONDO:0009310
MeSH	C565531
OMIM	233710
DOID	DOID:0070191
UMLS	C1856245
MedGen	383869
GARD	0015177
Is cancer (heuristic)	no

Also known as: CDG2 · chronic granulomatous disease 2, autosomal recessive · chronic granulomatous disease caused by mutation in NCF2 · granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2 · NCF2 chronic granulomatous disease

Data availability: 593 ClinVar variants · 3 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 2

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 1, 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

593 retrieved; paginated sample, class counts are floors:

308 likely benign, 157 uncertain significance, 44 pathogenic, 22 conflicting classifications of pathogenicity, 21 likely pathogenic, 12 benign, 10 pathogenic/likely pathogenic, 10 benign/likely benign, 9 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
2240	NM_000433.3(NCF2):c.[479A>T;481A>G]		Pathogenic	no assertion criteria provided
1076527	NM_000433.4(NCF2):c.910C>T (p.Gln304Ter)	NCF2	Pathogenic	criteria provided, single submitter
1323334	NM_000433.4(NCF2):c.713+1G>A	NCF2	Pathogenic	criteria provided, single submitter
1377437	NM_000433.4(NCF2):c.1162G>T (p.Glu388Ter)	NCF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1378377	NM_000433.4(NCF2):c.830G>A (p.Trp277Ter)	NCF2	Pathogenic	criteria provided, single submitter
1408244	NM_000433.4(NCF2):c.30G>A (p.Trp10Ter)	NCF2	Pathogenic	criteria provided, single submitter
1446473	NM_000433.4(NCF2):c.251_254del (p.Thr84fs)	NCF2	Pathogenic	criteria provided, single submitter
1458116	NC_000001.11:g.183586978del	NCF2	Pathogenic	criteria provided, single submitter
1458778	NC_000001.10:g.(?183543602)(183543776_?)del	NCF2	Pathogenic	criteria provided, single submitter
1952796	NM_000433.4(NCF2):c.65G>A (p.Trp22Ter)	NCF2	Pathogenic	criteria provided, single submitter
2202893	NM_000433.4(NCF2):c.728del (p.Glu243fs)	NCF2	Pathogenic	criteria provided, single submitter
2202894	NM_000433.4(NCF2):c.574C>T (p.Gln192Ter)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2239	NM_000433.4(NCF2):c.399_400dup (p.Lys134fs)	NCF2	Pathogenic	no assertion criteria provided
2241	NM_000433.4(NCF2):c.304C>T (p.Arg102Ter)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2242	NM_000433.4(NCF2):c.1171_1175del (p.Lys391fs)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2243	NM_000433.4(NCF2):c.366+1G>A	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2244	NM_000433.4(NCF2):c.298C>T (p.Gln100Ter)	NCF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2245	NM_000433.4(NCF2):c.55_63del (p.Lys19_Asp21del)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2423085	NC_000001.10:g.(?183542300)(183542447_?)del	NCF2	Pathogenic	criteria provided, single submitter
2445914	NM_000433.4(NCF2):c.417del (p.Ala140fs)	NCF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2501077	NM_000433.4(NCF2):c.500G>A (p.Trp167Ter)	NCF2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2581423	NM_000433.4(NCF2):c.1099C>T (p.Gln367Ter)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2697516	NM_000433.4(NCF2):c.1165_1171del (p.His389fs)	NCF2	Pathogenic	criteria provided, single submitter
2702941	NM_000433.4(NCF2):c.2T>C (p.Met1Thr)	NCF2	Pathogenic	criteria provided, single submitter
2734054	NM_000433.4(NCF2):c.1038_1039del (p.Ser347fs)	NCF2	Pathogenic	criteria provided, single submitter
2734055	NM_000433.4(NCF2):c.475del (p.Ile159fs)	NCF2	Pathogenic	criteria provided, single submitter
2734056	NM_000433.4(NCF2):c.229C>T (p.Arg77Ter)	NCF2	Pathogenic	criteria provided, multiple submitters, no conflicts
2769198	NC_000001.11:g.183563586del	NCF2	Pathogenic	criteria provided, single submitter
2770552	NM_000433.4(NCF2):c.236del (p.Met79fs)	NCF2	Pathogenic	criteria provided, single submitter
2786568	NM_000433.4(NCF2):c.172A>T (p.Lys58Ter)	NCF2	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · 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
NCF2	Definitive	Autosomal recessive	granulomatous disease, chronic, autosomal recessive, cytochrome b-positive, type 2	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
NCF2	Orphanet:379	Chronic granulomatous disease

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
NCF2	HGNC:7661	ENSG00000116701	P19878	Neutrophil cytosol factor 2	gencc,clinvar
ACBD6	HGNC:23339	ENSG00000230124	Q9BR61	Acyl-CoA-binding domain-containing protein 6	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
NCF2	Neutrophil cytosol factor 2	Subunit of the phagocyte NADPH oxidase complex that mediates the transfer of electrons from cytosolic NADPH to O2 to produce the superoxide anion (O2(-)).
ACBD6	Acyl-CoA-binding domain-containing protein 6	Binds long-chain acyl-coenzyme A molecules with a strong preference for unsaturated C18:1-CoA, lower affinity for unsaturated C20:4-CoA, and very weak affinity for saturated C16:0-CoA.

Protein-family classification

Druggable: 0 · Difficult: 2 · 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	2	17.3×	0.003

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
NCF2	Scaffold/PPI	no		PB1_dom, SH3_domain, TPR-like_helical_dom_sf
ACBD6	Scaffold/PPI	no		Acyl-CoA-binding_protein, Ankyrin_rpt, FERM/acyl-CoA-bd_prot_sf

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
leukocyte	1
monocyte	1
mononuclear cell	1
cortical plate	1
ganglionic eminence	1
left testis	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
NCF2	205	broad	marker	monocyte, mononuclear cell, leukocyte
ACBD6	231	ubiquitous	marker	cortical plate, ganglionic eminence, left testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
NCF2	2,168
ACBD6	1,486

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
NCF2	P19878	7
ACBD6	Q9BR61	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 27. Enrichment computed across 2 evidence-associated genes (2 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 2 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	713.8×	0.030	NCF2
RHO GTPases Activate NADPH Oxidases	1	228.4×	0.030	NCF2
Mitochondrial Fatty Acid Beta-Oxidation	1	190.3×	0.030	ACBD6
ROS and RNS production in phagocytes	1	167.9×	0.030	NCF2
Antigen processing-Cross presentation	1	158.6×	0.030	NCF2
Detoxification of Reactive Oxygen Species	1	150.3×	0.030	NCF2
Signaling by VEGF	1	109.8×	0.035	NCF2
Cellular response to chemical stress	1	71.4×	0.038	NCF2
VEGFA-VEGFR2 Pathway	1	69.6×	0.038	NCF2
Fatty acid metabolism	1	65.6×	0.038	ACBD6
RAC2 GTPase cycle	1	63.4×	0.038	NCF2
RAC3 GTPase cycle	1	59.5×	0.038	NCF2
Class I MHC mediated antigen processing & presentation	1	35.0×	0.056	NCF2
RHO GTPase Effectors	1	34.0×	0.056	NCF2
RAC1 GTPase cycle	1	30.5×	0.056	NCF2
RHO GTPase cycle	1	30.1×	0.056	NCF2
Signaling by Receptor Tyrosine Kinases	1	25.8×	0.061	NCF2
Cellular responses to stress	1	18.4×	0.077	NCF2
Signaling by Rho GTPases	1	17.1×	0.077	NCF2
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1	16.7×	0.077	NCF2
Metabolism of lipids	1	15.8×	0.077	ACBD6
Cellular responses to stimuli	1	15.7×	0.077	NCF2
Adaptive Immune System	1	14.9×	0.077	NCF2
Innate Immune System	1	12.8×	0.087	NCF2
Immune System	1	6.5×	0.160	NCF2
Metabolism	1	5.8×	0.171	ACBD6
Signal Transduction	1	5.1×	0.187	NCF2

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
respiratory burst	1	1296.3×	0.003	NCF2
superoxide metabolic process	1	991.3×	0.003	NCF2
superoxide anion generation	1	674.1×	0.003	NCF2
cellular defense response	1	318.0×	0.005	NCF2
phagocytosis	1	240.7×	0.005	NCF2
innate immune response	1	33.6×	0.030	NCF2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
NCF2	0	0
ACBD6	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; 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	2	NCF2, ACBD6

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
NCF2	0	—
ACBD6	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.