Details of Disease

General Information of Disease (ID: DIS1X7PX)

• Disease Name: Vitamin K-dependent clotting factors, combined deficiency of, type 1
• Synonyms: vitamin K-dependent clotting factors, combined deficiency of, 1; multiple coagulation Factor deficiency 3; glutamic acid, deficient gamma-carboxylation of; vitamin K-dependent coagulation defect; familial multiple coagulation Factor deficiency 3; VKCFD1; Vkcfd; hereditary combined deficiency of vitamin K-dependent clotting factors; FMFD 3; factors II, VII, IX, and X, combined deficiency of; vitamin K-dependent clotting factors, combined deficiency of, type 1; hereditary combined deficiency of factors II, VII, IX and X; GGCX congenital vitamin K-dependent coagulation factors combined deficiency; congenital vitamin K-dependent coagulation factors combined deficiency caused by mutation in GGCX
• Definition: Combined vitamin K-dependent clotting factors deficiency (VKCFD) is a congenital bleeding disorder resulting from variably decreased levels of coagulation factors II, VII, IX and X, as well as natural anticoagulants protein C, protein S and protein Z.|This term's classification was reviewed in the context of the Strategic Refinement project (2023) and was determined to be excluded from the 'metabolic disease' (MONDO:0005066) ontology branch (https://orcid.org/0000-0002-1780-5230)
• Disease Hierarchy:
  DIS9VV3W: Congenital vitamin K-dependent coagulation factors deficiency
  DIS1X7PX: Vitamin K-dependent clotting factors, combined deficiency of, type 1
• Disease Identifiers:
  MONDO ID: MONDO_0010187
  MESH ID: C564741
  UMLS CUI: C1848534
  OMIM ID: 277450
  MedGen ID: 376381
  Orphanet ID: 98434

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
VKORC1	OTOJNJRD	Supportive	Autosomal recessive	[1]
LMAN1	OTYHKDEO	Strong	Biomarker	[5]
MCFD2	OTM0XU0U	Strong	Biomarker	[5]
GGCX	OTE0FNAP	Definitive	Autosomal recessive	[4]

This Disease Is Related to 3 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
GGCX	TT76OLR	Strong	Genetic Variation	[2]
VKORC1	TTEUC8H	Strong	Genetic Variation	[3]
GGCX	TT76OLR	Definitive	Autosomal recessive	[4]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
VKORC1	DEVRYQN	Supportive	Autosomal recessive	[1]

References

• [1] Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Nature. 2004 Feb 5;427(6974):537-41. doi: 10.1038/nature02214.
• [2] Exon2 skipping eliminates -glutamyl carboxylase activity, indicating a partial splicing defect in a patient with vitaminK clotting factor deficiency.J Thromb Haemost. 2019 Jul;17(7):1053-1063. doi: 10.1111/jth.14456. Epub 2019 Jun 7.
• [3] Uniparental disomy causes deficiencies of vitamin K-dependent proteins.J Thromb Haemost. 2016 Dec;14(12):2410-2418. doi: 10.1111/jth.13517. Epub 2016 Nov 19.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders.J Thromb Haemost. 2004 Sep;2(9):1564-72. doi: 10.1111/j.1538-7836.2004.00857.x.