GRN granulin precursor [Homo sapiens (human)] - Gene

Summary

Official Symbol: GRNprovided by HGNC
Official Full Name: granulin precursorprovided by HGNC
Primary source: HGNC:HGNC:4601
See related: Ensembl:ENSG00000030582 MIM:138945; AllianceGenome:HGNC:4601
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: GEP; FTD2; GP88; PEPI; PGRN; CLN11; PCDGF
Summary: 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]
Expression: Ubiquitous expression in bone marrow (RPKM 141.7), lung (RPKM 139.8) and 25 other tissues See more
Orthologs: all
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Genomic context

Location:: 17q21.31

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	17	NC_000017.11 (44345302..44353106)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	17	NC_060941.1 (45199297..45207105)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (42422670..42430474)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.
Title: Sortilin is associated with progranulin deficiency and autism-like behaviors in valproic acid-induced autism rats.
GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.
Title: GRN mutation spectrum and genotype-phenotype correlation in Chinese dementia patients: data from PUMCH dementia cohort.
Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.
Title: Neurofilaments and progranulin are related to atrophy in frontotemporal lobar degeneration - A transdiagnostic study cross-validating atrophy and fluid biomarkers.
Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.
Title: Elevated serum level of progranulin is associated with increased mortality in critically ill patients with candidemia.
PGRN inhibits CD8[+]T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.
Title: PGRN inhibits CD8(+)T cell recruitment and promotes breast cancer progression by up-regulating ICAM-1 on TAM.
A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
Title: A systematic review of progranulin concentrations in biofluids in over 7,000 people-assessing the pathogenicity of GRN mutations and other influencing factors.
Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-alpha pathway in lupus nephritis.
Title: Granulin in renal tubular epithelia is associated with interstitial inflammation and activates the TLR9-IFN-α pathway in lupus nephritis.
Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1alpha pathway in ARDS.
Title: Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS.
Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.
Title: Identification of novel genetic variations in ABCB6 and GRN genes associated with HIV-associated lipodystrophy.
Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.
Title: Progranulin and neuropathological features of Alzheimer's disease: longitudinal study.

Submit: New GeneRIF Correction See all GeneRIFs (477)

Phenotypes

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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
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions MedGen: C1843792 OMIM: 607485 GeneReviews: GRN Frontotemporal Dementia	Compare labs
Neuronal ceroid lipofuscinosis 11 MedGen: C3539123 OMIM: 614706 GeneReviews: Neuronal Ceroid Lipofuscinoses Overview	Compare labs

EBI GWAS Catalog

Description
Common variants at 6q22 and 17q21 are associated with intracranial volume. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

Protein	Gene	Interaction	Pubs
Tat	tat	Granulin forms stable complexes with cyclin T1 and HIV-1 Tat and inhibits Tat transactivation of the viral LTR promoter	PubMed
	tat	The cysteine rich region of HIV-1 Tat (amino acids 21-37) mediates the binding of Tat to granulin amino acids 206-337 (granulin regions B+A) suggesting a role for granulin growth factors as biologically important extracellular Tat co-factors	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D17S1701 (e-PCR)
- UniSTS:153859

G54019 (e-PCR)
- UniSTS:109401

STS-T54360 (e-PCR)
- UniSTS:10957

STS-X62320 (e-PCR)
- UniSTS:33496

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables growth factor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-folding chaperone binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in astrocyte activation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in astrocyte activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in establishment of localization in cell	IEA Inferred from Electronic Annotation more info
involved_in lysosomal lumen acidification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lysosomal transport	IEA Inferred from Electronic Annotation more info
involved_in lysosomal transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in lysosomal transport	ISS Inferred from Sequence or Structural Similarity more info
involved_in lysosome organization	IEA Inferred from Electronic Annotation more info
involved_in lysosome organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in maintenance of synapse structure	IEA Inferred from Electronic Annotation more info
involved_in microglial cell activation involved in immune response	IEA Inferred from Electronic Annotation more info
involved_in microglial cell activation involved in immune response	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of innate immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of microglial cell activation	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of microglial cell activation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of neuron apoptotic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of neutrophil activation	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of respiratory burst involved in inflammatory response	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of angiogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of aspartic-type peptidase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of aspartic-type peptidase activity	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of axon regeneration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of axon regeneration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cellular component organization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of defense response to bacterium	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of defense response to bacterium	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of endothelial cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell migration	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of epithelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of inflammatory response to wounding	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of inflammatory response to wounding	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of lysosome organization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of lysosome organization	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of protein folding	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of protein folding	ISS Inferred from Sequence or Structural Similarity more info
involved_in protein stabilization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of developmental process	IEA Inferred from Electronic Annotation more info
involved_in regulation of inflammatory response	IBA Inferred from Biological aspect of Ancestor more info
involved_in signal transduction	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi apparatus	IEA Inferred from Electronic Annotation more info
located_in azurophil granule lumen	TAS Traceable Author Statement more info
is_active_in cerebellar climbing fiber to Purkinje cell synapse	IEA Inferred from Electronic Annotation more info
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in endosome	IDA Inferred from Direct Assay more info
located_in extracellular exosome	HDA more info	PubMed
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosomal membrane	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	EXP Inferred from Experiment more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IEA Inferred from Electronic Annotation more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in trans-Golgi network	IEA Inferred from Electronic Annotation more info
located_in trans-Golgi network	ISS Inferred from Sequence or Structural Similarity more info
located_in vesicle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: progranulin

Names: PC cell-derived growth factor; acrogranin; epithelin; glycoprotein 88; glycoprotein of 88 Kda; granulin-epithelin; granulins; proepithelin

NCBI Reference Sequences (RefSeq)

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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_007886.1 RefSeqGene

Range

4964..12984

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_661

mRNA and Protein(s)

NM_002087.4 → NP_002078.1 progranulin precursor

See identical proteins and their annotated locations for NP_002078.1

Status: REVIEWED

Source sequence(s)

AC003043

Consensus CDS

CCDS11483.1

UniProtKB/Swiss-Prot

D3DX55, P23781, P23782, P23783, P23784, P28799, Q53HQ8, Q53Y88, Q540U8, Q9BWE7, Q9H8S1, Q9UCH0

UniProtKB/TrEMBL

A0ACI8SDR8

Related

ENSP00000053867.2, ENST00000053867.8

Conserved Domains (3) summary

smart00277
Location:285 → 335

GRAN; Granulin

pfam00396
Location:377 → 415

Granulin

cl02546
Location:62 → 112

Granulin

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p14 Primary Assembly

Range

44345302..44353106

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060941.1 Alternate T2T-CHM13v2.0

Range

45199297..45207105

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_001012479.1: Suppressed sequence

Description

NM_001012479.1: This RefSeq was permanently suppressed because there is insufficient support for the transcript and the protein.