Human Gene CFC1 (ENST00000259216.6) from GENCODE V43
  Description: Homo sapiens cripto, FRL-1, cryptic family 1 (CFC1), transcript variant 1, mRNA. (from RefSeq NM_032545)
RefSeq Summary (NM_032545): This gene encodes a member of the epidermal growth factor (EGF)- Cripto, Frl-1, and Cryptic (CFC) family, which are involved in signalling during embryonic development. Proteins in this family share a variant EGF-like motif, a conserved cysteine-rich domain, and a C-terminal hydrophobic region. The protein encoded by this gene is necessary for patterning the left-right embryonic axis. Mutations in this gene are associated with defects in organ development, including autosomal visceral heterotaxy and congenital heart disease. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012].
Gencode Transcript: ENST00000259216.6
Gencode Gene: ENSG00000136698.10
Transcript (Including UTRs)
   Position: hg38 chr2:130,592,165-130,599,575 Size: 7,411 Total Exon Count: 6 Strand: -
Coding Region
   Position: hg38 chr2:130,592,877-130,599,287 Size: 6,411 Coding Exon Count: 6 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-02-17 13:02:02

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr2:130,592,165-130,599,575)mRNA (may differ from genome)Protein (223 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Cryptic protein; AltName: Full=Cryptic family protein 1; Flags: Precursor;
FUNCTION: NODAL coreceptor involved in the correct establishment of the left-right axis. May play a role in mesoderm and/or neural patterning during gastrulation.
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor. Secreted. Note=Does not exhibit a typical GPI-signal sequence. The C-ter hydrophilic extension of the GPI-signal sequence reduces the efficiency of processing and could lead to the production of an secreted unprocessed form. This extension is found only in primates.
PTM: N-glycosylated (By similarity).
DISEASE: Defects in CFC1 are the cause of visceral heterotaxy autosomal type 2 (HTX2) [MIM:605376]. A form of visceral heterotaxy, a complex disorder due to disruption of the normal left-right asymmetry of the thoracoabdominal organs. It results in an abnormal arrangement of visceral organs, and a wide variety of congenital defects including cardiac malformations and situs inversus or situs ambiguus.
DISEASE: Defects in CFC1 are a cause of transposition of the great arteries dextro-looped type 2 (DTGA2) [MIM:613853]. A congenital heart defect consisting of complete inversion of the great vessels, so that the aorta incorrectly arises from the right ventricle and the pulmonary artery incorrectly arises from the left ventricle. This creates completely separate pulmonary and systemic circulatory systems, an arrangement that is incompatible with life. Patients often have atrial and/or ventricular septal defects or other types of shunting that allow some mixing between the circulations in order to support life minimally, but surgical intervention is always required.
DISEASE: Defects in CFC1 are a cause of conotruncal heart malformations (CTHM) [MIM:217095]. CTHM consist of cardiac outflow tract defects, such as tetralogy of Fallot, pulmonary atresia, double-outlet right ventricle, truncus arteriosus communis, and aortic arch anomalies.
SIMILARITY: Contains 1 EGF-like domain.
CAUTION: This gene differs from CFC1B by only one residue at position 78:R -> W. R78W is also thought to be a CFC1 polymorphism which has been shown to lead to a different cell surface distribution and activity (PubMed:11799476 and PubMed:11062482).
WEB RESOURCE: Name=GeneReviews; URL="";

-  Primer design for this transcript

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3

-  MalaCards Disease Associations
  MalaCards Gene Search: CFC1
Diseases sorted by gene-association score: heterotaxy, visceral, 2, autosomal* (1229), cfc1-related visceral heterotaxy* (500), cfc1-related conotruncal heart malformations* (100), dextro-looped transposition of the great arteries* (29), heterotaxy (26), biliary atresia with splenic malformation syndrome* (25), visceral heterotaxy* (24), biliary atresia (6), heart disease (6), transposition of the great arteries (6), conotruncal heart malformations (5), heart septal defect (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.42 RPKM in Pituitary
Total median expression: 9.77 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -84.00288-0.292 Picture PostScript Text
3' UTR -212.70712-0.299 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR019011 - Cryptic/Cripto_CFC-dom
IPR000742 - EG-like_dom
IPR013032 - EGF-like_CS

Pfam Domains:
PF09443 - Cripto_Frl-1_Cryptic (CFC)

ModBase Predicted Comparative 3D Structure on P0CG37
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
Protein SequenceProtein Sequence    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003674 molecular_function
GO:0038100 nodal binding

Biological Process:
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0007369 gastrulation
GO:0038092 nodal signaling pathway

Cellular Component:
GO:0005575 cellular_component
GO:0005576 extracellular region
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0031225 anchored component of membrane

-  Descriptions from all associated GenBank mRNAs
  DQ786275 - Homo sapiens clone HLS_IMAGE_328821 mRNA sequence.
BC110080 - Homo sapiens cripto, FRL-1, cryptic family 1, mRNA (cDNA clone MGC:133213 IMAGE:40030641), complete cds.
AF312769 - Homo sapiens cryptic mRNA, complete cds.
AK290094 - Homo sapiens cDNA FLJ77897 complete cds, highly similar to Homo sapiens cripto, FRL-1, cryptic family 1 (CFC1), mRNA.
BC146897 - Homo sapiens cripto, FRL-1, cryptic family 1, mRNA (cDNA clone MGC:182000 IMAGE:9056825), complete cds.
BC069508 - Homo sapiens cripto, FRL-1, cryptic family 1, mRNA (cDNA clone MGC:96980 IMAGE:7262189), complete cds.
BC074825 - Homo sapiens cripto, FRL-1, cryptic family 1, mRNA (cDNA clone MGC:103931 IMAGE:30915323), complete cds.
BC074826 - Homo sapiens cripto, FRL-1, cryptic family 1, mRNA (cDNA clone MGC:104089 IMAGE:30915540), complete cds.
AK315326 - Homo sapiens cDNA, FLJ96362, Homo sapiens cripto, FRL-1, cryptic family 1 (CFC1), mRNA.
KJ894298 - Synthetic construct Homo sapiens clone ccsbBroadEn_03692 CFC1 gene, encodes complete protein.
KR711339 - Synthetic construct Homo sapiens clone CCSBHm_00022940 CFC1 (CFC1) mRNA, encodes complete protein.
KR711340 - Synthetic construct Homo sapiens clone CCSBHm_00022941 CFC1 (CFC1) mRNA, encodes complete protein.
KR711341 - Synthetic construct Homo sapiens clone CCSBHm_00022943 CFC1 (CFC1) mRNA, encodes complete protein.
KR711342 - Synthetic construct Homo sapiens clone CCSBHm_00022949 CFC1 (CFC1) mRNA, encodes complete protein.
CU686866 - Synthetic construct Homo sapiens gateway clone IMAGE:100022551 5' read CFC1 mRNA.
JD298386 - Sequence 279410 from Patent EP1572962.
JD235694 - Sequence 216718 from Patent EP1572962.
JD519205 - Sequence 500229 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P0CG37 (Reactome details) participates in the following event(s):

R-HSA-1225894 Type II Activin Receptor (ActRIIB/ACVR2B) phosphorylates Type I Activin Receptor (ActRIC/ACVR1C) in response to NODAL
R-HSA-1181156 Type II Activin Receptor (ActRII/ACVR2) phosphorylates Type I Activin Receptor (ActRIB/ACVR1B) in response to NODAL
R-HSA-1181155 The NODAL Receptor binds NODAL ligands
R-HSA-1181351 LEFTY binds the EGF-CFC coreceptor in the NODAL receptor
R-HSA-1181355 Phosphorylation of R-SMAD2/3 by NODAL receptor
R-HSA-1181150 Signaling by NODAL
R-HSA-1433617 Regulation of signaling by NODAL
R-HSA-1266738 Developmental Biology

-  Other Names for This Gene
  Alternate Gene Symbols: B2RCY0, B9EJD3, CFC1_HUMAN, ENST00000259216.1, ENST00000259216.2, ENST00000259216.3, ENST00000259216.4, ENST00000259216.5, NM_032545, P0CG37, Q53T05, Q9GZR3, uc002tro.1, uc002tro.2, uc002tro.3, uc002tro.4
UCSC ID: ENST00000259216.6
RefSeq Accession: NM_032545
Protein: P0CG37 (aka CFC1_HUMAN)
CCDS: CCDS2162.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.