Details of Disease

General Information of Disease (ID: DIS9ZR24)

• Disease Name: Chronic granulomatous disease
• Synonyms: granulomatous disease, chronic; CGD; Quie syndrome; Bridges-Good syndrome; chronic septic granulomatosis; congenital dysphagocytosis
• Disease Class: 4A00: Innate/adaptive immunodeficiency
• Definition: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency, mainly affecting phagocytes, which is characterized by an increased susceptibility to severe and recurrent bacterial and fungal infections, along with the development of granulomas.
• Disease Hierarchy:
  DIS184KT: Skin inflammation
  DIS30VAM: Defective phagocytic cell engulfment
  DIS699VO: Phagocyte bactericidal dysfunction
  DIS9ZR24: Chronic granulomatous disease
• ICD Code:
  ICD-11: ICD-11: 4A00.0Y
  ICD-9: ICD-9: 288.1
  Expand ICD-11: '4A00.0Y
  Expand ICD-9: 288.1
• Disease Identifiers:
  MONDO ID: MONDO_0018305
  UMLS CUI: C0018203
  MedGen ID: 5377
  Orphanet ID: 379
  SNOMED CT ID: 387759001

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Interferon gamma-1b	DMWUMRL	Approved	NA	[1]

This Disease is Treated as An Indication in 1 Discontinued Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
VM-106	DM9A1TK	Discontinued in Phase 1/2	NA	[2]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Granulosin	DMU8KT0	Investigative	NA	[3]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 12 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADA	TTLP57V	Limited	Biomarker	[4]
CD34	TTZAVYN	Disputed	Biomarker	[5]
CYBB	TT5T8MR	Supportive	Autosomal recessive	[6]
NCF1	TTZ4JC3	Supportive	Autosomal recessive	[6]
CD27	TTDO1MV	moderate	Altered Expression	[7]
G6PD	TTKN8W0	Strong	Genetic Variation	[8]
GCLM	TTNFESW	Strong	Genetic Variation	[9]
IRAK4	TTILUKB	Strong	Biomarker	[10]
NCF1	TTZ4JC3	Strong	Genetic Variation	[11]
OTC	TT5KIO9	Strong	Biomarker	[12]
PLN	TTMCVJF	Strong	Genetic Variation	[13]
TNFRSF13B	TTL9OD4	Strong	Altered Expression	[14]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
WARS1	DEPVE0M	Strong	Altered Expression	[15]

This Disease Is Related to 28 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DUOX1	OTQ2AEW0	Limited	Genetic Variation	[16]
DUOX2	OTU14HCN	Limited	Genetic Variation	[16]
CYBA	OT16N9ZO	Supportive	Autosomal recessive	[6]
CYBB	OTGSG868	Supportive	Autosomal recessive	[6]
CYBC1	OTGTH90I	Supportive	Autosomal recessive	[17]
NCF1	OTMHT3G6	Supportive	Autosomal recessive	[6]
NCF2	OTAUW7L2	Supportive	Autosomal recessive	[6]
NCF4	OTX007YL	Supportive	Autosomal recessive	[6]
AKAP13	OTOZAR14	Strong	Genetic Variation	[18]
CLEC11A	OT9KBH7C	Strong	Genetic Variation	[18]
CLPB	OT1I0IBK	Strong	Biomarker	[19]
DCTN3	OTQOSUES	Strong	Genetic Variation	[20]
DHX37	OTM1A5KP	Strong	Biomarker	[21]
DYNC1H1	OTD1KRKO	Strong	Genetic Variation	[20]
EFNA2	OTEAUKRX	Strong	Genetic Variation	[22]
EFS	OT06O7XL	Strong	Biomarker	[23]
ELF1	OTV5LKIA	Strong	Genetic Variation	[22]
ELOF1	OT8BXS5U	Strong	Genetic Variation	[22]
ING1	OTEZBRKW	Strong	Genetic Variation	[18]
LRBA	OTOUZN9G	Strong	Biomarker	[10]
NOX1	OTZPJQCC	Strong	Genetic Variation	[24]
NOX3	OT0FFJH8	Strong	Biomarker	[25]
NOX5	OTHTH59G	Strong	Genetic Variation	[26]
NSFL1C	OTIKQF3U	Strong	Genetic Variation	[18]
PLB1	OTZ6TTYV	Strong	Genetic Variation	[13]
PLEK	OTB73XXA	Strong	Genetic Variation	[18]
POLR3E	OT69PWBM	Strong	Biomarker	[23]
PRDM16	OT0BGA27	Strong	Altered Expression	[27]

References

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• [11] Differential Transgene Silencing of Myeloid-Specific Promoters in the AAVS1 Safe Harbor Locus of Induced Pluripotent Stem Cell-Derived Myeloid Cells.Hum Gene Ther. 2020 Feb;31(3-4):199-210. doi: 10.1089/hum.2019.194. Epub 2020 Jan 23.
• [12] Genetic localisation of the RP2 type of X linked retinitis pigmentosa in a large kindred.J Med Genet. 1991 Jul;28(7):453-7. doi: 10.1136/jmg.28.7.453.
• [13] CRISPR/Cas9-generated p47(phox)-deficient cell line for Chronic Granulomatous Disease gene therapy vector development.Sci Rep. 2017 Mar 13;7:44187. doi: 10.1038/srep44187.
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• [15] Gene expression in chronic granulomatous disease and interferon- receptor-deficient cells treated in vitro with interferon-.J Cell Biochem. 2019 Mar;120(3):4321-4332. doi: 10.1002/jcb.27718. Epub 2018 Sep 27.
• [16] Cytologic and Ultrastructural Findings of Bronchoalveolar Lavage in Patients With Chronic Granulomatous Disease.Pediatr Dev Pathol. 2018 Jul-Aug;21(4):347-354. doi: 10.1177/1093526617736188. Epub 2017 Oct 19.
• [17] A homozygous loss-of-function mutation leading to CYBC1 deficiency causes chronic granulomatous disease. Nat Commun. 2018 Oct 25;9(1):4447. doi: 10.1038/s41467-018-06964-x.
• [18] Aberrant [correction of Abberant] cytosolic calcium ion mobilization in chronic granulomatous disease neutrophils.Inflammation. 2004 Jun;28(3):133-8. doi: 10.1023/b:ifla.0000039559.96659.d9.
• [19] Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter bethesdensis Infection of Neutrophils from Healthy Subjects and Patients with Chronic Granulomatous Disease.Infect Immun. 2015 Nov;83(11):4277-92. doi: 10.1128/IAI.00778-15. Epub 2015 Aug 17.
• [20] Therapeutic effects of proteoliposomes on X-linked chronic granulomatous disease: proof of concept using macrophages differentiated from patient-specific induced pluripotent stem cells.Int J Nanomedicine. 2017 Mar 20;12:2161-2177. doi: 10.2147/IJN.S128611. eCollection 2017.
• [21] Clinical and molecular findings of chronic granulomatous disease in Oman: family studies.Clin Genet. 2015 Feb;87(2):185-9. doi: 10.1111/cge.12351. Epub 2014 Feb 17.
• [22] Elf-1 and PU.1 induce expression of gp91(phox) via a promoter element mutated in a subset of chronic granulomatous disease patients.Blood. 1999 May 15;93(10):3512-20.
• [23] Impaired X-CGD T cell compartment is gp91phox-NADPH oxidase independent.Clin Immunol. 2018 Aug;193:52-59. doi: 10.1016/j.clim.2018.01.010. Epub 2018 Feb 3.
• [24] Colitis susceptibility in mice with reactive oxygen species deficiency is mediated by mucus barrier and immune defense defects.Mucosal Immunol. 2019 Nov;12(6):1316-1326. doi: 10.1038/s41385-019-0205-x. Epub 2019 Sep 25.
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• [27] Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1.Nat Med. 2006 Apr;12(4):401-9. doi: 10.1038/nm1393. Epub 2006 Apr 2.