VKCFD1
MCID: VTM009
MIFTS: 32

Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 (VKCFD1)

Categories: Blood diseases, Genetic diseases, Oral diseases

Aliases & Classifications for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

MalaCards integrated aliases for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

Name: Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 57 29 6 44 70
Vkcfd1 57 12 72
Combined Deficiency of Vitamin K-Dependent Clotting Factors 1 12 72
Multiple Coagulation Factor Deficiency Iii 57 72
Vitamin K-Dependent Coagulation Defect 57 13
Mcfd3 57 72
Vitamin K-Dependent Clotting Factors, Combined Deficiency of, Type 1 39
Familial Multiple Coagulation Factor Deficiency Iii 57
Factors Ii, Vii, Ix, and X, Combined Deficiency of 57
Multiple Coagulation Factor Deficiency Iii; Mcfd3 57
Glutamic Acid, Deficient Gamma-Carboxylation of 57
Fmfd Iii 57
Vkcfd 57

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive


HPO:

31
vitamin k-dependent clotting factors, combined deficiency of, 1:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

Disease Ontology 12 DOID:0112173
OMIM® 57 277450
OMIM Phenotypic Series 57 PS277450
MeSH 44 C564741
MedGen 41 C1848534
UMLS 70 C1848534

Summaries for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

OMIM® : 57 Deficiency of all vitamin K-dependent clotting factors leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. Acquired forms of the disorder can be caused by intestinal malabsorption of vitamin K. Familial multiple coagulation factor deficiency is rare. Clinical symptoms of the disease include episodes of intracranial hemorrhage in the first weeks of life, sometimes leading to a fatal outcome. The pathomechanism is based on a reduced hepatic gamma-carboxylation of glutamic acid residues of all vitamin K-dependent blood coagulation factors, as well as the anticoagulant factors protein C (612283) and protein S (176880). Posttranslational gamma-carboxylation of proteins enables the calcium-dependent attachment of the proteins to the phospholipid bilayer of membranes, an essential prerequisite for blood coagulation. Vitamin K1 acts as a cofactor for the vitamin K-dependent carboxylase in liver microsomes, GGCX. (277450) (Updated 20-May-2021)

MalaCards based summary : Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1, also known as vkcfd1, is related to hereditary combined deficiency of vitamin k-dependent clotting factors and vitamin k-dependent clotting factors, combined deficiency of, 2. An important gene associated with Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 is GGCX (Gamma-Glutamyl Carboxylase), and among its related pathways/superpathways is Biosynthesis of cofactors. Related phenotypes are short nose and epiphyseal stippling

Disease Ontology : 12 A hereditary combined deficiency of vitamin K-dependent clotting factors that has material basis in homozygous or compound heterozygous mutation in GGCX on chromosome 2p11.2.

UniProtKB/Swiss-Prot : 72 Combined deficiency of vitamin K-dependent clotting factors 1: VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K.

Related Diseases for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Diseases related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 hereditary combined deficiency of vitamin k-dependent clotting factors 11.0
2 vitamin k-dependent clotting factors, combined deficiency of, 2 10.9
3 vitamin k deficiency bleeding 10.0
4 rare hemorrhagic disorder 10.0

Symptoms & Phenotypes for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Human phenotypes related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 short nose 31 HP:0003196
2 epiphyseal stippling 31 HP:0010655
3 epistaxis 31 HP:0000421
4 bruising susceptibility 31 HP:0000978
5 short distal phalanx of finger 31 HP:0009882
6 abnormal bleeding 31 HP:0001892
7 prolonged partial thromboplastin time 31 HP:0003645
8 joint hemorrhage 31 HP:0005261
9 ecchymosis 31 HP:0031364

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Nose:
epistaxis
nasal hypoplasia

Joints:
hemarthrosis

Skel:
stippled epiphyses

Lab:
abnormal partial thromboplastin time
variably abnormal prothrombin time
deficiency of procoagulant factors ii, vii, ix, and x and natural anticoagulant proteins c and s
vitamin k-dependent gamma-carboxylation defect

Skin:
ecchymoses

Limbs:
distal phalangeal hypoplasia

Heme:
neonatal bleeding tendency

Clinical features from OMIM®:

277450 (Updated 20-May-2021)

GenomeRNAi Phenotypes related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased ionizing radiation sensitivity GR00232-A-1 8.32 MAT2A

Drugs & Therapeutics for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Search Clinical Trials , NIH Clinical Center for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Cochrane evidence based reviews: vitamin k-dependent clotting factors, combined deficiency of, 1

Genetic Tests for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Genetic tests related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

# Genetic test Affiliating Genes
1 Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 29 GGCX

Anatomical Context for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Publications for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Articles related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

(show all 25)
# Title Authors PMID Year
1
A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors. 57 6
9845520 1998
2
Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants. 57 6
2145029 1990
3
Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. 61 6
15287948 2004
4
Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors. 6
11071668 2000
5
Expression and characterization of the naturally occurring mutation L394R in human gamma-glutamyl carboxylase. 6
10934213 2000
6
Vitamin K deficiency embryopathy. 57
9738872 1998
7
Vitamin K deficiency embryopathy: a phenocopy of the warfarin embryopathy due to a disorder of embryonic vitamin K metabolism. 57
9382132 1997
8
Severe cervical dysplasia and nasal cartilage calcification following prenatal warfarin exposure. 57
9286443 1997
9
Molecular basis of vitamin K-dependent gamma-carboxylation. 57
2184900 1990
10
Association of congenital deficiency of multiple vitamin K-dependent coagulation factors and the phenotype of the warfarin embryopathy: clues to the mechanism of teratogenicity of coumarin derivatives. 57
3499071 1987
11
Vitamin K-dependent carboxylase. 57
3896125 1985
12
Studies on a family with combined functional deficiencies of vitamin K-dependent coagulation factors. 57
7085873 1982
13
Familial multiple coagulation factor deficiencies. I. Review of the literature: Differentiation of single hereditary disorders associated with multiple factor deficiencies from coincidental concurrence of single factor deficiency states. 57
6794149 1981
14
Characterization of a variant prothrombin in a patient congenitally deficient in factors II, VII, IX and X. 57
7378310 1980
15
Maternal and fetal sequelae of anticoagulation during pregnancy. 57
6985765 1980
16
Congenital deficiency of blood clotting factors II, VII, IX, and X. 57
426915 1979
17
Congenital combined deficiency of coagulation factors II, VII, IX and X. Report of a case. 57
5936414 1966
18
Congenital hemorrhagic diathesis of the prothrombin complex. 57
13313579 1956
19
GGCX mutations show different responses to vitamin K thereby determining the severity of the hemorrhagic phenotype in VKCFD1 patients. 61
33590680 2021
20
[Development of a cell-based diagnostic system for vitamin K-dependent coagulation factor deficiency 1]. 61
32761584 2020
21
Exon 2 skipping eliminates γ-glutamyl carboxylase activity, indicating a partial splicing defect in a patient with vitamin K clotting factor deficiency. 61
31009158 2019
22
GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations. 61
28125048 2017
23
Uniparental disomy causes deficiencies of vitamin K-dependent proteins. 61
27681307 2016
24
Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations. 61
25151188 2014
25
Familial deficiency of vitamin K-dependent clotting factors. 61
19141161 2008

Variations for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

ClinVar genetic disease variations for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

6 (show top 50) (show all 188)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 GGCX NM_000821.7(GGCX):c.1181T>G (p.Leu394Arg) SNV Pathogenic 16194 rs121909675 GRCh37: 2:85780168-85780168
GRCh38: 2:85553045-85553045
2 GGCX NM_000821.7(GGCX):c.1502G>C (p.Trp501Ser) SNV Pathogenic 16195 rs28928872 GRCh37: 2:85779042-85779042
GRCh38: 2:85551919-85551919
3 GGCX NM_000821.7(GGCX):c.1454G>C (p.Arg485Pro) SNV Pathogenic 16197 rs121909676 GRCh37: 2:85779090-85779090
GRCh38: 2:85551967-85551967
4 GGCX NM_000821.7(GGCX):c.215-1G>T SNV Pathogenic 16198 rs786205096 GRCh37: 2:85786199-85786199
GRCh38: 2:85559076-85559076
5 GGCX NM_000821.7(GGCX):c.773G>A (p.Gly258Asp) SNV Likely pathogenic 992373 GRCh37: 2:85781382-85781382
GRCh38: 2:85554259-85554259
6 GGCX NM_000821.7(GGCX):c.1987C>T (p.Gln663Ter) SNV Likely pathogenic 992374 GRCh37: 2:85777775-85777775
GRCh38: 2:85550652-85550652
7 GGCX NM_000821.7(GGCX):c.57A>T (p.Lys19Asn) SNV Uncertain significance 896545 GRCh37: 2:85788095-85788095
GRCh38: 2:85560972-85560972
8 GGCX NM_000821.7(GGCX):c.26G>A (p.Arg9Gln) SNV Uncertain significance 896546 GRCh37: 2:85788526-85788526
GRCh38: 2:85561403-85561403
9 GGCX , MAT2A NM_000821.7(GGCX):c.*4798G>A SNV Uncertain significance 898901 GRCh37: 2:85772259-85772259
GRCh38: 2:85545136-85545136
10 GGCX NM_000821.7(GGCX):c.*3841T>A SNV Uncertain significance 898974 GRCh37: 2:85773216-85773216
GRCh38: 2:85546093-85546093
11 GGCX NM_000821.7(GGCX):c.*3770T>C SNV Uncertain significance 898975 GRCh37: 2:85773287-85773287
GRCh38: 2:85546164-85546164
12 GGCX NM_000821.7(GGCX):c.*3756A>G SNV Uncertain significance 898976 GRCh37: 2:85773301-85773301
GRCh38: 2:85546178-85546178
13 GGCX NM_000821.7(GGCX):c.1355G>C (p.Ser452Thr) SNV Uncertain significance 896482 GRCh37: 2:85779623-85779623
GRCh38: 2:85552500-85552500
14 GGCX NM_000821.7(GGCX):c.*2774A>G SNV Uncertain significance 899041 GRCh37: 2:85774283-85774283
GRCh38: 2:85547160-85547160
15 GGCX NM_000821.7(GGCX):c.*2740A>C SNV Uncertain significance 899042 GRCh37: 2:85774317-85774317
GRCh38: 2:85547194-85547194
16 GGCX NM_000821.7(GGCX):c.*2716A>G SNV Uncertain significance 899043 GRCh37: 2:85774341-85774341
GRCh38: 2:85547218-85547218
17 GGCX NM_000821.7(GGCX):c.*2490T>C SNV Uncertain significance 899044 GRCh37: 2:85774567-85774567
GRCh38: 2:85547444-85547444
18 GGCX NM_000821.7(GGCX):c.*1145G>A SNV Uncertain significance 899104 GRCh37: 2:85775912-85775912
GRCh38: 2:85548789-85548789
19 GGCX NM_000821.7(GGCX):c.*1037A>G SNV Uncertain significance 899105 GRCh37: 2:85776020-85776020
GRCh38: 2:85548897-85548897
20 GGCX NM_000821.7(GGCX):c.*973A>G SNV Uncertain significance 899106 GRCh37: 2:85776084-85776084
GRCh38: 2:85548961-85548961
21 GGCX NM_000821.7(GGCX):c.2254G>C (p.Asp752His) SNV Uncertain significance 899164 GRCh37: 2:85777080-85777080
GRCh38: 2:85549957-85549957
22 GGCX NM_000821.7(GGCX):c.2119A>C (p.Ile707Leu) SNV Uncertain significance 899165 GRCh37: 2:85777215-85777215
GRCh38: 2:85550092-85550092
23 GGCX NM_000821.7(GGCX):c.1994G>A (p.Arg665Lys) SNV Uncertain significance 899166 GRCh37: 2:85777768-85777768
GRCh38: 2:85550645-85550645
24 GGCX NM_000821.7(GGCX):c.1815C>G (p.Asn605Lys) SNV Uncertain significance 899167 GRCh37: 2:85778121-85778121
GRCh38: 2:85550998-85550998
25 GGCX NM_000821.7(GGCX):c.745C>T (p.Leu249=) SNV Uncertain significance 899224 GRCh37: 2:85781410-85781410
GRCh38: 2:85554287-85554287
26 GGCX NM_000821.7(GGCX):c.654G>A (p.Lys218=) SNV Uncertain significance 899225 GRCh37: 2:85782678-85782678
GRCh38: 2:85555555-85555555
27 GGCX NM_000821.7(GGCX):c.614G>A (p.Gly205Asp) SNV Uncertain significance 899226 GRCh37: 2:85783309-85783309
GRCh38: 2:85556186-85556186
28 GGCX NM_000821.7(GGCX):c.849G>C (p.Val283=) SNV Uncertain significance 337269 rs149603998 GRCh37: 2:85781306-85781306
GRCh38: 2:85554183-85554183
29 GGCX NM_000821.7(GGCX):c.*4215G>A SNV Uncertain significance 337183 rs886056358 GRCh37: 2:85772842-85772842
GRCh38: 2:85545719-85545719
30 GGCX NM_000821.7(GGCX):c.*270T>G SNV Uncertain significance 337249 rs886056377 GRCh37: 2:85776787-85776787
GRCh38: 2:85549664-85549664
31 GGCX NM_000821.7(GGCX):c.*3924A>G SNV Uncertain significance 337186 rs886056359 GRCh37: 2:85773133-85773133
GRCh38: 2:85546010-85546010
32 GGCX NM_000821.7(GGCX):c.*2560A>G SNV Uncertain significance 337215 rs886056366 GRCh37: 2:85774497-85774497
GRCh38: 2:85547374-85547374
33 GGCX NM_000821.7(GGCX):c.*2304T>C SNV Uncertain significance 337218 rs886056367 GRCh37: 2:85774753-85774753
GRCh38: 2:85547630-85547630
34 GGCX NM_000821.7(GGCX):c.159C>A (p.Thr53=) SNV Uncertain significance 337278 rs61733104 GRCh37: 2:85787993-85787993
GRCh38: 2:85560870-85560870
35 GGCX NM_000821.7(GGCX):c.24G>A (p.Ala8=) SNV Uncertain significance 337281 rs371622780 GRCh37: 2:85788528-85788528
GRCh38: 2:85561405-85561405
36 GGCX NM_000821.7(GGCX):c.*106T>G SNV Uncertain significance 337255 rs530539627 GRCh37: 2:85776951-85776951
GRCh38: 2:85549828-85549828
37 GGCX NM_000821.7(GGCX):c.1107C>T (p.Leu369=) SNV Uncertain significance 337267 rs145056129 GRCh37: 2:85780403-85780403
GRCh38: 2:85553280-85553280
38 GGCX NM_000821.7(GGCX):c.-53C>T SNV Uncertain significance 337284 rs886056381 GRCh37: 2:85788604-85788604
GRCh38: 2:85561481-85561481
39 GGCX NM_000821.7(GGCX):c.*2284C>G SNV Uncertain significance 337221 rs572084939 GRCh37: 2:85774773-85774773
GRCh38: 2:85547650-85547650
40 GGCX NM_000821.7(GGCX):c.*610C>T SNV Uncertain significance 337241 rs532781606 GRCh37: 2:85776447-85776447
GRCh38: 2:85549324-85549324
41 GGCX NM_000821.7(GGCX):c.*4047T>C SNV Uncertain significance 337184 rs189391524 GRCh37: 2:85773010-85773010
GRCh38: 2:85545887-85545887
42 GGCX NM_000821.7(GGCX):c.*470G>A SNV Uncertain significance 337244 rs746348970 GRCh37: 2:85776587-85776587
GRCh38: 2:85549464-85549464
43 GGCX NM_000821.7(GGCX):c.1492C>T (p.Arg498Cys) SNV Uncertain significance 337264 rs372161185 GRCh37: 2:85779052-85779052
GRCh38: 2:85551929-85551929
44 GGCX NM_000821.7(GGCX):c.*108G>T SNV Uncertain significance 337253 rs886056378 GRCh37: 2:85776949-85776949
GRCh38: 2:85549826-85549826
45 GGCX NM_000821.7(GGCX):c.*1721G>A SNV Uncertain significance 337227 rs187452629 GRCh37: 2:85775336-85775336
GRCh38: 2:85548213-85548213
46 GGCX NM_000821.7(GGCX):c.789C>T (p.Asp263=) SNV Uncertain significance 337270 rs146085955 GRCh37: 2:85781366-85781366
GRCh38: 2:85554243-85554243
47 GGCX NM_000821.7(GGCX):c.529A>G (p.Asn177Asp) SNV Uncertain significance 337273 rs149039591 GRCh37: 2:85785573-85785573
GRCh38: 2:85558450-85558450
48 GGCX NM_000821.7(GGCX):c.*1245G>C SNV Uncertain significance 337230 rs190566964 GRCh37: 2:85775812-85775812
GRCh38: 2:85548689-85548689
49 GGCX NM_000821.7(GGCX):c.198C>T (p.Val66=) SNV Uncertain significance 337276 rs147427088 GRCh37: 2:85787954-85787954
GRCh38: 2:85560831-85560831
50 GGCX NM_000821.7(GGCX):c.*3921G>A SNV Uncertain significance 337187 rs886056360 GRCh37: 2:85773136-85773136
GRCh38: 2:85546013-85546013

UniProtKB/Swiss-Prot genetic disease variations for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1:

72
# Symbol AA change Variation ID SNP ID
1 GGCX p.Leu394Arg VAR_005781 rs121909675
2 GGCX p.Trp501Ser VAR_015218 rs28928872
3 GGCX p.Arg485Pro VAR_021826 rs121909676

Expression for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Search GEO for disease gene expression data for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1.

Pathways for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Pathways related to Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
10.85 MAT2A GGCX

GO Terms for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

Sources for Vitamin K-Dependent Clotting Factors, Combined Deficiency of, 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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