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

    Gene ID: 90411, updated on 2-Nov-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
    mouse all
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    Genomic context

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    See MCFD2 in Genome Data Viewer
    Location:
    2p21
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (46901870..46941855, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (46906646..46946631, complement)
    RS_2024_09 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 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. Repetitive nucleotide sequence insertions into a novel calmodulin-related gene and its processed pseudogene. Deka N, et al. Gene, 1988 Nov 15. PMID 2463956
    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. 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
    4. 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
    5. 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

    See all (52) 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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    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
    		Compare labs

    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)

    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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    NEW Try the new Transcript table

    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_2024_08

    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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    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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