MCFD2 Gene

HGNC Family	EF-hand domain containing
Name	multiple coagulation factor deficiency 2
Description	This gene encodes a soluble luminal protein with two calmodulin-like EF-hand motifs at its C-terminus. This protein forms a complex with LMAN1 (lectin mannose binding protein 1; also known as ERGIC-53) that facilitates the transport of coagulation factors V (FV) and VIII (FVIII) from the endoplasmic reticulum to the Golgi apparatus via an endoplasmic reticulum Golgi intermediate compartment (ERGIC). Mutations in this gene cause combined deficiency of FV and FVIII (F5F8D); a rare autosomal recessive bleeding disorder characterized by mild to moderate bleeding and coordinate reduction in plasma FV and FVIII levels. This protein has also been shown to maintain stem cell potential in adult central nervous system and is a marker for testicular germ cell tumors. The 3' UTR of this gene contains a transposon-like human repeat element named 'THE 1'. A processed RNA pseudogene of this gene is on chromosome 6p22.1. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMCFD2 is a soluble, EF‐hand–containing protein that plays a critical role in mediating ER‐to‐Golgi transport of select glycoproteins. In partnership with the transmembrane lectin LMAN1 (ERGIC‑53), MCFD2 forms a calcium‐dependent cargo receptor complex essential for the efficient secretion of blood coagulation factors V and VIII, as well as other secreted proteins like α₁‐antitrypsin. Ca²⁺ binding induces a conformational change in MCFD2’s EF‐hand domains that enables it to bind both LMAN1 and its cargo through distinct sites. Mutations that disrupt this calcium‐induced folding or impair the binding surfaces of MCFD2 lead to defective receptor complex formation and underlie the pathogenesis of the combined deficiency of factors V and VIII. Detailed biochemical and structural studies, together with patient‐derived mutations, have established that perturbations in MCFD2 impair its interactions with LMAN1 and with the cargo molecules, ultimately resulting in compromised protein transport through the early secretory pathway."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in protein trafficking and ensuring hemostatic balance, MCFD2 appears to be involved in additional cellular processes. Its expression has been detected as a germ cell and seminoma marker—suggesting involvement in early gonocyte differentiation—while coordinated regulation with LMAN1 during stress conditions indicates a broader function in maintaining secretory pathway homeostasis. Furthermore, recent findings implicate MCFD2 in supporting stem cell pluripotency and in modulating cellular adhesion, migration, and metastasis in malignancies such as oral squamous cell carcinoma. These observations underscore that, in addition to its well‐characterized function as a cargo receptor core component, MCFD2 may participate in diverse signaling and developmental pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Bin Zhang, Michael A Cunningham, William C Nichols, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1153"}], "href": "https://doi.org/10.1038/ng1153"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12717434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12717434"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Bin Zhang, Randal J Kaufman, David Ginsburg "}, {"type": "b", "children": [{"type": "t", "text": "LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502160200"}], "href": "https://doi.org/10.1074/jbc.M502160200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15886209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15886209"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dipika Mohanty, Kanjaksha Ghosh, Shrimati Shetty, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the MCFD2 gene and a novel mutation in the LMAN1 gene in Indian families with combined deficiency of factor V and VIII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hematol (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajh.20397"}], "href": "https://doi.org/10.1002/ajh.20397"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16044454"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16044454"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Beat Nyfeler, Bin Zhang, David Ginsburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cargo selectivity of the ERGIC-53/MCFD2 transport receptor complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1600-0854.2006.00483.x"}], "href": "https://doi.org/10.1111/j.1600-0854.2006.00483.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17010120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17010120"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "G Jayandharan, M Spreafico, A Viswabandya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Haemophilia (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1365-2516.2007.01477.x"}], "href": "https://doi.org/10.1111/j.1365-2516.2007.01477.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17610559"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17610559"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Norihito Kawasaki, Yoko Ichikawa, Ichiro Matsuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The sugar-binding ability of ERGIC-53 is enhanced by its interaction with MCFD2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-06-097022"}], "href": "https://doi.org/10.1182/blood-2007-06-097022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18056485"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18056485"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Bin Zhang, Marta Spreafico, Chunlei Zheng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genotype-phenotype correlation in combined deficiency of factor V and factor VIII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-10-113951"}], "href": "https://doi.org/10.1182/blood-2007-10-113951"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18391077"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18391077"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jodie E Guy, Edvard Wigren, Maria Svärd, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2008.06.042"}], "href": "https://doi.org/10.1016/j.jmb.2008.06.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18590741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18590741"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Vytautas Ivaskevicius, Jerzy Windyga, Beata Baran, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The first case of combined coagulation factor V and coagulation factor VIII deficiency in Poland due to a novel p.Tyr135Asn missense mutation in the MCFD2 gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood Coagul Fibrinolysis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MBC.0b013e3283061103"}], "href": "https://doi.org/10.1097/MBC.0b013e3283061103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18685427"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18685427"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Chunlei Zheng, Hui-hui Liu, Jiahai Zhou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2009-09-241877"}], "href": "https://doi.org/10.1182/blood-2009-09-241877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20007547"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20007547"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Edvard Wigren, Jean-Marie Bourhis, Inari Kursula, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2010.02.009"}], "href": "https://doi.org/10.1016/j.febslet.2010.02.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20138881"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20138881"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Chunlei Zheng, Richard C Page, Vaijayanti Das, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural characterization of carbohydrate binding by LMAN1 protein provides new insight into the endoplasmic reticulum export of factors V (FV) and VIII (FVIII)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.461434"}], "href": "https://doi.org/10.1074/jbc.M113.461434"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23709226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23709226"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Chunlei Zheng, Bin Zhang "}, {"type": "b", "children": [{"type": "t", "text": "Combined deficiency of coagulation factors V and VIII: an update."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Semin Thromb Hemost (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1055/s-0033-1349223"}], "href": "https://doi.org/10.1055/s-0033-1349223"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23852824"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23852824"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Megumi Fukamachi, Atsushi Kasamatsu, Yosuke Endo-Sakamoto, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport of α1-antitrypsin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20220055"}], "href": "https://doi.org/10.1042/BCJ20220055"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35322856"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35322856"}]}]}]}
Synonyms	LMAN1IP, SDNSF, F5F8D2
Proteins	MCFD2_HUMAN
NCBI Gene ID	90411
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

MCFD2 has 6,317 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 111 datasets.

Click the + buttons to view associations for MCFD2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

MCFD2 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MCFD2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of MCFD2 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of MCFD2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of MCFD2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of MCFD2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of MCFD2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MCFD2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of MCFD2 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of MCFD2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of MCFD2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with MCFD2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with MCFD2 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MCFD2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of MCFD2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of MCFD2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with MCFD2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of MCFD2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing MCFD2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing MCFD2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with MCFD2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with MCFD2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of MCFD2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with MCFD2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with MCFD2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of MCFD2 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by MCFD2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with MCFD2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with MCFD2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with MCFD2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with MCFD2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for MCFD2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at MCFD2 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of MCFD2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of MCFD2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing MCFD2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with MCFD2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with MCFD2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of MCFD2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with MCFD2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing MCFD2 from the GeneSigDB Published Gene Signatures dataset.