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

Summary

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
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

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_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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).
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.
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.
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

Go to the top of the page Help

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	not available

EBI GWAS Catalog

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

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D21S1698 (e-PCR)
- UniSTS:150410

SHGC-77786 (e-PCR)
- UniSTS:101006

RH92899 (e-PCR)
- UniSTS:92584

G20415 (e-PCR)
- UniSTS:11500

A005Q18 (e-PCR)
- UniSTS:11501

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

Go to the top of the page Help

Preferred Names: multiple coagulation factor deficiency protein 2

Names: neural stem cell-derived neuronal survival protein

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

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

NG_016428.2 RefSeqGene

Range

5001..44986

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_566

mRNA and Protein(s)

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
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
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
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
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
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
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