Human Gene GRN (uc002igp.1)
  Description: Homo sapiens granulin (GRN), mRNA.
RefSeq Summary (NM_002087): Granulins are a family of secreted, glycosylated peptides that are cleaved from a single precursor protein with 7.5 repeats of a highly conserved 12-cysteine granulin/epithelin motif. The 88 kDa precursor protein, progranulin, is also called proepithelin and PC cell-derived growth factor. Cleavage of the signal peptide produces mature granulin which can be further cleaved into a variety of active, 6 kDa peptides. These smaller cleavage products are named granulin A, granulin B, granulin C, etc. Epithelins 1 and 2 are synonymous with granulins A and B, respectively. Both the peptides and intact granulin protein regulate cell growth. However, different members of the granulin protein family may act as inhibitors, stimulators, or have dual actions on cell growth. Granulin family members are important in normal development, wound healing, and tumorigenesis. [provided by RefSeq, Jul 2008]. Sequence Note: The RefSeq transcript and protein were derived from genomic sequence to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on alignments.
Transcript (Including UTRs)
   Position: hg19 chr17:42,422,491-42,430,470 Size: 7,980 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr17:42,426,533-42,430,166 Size: 3,634 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr17:42,422,491-42,430,470)mRNA (may differ from genome)Protein (593 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
GeneNetworkH-INVHGNCHPRDLynxMalacards
MGIneXtProtOMIMPubMedReactomeTreefam
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: GRN_HUMAN
DESCRIPTION: RecName: Full=Granulins; AltName: Full=Proepithelin; Short=PEPI; Contains: RecName: Full=Acrogranin; Contains: RecName: Full=Paragranulin; Contains: RecName: Full=Granulin-1; AltName: Full=Granulin G; Contains: RecName: Full=Granulin-2; AltName: Full=Granulin F; Contains: RecName: Full=Granulin-3; AltName: Full=Granulin B; Contains: RecName: Full=Granulin-4; AltName: Full=Granulin A; Contains: RecName: Full=Granulin-5; AltName: Full=Granulin C; Contains: RecName: Full=Granulin-6; AltName: Full=Granulin D; Contains: RecName: Full=Granulin-7; AltName: Full=Granulin E; Flags: Precursor;
FUNCTION: Granulins have possible cytokine-like activity. They may play a role in inflammation, wound repair, and tissue remodeling.
FUNCTION: Granulin-4 promotes proliferation of the epithelial cell line A431 in culture while granulin-3 acts as an antagonist to granulin-4, inhibiting the growth.
INTERACTION: O00555:CACNA1A; NbExp=2; IntAct=EBI-747754, EBI-766279;
SUBCELLULAR LOCATION: Secreted.
TISSUE SPECIFICITY: In myelogenous leukemic cell lines of promonocytic, promyelocytic, and proerythroid lineage, in fibroblasts, and very strongly in epithelial cell lines. Present in inflammatory cells and bone marrow. Highest levels in kidney.
PTM: Granulins are disulfide bridged.
DISEASE: Defects in GRN are the cause of ubiquitin-positive frontotemporal dementia (UP-FTD) [MIM:607485]; also known as tau- negative frontotemporal dementia linked to chromosome 17. Frontotemporal dementia (FTD) is the second most common cause of dementia in people under the age of 65 years. It is an autosomal dominant neurodegenerative disease.
DISEASE: Defects in GRN are the cause of neuronal ceroid lipofuscinosis type 11 (CLN11) [MIM:614706]. A form of neuronal ceroid lipofuscinosis characterized by rapidly progressive visual loss due to retinal dystrophy, seizures, cerebellar ataxia, and cerebellar atrophy. Cognitive decline may also occur. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material.
SIMILARITY: Belongs to the granulin family.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/GRNID40757ch17q21.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GRN";

-  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


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): GRN
CDC HuGE Published Literature: GRN
Positive Disease Associations: Frontotemporal Dementia , Frontotemporal Lobar Degeneration
Related Studies:
  1. Frontotemporal Dementia
    Johannes Carolus Magnus Schlachetzki , et al. Journal of neurology 2009 256(12):2043-51, Frequency of progranulin mutations in a German cohort of 79 frontotemporal dementia patients., Journal of neurology 2009 256(12):2043-51. [PubMed 19618231]
  2. Frontotemporal Lobar Degeneration
    Daniela Galimberti , et al. Journal of Alzheimers disease 2010 19(1):171-7, GRN variability contributes to sporadic frontotemporal lobar degeneration., Journal of Alzheimers disease 2010 19(1):171-7. [PubMed 20061636]
    GRN rs4792938 CC genotype represents a susceptibility factor for the development of FTLD in individuals who do not carry GRN causal mutations

-  MalaCards Disease Associations
  MalaCards Gene Search: GRN
Diseases sorted by gene-association score: ceroid lipofuscinosis, neuronal, 11* (1375), frontotemporal lobar degeneration with ubiquitin-positive inclusions* (1230), dementia, frontotemporal* (278), grn-related frontotemporal dementia* (100), progressive non-fluent aphasia* (44), neuronal ceroid-lipofuscinoses* (38), aphasia (25), dementia (22), gait apraxia (16), speech and communication disorders (15), echolalia (15), semantic dementia (14), adrenal carcinoma (13), motor neuron disease (12), nominal aphasia (12), prosopagnosia (11), amusia (11), phonagnosia (11), impulse control disorder (10), perry syndrome (10), neuronal ceroid lipofuscinosis (10), behavioral variant of frontotemporal dementia* (9), associative agnosia (8), apraxia (8), basal ganglia disease (8), writing disorder (8), teratoma (8), visual agnosia (7), agraphia (7), anosognosia (7), pedophilia (7), mutism (6), frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (5), speech disorder (5), chronic dacryocystitis (5), chronic inflammation of lacrimal passage (5), ideomotor apraxia (5), supranuclear palsy, progressive (5), paraphilia disorder (4), amyotrophic lateral sclerosis 1 (4), breast cancer (2), specific developmental disorder (1), dementia, lewy body (1), nervous system disease (1), disease of mental health (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D014635 Valproic Acid
  • D000082 Acetaminophen
  • D002945 Cisplatin
  • D004997 Ethinyl Estradiol
  • D013749 Tetrachlorodibenzodioxin
  • C111237 vorinostat
  • C044755 1-methyl-4-phenyl-2,3-dihydropyridinium
  • C404910 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane
  • C093973 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one
  • C085911 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 232.23 RPKM in Esophagus - Mucosa
Total median expression: 3393.31 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 -77.30219-0.353 Picture PostScript Text
3' UTR -109.70304-0.361 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
IPR006150 - Cys_repeat_1
IPR000118 - Granulin

Pfam Domains:
PF00396 - Granulin

SCOP Domains:
57277 - Granulin repeat

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1G26 - NMR 2JYE - NMR MuPIT 2JYT - NMR MuPIT 2JYU - NMR MuPIT 2JYV - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P28799
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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
No orthologGenome BrowserGenome BrowserNo orthologGenome BrowserNo ortholog
Gene DetailsGene Details  Gene Details 
Gene SorterGene Sorter  Gene Sorter 
 RGDEnsembl WormBase 
 Protein SequenceProtein Sequence Protein Sequence 
 AlignmentAlignment Alignment 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0005125 cytokine activity
GO:0005515 protein binding
GO:0008083 growth factor activity

Biological Process:
GO:0007165 signal transduction
GO:0010469 regulation of receptor activity
GO:0043312 neutrophil degranulation

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005764 lysosome
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0035578 azurophil granule lumen
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  BC000324 - Homo sapiens granulin, mRNA (cDNA clone MGC:8480 IMAGE:2821810), complete cds.
LF384808 - JP 2014500723-A/192311: Polycomb-Associated Non-Coding RNAs.
AF055008 - Homo sapiens clone 24720 epithelin 1 and 2 mRNA, complete cds.
JD055354 - Sequence 36378 from Patent EP1572962.
JD026603 - Sequence 7627 from Patent EP1572962.
AK296090 - Homo sapiens cDNA FLJ53342 complete cds, highly similar to Granulins precursor.
AK222522 - Homo sapiens mRNA for granulin variant, clone: adSE02012.
AK000607 - Homo sapiens cDNA FLJ20600 fis, clone KAT07521, highly similar to AF055008 Homo sapiens clone 24720 epithelin 1 and 2 mRNA.
X62320 - H.sapiens mRNA for epithelin 1 and 2.
AK303830 - Homo sapiens cDNA FLJ53692 complete cds, moderately similar to Granulins precursor.
M75161 - H.sapiens granulin mRNA, complete cds.
AY124489 - Homo sapiens PC cell-derived growth factor (GRN) mRNA, complete cds.
BC010577 - Homo sapiens granulin, mRNA (cDNA clone MGC:9342 IMAGE:3457813), complete cds.
L01117 - Human granulin gene, exons 1-12.
KJ891296 - Synthetic construct Homo sapiens clone ccsbBroadEn_00690 GRN gene, encodes complete protein.
KJ901468 - Synthetic construct Homo sapiens clone ccsbBroadEn_10862 GRN gene, encodes complete protein.
KR709575 - Synthetic construct Homo sapiens clone CCSBHm_00003613 GRN (GRN) mRNA, encodes complete protein.
KR709576 - Synthetic construct Homo sapiens clone CCSBHm_00003622 GRN (GRN) mRNA, encodes complete protein.
KR709577 - Synthetic construct Homo sapiens clone CCSBHm_00003634 GRN (GRN) mRNA, encodes complete protein.
KR709578 - Synthetic construct Homo sapiens clone CCSBHm_00003635 GRN (GRN) mRNA, encodes complete protein.
AB463696 - Synthetic construct DNA, clone: pF1KB8138, Homo sapiens GRN gene for granulin, without stop codon, in Flexi system.
CU679753 - Synthetic construct Homo sapiens gateway clone IMAGE:100019920 5' read GRN mRNA.
CU674156 - Synthetic construct Homo sapiens gateway clone IMAGE:100018293 5' read GRN mRNA.
BT006844 - Homo sapiens granulin mRNA, complete cds.
JD031343 - Sequence 12367 from Patent EP1572962.
AK023348 - Homo sapiens cDNA FLJ13286 fis, clone OVARC1001154, highly similar to Homo sapiens clone 24720 epithelin 1 and 2 mRNA.
LF328081 - JP 2014500723-A/135584: Polycomb-Associated Non-Coding RNAs.
LF328082 - JP 2014500723-A/135585: Polycomb-Associated Non-Coding RNAs.
LF328083 - JP 2014500723-A/135586: Polycomb-Associated Non-Coding RNAs.
LF328084 - JP 2014500723-A/135587: Polycomb-Associated Non-Coding RNAs.
JD023462 - Sequence 4486 from Patent EP1572962.
JD031533 - Sequence 12557 from Patent EP1572962.
JD019288 - Sequence 312 from Patent EP1572962.
JD030475 - Sequence 11499 from Patent EP1572962.
LF328085 - JP 2014500723-A/135588: Polycomb-Associated Non-Coding RNAs.
JD318672 - Sequence 299696 from Patent EP1572962.
LF328086 - JP 2014500723-A/135589: Polycomb-Associated Non-Coding RNAs.
JD546664 - Sequence 527688 from Patent EP1572962.
MA620385 - JP 2018138019-A/192311: Polycomb-Associated Non-Coding RNAs.
MA563658 - JP 2018138019-A/135584: Polycomb-Associated Non-Coding RNAs.
MA563659 - JP 2018138019-A/135585: Polycomb-Associated Non-Coding RNAs.
MA563660 - JP 2018138019-A/135586: Polycomb-Associated Non-Coding RNAs.
MA563661 - JP 2018138019-A/135587: Polycomb-Associated Non-Coding RNAs.
MA563662 - JP 2018138019-A/135588: Polycomb-Associated Non-Coding RNAs.
MA563663 - JP 2018138019-A/135589: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_pepiPathway - Proepithelin Conversion to Epithelin and Wound Repair Control

Reactome (by CSHL, EBI, and GO)

Protein P28799 (Reactome details) participates in the following event(s):

R-HSA-6798751 Exocytosis of azurophil granule lumen proteins
R-HSA-6798695 Neutrophil degranulation
R-HSA-168249 Innate Immune System
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: D3DX55, GRN_HUMAN, NM_002087, NP_002078, P23781, P23782, P23783, P23784, P28799, Q53Y88, Q540U8, Q9BWE7, Q9UCH0
UCSC ID: uc002igp.1
RefSeq Accession: NM_002087
Protein: P28799 (aka GRN_HUMAN)
CCDS: CCDS11483.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene GRN:
dystonia-ov (Hereditary Dystonia Overview)
ftd-grn (GRN Frontotemporal Dementia)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_002087.2
exon count: 13CDS single in 3' UTR: no RNA size: 2323
ORF size: 1782CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 3044.00frame shift in genome: no % Coverage: 99.23
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

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