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MCFD2 multiple coagulation factor deficiency 2, ER cargo receptor complex subunit [ Homo sapiens (human) ]

Gene ID: 90411, updated on 5-Mar-2024

Summary

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Official Symbol
MCFD2provided by HGNC
Official Full Name
multiple coagulation factor deficiency 2, ER cargo receptor complex subunitprovided by HGNC
Primary source
HGNC:HGNC:18451
See related
Ensembl:ENSG00000180398 MIM:607788; AllianceGenome:HGNC:18451
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
F5F8D; SDNSF; F5F8D2; LMAN1IP
Summary
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]
Expression
Ubiquitous expression in adrenal (RPKM 49.7), thyroid (RPKM 38.1) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
2p21
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (46901870..46941855, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (46906646..46946631, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (47129009..47168994, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1119 Neighboring gene uncharacterized LOC107985880 Neighboring gene Sharpr-MPRA regulatory region 12526 Neighboring gene uncharacterized LOC124906004 Neighboring gene Sharpr-MPRA regulatory region 4552 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:47100539-47101038 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47105752-47106252 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47106253-47106753 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:47117443-47117627 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11457 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:47143015-47143989 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11459 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11458 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15716 Neighboring gene tetratricopeptide repeat domain 7A Neighboring gene Sharpr-MPRA regulatory region 4700 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47184163-47184662 Neighboring gene Sharpr-MPRA regulatory region 1272/3994 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:47201305-47202504 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15717 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15718 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15719 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47214570-47215070 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47215071-47215571 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:47229712-47229877 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:47231529-47232241 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47233455-47234351 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47247642-47248142 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47252405-47252904 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:47260876-47262075 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47272944-47273444 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47273445-47273945 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:47276757-47277730 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:47278786-47278992 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47282739-47283687 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15721 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:47293527-47294085 Neighboring gene VISTA enhancer hs1967 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:47307103-47307880 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:47307881-47308656 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr2:47316060-47317259 Neighboring gene sperm-tail PG-rich repeat containing 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15722 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr2:47402112-47402778 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:47402802-47402952 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15724 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15725 Neighboring gene calmodulin 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Combined FV and FVIII deficiency (F5F8D) in a Chinese family with a novel missense mutation in MCFD2 gene. Wang A, et al. Haemophilia, 2014 Nov. PMID 25354775
  2. Identification of a novel mutation in the MCFD2 gene in a Tunisian family with combined factor V and VIII deficiency. Hejer E, et al. Tunis Med, 2012 Apr. PMID 22535353
  3. Structural analysis of two novel mutations in MCFD2 gene causing combined coagulation factors V and VIII deficiency. Abdallah HE, et al. Blood Cells Mol Dis, 2010 Mar-Apr. PMID 20004600
  4. 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. Ivaskevicius V, et al. Blood Coagul Fibrinolysis, 2008 Sep. PMID 18685427
  5. New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2. Guy JE, et al. J Mol Biol, 2008 Sep 12. PMID 18590741

See all (50) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport of alpha1-antitrypsin.
    Title: LMAN1-MCFD2 complex is a cargo receptor for the ER-Golgi transport of α1-antitrypsin.
  2. that Multiple coagulation factor deficiency protein 2 promotes cancer metastasis by regulating lectin mannose binding 1 and level of galactoside-binding soluble 3 binding protein expression levels
    Title: Multiple coagulation factor deficiency protein 2 as a crucial component in metastasis of human oral cancer.
  3. Combined deficiency of factors V and VIII by chance coinheritance of parahaemophilia and haemophilia A, but not by mutations of either LMAN1 or MCFD2
    Title: Combined deficiency of factors V and VIII by chance coinheritance of parahaemophilia and haemophilia A, but not by mutations of either LMAN1 or MCFD2, in a Japanese family.
  4. A novel missense mutation, namely Asp81Ala in exon 3 of MCFD2 gene, is firstly reported and described as a cause of combined FV and FVIII deficiency in a Chinese family.
    Title: Combined FV and FVIII deficiency (F5F8D) in a Chinese family with a novel missense mutation in MCFD2 gene.
  5. Studies indicate that the LMAN1-CRD contains distinct, separable binding sites for both its partner protein MCFD2 and the cargo proteins FV/FVIII.
    Title: Combined deficiency of coagulation factors V and VIII: an update.
  6. Results indicate the biological roles of MCFD2 in both vertebrates and invertebrates.
    Title: Multiple coagulation factor deficiency protein 2 contains the ability to support stem cell self-renewal.
  7. Data indicate that together with its soluble coreceptor MCFD2, LMAN1 transports coagulation factors V (FV) and VIII (FVIII).
    Title: Structural characterization of carbohydrate binding by LMAN1 protein provides new insight into the endoplasmic reticulum export of factors V (FV) and VIII (FVIII).
  8. Mutations in MCFD2 lead to F5F8D (combined deficiency of factor V And factor VIII) due to alterations in MCFD2-LMAN1 complex of coat protein (COP)II complex trafficking machinery; 30% of F5F8D patients have mutations in MCFD2. [REVIEW]
    Title: Inherited hematological disorders due to defects in coat protein (COP)II complex.
  9. We present the identification of a novel MCFD2 gene missense mutation by direct sequencing.
    Title: Identification of a novel mutation in the MCFD2 gene in a Tunisian family with combined factor V and VIII deficiency.
  10. The study reports for the first time a case of Combined factor V and factor VIII deficiency disorder in a Tunisian family, resulting from two novel mutations in exon 3 of the MCFD2 gene.
    Title: Structural analysis of two novel mutations in MCFD2 gene causing combined coagulation factors V and VIII deficiency.
Submit: New GeneRIF Correction See all GeneRIFs (24)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Factor 5 and Factor VIII, combined deficiency of, 2
MedGen: C3150889 OMIM: 613625 GeneReviews: Not available
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EBI GWAS Catalog

Description
Genome-wide association of lipid-lowering response to statins in combined study populations.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • DKFZp686G21263

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables calcium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in protein transport IEA
Inferred from Electronic Annotation
more info
  
involved_in vesicle-mediated transport IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in ER to Golgi transport vesicle membrane TAS
Traceable Author Statement
more info
  
located_in Golgi apparatus IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum-Golgi intermediate compartment membrane TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
multiple coagulation factor deficiency protein 2
Names
neural stem cell-derived neuronal survival protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016428.2 RefSeqGene

    Range
    5001..44986
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_566

mRNA and Protein(s)

  1. NM_001171506.2 → NP_001164977.1  multiple coagulation factor deficiency protein 2 isoform A precursor

    See identical proteins and their annotated locations for NP_001164977.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 encode the same isoform (A).
    Source sequence(s)
    AF537214, AI371370, CF994192, DA324623, DA330030
    Consensus CDS
    CCDS33192.1
    UniProtKB/Swiss-Prot
    A8K7W2, D6W5A9, E9PD95, Q53SS3, Q68D61, Q8N3M5, Q8NI22
    Related
    ENSP00000386279.1, ENST00000409973.5
    Conserved Domains (1) summary
    pfam13499
    Location:77 → 143
    EF-hand_7; EF-hand domain pair

  2. NM_001171507.2 → NP_001164978.1  multiple coagulation factor deficiency protein 2 isoform A precursor

    See identical proteins and their annotated locations for NP_001164978.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 encode the same isoform (A).
    Source sequence(s)
    AF537214, AI371370, DA404031
    Consensus CDS
    CCDS33192.1
    UniProtKB/Swiss-Prot
    A8K7W2, D6W5A9, E9PD95, Q53SS3, Q68D61, Q8N3M5, Q8NI22
    Related
    ENSP00000386261.1, ENST00000409218.5
    Conserved Domains (1) summary
    pfam13499
    Location:77 → 143
    EF-hand_7; EF-hand domain pair

  3. NM_001171508.2 → NP_001164979.1  multiple coagulation factor deficiency protein 2 isoform A precursor

    See identical proteins and their annotated locations for NP_001164979.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3 and 4 encode the same isoform (A).
    Source sequence(s)
    AF537214, AI371370, AK292127, DC321899, DC332658
    Consensus CDS
    CCDS33192.1
    UniProtKB/Swiss-Prot
    A8K7W2, D6W5A9, E9PD95, Q53SS3, Q68D61, Q8N3M5, Q8NI22
    Related
    ENSP00000386386.1, ENST00000409207.5
    Conserved Domains (1) summary
    pfam13499
    Location:77 → 143
    EF-hand_7; EF-hand domain pair

  4. NM_001171509.3 → NP_001164980.1  multiple coagulation factor deficiency protein 2 isoform B

    See identical proteins and their annotated locations for NP_001164980.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) lacks the first coding exon, compared to variant 1. This difference results in the use of an in-frame downstream start codon. The encoded protein (isoform B) has a shorter N-terminus, compared to isoform A, that is not predicted to have a signal peptide. Variants 5 and 6 encode the same isoform (B).
    Source sequence(s)
    AF537214, AI371370, BC037845, DA330030
    Consensus CDS
    CCDS54354.1
    UniProtKB/Swiss-Prot
    Q8NI22
    Related
    ENSP00000386941.1, ENST00000409913.5
    Conserved Domains (1) summary
    pfam13499
    Location:25 → 91
    EF-hand_7; EF-hand domain pair

  5. NM_001171510.3 → NP_001164981.1  multiple coagulation factor deficiency protein 2 isoform B

    See identical proteins and their annotated locations for NP_001164981.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks the first coding exon and differs in the 5' UTR, compared to variant 1. These differences result in the use of an in-frame downstream start codon. The encoded protein (isoform B) has a shorter N-terminus, compared to isoform A, that is not predicted to have a signal peptide. Variants 5 and 6 encode the same isoform (B).
    Source sequence(s)
    AF537214, AI371370, DA404031, DB096245
    Consensus CDS
    CCDS54354.1
    UniProtKB/Swiss-Prot
    Q8NI22
    Related
    ENSP00000387202.1, ENST00000409800.5
    Conserved Domains (1) summary
    pfam13499
    Location:25 → 91
    EF-hand_7; EF-hand domain pair

  6. NM_001171511.3 → NP_001164982.1  multiple coagulation factor deficiency protein 2 isoform C

    See identical proteins and their annotated locations for NP_001164982.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) contains a distinct 5' UTR and 5' coding region, compared to variant 1. These differences result in the use of a novel start codon, compared to variant 1 and a protein (isoform C) with a novel N-terminus, compared to isoform A, that is not predicted to have a signal peptide.
    Source sequence(s)
    AF537214, AI371370, AK292127, AK293889
    Consensus CDS
    CCDS54355.1
    UniProtKB/TrEMBL
    B4DF17
    Related
    ENSP00000394647.2, ENST00000444761.6
    Conserved Domains (1) summary
    pfam13499
    Location:58 → 124
    EF-hand_7; EF-hand domain pair

  7. NM_139279.6 → NP_644808.1  multiple coagulation factor deficiency protein 2 isoform A precursor

    See identical proteins and their annotated locations for NP_644808.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes isoform A. Variants 1, 2, 3 and 4 encode the same isoform (A).
    Source sequence(s)
    AF537214, AI371370, DA330030
    Consensus CDS
    CCDS33192.1
    UniProtKB/Swiss-Prot
    A8K7W2, D6W5A9, E9PD95, Q53SS3, Q68D61, Q8N3M5, Q8NI22
    Related
    ENSP00000317271.4, ENST00000319466.9
    Conserved Domains (1) summary
    pfam13499
    Location:77 → 143
    EF-hand_7; EF-hand domain pair

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    46901870..46941855 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    46906646..46946631 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8NI22.1 GenPept UniProtKB/Swiss-Prot:Q8NI22

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