GRN

Chr 17ADAR

granulin precursor

Also known as: CLN11, FTD2, GEP, GP88, PCDGF, PEPI, PGRN

NCBI Gene: 2896 ENSG00000030582 UniProt: P28799 OMIM: 138945

Progranulin is a secreted glycoprotein that regulates cell growth and is important in development, wound healing, and inflammatory responses. Mutations cause frontotemporal dementia and primary progressive aphasia through autosomal dominant inheritance, typically via haploinsufficiency from loss-of-function variants, while biallelic mutations cause autosomal recessive neuronal ceroid lipofuscinosis type 11. The dominant conditions result from reduced progranulin levels leading to neurodegeneration, while the recessive form involves more severe loss of protein function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Aphasia, primary progressiveMIM #607485

ADAR

Ceroid lipofuscinosis, neuronal, 11MIM #614706

Frontotemporal dementia 2MIM #607485

ADAR

Clinical highlights

Management implications

GRN has therapies in development

Gene-disease validity (ClinGen)

neuronal ceroid lipofuscinosis · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

519

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — GRN

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

latozinemab (AL001)
antibodyPhase 3
Raises progranulin by blocking sortilin-mediated degradation.
Delivery: IV
progranulin-delivery AAV (e.g. PBFT02)
AAV gene therapyPhase 1/2
Deliver GRN to raise progranulin.
Delivery: Intra-cisterna magna

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.48LOEUF

pLI 0.070

Z-score 3.71

OE 0.27 (0.16–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.28Z-score

OE missense 0.96 (0.88–1.05)

341 obs / 355.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.27 (0.16–0.48)

0≤0.351.4

Missense OE?0.96 (0.88–1.05)

0≤0.61.4

Synonymous OE?1.13

0≤1.21.6

LoF obs/exp: 8 / 29.9Missense obs/exp: 341 / 355.6Syn Z: -1.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

GRN · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

📖

GeneReview available — GRN

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Frontotemporal Lobar DegenerationAlzheimer DiseaseCognitively Normal

PET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using [18F]-PI-2620

RECRUITING

NCT05456503Phase PHASE3University of PennsylvaniaStarted 2022-09-19

[18F]-PI-2620

Neuronal Ceroid LipofuscinosisBatten DiseaseCLN1 Disease

Natural History and Longitudinal Clinical Assessments in NCL / Batten Disease, the International DEM-CHILD Database

RECRUITING

NCT04613089Universitätsklinikum Hamburg-EppendorfStarted 2020-04-08

Natural History

Frontotemporal Lobar Degeneration (FTLD)Progressive Supranuclear Palsy (PSP)Corticobasal Degeneration (CBD)

ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD)

RECRUITING

NCT04363684Mayo ClinicStarted 2020-03-01

Frontotemporal DementiaFTDFTD-GRN

A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes

ACTIVE NOT RECRUITING

NCT04747431Phase PHASE1, PHASE2Passage Bio, Inc.Started 2021-09-14

PBFT02

Neurodegenerative DiseaseBehavioral Variant Frontotemporal Dementia (bvFTD)Primary Progressive Aphasia(PPA)

Tracking and Predicting How Brain Damage Spreads in Neurodegenerative Diseases

ENROLLING BY INVITATION

NCT07567664Phase NAIRCCS San RaffaeleStarted 2017-06-01

3 Tesla MRI without contrast mediumBlood sample for genetic analysisCerebrospinal fluid sampling (CSF)

Frontotemporal DementiaFTDFTD-GRN

A Study to Evaluate the Safety and Effect of AVB-101, a Gene Therapy Product, in Subjects With a Genetic Sub-type of Frontotemporal Dementia (FTD-GRN)

RECRUITING

NCT06064890Phase PHASE1, PHASE2AviadoBio LtdStarted 2023-08-30

Intrathalamic AAV.PGRN administrationIntrathalamic AVB-101

Amyotrophic Lateral Sclerosis

Development of Targeted RNA-Seq for Amyotrophic Lateral Sclerosis Diagnosis

RECRUITING

NCT06083584Centre Hospitalier Universitaire de NīmesStarted 2023-11-22

RNA sequencing

Spinal StenosisLigamentum Flavum Hypertrophy

Cytokines, Neuroplasticity Modulators, and Biomarkers in Spinal Canal Stenosis and Endoscopic Decompression

NOT YET RECRUITING

NCT07232836Phase NAPoznan University of Physical EducationStarted 2025-11-17