Grn Gene Detail

Summary

• Symbol
  Grn
• Name
  granulin
• Synonyms
  acrogranulin, epithelin, PC cell-derived growth factor, Pgrn, progranulin

• Feature Type
  protein coding gene
• IDs
  MGI:95832
  NCBI Gene: 14824
• Alliance
  gene page
• Transcription Start Sites
  44 TSS
• Candidate for QTL
  1 QTL

Location &
Maps

• Sequence Map
  Chr11:102321333-102327635 bp, + strand

  From NCBI annotation of GRCm39
  

• View this region in JBrowse
  

• Genome Browsers
  Ensembl | UCSC | NCBI

• Genetic Map
  Chromosome 11, 66.29 cM
• Mapping Data
  13 experiments

Strain
Comparison

• SNPs within 2kb
  167 from dbSNP Build 142
• Strain Annotations
  18
• RFLP
  1

Strain	Gene Model ID	Feature Type	Coordinates
C57BL/6J	MGI_C57BL6J_95832	protein coding gene	Chr11:102321141-102327874 (+)
129S1/SvImJ	MGP_129S1SvImJ_G0019235	protein coding gene	Chr11:105407037-105413766 (+)
A/J	MGP_AJ_G0019203	protein coding gene	Chr11:100958303-100964996 (+)
AKR/J	MGP_AKRJ_G0019172	protein coding gene	Chr11:104075943-104082533 (+)
BALB/cJ	MGP_BALBcJ_G0019177	protein coding gene	Chr11:101440796-101448057 (+)
C3H/HeJ	MGP_C3HHeJ_G0018986	protein coding gene	Chr11:104282350-104290028 (+)
C57BL/6NJ	MGP_C57BL6NJ_G0019626	protein coding gene	Chr11:108695289-108702043 (+)
CAROLI/EiJ	MGP_CAROLIEiJ_G0017252	protein coding gene	Chr11:98384693-98391187 (+)
CAST/EiJ	MGP_CASTEiJ_G0018540	protein coding gene	Chr11:105277499-105284363 (+)
CBA/J	MGP_CBAJ_G0018955	protein coding gene	Chr11:113179624-113189285 (+)
DBA/2J	MGP_DBA2J_G0019067	protein coding gene	Chr11:100472806-100479490 (+)
FVB/NJ	MGP_FVBNJ_G0019057	protein coding gene	Chr11:100005509-100012864 (+)
LP/J	MGP_LPJ_G0019136	protein coding gene	Chr11:105928306-105935051 (+)
NOD/ShiLtJ	MGP_NODShiLtJ_G0019088	protein coding gene	Chr11:112679708-112686607 (+)
NZO/HlLtJ	MGP_NZOHlLtJ_G0019664	protein coding gene	Chr11:104448756-104455910 (+)
PWK/PhJ	MGP_PWKPhJ_G0018303	protein coding gene	Chr11:101542367-101549054 (+)
SPRET/EiJ	MGP_SPRETEiJ_G0018095	protein coding gene	Chr11:104202172-104208796 (+)
WSB/EiJ	MGP_WSBEiJ_G0018589	protein coding gene	Chr11:104443548-104451919 (+)

Homology

• Human Ortholog
  GRN, granulin precursor

• Vertebrate Orthologs
  4

Vertebrate Orthology Source

Alliance of Genome Resources

• Human Ortholog
  GRN, granulin precursor
  
• Synonyms
  CLN11, FTD2, GEP, GP88, PCDGF, PEPI, PGRN
• Links
  HGNC:4601

  NCBI Gene ID: 2896

  neXtProt AC: NX_P28799

  UniProt: P28799

  
  
• Chr Location
  17q21.31; chr17:44345246-44353106 (+)  GRCh38

---

• MGI Vertebrate Homology
  Grn stringent orthology
  1 human;1 mouse;1 rat;2 zebrafish
  
• HCOP
  vertebrate homology predictions: GRN
• Gene Tree
  Grn
  

Human Diseases

• Diseases
  2 with Grn mouse models; 7 with human GRN associations

Human Disease

Mouse Models

Grn-related frontotemporal lobar degeneration with Tdp43 inclusions

IDs

Grn-related frontotemporal lobar degeneration with Tdp43 inclusions      

DOID:0060672
ICD10CM:G31.0
OMIM:607485

View 3 models

Mouse Models

Human Disease Modeled: Grn-related frontotemporal lobar degeneration with Tdp43 inclusions

Allelic Composition	Genetic Background	Reference	Phenotypes
Grntm1.1Hiok/Grn+	involves: C57BL/6J	J:259943	View
Grntm2.1Far/Grntm2.1Far	involves: 129S4/SvJae * C57BL/6	J:259651	View
Grntm1.1Far/Grntm1.1Far	involves: 129S4/SvJae * C57BL/6J * FVB/N	J:218705	View

nephrogenic diabetes insipidus

IDs

nephrogenic diabetes insipidus      

DOID:12387
ICD10CM:N25.1
ICD9CM:588.1
MESH:D018500
NCI:C84919
ORDO:223
UMLS_CUI:C0162283

View 1 model

Mouse Models

Human Disease Modeled: nephrogenic diabetes insipidus

Allelic Composition	Genetic Background	Reference	Phenotypes
Grntm1.1Aidi/Grntm1.1Aidi	involves: C57BL/6J	J:268827	View

Alzheimer's disease

IDs

Alzheimer's disease      

DOID:10652
ICD10CM:G30
ICD9CM:331.0
KEGG:05010
MESH:D000544
NCI:C2866
UMLS_CUI:C0002395

amyotrophic lateral sclerosis

IDs

amyotrophic lateral sclerosis      

DOID:332
ICD10CM:G12.21
ICD9CM:335.20
KEGG:05014
MESH:D000690
NCI:C34373
OMIM:PS105400
ORDO:803
UMLS_CUI:C0002736

dementia

IDs

dementia      

DOID:1307
ICD9CM:290.8
UMLS_CUI:C0154319

frontotemporal dementia

IDs

frontotemporal dementia      

DOID:9255
MESH:C563003
OMIM:600274
ORDO:282
UMLS_CUI:C0520716

neuronal ceroid lipofuscinosis 11

IDs

neuronal ceroid lipofuscinosis 11      

DOID:0110732
ICD10CM:E75.4
OMIM:614706
ORDO:314629

primary progressive multiple sclerosis

IDs

primary progressive multiple sclerosis      

DOID:0050784
MESH:D020528
UMLS_CUI:C0751964

Click on a disease name to see all genes associated with that disease.

• Mutations/Alleles
  4 with disease annotations

• References
  4 with disease annotations

Mutations,
Alleles, and
Phenotypes

• Phenotype Summary
  100 phenotypes from 9 alleles in 10 genetic backgrounds
  5 images
  146 phenotype references
  

• All Mutations and Alleles
  27
• Endonuclease-mediated
  6
• Targeted
  18
• Transgenic
  3
• Genomic Mutations
  1 involving Grn
• Incidental Mutations
  Mutagenetix , APF
• Find Mice (IMSR)
  48 strains or lines available
• Comparison Matrix
  Gene Expression + Phenotype

Mice homozygous for some knock-out alleles display enhanced macrophage functions. Mice homozygous for another knock-out allele display reproductive and behavioral abnormalities. Mice homozygous for a third null allele display premature death and increased cellular aging. Heterozygosity for p.R504* mutation affects neural stem cells and leads to neurological defects.

Gene Ontology
(GO)
Classifications

• All GO Annotations
  91
• GO References
  22

Expression

• Assay Results
  895
• Tissues
  108
• cDNA Data
  487
• Literature Summary
  9

Images

Tissue x Stage Matrix

Comparison Matrix

Gene Expression + Phenotype

• Other Mouse Links
  Allen Institute
  GEO
  Expression Atlas
• Other Vertebrate Links
  Xenbase grn
  ZFIN grna

Sequences &
Gene Models

• All Sequences
  123
• RefSeq
  2
• UniProt
  18
• CCDS
  CCDS48943.1

• Ensembl
  ENSMUSG00000034708 (Evidence)
• NCBI Gene
  14824

Representative Sequences			Length	Strain/Species
genomic	14824	NCBI Gene Model | MGI Sequence Detail	6303	C57BL/6J
transcript	NM_008175	RefSeq | MGI Sequence Detail	2148	ZRU/MplStud
polypeptide	P28798	UniProt | EBI | MGI Sequence Detail	589	Not Applicable

Protein
Information

• UniProt
  18 Sequences
• Protein Ontology
  PR:000008271 progranulin
  (term hierarchy)
• InterPro Domains
  IPR000118 Granulin
  IPR039036 Granulin family
  IPR037277 Granulin superfamily
• GlyGen
  P28798 5 sites, 2 N-linked glycans (3 sites), 1 O-linked glycan (1 site)

Molecular
Reagents

• All nucleic 496

  Genomic 2

  cDNA 488

  Primer pair 4

  Other 2

  
  

  Microarray probesets 7

Other
Accession IDs

MGD-MRK-10272

References

• Summaries
  All 223

  Developmental Gene Expression 9

  Diseases 4

  Gene Ontology 22

  Phenotypes 146
• Earliest
  J:4982 Baba T, et al., Exon/intron organization of the gene encoding the mouse epithelin/granulin precursor (acrogranin). FEBS Lett. 1993 May 10;322(2):89-94
• Latest
  J:358086 Tsuji S, et al., The role of progranulin in macrophages of a glioblastoma model. J Neurooncol. 2024 Aug 14;

TSS for Grn:

(View these features in JBrowse)

Transcription Start Site	Location	Distance from Gene 5'-end
Tssr105225	Chr11:102320179-102320199 (+)	-1,144 bp
Tssr105226	Chr11:102321194-102321225 (+)	-123 bp
Tssr105227	Chr11:102321289-102321349 (+)	-14 bp
Tssr105228	Chr11:102323381-102323407 (+)	2,061 bp
Tssr105229	Chr11:102323612-102323628 (+)	2,287 bp
Tssr105230	Chr11:102323648-102323671 (+)	2,327 bp
Tssr105231	Chr11:102323676-102323690 (+)	2,350 bp
Tssr105232	Chr11:102323712-102323736 (+)	2,391 bp
Tssr105233	Chr11:102323826-102323853 (+)	2,507 bp
Tssr105234	Chr11:102323856-102323877 (+)	2,534 bp
Tssr105235	Chr11:102323895-102323908 (+)	2,569 bp
Tssr105236	Chr11:102324042-102324063 (+)	2,720 bp
Tssr105237	Chr11:102324065-102324141 (+)	2,770 bp
Tssr105238	Chr11:102324144-102324155 (+)	2,817 bp
Tssr105239	Chr11:102324299-102324340 (+)	2,987 bp
Tssr105240	Chr11:102324344-102324360 (+)	3,019 bp
Tssr105241	Chr11:102324750-102324783 (+)	3,434 bp
Tssr105242	Chr11:102324786-102324817 (+)	3,469 bp
Tssr105243	Chr11:102324952-102324960 (+)	3,623 bp
Tssr105244	Chr11:102324967-102324980 (+)	3,641 bp
Tssr105245	Chr11:102324986-102324997 (+)	3,659 bp
Tssr105246	Chr11:102325005-102325016 (+)	3,678 bp
Tssr105247	Chr11:102325033-102325064 (+)	3,716 bp
Tssr105248	Chr11:102325217-102325264 (+)	3,908 bp
Tssr105249	Chr11:102325270-102325297 (+)	3,951 bp
Tssr105250	Chr11:102325304-102325315 (+)	3,977 bp
Tssr105251	Chr11:102325526-102325628 (+)	4,244 bp
Tssr105252	Chr11:102325887-102325901 (+)	4,561 bp
Tssr105253	Chr11:102325904-102325939 (+)	4,589 bp
Tssr105254	Chr11:102326064-102326083 (+)	4,741 bp
Tssr105255	Chr11:102326084-102326093 (+)	4,756 bp
Tssr105256	Chr11:102326104-102326123 (+)	4,781 bp
Tssr105257	Chr11:102326141-102326155 (+)	4,815 bp
Tssr105258	Chr11:102326171-102326196 (+)	4,851 bp
Tssr105259	Chr11:102326530-102326553 (+)	5,209 bp
Tssr105260	Chr11:102326567-102326582 (+)	5,242 bp
Tssr105261	Chr11:102326621-102326690 (+)	5,323 bp
Tssr105262	Chr11:102326706-102326721 (+)	5,381 bp
Tssr105263	Chr11:102326866-102326878 (+)	5,539 bp
Tssr105264	Chr11:102326925-102326976 (+)	5,618 bp
Tssr105265	Chr11:102326990-102327015 (+)	5,670 bp
Tssr105266	Chr11:102327195-102327206 (+)	5,868 bp
Tssr105267	Chr11:102327301-102327310 (+)	5,973 bp
Tssr105268	Chr11:102327346-102327360 (+)	6,020 bp

Grn is Candidate Gene for:

QTL	Genetic Location*	Genome Location (GRCm39)	Reference	QTL Note
Par8	Chr11, syntenic	Chr11:94063779-94063918	J:78525	Microarray gene expression analysis was used to identify candidate genes for tumor resistant and tumor susceptibility QTLs Par8,2,3,4 and and Pas1-4, respectively. Transcripts found within the flanking markers of each QTL were identified and matched to transcripts from Affymetrix probe sets. RNA from A/J, BALB/cJ, C57BL/6J, and SM/J were used for analysis. Pas1 is located between 48.2 cM and 75 cM on mouse Chromosome 6 and was identified in a cross between A/J and C57BL/6J. Candidate oncogenic genes identified by microarray analysis are hes related protein (**Note- this gene is not found in MGD), Ppih (cyclophilin H **Note-this gene is positioned on mouse Chromosome 4 in MGD), Ptpro, Mglap, Recql, and Bcat1 (ECA39). Other candidate genes identified via differential expression are Ccnd2 (cyclin D2) and high mobility group protein 2A,4 (**Note-this gene is not found in MGD). K-ras, a positional candidate gene, did not show significantly different expression between A/J and C57BL/6J. Pas2 is located between 17 cMand 23.2 cM on mouse Chromosome 17 and was identified in crosses involving A/J and C57BL/6J. Candidate oncogenic genes identified by microarray analysis are Notch4, Hnrpk (**Note-this gene is positioned on mouse Chromosome 13 in MGD), and Enpp4. Other candidate genes identified via differential expression are Cdc5l, Tapbp (tapasin), H2-Ke2, Rbx1 (regulator of cullins 1 **Note- this gene is found on mouse Chromosome 15 in MGD), Psors1c2, H2-Ke6, and H2-M9. Positional candidate genes Tnf (Tnfa) and Lta (Tnfb) did not show significantly different expression between A/J and C57BL/6J. Pas3 is located between 2 cM and 25 cM on mouse Chromosome 19 and was identified in a cross between A/J and C57BL/6J. Candidate oncogenic genes identified by microarray analysis are golgi specific Gbf1 (brefeldin A resistance factor 1) and Sema4g. Other candidate genes identified via differential expression are Pdcd4, Adrb1, and Cdc25l. Pas4 is located between 42 cM and 72 cM on mouse Chromosome 9 and was identified in a cross between A/J and C57BL/6J. Candidate oncogenic genes identified by microarray analysis are Nck1, Pthr1, and Topbp1. Candidate tumor suppressor genes for Pas4 are G protein alpha I 2 (**Note-this gene is not found in MGD), Cdk5 (**Note-this gene is positioned on mouse Chromosome 5 in MGD), Smarcd3 (**Note-this gene is positioned on mouse Chromosome 5 in MGD), and Nckipsd. Another candidate gene identified via differential expression is Stag1. Par1 is located between 37 cM and 59 cM on mouse Chromosome 11 and was identified in a cross between A/J and SM/J. Candidate oncogenic genes identified by microarray analysis are Alox12 (12-lipoxygenase), Zfp617 (zinc finger protein s11-6), Grn, and Rpl29 (**Note-this gene is positioned on mouse Chromosome 9 in MGD). A tumor suppressor candidate gene for Par1 is Spop. 02.05.2016 Curator Note: Because Par1 was originally mapped in J:32079 using an (A/J x M. spretus) x C57BL/6J interspecific backcross, which differs from the cross used here, we have equated this QTL with Par8 which was mapped using A/J and SM/J mice, see J:41849. Par2 is located between 32 cM and 57 cM on mouse Chromosome 18 and was identified in a cross between A/J and BALB/cJ. Candidate oncogenic genes identified by microarray analysis are Adrb2, Mbd2, Htr4, Hmgb1-rs12, and Iigp1. Dcc is an expected candidate gene of Par2 but its expression pattern (A/J=high expression) is not consistent with its effect on tumor resistance/susceptibility. Mc2r is another candidate gene identified via differential gene expression between A/J and SM/J. Par3 is located between 13 cM and 44 cM on mouse Chromosome 12 and was identified in a cross between A/J and SM/J. Only one candidate oncogenic gene was identified for Par3. This is placental growth factor, Pgf. Par4 is located between 10.6 cM and 42.5 cM on mouse Chromosome 4 and was identified in a cross between A/J and BALB/cJ. Candidate tumor suppressor genes identified via differential gene expression are Cdkn2a, Egfl5, Ambp (bikunin), Pole3, Tyrp1, Ifnab, and Igfbpl1.Candidate oncogenes are T complex protein 1 alpha (**Note-this gene is not found in MGD) and Stmn1. Another candidate gene identified via differential expression between A/J and SM/J is Ptprd.

*cM position of peak correlated region/marker