Human Gene GPC6 (ENST00000377047.9) from GENCODE V44
  Description: Homo sapiens glypican 6 (GPC6), mRNA. (from RefSeq NM_005708)
RefSeq Summary (NM_005708): The glypicans comprise a family of glycosylphosphatidylinositol-anchored heparan sulfate proteoglycans, and they have been implicated in the control of cell growth and cell division. The glypican encoded by this gene is a putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases. Mutations in this gene are associated with omodysplasia 1. [provided by RefSeq, Nov 2016]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data because no quality transcript was available for the full length of the gene. The extent of this transcript is supported by transcript alignments.
Gencode Transcript: ENST00000377047.9
Gencode Gene: ENSG00000183098.12
Transcript (Including UTRs)
   Position: hg38 chr13:93,226,807-94,408,020 Size: 1,181,214 Total Exon Count: 9 Strand: +
Coding Region
   Position: hg38 chr13:93,227,457-94,403,217 Size: 1,175,761 Coding Exon Count: 9 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr13:93,226,807-94,408,020)mRNA (may differ from genome)Protein (555 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
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HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GPC6_HUMAN
DESCRIPTION: RecName: Full=Glypican-6; Contains: RecName: Full=Secreted glypican-6; Flags: Precursor;
FUNCTION: Cell surface proteoglycan that bears heparan sulfate. Putative cell surface coreceptor for growth factors, extracellular matrix proteins, proteases and anti-proteases (By similarity). Enhances migration and invasion of cancer cells through WNT5A signaling.
SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor; Extracellular side (By similarity).
SUBCELLULAR LOCATION: Secreted glypican-6: Secreted, extracellular space (By similarity).
TISSUE SPECIFICITY: Widely expressed. High expression in fetal kidney and lung and lower expressions in fetal liver and brain. In adult tissues, very abundant in ovary, high levels also observed in liver, kidney, small intestine and colon. Not detected in peripheral blood leukocytes. Detected in breast cancer cells (at protein level).
INDUCTION: Expression is induced by NFATC2.
DISEASE: Defects in GPC6 are a cause of omodysplasia type 1 (OMOD1) [MIM:258315]. OMOD1 is a rare autosomal recessive skeletal dysplasia characterized by severe congenital micromelia with shortening and distal tapering of the humeri and femora to give a club-like appearance. Typical facial features include a prominent forehead, frontal bossing, short nose with a depressed broad bridge, short columella, anteverted nostrils, long philtrum, and small chin. Note=Point mutations leading to protein truncation, as well as larger genomic rearrangements resulting in exon deletions, have been found in family segregating omodysplasia type 1. All mutations identified in individuals affected by omodysplasia could lead to the absence of a functional protein, the mutant RNAs being suspected to be nonsense-mediated mRNA decay (NMD) targets. Even if the mRNA escapes NMD and is translated, all mutations are expected to disrupt the three-dimensional protein structure and often to abolish multiple highly conserved cysteine residues.
SIMILARITY: Belongs to the glypican family.

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: GPC6
Diseases sorted by gene-association score: omodysplasia 1* (1379), omodysplasia* (447), atelosteogenesis (9), body dysmorphic disorder (8), simpson-golabi-behmel syndrome (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 8.54 RPKM in Artery - Tibial
Total median expression: 95.74 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 -240.05650-0.369 Picture PostScript Text
3' UTR -1107.404803-0.231 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
IPR001863 - Glypican
IPR019803 - Glypican_CS

Pfam Domains:
PF01153 - Glypican

ModBase Predicted Comparative 3D Structure on Q9Y625
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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 BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
Gene Details     
Gene Sorter     
MGIRGDEnsembl WormBase 
Protein SequenceProtein SequenceProtein Sequence Protein Sequence 
AlignmentAlignmentAlignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0043395 heparan sulfate proteoglycan binding
GO:1904929 coreceptor activity involved in Wnt signaling pathway, planar cell polarity pathway

Biological Process:
GO:0001523 retinoid metabolic process
GO:0006024 glycosaminoglycan biosynthetic process
GO:0006027 glycosaminoglycan catabolic process
GO:0009966 regulation of signal transduction
GO:0016477 cell migration
GO:0060071 Wnt signaling pathway, planar cell polarity pathway

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005634 nucleus
GO:0005796 Golgi lumen
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0016020 membrane
GO:0031225 anchored component of membrane
GO:0043202 lysosomal lumen
GO:0046658 anchored component of plasma membrane


-  Descriptions from all associated GenBank mRNAs
  AF111178 - Homo sapiens glypican-6 (GPC6) mRNA, complete cds.
AF105267 - Homo sapiens glypican-6 (GPC6) mRNA, complete cds.
AY358462 - Homo sapiens clone DNA50914 GPC6 (UNQ369) mRNA, complete cds.
BC106947 - Homo sapiens glypican 6, mRNA (cDNA clone MGC:126288 IMAGE:40034564), complete cds.
AK304338 - Homo sapiens cDNA FLJ58478 complete cds, highly similar to Glypican-6 precursor.
AK130013 - Homo sapiens cDNA FLJ26503 fis, clone KDN07052, highly similar to Glypican-6 precursor.
AK290144 - Homo sapiens cDNA FLJ76769 complete cds, highly similar to Homo sapiens glypican 6 (GPC6), mRNA.
AK074741 - Homo sapiens cDNA FLJ90260 fis, clone NT2RM4000648, moderately similar to K-GLYPICAN PRECURSOR.
KJ892911 - Synthetic construct Homo sapiens clone ccsbBroadEn_02305 GPC6 gene, encodes complete protein.
JD050272 - Sequence 31296 from Patent EP1572962.
JD325340 - Sequence 306364 from Patent EP1572962.
JD404680 - Sequence 385704 from Patent EP1572962.
JD300134 - Sequence 281158 from Patent EP1572962.
JD158554 - Sequence 139578 from Patent EP1572962.
LF210200 - JP 2014500723-A/17703: Polycomb-Associated Non-Coding RNAs.
MA445777 - JP 2018138019-A/17703: Polycomb-Associated Non-Coding RNAs.
JD330166 - Sequence 311190 from Patent EP1572962.
JA785045 - Sequence 7 from Patent WO2012069613.
JD186048 - Sequence 167072 from Patent EP1572962.
BX640888 - Homo sapiens mRNA; cDNA DKFZp686H20120 (from clone DKFZp686H20120).

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

Protein Q9Y625 (Reactome details) participates in the following event(s):

R-HSA-1878002 XYLTs transfer Xyl to core protein
R-HSA-1889981 B4GALT7 transfers Gal group to xylosyl-unit of the tetrasaccharide linker
R-HSA-1889978 B3GALT6 transfers Gal to the tetrasaccharide linker
R-HSA-1889955 B3GATs transfer GlcA to tetrasaccharide linker
R-HSA-2022919 EXT1:EXT2 transfers GlcNAc to the terminal GlcA residue
R-HSA-2076419 HS6STs sulfate GlcN at C6 in heparan sulfate/heparin
R-HSA-2076371 GLCE epimerises more GlcA to IdoA as sulfate content rises
R-HSA-2076508 HS2ST1 sulfates IdoA at C2 in heparan sulfate
R-HSA-2024100 GLCE epimerises GlcA to IdoA
R-HSA-2022851 EXT1:EXT2 transfer GlcNAc to the heparan chain
R-HSA-2022856 EXT1:EXT2 transfers GlcNAc to heparan
R-HSA-2022860 NDST1-4 can sulfate a glucosamine residue in heparan to form heparan sulfate (HS)
R-HSA-2076392 EXT1:EXT2 transfers GlcA to heparan
R-HSA-2022887 NDST1-4 N-deacetylates GlcNAc residues in heparan
R-HSA-2076383 HS3ST1 sulfates GlcN at C3 in heparan sulfate
R-HSA-2076611 HS3STs sulfate GlcN at C3 in heparan sulfate
R-HSA-1678694 Heparanase 2 (HPSE2) cleaves heparan sulfate from its proteoglycan (plasma membrane)
R-HSA-1667005 Heparanase (HPSE) cleaves heparan sulfate from its proteoglycan (lysosome)
R-HSA-2423785 CR:atREs binds apoE and HSPG
R-HSA-2429643 NREH hydrolyses atREs (HSPG:apoE) to atROL and FAs
R-HSA-2404131 LRPs transport extracellular CR:atREs:HSPG:apoE to cytosol
R-HSA-1971475 A tetrasaccharide linker sequence is required for GAG synthesis
R-HSA-3560783 Defective B4GALT7 causes EDS, progeroid type
R-HSA-4420332 Defective B3GALT6 causes EDSP2 and SEMDJL1
R-HSA-3560801 Defective B3GAT3 causes JDSSDHD
R-HSA-2022928 HS-GAG biosynthesis
R-HSA-3656253 Defective EXT1 causes exostoses 1, TRPS2 and CHDS
R-HSA-3656237 Defective EXT2 causes exostoses 2
R-HSA-2024096 HS-GAG degradation
R-HSA-1638091 Heparan sulfate/heparin (HS-GAG) metabolism
R-HSA-1793185 Chondroitin sulfate/dermatan sulfate metabolism
R-HSA-3560782 Diseases associated with glycosaminoglycan metabolism
R-HSA-975634 Retinoid metabolism and transport
R-HSA-1630316 Glycosaminoglycan metabolism
R-HSA-3781865 Diseases of glycosylation
R-HSA-2187338 Visual phototransduction
R-HSA-6806667 Metabolism of fat-soluble vitamins
R-HSA-71387 Metabolism of carbohydrates
R-HSA-1643685 Disease
R-HSA-418594 G alpha (i) signalling events
R-HSA-196854 Metabolism of vitamins and cofactors
R-HSA-1430728 Metabolism
R-HSA-388396 GPCR downstream signalling
R-HSA-372790 Signaling by GPCR
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: A8K279, ENST00000377047.1, ENST00000377047.2, ENST00000377047.3, ENST00000377047.4, ENST00000377047.5, ENST00000377047.6, ENST00000377047.7, ENST00000377047.8, GPC6_HUMAN, NM_005708, Q96SG5, Q96SG8, Q9H1P4, Q9Y625, uc001vlt.1, uc001vlt.2, uc001vlt.3, uc001vlt.4, uc001vlt.5, UNQ369/PRO705
UCSC ID: ENST00000377047.9
RefSeq Accession: NM_005708
Protein: Q9Y625 (aka GPC6_HUMAN)
CCDS: CCDS9469.1

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