GGCX

Summary

GGCX (gamma-glutamyl carboxylase, HGNC:4247) is a protein-coding gene on chromosome 2p11.2, encoding Vitamin K-dependent gamma-carboxylase (P38435). Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant epoxidation of vitamin K hydroquinone to vitamin K epoxide.

This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2677 — RefSeq curated summary.

At a glance

• Gene–disease (curated): vitamin K-dependent clotting factors, combined deficiency of, type 1 (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 609 total — 37 pathogenic, 13 likely-pathogenic
• Phenotypes (HPO): 53
• Druggable target: yes
• MANE Select transcript: NM_000821

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4247
Approved symbol	GGCX
Name	gamma-glutamyl carboxylase
Location	2p11.2
Locus type	gene with protein product
Status	Approved
Aliases	VKCFD1
Ensembl gene	ENSG00000115486
Ensembl biotype	protein_coding
OMIM	137167
Entrez	2677

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 22 protein_coding, 8 nonsense_mediated_decay, 8 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000233838, ENST00000421496, ENST00000423570, ENST00000428479, ENST00000430215, ENST00000465637, ENST00000473665, ENST00000481541, ENST00000482662, ENST00000496962, ENST00000685865, ENST00000687250, ENST00000687995, ENST00000688205, ENST00000688788, ENST00000689276, ENST00000689576, ENST00000690108, ENST00000690468, ENST00000690595, ENST00000691348, ENST00000691410, ENST00000693287, ENST00000693354, ENST00000693681, ENST00000896458, ENST00000896459, ENST00000896460, ENST00000896461, ENST00000896462, ENST00000896463, ENST00000896464, ENST00000896465, ENST00000911478, ENST00000942081, ENST00000942082, ENST00000942083, ENST00000942084, ENST00000942085

RefSeq mRNA: 3 — MANE Select: NM_000821 NM_000821, NM_001142269, NM_001311312

CCDS: CCDS1978, CCDS46353, CCDS92792

Canonical transcript exons

ENST00000233838 — 15 exons

Exon	Start	End
ENSE00000767392	85554143	85554306
ENSE00001130335	85544720	85550126
ENSE00001135480	85550555	85550750
ENSE00001135491	85550925	85551072
ENSE00001135503	85551480	85551610
ENSE00001135511	85551812	85551981
ENSE00001135520	85552416	85552567
ENSE00001135557	85555484	85555590
ENSE00001135574	85558440	85558605
ENSE00001135583	85558917	85559075
ENSE00003466790	85553232	85553497
ENSE00003473017	85552939	85553070
ENSE00003479084	85561386	85561493
ENSE00003479852	85556182	85556260
ENSE00003635113	85560815	85560985

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 97.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.5252 / max 187.6435, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
29416	8.1439	1770
29417	7.8085	1791
29418	1.1179	849
29419	0.3776	157
29420	0.0773	18

Top tissues by expression

292 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	97.93	gold quality
tendon of biceps brachii	UBERON:0008188	97.37	gold quality
liver	UBERON:0002107	94.75	gold quality
cervix squamous epithelium	UBERON:0006922	94.28	gold quality
right lobe of liver	UBERON:0001114	94.14	gold quality
endothelial cell	CL:0000115	93.88	gold quality
stromal cell of endometrium	CL:0002255	91.89	gold quality
medial globus pallidus	UBERON:0002477	91.56	gold quality
saphenous vein	UBERON:0007318	91.34	gold quality
body of pancreas	UBERON:0001150	90.50	gold quality
oviduct epithelium	UBERON:0004804	90.34	gold quality
pancreas	UBERON:0001264	90.12	gold quality
parotid gland	UBERON:0001831	90.07	gold quality
islet of Langerhans	UBERON:0000006	89.94	gold quality
oocyte	CL:0000023	89.58	gold quality
gastrocnemius	UBERON:0001388	89.11	gold quality
globus pallidus	UBERON:0001875	88.49	gold quality
muscle of leg	UBERON:0001383	88.40	gold quality
epithelial cell of pancreas	CL:0000083	88.39	gold quality
gingival epithelium	UBERON:0001949	88.35	gold quality
left adrenal gland	UBERON:0001234	88.30	gold quality
right adrenal gland	UBERON:0001233	88.20	gold quality
adrenal cortex	UBERON:0001235	88.19	gold quality
corpus epididymis	UBERON:0004359	88.18	gold quality
fallopian tube	UBERON:0003889	88.17	gold quality
left adrenal gland cortex	UBERON:0035825	88.04	gold quality
adrenal gland	UBERON:0002369	87.81	gold quality
upper lobe of left lung	UBERON:0008952	87.80	gold quality
pylorus	UBERON:0001166	87.79	gold quality
right adrenal gland cortex	UBERON:0035827	87.56	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	25.62
E-ANND-3	yes	12.11

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
RUNX2	Activation
SMAD2	Activation
SMAD7	Activation
TGFB1	Activation

miRNA regulators (miRDB)

195 targeting GGCX, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 40)

• Cys-99 and Cys-450 are free sulfhydryls in the gamma-glutamyl carboxylase active site. The free sulfhydryls were mapped by isolating a native carboxylase-factor IX enzyme substrate complex, modification with NEM and mass spectral mapping. (PMID:11087858)
• characterization of vitamin K-dependent gamma-glutamyl carboxylase internal propeptide (PMID:12034728)
• Cys-99 and Cys-450 form the only disulfide bond in carboxylase (PMID:12963724)
• mutations in residues between 393 and 404 in gamma-glutamyl carboxylase cause impaired glutamate binding (PMID:12968027)
• A 14-base deletion was found in intron 1 (bases 1056-1069) of the gamma-carboxylase gene. It destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. This element may regulation the enzyme’s expression. (PMID:14567538)
• binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site has a role in carboxylation and regulation of release of carboxylated product (PMID:14660587)
• An activated amine initiates the vitamin K-dependent carboxylation reaction, while the Cys-99 and Cys-450 free sulfhydryls play other important roles in the carboxylase reaction (PMID:15365175)
• Quantitative radiolabeled N-ethylmaleimide modification of a carboxylase with all Cys residues changed to Ala supports the identification of Cys-99 and Cys-450 as the free sulfhydryls in the active site. (PMID:15365175)
• GGCX SNP showed a small but significant effect on warfarin dose. (PMID:15883587)
• Crystallization of human GGCX. (PMID:16979907)
• report demonstrates the different activities of GGCX between the common genotypes and their association with bone mineral density (PMID:17029979)
• In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients. (PMID:17049586)
• Mass spectrometric results show that the N-linked glycosylation in carboxylase occurs at positions N459, N550, N605, and N627. (PMID:17144668)
• identified 37 SNPs in GGCX. The GGCX-12970 SNP had a small, but significant effect, on warfarin maintenance dose (PMID:17764537)
• There is no significant association between the polymorphisms in GGCX and the warfarin dose requirement. (PMID:17786385)
• GGCX R325Q genotype did not provide significant differences in acenocoumarol dose requirements in patients (PMID:18234294)
• A homology model of gamma-glutamyl carboxylase transmembrane domains 2 and 5 suggests that not only do these two domains associate but that transmembrane domain 2 may interact with another transmembrane domain. (PMID:18498174)
• analysis of GGCX and ABCC6 mutations in a family with pseudoxanthoma elasticum-like phenotypes [case report] (PMID:18800149)
• Our findings also confirm GGCX as the second gene locus causing Pseudoxanthoma elasticum (PMID:19116367)
• exon 2 deletion splice variant of GGCX causes dysfunction of GGCX enzyme activity resulting in des-gamma-carboxy prothrombin production in HCC cell lines (PMID:19383345)
• heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower percent undercarboxylated osteocalcin relative to either homozygous group. (PMID:19436136)
• Polymorphisms in VKORC1 and GGCX are not major genetic determinants of vitamin K-dependent coagulation factor activity in Western Germans. (PMID:19652895)
• there may be no significant association between the low activity and mutation of GGCX in calcium oxalate urolithiasis (PMID:19821094)
• Gene polymorphisms of VKORC1 significantly associated with the variation of interindividual warfarin dose requirement variation, and the effects are different in ethnicities. (PMID:19942260)
• Subtle polymorphisms, including those in GGCX, NQO1, and VKORC1 genes, influence individual susceptibility to the development of atherosclerotic stroke. (PMID:20193673)
• The activity and expression of GGCX are decreased in renal tissues of patients with calcium oxolate urolithiasis. (PMID:20332604)
• genetic polymorphism affects therapeutic dose of warfarin (PMID:20694283)
• Effect of vitamin K-dependent protein precursor propeptide, vitamin K hydroquinone, and glutamate substrate binding on the structure and function of {gamma}-glutamyl carboxylase. (PMID:20716530)
• GGCX polymorphism appeared to have an influence over the reduction of undercarboxylated osteocalcin, especially in older women (age >/=65). (PMID:21344298)
• no effects of genetic variants on maintenance warfarin dose in a multi-ethnic Asian population (PMID:21475774)
• Molecular analysis of the gamma-glutamylcarboxylase gene revealed a heterozygous single nucleotide polymorphism, which decreases carboxylase activity and induces VK-dependent coagulation deficiency. (PMID:21704322)
• no association between haplotypes and venous thrombosis (PMID:21800014)
• Quantitative PCR assays for VKORC1, CYP4F2, GGCX and CALU identified two copies in all populations. (PMID:22188360)
• evaluation of urinary Gla excretion in relation with apo E genotype (PMID:23817635)
• These findings indicate that individuals carrying the CYP2C19 rs3814637CC or CYP2C9 rs1057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population. (PMID:23941071)
• In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in the gamma-glutamyl carboxylase gene rs259251 loci required significantly higher warfarin dose than those with CC genotype. (PMID:24148610)
• study demonstrated the effects of SNP (974G>A) in the GGCX gene on the correlation between dietary vitamin K intake and gamma-carboxylation of serum osteocalcin (PMID:24231026)
• GGCX mutation found in families with pseudoxanthoma elasticum with retinitis pigmentosa and cutis laxa. (PMID:24739904)
• The allele frequency for GGCX 12970 C > G is 1.43 in north Indians and did not have a significant bearing on the maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients. (PMID:24927344)
• GGCX c.2084+45G polymorphisms has a moderate effect on VKAs dose requirements in Slavic population from Central-Eastern Europe. (PMID:25042728)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ggcx	ENSDARG00000067805
mus_musculus	Ggcx	ENSMUSG00000053460
rattus_norvegicus	Ggcx	ENSRNOG00000012975
drosophila_melanogaster	GC	FBGN0035245

Protein

Protein identifiers

Vitamin K-dependent gamma-carboxylase — P38435 (reviewed: P38435)

Alternative names: Gamma-glutamyl carboxylase, Peptidyl-glutamate 4-carboxylase, Vitamin K gamma glutamyl carboxylase

All UniProt accessions (14): P38435, A0A8I5KT68, A0A8I5KV68, A0A8I5KXJ8, A0A8I5KXQ8, A0A8I5KXY4, A0A8I5KY98, A0A8I5KZ18, A0A8I5QJ91, A0A8I5QJA4, A0A8I5QJS0, A0A8I5QKY1, F8WB98, F8WCF0

UniProt curated annotations — full annotation on UniProt →

Function. Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant epoxidation of vitamin K hydroquinone to vitamin K epoxide. Couples epoxidation and carboxylation in the same active site. Catalyzes gamma-carboxylation of blood coagulation factors (F2, F7, F9 and F10) and anticoagulants such as PROC, which are essential for thrombosis. Catalyzes gamma-carboxylation of osteocalcin/BGLAP, which is essential for bone metabolism. Catalyzes gamma-carboxylation of matrix Gla protein (MGP) and other transmembrane gamma-Gla proteins such as PRRG2, which are essential for calcium homeostasis and haemostasis.

Subunit / interactions. Monomer. May interact with CALU.

Subcellular location. Endoplasmic reticulum membrane.

Disease relevance. Combined deficiency of vitamin K-dependent clotting factors 1 (VKCFD1) [MIM:277450] VKCFD leads to a bleeding tendency that is usually reversed by oral administration of vitamin K. The disease is caused by variants affecting the gene represented in this entry. Pseudoxanthoma elasticum-like disorder with multiple coagulation factor deficiency (PXEL-MCFD) [MIM:610842] Characterized by hyperlaxity of the skin involving the entire body. Important phenotypic differences with classical PXE include much more severe skin laxity with spreading toward the trunk and limbs with thick, leathery skin folds rather than confinement to flexural areas, and no decrease in visual acuity. Moreover, detailed electron microscopic analyses revealed that alterations of elastic fibers as well as their mineralization are slightly different from those in classic PXE. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Interacts with lipids such as phosphatidylcholine and cholesterol; this interaction is required for optimal carboxylation activity.

Miscellaneous. The vitamin K-dependent protein substrates have an N-terminal propeptide that is recognized by the carboxylase.

Similarity. Belongs to the vitamin K-dependent gamma-carboxylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P38435-1	1	yes
P38435-2	2

RefSeq proteins (3): NP_000812, NP_001135741, NP_001298241 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007782	VKG_COase	Family
IPR011020	HTTM-like	Domain
IPR011051	RmlC_Cupin_sf	Homologous_superfamily
IPR014710	RmlC-like_jellyroll	Homologous_superfamily
IPR053934	HTTM_dom	Domain
IPR053935	VKGC_lumenal_dom	Domain

Pfam: PF05090, PF22777

Enzyme classification (BRENDA):

• EC 4.1.1.90 — peptidyl-glutamate 4-carboxylase (BRENDA: 8 organisms, 81 substrates, 38 inhibitors, 60 Km, 41 kcat entries)

Substrate kinetics (BRENDA)

12 substrates with measured Km, best-characterized 12. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FLEEL	0.42–24.3	22
YVFLDHQDADANLILNRPKR	0.0023–2.06	17
VITAMIN KH2	0.0038–0.097	9
REDUCED VITAMIN K	—	3
28-RESIDUE PEPTIDES BASED ON RESIDUES -18 TO +10	0.0017	1
CO2	0.3	1
CONOTOXIN EPSILON-TXIX	0.565	1
PRECURSOR ANALOG CONTAINING 12 OF THE PROPEPTIDE	0.075	1
PRECURSOR ANALOG CONTAINING 29 AMINO ACIDS OF TH	0.074	1
PROFACTOR IX	0.006	1
REDUCED VITAMIN K1	0.052	1
TVFLDHENANKILNRPKRANTBLEEVRK	0.0068	1

Catalyzed reactions (Rhea), 1 shown:

• 4-carboxy-L-glutamyl-[protein] + 2,3-epoxyphylloquinone + H2O + H(+) = phylloquinol + L-glutamyl-[protein] + CO2 + O2 (RHEA:45140)

UniProt features (124 total): helix 36, strand 20, turn 12, mutagenesis site 11, topological domain 10, transmembrane region 9, sequence variant 9, glycosylation site 4, region of interest 2, binding site 2, sequence conflict 2, initiator methionine 1, chain 1, compositionally biased region 1, active site 1, modified residue 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

29 structures.

PDB	Method	Resolution (Å)
9L25	ELECTRON MICROSCOPY	2.41
9L6S	ELECTRON MICROSCOPY	2.58
9L6R	ELECTRON MICROSCOPY	2.59
9L21	ELECTRON MICROSCOPY	2.62
9L23	ELECTRON MICROSCOPY	2.62
9WF3	ELECTRON MICROSCOPY	2.65
9WFL	ELECTRON MICROSCOPY	2.75
9L6Q	ELECTRON MICROSCOPY	2.78
9L20	ELECTRON MICROSCOPY	2.82
9WF9	ELECTRON MICROSCOPY	2.83
9WF2	ELECTRON MICROSCOPY	2.94
9WFN	ELECTRON MICROSCOPY	2.94
9BUR	ELECTRON MICROSCOPY	2.95
9L54	ELECTRON MICROSCOPY	3.04
9BUX	ELECTRON MICROSCOPY	3.06
9L24	ELECTRON MICROSCOPY	3.1
9MQC	ELECTRON MICROSCOPY	3.13
9BVP	ELECTRON MICROSCOPY	3.3
9BVQ	ELECTRON MICROSCOPY	3.3
9WFC	ELECTRON MICROSCOPY	3.33
9MQB	ELECTRON MICROSCOPY	3.37
9BVL	ELECTRON MICROSCOPY	3.4
9BVM	ELECTRON MICROSCOPY	3.4
9L1Y	ELECTRON MICROSCOPY	3.46
9BVR	ELECTRON MICROSCOPY	3.5
9MQE	ELECTRON MICROSCOPY	3.56
9BVK	ELECTRON MICROSCOPY	3.6
9BUM	ELECTRON MICROSCOPY	3.63
9BVO	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P38435-F1	86.61	0.64

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 218 (proton acceptor)

Ligand- & substrate-binding residues (2): 373; 374

Post-translational modifications (1): 2

Disulfide bonds (1): 99–450

Glycosylation sites (4): 459, 550, 570, 605

Mutagenesis-validated functional residues (11):

Position	Phenotype
160	no effect on epoxidase activity. impairs carboxylase activity.
160	abolishes carboxylase activity.
218	abolishes epoxidase activity. impairs carboxylase activity.
287	no effect on epoxidase activity.
299	abolishes carboxylase activity. no effect on epoxidase activity.
381	no effect on epoxidase activity.
395	impairs carboxylase activity.
401	abolishes carboxylase activity. no effect on epoxidase activity.
402	abolishes carboxylase activity. no effect on epoxidase activity.
601	abolishes carboxylase activity; when associated with a-603.
603	abolishes carboxylase activity; when associated with a-601.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-159740	Gamma-carboxylation of protein precursors
R-HSA-9673240	Defective gamma-carboxylation of F9

MSigDB gene sets: 320 (showing top): BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_LIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_STEROID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_NEUROTRANSMITTER_TRANSPORT, HNF1_Q6, GOBP_KETONE_METABOLIC_PROCESS, GOBP_CELL_CELL_SIGNALING, GOBP_WOUND_HEALING, GOBP_REGULATION_OF_LIPID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_BONE_DEVELOPMENT, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_NEUROTRANSMITTER_TRANSPORT, GOBP_REGULATION_OF_LIPID_METABOLIC_PROCESS

GO Biological Process (11): blood coagulation (GO:0007596), cellular response to insulin stimulus (GO:0032869), protein modification process (GO:0036211), vitamin K metabolic process (GO:0042373), glucose homeostasis (GO:0042593), type B pancreatic cell proliferation (GO:0044342), negative regulation of neurotransmitter secretion (GO:0046929), protein maturation (GO:0051604), negative regulation of bone development (GO:1903011), negative regulation of testosterone biosynthetic process (GO:2000225), peptidyl-glutamic acid carboxylation (GO:0017187)

GO Molecular Function (3): gamma-glutamyl carboxylase activity (GO:0008488), vitamin binding (GO:0019842), lyase activity (GO:0016829)

GO Cellular Component (5): endoplasmic reticulum lumen (GO:0005788), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), endoplasmic reticulum (GO:0005783), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gamma-carboxylation, transport, and amino-terminal cleavage of proteins	1
Defective factor IX causes hemophilia B	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	2
cellular anatomical structure	2
hemostasis	1
wound healing	1
coagulation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
macromolecule modification	1
ketone metabolic process	1
carbohydrate homeostasis	1
epithelial cell proliferation	1
neurotransmitter secretion	1
regulation of neurotransmitter secretion	1
negative regulation of neurotransmitter transport	1
negative regulation of secretion by cell	1
gene expression	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
bone development	1
regulation of bone development	1
negative regulation of steroid biosynthetic process	1
testosterone biosynthetic process	1
negative regulation of small molecule metabolic process	1
regulation of testosterone biosynthetic process	1
peptidyl-glutamic acid modification	1
protein carboxylation	1
carboxy-lyase activity	1
small molecule binding	1
catalytic activity	1
endoplasmic reticulum	1
intracellular organelle lumen	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

944 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GGCX	VKORC1	Q9BQB6	988
GGCX	PROS1	P07225	967
GGCX	MGP	P08493	952
GGCX	PRRG1	O14668	932
GGCX	ABCC6	P78420	927
GGCX	CYP4F2	P78329	912
GGCX	CYP2C9	P11712	905
GGCX	F9	P00740	889
GGCX	PRRG2	O14669	873
GGCX	BGLAP	P02818	862
GGCX	F2	P00734	849
GGCX	F7	P08709	832
GGCX	EPHX1	P07099	824
GGCX	CALU	O43852	714
GGCX	KCNG1	Q9UIX4	701

IntAct

72 interactions, top by confidence:

A	B	Type	Score
	PMPCB	psi-mi:“MI:0914”(association)	0.640
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
TMEM9	ESYT2	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
CD70	METTL15	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
CXCR4	FANCA	psi-mi:“MI:0914”(association)	0.530
	VAPB	psi-mi:“MI:0914”(association)	0.500
SAFB	GGCX	psi-mi:“MI:0915”(physical association)	0.400
GGCX	HNRNPDL	psi-mi:“MI:0915”(physical association)	0.400
Tubg1	BDP1	psi-mi:“MI:0914”(association)	0.350
Cdc16	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Anapc2	ANAPC15	psi-mi:“MI:0914”(association)	0.350
Mad2l1bp	ARHGAP32	psi-mi:“MI:0914”(association)	0.350
Mgp	TTI1	psi-mi:“MI:0914”(association)	0.350
AP1S2	SLC43A3	psi-mi:“MI:0914”(association)	0.350
FGD1		psi-mi:“MI:0914”(association)	0.350
Ncstn	DERL1	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
TENT5A	GOLGA8R	psi-mi:“MI:0914”(association)	0.350
TERF2IP	SLC16A3	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
	ESYT2	psi-mi:“MI:0914”(association)	0.350
	PGRMC1	psi-mi:“MI:0914”(association)	0.350
HA	ESYT2	psi-mi:“MI:0914”(association)	0.350
M2	AGPS	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): GGCX (Biochemical Activity), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-MS), GGCX (Affinity Capture-RNA), GGCX (Affinity Capture-MS)

ESM2 similar proteins: A0A8C2M425, A1L1J9, A1L504, B0BNG2, D3ZBP4, F1MH07, O08984, O75908, O77759, O88496, O88908, P38435, P70606, Q07175, Q0P4Y8, Q32LM8, Q3U9G9, Q3UDW8, Q5KR61, Q5RF50, Q5RKL5, Q5T197, Q5T1A1, Q5ZKZ9, Q643R3, Q658P3, Q68CP4, Q6NVG1, Q767L9, Q7TNJ2, Q7TPN3, Q7TQM4, Q7ZWN0, Q8BKF1, Q8C3X8, Q8CI59, Q8IUH8, Q8IZY2, Q8R1J1, Q8TDZ2

Diamond homologs: O88496, P38435, Q07175, Q5RF50, Q9GL59, Q9MYY3, Q9QYC7

SIGNOR signaling

49 interactions.

A	Effect	B	Mechanism
GGCX	“down-regulates quantity”	“Reduced Vitamin K”	“chemical modification”
GGCX	“up-regulates activity”	“vitamin K epoxide”	“chemical modification”
GGCX	“up-regulates activity”	F2	carboxylation
GGCX	“up-regulates activity”	F7	carboxylation
GGCX	“up-regulates activity”	F9	carboxylation
GGCX	“up-regulates activity”	F10	carboxylation
GGCX	“up-regulates activity”	BGLAP	carboxylation
GGCX	“up-regulates activity”	GAS6	carboxylation
GGCX	“up-regulates activity”	PROS1	carboxylation
GGCX	“up-regulates activity”	PROC	carboxylation
GGCX	“up-regulates activity”	PROZ	carboxylation
GGCX	“up-regulates quantity by expression”	RUNX2	“transcriptional regulation”
GGCX	“up-regulates quantity by expression”	TGFB1	“transcriptional regulation”
GGCX	“up-regulates quantity by expression”	SMAD2	“transcriptional regulation”
GGCX	“up-regulates quantity by expression”	SMAD7	“transcriptional regulation”
CALU	“down-regulates activity”	GGCX	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

609 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	13
Uncertain significance	255
Likely benign	188
Benign	57

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1434990	NM_000821.7(GGCX):c.126G>A (p.Trp42Ter)	Pathogenic
16194	NM_000821.7(GGCX):c.1181T>G (p.Leu394Arg)	Pathogenic
16195	NM_000821.7(GGCX):c.1502G>C (p.Trp501Ser)	Pathogenic
16197	NM_000821.7(GGCX):c.1454G>C (p.Arg485Pro)	Pathogenic
16198	NM_000821.7(GGCX):c.215-1G>T	Pathogenic
16199	NM_000821.7(GGCX):c.896T>C (p.Phe299Ser)	Pathogenic
16200	NM_000821.7(GGCX):c.1672G>A (p.Gly558Arg)	Pathogenic
16201	NM_000821.7(GGCX):c.1478G>C (p.Trp493Ser)	Pathogenic
16202	NM_000821.7(GGCX):c.1120C>T (p.Gln374Ter)	Pathogenic
16203	G537Y	Pathogenic
16204	NM_000821.7(GGCX):c.1426C>T (p.Arg476Cys)	Pathogenic
16205	NM_000821.7(GGCX):c.1427G>A (p.Arg476His)	Pathogenic
1968318	NM_000821.7(GGCX):c.826A>T (p.Arg276Ter)	Pathogenic
2019870	NM_000821.7(GGCX):c.892_895del (p.Met298fs)	Pathogenic
2034469	NM_000821.7(GGCX):c.816dup (p.Asp273Ter)	Pathogenic
2049984	NM_000821.7(GGCX):c.1878_1879dup (p.Asn627fs)	Pathogenic
2097244	NM_000821.7(GGCX):c.387_388insTGGGC (p.Met130fs)	Pathogenic
2203110	NM_000821.7(GGCX):c.944G>A (p.Trp315Ter)	Pathogenic
2203111	NM_000821.7(GGCX):c.247C>T (p.Arg83Trp)	Pathogenic
2759418	NM_000821.7(GGCX):c.444T>A (p.Tyr148Ter)	Pathogenic
2956420	NM_000821.7(GGCX):c.2017C>T (p.Arg673Ter)	Pathogenic
3004458	NM_000821.7(GGCX):c.2038C>T (p.Arg680Ter)	Pathogenic
3011860	NM_000821.7(GGCX):c.1720C>T (p.Arg574Ter)	Pathogenic
3247471	NC_000002.11:g.(?85778214)(85779781_?)del	Pathogenic
3609969	NM_000821.7(GGCX):c.1153C>T (p.Gln385Ter)	Pathogenic
3614216	NM_000821.7(GGCX):c.1915C>T (p.Gln639Ter)	Pathogenic
3624296	NM_000821.7(GGCX):c.1794C>A (p.Cys598Ter)	Pathogenic
3675440	NM_000821.7(GGCX):c.973C>T (p.Arg325Ter)	Pathogenic
3683782	NM_000821.7(GGCX):c.990del (p.Leu331fs)	Pathogenic
3700225	NM_000821.7(GGCX):c.1435C>T (p.Gln479Ter)	Pathogenic

SpliceAI

2361 predictions. Top by Δscore:

Variant	Effect	Δscore
2:85550551:TTAC:T	donor_loss	1.0000
2:85550552:TACC:T	donor_loss	1.0000
2:85550553:A:AC	donor_gain	1.0000
2:85550553:AC:A	donor_gain	1.0000
2:85550554:C:CC	donor_gain	1.0000
2:85550554:CC:C	donor_gain	1.0000
2:85550554:CCT:C	donor_gain	1.0000
2:85550554:CCTG:C	donor_gain	1.0000
2:85550746:TGTTT:T	acceptor_gain	1.0000
2:85550748:TTT:T	acceptor_gain	1.0000
2:85550748:TTTCT:T	acceptor_loss	1.0000
2:85550749:TTCTG:T	acceptor_loss	1.0000
2:85550750:TC:T	acceptor_loss	1.0000
2:85550751:C:CC	acceptor_gain	1.0000
2:85550751:CTG:C	acceptor_loss	1.0000
2:85550752:T:G	acceptor_loss	1.0000
2:85550756:C:CT	acceptor_gain	1.0000
2:85550756:C:T	acceptor_gain	1.0000
2:85550757:G:T	acceptor_gain	1.0000
2:85550764:A:T	acceptor_gain	1.0000
2:85550924:CCA:C	donor_gain	1.0000
2:85550929:T:TA	donor_gain	1.0000
2:85551068:GGCAA:G	acceptor_gain	1.0000
2:85551069:GCAA:G	acceptor_gain	1.0000
2:85551070:CAA:C	acceptor_gain	1.0000
2:85551070:CAAC:C	acceptor_gain	1.0000
2:85551071:AA:A	acceptor_gain	1.0000
2:85551071:AAC:A	acceptor_loss	1.0000
2:85551072:ACTGA:A	acceptor_loss	1.0000
2:85551073:C:CC	acceptor_gain	1.0000

AlphaMissense

4922 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:85552546:A:G	W437R	1.000
2:85552546:A:T	W437R	1.000
2:85552983:A:C	Y415D	1.000
2:85553031:A:G	W399R	1.000
2:85553031:A:T	W399R	1.000
2:85552428:C:G	R476P	0.999
2:85552434:T:A	N474I	0.999
2:85552441:A:G	S472P	0.999
2:85552503:A:G	L451P	0.999
2:85552513:C:G	A448P	0.999
2:85552544:C:A	W437C	0.999
2:85552544:C:G	W437C	0.999
2:85553029:C:A	W399C	0.999
2:85553029:C:G	W399C	0.999
2:85553056:C:A	W390C	0.999
2:85553056:C:G	W390C	0.999
2:85553058:A:G	W390R	0.999
2:85553058:A:T	W390R	0.999
2:85553490:G:C	F299L	0.999
2:85553490:G:T	F299L	0.999
2:85553492:A:G	F299L	0.999
2:85554150:G:C	F294L	0.999
2:85554150:G:T	F294L	0.999
2:85554152:A:G	F294L	0.999
2:85555540:C:A	W223C	0.999
2:85555540:C:G	W223C	0.999
2:85555542:A:G	W223R	0.999
2:85555542:A:T	W223R	0.999
2:85558499:G:C	H160Q	0.999
2:85558499:G:T	H160Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000058455 (2:85547060 G>A,C,T), RS1000273153 (2:85561979 C>T), RS1000304511 (2:85561755 C>T), RS1000448132 (2:85560192 AG>A), RS1000512804 (2:85554817 C>G,T), RS1000517861 (2:85548116 A>G), RS1000590084 (2:85548269 G>A,C), RS1000682161 (2:85554395 A>C,G), RS1001054746 (2:85561570 T>C,G), RS1001078102 (2:85548444 G>A), RS1001400306 (2:85548965 C>G), RS1001617841 (2:85549190 G>C,T), RS1001721327 (2:85544729 CTTTGT>C), RS1001773700 (2:85545023 A>G), RS1002102441 (2:85561534 C>G,T)

Disease associations

OMIM: gene MIM:137167 | disease phenotypes: MIM:610842, MIM:277450, MIM:601626

GenCC curated gene-disease

Disease	Classification	Inheritance
vitamin K-dependent clotting factors, combined deficiency of, type 1	Definitive	Autosomal recessive
body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency	Definitive	Autosomal recessive
pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
vitamin K-dependent clotting factors, combined deficiency of, type 1	Definitive	AR
pulmonary arterial hypertension	Moderate	AD

Mondo (5): body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency (MONDO:0012570), vitamin K-dependent clotting factors, combined deficiency of, type 1 (MONDO:0010187), acute myeloid leukemia (MONDO:0018874), thrombocytopenia (MONDO:0002049), pseudoxanthoma elasticum-like skin manifestations with retinitis pigmentosa (MONDO:0018577)

Orphanet (3): Body skin hyperlaxity due to vitamin K-dependent coagulation factor deficiency (Orphanet:91135), Hereditary combined deficiency of vitamin K-dependent clotting factors (Orphanet:98434), Acute myeloid leukemia (Orphanet:519)

HPO phenotypes

53 total (30 of 53 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000132	Menorrhagia
HP:0000421	Epistaxis
HP:0000486	Strabismus
HP:0000510	Rod-cone dystrophy
HP:0000587	Abnormal optic nerve morphology
HP:0000662	Nyctalopia
HP:0000939	Osteoporosis
HP:0000973	Cutis laxa
HP:0000978	Bruising susceptibility
HP:0001098	Abnormal fundus morphology
HP:0001102	Angioid streaks
HP:0001342	Cerebral hemorrhage
HP:0001582	Redundant skin
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001892	Abnormal bleeding
HP:0001928	Abnormality of coagulation
HP:0002170	Intracranial hemorrhage
HP:0002239	Gastrointestinal hemorrhage
HP:0002621	Atherosclerosis
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0003196	Short nose
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0003645	Prolonged partial thromboplastin time
HP:0004415	Pulmonary artery stenosis
HP:0004646	Hypoplasia of the nasal bone
HP:0004855	Reduced protein S activity
HP:0004944	Dilatation of the cerebral artery

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001148_4	Prostate cancer	3.000000e-15
GCST003116_32	Coronary artery disease	4.000000e-10
GCST003117_3	Myocardial infarction	3.000000e-10
GCST004787_22	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-13
GCST005195_43	Coronary artery disease	2.000000e-23
GCST010244_210	Triglyceride levels	2.000000e-08
GCST90002385_133	High light scatter reticulocyte count	8.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0007986	reticulocyte count

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D015470	Leukemia, Myeloid, Acute	C04.557.337.539.275; C15.378.508.539.275
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C563654	Pseudoxanthoma Elasticum-Like Disorder with Multiple Coagulation Factor Deficiency (supp.)
C564741	Vitamin K-Dependent Clotting Factors, Combined Deficiency Of, 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2012 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11676382	Efficacy	3	warfarin
rs11676382	Dosage	3	warfarin
rs11676382	Dosage	4	acenocoumarol
rs12714145	Dosage	4	warfarin
rs2592551	Dosage	3	warfarin	Atrial Fibrillation
rs699664	Efficacy	3	warfarin
rs699664	Dosage	4	warfarin

PharmGKB variants

6 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs699664	GGCX	3	2.00	2	warfarin
rs2592551	GGCX	3	3.25	1	warfarin
rs11676382	GGCX	3	3.75	4	acenocoumarol;warfarin
rs12714145	GGCX	4	-10.75	1	warfarin
rs112936952	GGCX		0.00	0
rs60769490	GGCX		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Carboxylases

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Warfarin	affects response to substance, decreases response to substance, increases response to substance	9
Valproic Acid	increases expression	3
Cyclosporine	decreases expression	3
sodium arsenite	increases expression, increases abundance	2
Doxorubicin	decreases expression, affects response to substance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
TAK-243	decreases sumoylation	1
cobaltous chloride	decreases expression	1
nickel chloride	decreases expression	1
celastrol	increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Arsenic	increases abundance, increases expression	1
Cadmium	increases abundance, increases expression	1
Carbamazepine	affects expression	1
Chromium	decreases expression	1
Dimethylnitrosamine	decreases expression	1
Mercury	decreases expression	1
Methotrexate	decreases expression	1
Phenobarbital	affects expression	1
Potassium Dichromate	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vinblastine	affects response to substance	1
Isotretinoin	decreases expression	1
Cadmium Chloride	increases abundance, increases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3871107	Binding	Activation of gamma-glutamyl carboxylase in human MG63 cells assessed as increase in carboxylated osteocalcin level at 50 nM after 72 hrs by enzyme immuno assay	Synthesis of 2-methyl-1,4-naphthoquinones with higher gamma-glutamyl carboxylase activity than MK-4 both in vitro and in vivo. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1SU	Abcam HeLa GGCX KO	Cancer cell line	Female
CVCL_D9FG	Ubigene HEK293 GGCX KO	Transformed cell line	Female
CVCL_SP96	HAP1 GGCX (-)	Cancer cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00199147	PHASE4	UNKNOWN	Efficacy of G-CSF-Priming in Elderly AML Patients
NCT00304447	PHASE4	COMPLETED	Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia
NCT00464217	PHASE4	COMPLETED	Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years
NCT00487448	PHASE4	COMPLETED	SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia
NCT00488709	PHASE4	COMPLETED	Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia
NCT00686543	PHASE4	COMPLETED	Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115)
NCT01041040	PHASE4	COMPLETED	LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML)
NCT01198054	PHASE4	TERMINATED	LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML)
NCT01200355	PHASE4	COMPLETED	Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome
NCT01347996	PHASE4	COMPLETED	Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia
NCT01587430	PHASE4	UNKNOWN	3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia
NCT01819792	PHASE4	COMPLETED	Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia
NCT02024308	PHASE4	UNKNOWN	AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy
NCT02027064	PHASE4	UNKNOWN	Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT
NCT02277847	PHASE4	UNKNOWN	Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia
NCT02386800	PHASE4	ACTIVE_NOT_RECRUITING	CINC424A2X01B Rollover Protocol
NCT02926586	PHASE4	COMPLETED	Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML
NCT02933333	PHASE4	UNKNOWN	G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor
NCT03026842	PHASE4	UNKNOWN	Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21)
NCT03150134	PHASE4	UNKNOWN	Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients
NCT05144243	PHASE4	ACTIVE_NOT_RECRUITING	Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China
NCT06370000	PHASE4	RECRUITING	Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality
NCT06571825	PHASE4	RECRUITING	RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR
NCT07016165	PHASE4	RECRUITING	Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies
NCT07044687	PHASE4	RECRUITING	Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT07561892	PHASE4	RECRUITING	Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3).
NCT00000589	PHASE3	COMPLETED	Trial to Reduce Alloimmunization to Platelets (TRAP)
NCT00044486	PHASE3	COMPLETED	Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899)
NCT00093990	PHASE3	COMPLETED	Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML)
NCT00125606	PHASE3	TERMINATED	Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide
NCT00136084	PHASE3	COMPLETED	Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia
NCT00146120	PHASE3	COMPLETED	Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result
NCT00150878	PHASE3	TERMINATED	Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission
NCT00151255	PHASE3	COMPLETED	All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia
NCT00152139	PHASE3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00152594	PHASE3	TERMINATED	Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia
NCT00186966	PHASE3	COMPLETED	Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia
NCT00226512	PHASE3	WITHDRAWN	To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning
NCT00260832	PHASE3	COMPLETED	Trial of Decitabine in Patients With Acute Myeloid Leukemia