GRN

Summary

GRN (granulin precursor, HGNC:4601) is a protein-coding gene on chromosome 17q21.31, encoding Progranulin (P28799). Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation.

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.

Source: NCBI Gene 2896 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuronal ceroid lipofuscinosis (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 6
• Clinical variants (ClinVar): 825 total — 109 pathogenic, 21 likely-pathogenic
• Phenotypes (HPO): 83
• Druggable target: yes
• MANE Select transcript: NM_002087

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4601
Approved symbol	GRN
Name	granulin precursor
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	PCDGF, PGRN, CLN11
Ensembl gene	ENSG00000030582
Ensembl biotype	protein_coding
OMIM	138945
Entrez	2896

Gene structure

Transcript identifiers

Ensembl transcripts: 39 — 32 protein_coding, 5 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000053867, ENST00000585348, ENST00000585512, ENST00000586242, ENST00000586443, ENST00000586782, ENST00000587109, ENST00000587387, ENST00000587518, ENST00000587958, ENST00000588143, ENST00000588170, ENST00000588237, ENST00000589265, ENST00000589536, ENST00000589923, ENST00000590984, ENST00000591740, ENST00000592323, ENST00000592783, ENST00000593167, ENST00000900926, ENST00000900927, ENST00000900928, ENST00000900929, ENST00000900930, ENST00000900931, ENST00000900932, ENST00000900933, ENST00000900934, ENST00000900935, ENST00000918283, ENST00000918284, ENST00000918285, ENST00000918286, ENST00000918287, ENST00000944505, ENST00000944506, ENST00000944507

RefSeq mRNA: 1 — MANE Select: NM_002087 NM_002087

CCDS: CCDS11483

Canonical transcript exons

ENST00000053867 — 13 exons

Exon	Start	End
ENSE00000732197	44352341	44352571
ENSE00000732199	44352015	44352248
ENSE00001376066	44352661	44353106
ENSE00002337665	44350228	44350340
ENSE00002344685	44349667	44349751
ENSE00002971866	44345302	44345334
ENSE00003466751	44350691	44350800
ENSE00003576251	44350442	44350577
ENSE00003589157	44351550	44351795
ENSE00003606043	44349158	44349302
ENSE00003646360	44349426	44349551
ENSE00003647696	44351363	44351460
ENSE00003667214	44351037	44351163

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 248.9431 / max 3081.7431, expressed in 1826 samples.

FANTOM5 promoters (18 alternative TSS)

Promoter ID	TPM avg	Samples expressed
161142	198.7535	1824
161141	34.3839	1807
161140	9.9647	1734
161159	1.3246	656
161158	1.1257	631
161153	0.8407	467
161154	0.7264	421
161155	0.5801	317
161151	0.4457	240
161152	0.3722	204

Top tissues by expression

304 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.51	gold quality
granulocyte	CL:0000094	99.46	gold quality
stromal cell of endometrium	CL:0002255	99.40	gold quality
leukocyte	CL:0000738	99.39	gold quality
mononuclear cell	CL:0000842	99.38	gold quality
esophagus mucosa	UBERON:0002469	99.26	gold quality
lower esophagus mucosa	UBERON:0035834	99.21	gold quality
spleen	UBERON:0002106	99.07	gold quality
right lung	UBERON:0002167	99.06	gold quality
upper lobe of left lung	UBERON:0008952	98.95	gold quality
gall bladder	UBERON:0002110	98.91	gold quality
upper lobe of lung	UBERON:0008948	98.91	gold quality
minor salivary gland	UBERON:0001830	98.90	gold quality
mouth mucosa	UBERON:0003729	98.83	gold quality
bone marrow cell	CL:0002092	98.81	gold quality
endometrium epithelium	UBERON:0004811	98.74	gold quality
transverse colon	UBERON:0001157	98.60	gold quality
mucosa of transverse colon	UBERON:0004991	98.59	gold quality
metanephros cortex	UBERON:0010533	98.50	gold quality
saliva-secreting gland	UBERON:0001044	98.48	gold quality
skin of leg	UBERON:0001511	98.46	gold quality
right coronary artery	UBERON:0001625	98.46	gold quality
lymph node	UBERON:0000029	98.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	98.42	gold quality
type B pancreatic cell	CL:0000169	98.41	gold quality
skin of abdomen	UBERON:0001416	98.38	gold quality
lower lobe of lung	UBERON:0008949	98.38	gold quality
esophagus	UBERON:0001043	98.35	gold quality
pharyngeal mucosa	UBERON:0000355	98.29	gold quality
epithelium of esophagus	UBERON:0001976	98.23	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 26.

Experiment	Marker?	Max mean expression
E-HCAD-15	yes	3221.25
E-CURD-122	yes	1969.50
E-GEOD-150728	yes	1810.23
E-MTAB-6653	yes	1731.98
E-MTAB-10042	yes	1247.11
E-GEOD-139324	yes	1240.87
E-HCAD-4	yes	89.72
E-HCAD-1	yes	85.82
E-MTAB-6701	yes	73.38
E-MTAB-8410	yes	51.20
E-HCAD-10	yes	45.57
E-MTAB-10553	yes	43.61
E-MTAB-6678	yes	43.19
E-CURD-46	yes	37.68
E-HCAD-6	yes	36.86

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting GRN, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-181A-2-3P	98.91	67.60	1168
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-6804-3P	98.72	64.82	852
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-615-5P	98.10	63.76	591
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4278	95.28	65.49	351

Literature-anchored findings (GeneRIF, showing 40)

• downregulated significantly in acute myeloid leukemia patients whose white blood cell count was higher than 100 x 10(9)/L cells (PMID:12031912)
• PEPI has a role in wound healing and innate immunity (PMID:12526812)
• PCDGF has a role as a new autocrine growth factor in epithelial ovarian cancer (PMID:12538450)
• granulin is a cellular protein that interacts with cyclin T1 to inhibit transcription (PMID:12588988)
• PC-cell-derived growth factor has a critical role in breast cancer tumorigenesis. (PMID:12914763)
• identified two proteins that interacted with the Tat protein of the caprine arthritis encephalitis virus: the EGF-like repeats 1-6 of the extracellular domain of the human Notch2 receptor and the epithelin/granulin growth factor precursor (PMID:12931033)
• an important role of PCDGF in breast cancer pathogenesis and a potential novel target for the treatment of breast cancer (PMID:14652816)
• PCDGF has a role in the development of prostatic intraepithelial neoplasia (PMID:14977833)
• the Granulin-epithelin precursor has a role in hepatocellular carcinoma growth, invasion, and metastasis (PMID:15569995)
• Data show that the granulin/epithelin precursor and some of its constituent granulin repeats can inhibit HIV-1 transcription via Tat without directly binding to cyclin T1. (PMID:15653695)
• Overexpression of acrogranin is associated with uterine leiomyosarcoma (PMID:16533762)
• PC cell-derived growth factor stimulates proliferation and confers Trastuzumab resistance to Her-2-overexpressing breast cancer cells (PMID:16857791)
• PGRN haploinsufficiency leads to neurodegeneration because of reduced PGRN-mediated neuronal survival; and involvement of PGRN in frontotemporal dementia pathogenesis (PMID:16862115)
• results identify mutations in PGRN as a cause of neurodegenerative disease and indicate the importance of PGRN function for neuronal survival (PMID:16862116)
• Patients with PGRN mutations revealed variable onset ages with language dysfunction as a common presenting symptom, neuropathological examination showed dementia with ubiquitin-positive inclusions in all PGRN mutation carriers. (PMID:16950801)
• This study discovered a new PGRN mutation (R493X) resulting in a stop codon in two frontotemporal dementia patients. (PMID:16983677)
• familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions caused by a missense mutation in the signal peptide of progranulin.(ALA-9 ASP). (PMID:16983685)
• This study identified a novel 4 bp deletion mutation in exon 7 of PGRN gene (Leu271LeufsX10) associated with a variable clinical presentation ranging from FTDP-17 to corticobasal syndrome. (PMID:17157414)
• Mutations in progranulin (PGRN), predicted to cause premature truncation of the PGRN coding sequence, are found in patients with inherited FTLD with immunoreactive ubiquitin (ub-ir) inclusions (FTDL-U) and ub-ir neuronal intranuclear inclusions. (PMID:17202431)
• primary progressive aphasia has Progranulin mutations. (PMID:17210807)
• Two novel frameshift mutations and three possible pathogenic missense mutations are reported. (PMID:17228326)
• PCDGF plays an important role in stimulating proliferation and promoting invasion in ovarian cancer. (PMID:17261172)
• Granulin-epithelin precursor overexpression was associated with CDDP chemoresistance. Finally, GEP overexpression increased tumor formation and protected cells from tumor regression in response to CDDP treatment in vivo (PMID:17266030)
• Increased PGRN expression by microglia may play a pivotal role in the response to brain injury, neuroinflammation and neurodegeneration. (PMID:17291356)
• the mutation spectrum in PGRN leading to loss of functional PGRN as the basis for frontotemporal dementia (PMID:17345602)
• Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with ubiquitin-positive inclusions. (PMID:17353379)
• PGRN mutations are not a common cause of amyotrophic lateral sclerosis phenotypes (PMID:17371905)
• The results revealed that the common variations in IFT74 and GRN neither constitute strong ALS risk factors nor modify the age-at-onset. (PMID:17383054)
• We describe a new mutation in the PGRN gene (A303AfsX57) associated with late-onset frontotemporal dementia and with “cat’s eye” shaped intranuclear and cytoplasmatic ubiquitin immunoreactive inclusions in the neuropathological exam. (PMID:17417739)
• Progranulin null mutations in both sporadic and familial frontotemporal dementia. (PMID:17436289)
• A single GRN mutation in the two families studied was associated with variable clinical presentations consistent with the frontotemporal dementia syndrome (PMID:17439980)
• Marked variation of the clinical phenotype makes it difficult to predict which cases of familial frontotemporal dementia will turn out to have a progranulin mutation. (PMID:17458552)
• PGRN mutations at 17q21 may occur in apparently sporadic frontotemporal lobar dementia with ubiquitinated inclusions cases and in cases presenting with either primary progressive aphasia or the behavioral variant of frontotemporal dementia. (PMID:17522386)
• Progranulin mutations cause haploinsufficiency leading to TDP-43 accumulation in frontotemporal lobar degeneration. (PMID:17572900)
• The current results imply further genetic heterogeneity of frontotemporal dementia, as we detected only one GRN-linked family (about 1%). The value of discovering large kindred includes the possibility of a longitudinal study of GRN mutation carriers. (PMID:17620546)
• Patients with a GRN mutation differ clinically from those with the same pathologic diagnosis but no GRN mutation. (PMID:17698705)
• Clinical heterogeneity is associated with GRN haploinsufficiency, and genetic variability on the wild-type GRN allele might have a role in the age-related disease penetrance of GRN mutations. (PMID:17826340)
• Age of onset, clinical phenotypes and MRI findings associated with most PGRN mutations varied significantly both within and among kindreds. Some kindreds with PGRN mutations exhibited lateralized topography of degeneration across all affected individuals. (PMID:17949857)
• Progranulopathies are a major cause of the main phenotypes included in the FTLD complex. (PMID:17950702)
• A progranulin mutation located within the signal sequence (PGRN A9D) results in cytoplasmic missorting with extremely low expression. (PMID:17984093)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	grnb	ENSDARG00000025081
mus_musculus	Grn	ENSMUSG00000034708
rattus_norvegicus	Grn	ENSRNOG00000021031

Protein

Protein identifiers

Progranulin — P28799 (reviewed: P28799)

Alternative names: Acrogranin, Epithelin precursor, Glycoprotein of 88 Kda, Granulin precursor, PC cell-derived growth factor, Proepithelin

All UniProt accessions (15): P28799, K7EJY4, K7EK92, K7EKL3, K7ELY1, K7EM89, K7EMR1, K7ENI2, K7ENN1, K7EPL0, K7EQ05, K7EQA7, K7EQI0, K7EQK6, K7ERM2

UniProt curated annotations — full annotation on UniProt →

Function. Secreted protein that acts as a key regulator of lysosomal function and as a growth factor involved in inflammation, wound healing and cell proliferation. Regulates protein trafficking to lysosomes, and also the activity of lysosomal enzymes. Also facilitates the acidification of lysosomes, causing degradation of mature CTSD by CTSB. In addition, functions as a wound-related growth factor that acts directly on dermal fibroblasts and endothelial cells to promote division, migration and the formation of capillary-like tubule structures. Also promotes epithelial cell proliferation by blocking TNF-mediated neutrophil activation preventing release of oxidants and proteases. Moreover, modulates inflammation in neurons by preserving neurons survival, axonal outgrowth and neuronal integrity. Promotes proliferation of the epithelial cell line A431 in culture. Inhibits epithelial cell proliferation and induces epithelial cells to secrete IL-8. Stabilizes CTSD through interaction with CTSD leading to maintain its aspartic-type peptidase activity.

Subunit / interactions. Progranulin is secreted as a homodimer. Interacts with SLPI; interaction protects progranulin from proteolysis. Interacts (via region corresponding to granulin-7 peptide) with CTSD; stabilizes CTSD and increases its proteolytic activity. Interacts (via region corresponding to granulin-7 peptide) with SORT1; this interaction mediates endocytosis and lysosome delivery of progranulin; interaction occurs at the neuronal cell surface in a stressed nervous system. Interacts with PSAP; facilitates lysosomal delivery of progranulin from the extracellular space and the biosynthetic pathway. Forms a complex with PSAP and M6PR; PSAP bridges the binding between progranulin and M6PR. Forms a complex with PSAP and SORT1; progranulin bridges the interaction between PSAP and SORT1; facilitates lysosomal targeting of PSAP via SORT1; interaction enhances PSAP uptake in primary cortical neurons. Interacts (via regions corresponding to granulin-2 and granulin-7 peptides) with GBA1; this interaction prevents aggregation of GBA1-SCARB2 complex via interaction with HSPA1A upon stress. Interacts (via region corresponding to granulin-7 peptide) with HSPA1A; mediates recruitment of HSPA1A to GBA1 and prevents GBA1 aggregation in response to stress.

Subcellular location. Secreted. Lysosome.

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.

Post-translational modifications. Cleaved by ELANE; proteolysis is blocked by SLPI and is concentration- and time-dependent and induces CXCL8/IL-8 production; granulin-3 and granulin-4 are resistant to ELANE. Cleaved by CTSL in lysosome thus regulating the maturation and turnover of progranulin within the lysosome.

Disease relevance. Frontotemporal dementia 2 (FTD2) [MIM:607485] A form of dementia characterized by pathologic finding of frontotemporal lobar degeneration, presenile dementia with behavioral changes, deterioration of cognitive capacities and loss of memory. Gestural apraxia, parkinsonism, visual loss, and visual hallucinations are present in 25 to 40% of patients. The disease is caused by variants affecting the gene represented in this entry. Ceroid lipofuscinosis, neuronal, 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. The disease is caused by variants affecting the gene represented in this entry.

Induction. Increased in response to lysosome alkalization.

Similarity. Belongs to the granulin family.

Isoforms (3)

UniProt ID	Names	Canonical?
P28799-1	1	yes
P28799-2	2
P28799-3	3

RefSeq proteins (1): NP_002078* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000118	Granulin	Domain
IPR037277	Granulin_sf	Homologous_superfamily
IPR039036	Granulin_fam	Family

Pfam: PF00396

UniProt features (71 total): sequence variant 14, strand 13, disulfide bond 12, sequence conflict 10, peptide 8, glycosylation site 5, turn 4, splice variant 3, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
8T8R	X-RAY DIFFRACTION	2.87
8T8S	X-RAY DIFFRACTION	2.99
1G26	SOLUTION NMR
2JYE	SOLUTION NMR
2JYT	SOLUTION NMR
2JYU	SOLUTION NMR
2JYV	SOLUTION NMR
6NUG	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P28799-F1	76.74	0.20

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (12): 126–139, 133–149, 284–296, 290–306, 297–314, 307–321, 315–328, 322–335, 366–378, 372–388, 397–410, 404–416

Glycosylation sites (5): 118, 236, 265, 368, 530

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 685 (showing top): GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_REGULATION_OF_CELL_ACTIVATION, MODULE_52, MODULE_92, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, KOBAYASHI_EGFR_SIGNALING_24HR_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_LYSOSOMAL_TRANSPORT, GOBP_BEHAVIOR, GOBP_VACUOLE_ORGANIZATION, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_MACROPHAGE_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE

GO Biological Process (39): trophectodermal cell proliferation (GO:0001834), blastocyst hatching (GO:0001835), astrocyte activation involved in immune response (GO:0002265), microglial cell activation involved in immune response (GO:0002282), lysosome organization (GO:0007040), lysosomal transport (GO:0007041), lysosomal lumen acidification (GO:0007042), signal transduction (GO:0007165), embryo implantation (GO:0007566), positive regulation of endothelial cell migration (GO:0010595), positive regulation of cell migration (GO:0030335), locomotory exploration behavior (GO:0035641), negative regulation of neuron apoptotic process (GO:0043524), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of angiogenesis (GO:0045766), positive regulation of axon regeneration (GO:0048680), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), regulation of inflammatory response (GO:0050727), protein stabilization (GO:0050821), retina development in camera-type eye (GO:0060041), negative regulation of respiratory burst involved in inflammatory response (GO:0060266), maintenance of synapse structure (GO:0099558), positive regulation of inflammatory response to wounding (GO:0106016), positive regulation of defense response to bacterium (GO:1900426), negative regulation of neutrophil activation (GO:1902564), positive regulation of protein folding (GO:1903334), negative regulation of microglial cell activation (GO:1903979), positive regulation of trophectodermal cell proliferation (GO:1904075), lysosomal protein catabolic process (GO:1905146), positive regulation of aspartic-type peptidase activity (GO:1905247), positive regulation of lysosome organization (GO:1905673), positive regulation of cell population proliferation (GO:0008284), negative regulation of innate immune response (GO:0045824), negative regulation of inflammatory response (GO:0050728), regulation of developmental process (GO:0050793), positive regulation of cellular component organization (GO:0051130), establishment of localization in cell (GO:0051649), regulation of lysosome organization (GO:1905671)

GO Molecular Function (5): RNA binding (GO:0003723), cytokine activity (GO:0005125), growth factor activity (GO:0008083), protein-folding chaperone binding (GO:0051087), protein binding (GO:0005515)

GO Cellular Component (15): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), lysosomal membrane (GO:0005765), endosome (GO:0005768), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), membrane (GO:0016020), azurophil granule lumen (GO:0035578), extracellular exosome (GO:0070062), cerebellar climbing fiber to Purkinje cell synapse (GO:0150053), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
cell population proliferation	2
immune response	2
regulation of neuron apoptotic process	2
neuron apoptotic process	2
receptor ligand activity	2
cellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
blastocyst growth	1
blastocyst development	1
hatching	1
cell activation involved in immune response	1
astrocyte activation	1
microglial cell activation	1
macrophage activation involved in immune response	1
lytic vacuole organization	1
vacuolar transport	1
vacuolar acidification	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
locomotory behavior	1
exploration behavior	1
negative regulation of apoptotic process	1
positive regulation of apoptotic process	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

1156 interactions, top by confidence:

A	B	Type	Score
HOXA1	GRN	psi-mi:“MI:0915”(physical association)	0.950
GRN	HOXA1	psi-mi:“MI:0915”(physical association)	0.950
GLRX3	GRN	psi-mi:“MI:0915”(physical association)	0.870
GRN	GLRX3	psi-mi:“MI:0915”(physical association)	0.870
GRN	OTX1	psi-mi:“MI:0915”(physical association)	0.850
OTX1	GRN	psi-mi:“MI:0915”(physical association)	0.850
GRN	SGTA	psi-mi:“MI:0915”(physical association)	0.780
GRN	KRTAP26-1	psi-mi:“MI:0915”(physical association)	0.780
NLK	GRN	psi-mi:“MI:0915”(physical association)	0.780
SGTA	GRN	psi-mi:“MI:0915”(physical association)	0.780

BioGRID (334): GRN (Two-hybrid), HOXA1 (Two-hybrid), OTX1 (Two-hybrid), SGTA (Two-hybrid), GLRX3 (Two-hybrid), NLK (Two-hybrid), FANCL (Two-hybrid), ARFGAP1 (Two-hybrid), CCDC33 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP26-1 (Two-hybrid), GRN (Affinity Capture-RNA), GRN (Affinity Capture-MS), GRN (Affinity Capture-MS), GRN (Affinity Capture-MS)

ESM2 similar proteins: A0A1D5NSM8, A0A4Y5X186, A0A4Y5X1A7, A2AVA0, B2BS84, D3YXF5, D3ZHH1, O43278, O89103, P05486, P0C5J5, P0C6B8, P0DN42, P0DN43, P0DTJ2, P23785, P28797, P28798, P28799, P80059, P81481, P97677, Q00945, Q08E66, Q11101, Q2XXR7, Q2XXR8, Q4LDE5, Q61483, Q6DFV8, Q6NUX0, Q6NZL8, Q7TQN3, Q7Z1K3, Q7Z5A8, Q80YN4, Q8JZM4, Q8NFT8, Q8R0S6, Q8TEU8

Diamond homologs: B2LSD2, P20721, P23785, P25776, P25777, P28797, P28798, P28799, P80059, P80930, P81013, P81014, P81015, Q54QR7, Q9FMH8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
GRN	down-regulates	TNFRSF1A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 120 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Keratinization	21	13.0×	2e-15
Formation of the cornified envelope	9	8.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	10	22.7×	1e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

825 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	109
Likely pathogenic	21
Uncertain significance	344
Likely benign	229
Benign	17

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072132	NM_002087.4(GRN):c.614C>A (p.Ser205Ter)	Pathogenic
1075941	NM_002087.4(GRN):c.299del (p.Pro100fs)	Pathogenic
1175911	NM_002087.4(GRN):c.1496del (p.Val499fs)	Pathogenic
1184870	NM_002087.4(GRN):c.78C>A (p.Cys26Ter)	Pathogenic
1335274	NM_002087.4(GRN):c.1216del (p.Gln406fs)	Pathogenic
1352426	NM_002087.4(GRN):c.1A>G (p.Met1Val)	Pathogenic
1371968	NM_002087.4(GRN):c.1153del (p.Glu385fs)	Pathogenic
1453069	NM_002087.4(GRN):c.39dup (p.Leu14fs)	Pathogenic
1455419	NM_002087.4(GRN):c.1216C>T (p.Gln406Ter)	Pathogenic
1457149	NM_002087.4(GRN):c.775_778del (p.Lys259fs)	Pathogenic
1458018	NC_000017.10:g.(?42426434)(42430018_?)del	Pathogenic
16007	NM_002087.4(GRN):c.373C>T (p.Gln125Ter)	Pathogenic
16008	NM_002087.4(GRN):c.2T>C (p.Met1Thr)	Pathogenic
16009	NM_002087.4(GRN):c.3G>A (p.Met1Ile)	Pathogenic
16010	NM_002087.4(GRN):c.93_96dup (p.Asp33fs)	Pathogenic
16011	NM_002087.4(GRN):c.388_391del (p.Gln130fs)	Pathogenic
16013	NM_002087.4(GRN):c.26C>A (p.Ala9Asp)	Pathogenic
16014	NM_002087.4(GRN):c.1477C>T (p.Arg493Ter)	Pathogenic
16020	NM_002087.4(GRN):c.813_816del (p.Thr272fs)	Pathogenic
1687738	NM_002087.4(GRN):c.52A>G (p.Thr18Ala)	Pathogenic
1694848	NM_002087.4(GRN):c.1558G>T (p.Glu520Ter)	Pathogenic
1697215	NM_002087.4(GRN):c.599-2A>G	Pathogenic
1734749	NM_002087.4(GRN):c.1153G>T (p.Glu385Ter)	Pathogenic
1767743	NM_002087.4(GRN):c.967_976del (p.Pro323fs)	Pathogenic
1922048	NM_002087.4(GRN):c.472_496dup (p.Pro166delinsLeuTer)	Pathogenic
1955531	NM_002087.4(GRN):c.1492_1495del (p.Glu498fs)	Pathogenic
1994860	NM_002087.4(GRN):c.180dup (p.Cys61fs)	Pathogenic
1999202	NM_002087.4(GRN):c.264+1del	Pathogenic
2007840	NM_002087.4(GRN):c.1179+1G>C	Pathogenic
2028731	NM_002087.4(GRN):c.118_121dup (p.Cys41Ter)	Pathogenic

SpliceAI

1542 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44350339:AG:A	donor_loss	1.0000
17:44350340:GG:G	donor_loss	1.0000
17:44350342:T:G	donor_loss	1.0000
17:44350440:A:AG	acceptor_gain	1.0000
17:44350441:G:GG	acceptor_gain	1.0000
17:44350576:AG:A	donor_loss	1.0000
17:44350577:GGTG:G	donor_loss	1.0000
17:44350578:G:GC	donor_loss	1.0000
17:44350579:T:G	donor_loss	1.0000
17:44350689:A:AG	acceptor_gain	1.0000
17:44350689:AGTG:A	acceptor_gain	1.0000
17:44350690:G:GG	acceptor_gain	1.0000
17:44350690:GT:G	acceptor_gain	1.0000
17:44350690:GTGG:G	acceptor_gain	1.0000
17:44350773:G:GT	donor_gain	1.0000
17:44350773:G:T	donor_gain	1.0000
17:44350801:G:GG	donor_gain	1.0000
17:44351031:A:AG	acceptor_gain	1.0000
17:44351032:CTCA:C	acceptor_loss	1.0000
17:44351035:A:AG	acceptor_gain	1.0000
17:44351036:G:A	acceptor_loss	1.0000
17:44351036:G:GG	acceptor_gain	1.0000
17:44351036:GGCC:G	acceptor_gain	1.0000
17:44351159:CACAG:C	donor_loss	1.0000
17:44351160:ACAGG:A	donor_loss	1.0000
17:44351161:CAG:C	donor_loss	1.0000
17:44351162:AG:A	donor_loss	1.0000
17:44351163:GGTAC:G	donor_loss	1.0000
17:44351164:G:GA	donor_loss	1.0000
17:44351165:T:G	donor_loss	1.0000

AlphaMissense

3909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44351439:G:C	W304C	0.995
17:44351439:G:T	W304C	0.995
17:44352756:G:C	W580C	0.992
17:44352756:G:T	W580C	0.992
17:44352389:T:A	C488S	0.991
17:44352390:G:C	C488S	0.991
17:44352550:G:C	W541C	0.991
17:44352550:G:T	W541C	0.991
17:44351085:T:A	C253S	0.990
17:44351086:G:C	C253S	0.990
17:44351377:T:A	C284S	0.990
17:44351378:G:C	C284S	0.990
17:44352227:G:C	W464C	0.990
17:44352227:G:T	W464C	0.990
17:44352410:T:A	C495S	0.989
17:44352411:G:C	C495S	0.989
17:44351106:T:A	C260S	0.988
17:44351107:G:C	C260S	0.988
17:44352351:G:A	C475Y	0.988
17:44350319:G:C	W147C	0.986
17:44350319:G:T	W147C	0.986
17:44352350:T:A	C475S	0.986
17:44352351:G:C	C475S	0.986
17:44352371:T:A	C482S	0.986
17:44352372:G:C	C482S	0.986
17:44351046:T:A	C240S	0.985
17:44351047:G:C	C240S	0.985
17:44350254:T:A	C126S	0.984
17:44350255:G:C	C126S	0.984
17:44352411:G:A	C495Y	0.984

dbSNP variants (sampled 300 via entrez): RS1000038539 (17:44346731 C>G,T), RS1000739047 (17:44349340 G>A,C), RS1000944253 (17:44343507 A>T), RS1001032652 (17:44345347 C>A,T), RS1001261540 (17:44350948 G>A), RS1001409658 (17:44351873 C>A,T), RS1001556908 (17:44353312 C>A,T), RS1001627261 (17:44346315 C>T), RS1001742241 (17:44347884 C>T), RS1001799029 (17:44353501 C>T), RS1002089709 (17:44348167 A>C), RS1002503065 (17:44344816 C>T), RS1002555371 (17:44344551 T>G), RS1003142217 (17:44353343 G>T), RS1003196411 (17:44347282 T>A,C,G)

Disease associations

OMIM: gene MIM:138945 | disease phenotypes: MIM:607485, MIM:614706, MIM:616437, MIM:105500, MIM:612069

GenCC curated gene-disease

Disease	Classification	Inheritance
neuronal ceroid lipofuscinosis 11	Strong	Autosomal recessive
GRN-related frontotemporal lobar degeneration with Tdp43 inclusions	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neuronal ceroid lipofuscinosis	Definitive	AR
frontotemporal dementia and/or amyotrophic lateral sclerosis	Definitive	AD

Mondo (10): GRN-related frontotemporal lobar degeneration with Tdp43 inclusions (MONDO:0011842), neuronal ceroid lipofuscinosis 11 (MONDO:0013866), frontotemporal dementia and/or amyotrophic lateral sclerosis 3 (MONDO:0014640), primary progressive aphasia (MONDO:0019806), frontotemporal dementia (MONDO:0017276), parkinsonian disorder (MONDO:0021095), frontotemporal dementia and/or amyotrophic lateral sclerosis (MONDO:0030923), ischemic stroke (MONDO:1060198), Alzheimer disease (MONDO:0004975), amyotrophic lateral sclerosis type 10 (MONDO:0012790)

Orphanet (10): Progressive non-fluent aphasia (Orphanet:100070), Frontotemporal dementia (Orphanet:282), CLN11 disease (Orphanet:314629), OBSOLETE: Adult neuronal ceroid lipofuscinosis (Orphanet:79262), Behavioral variant of frontotemporal dementia (Orphanet:275864), Frontotemporal dementia with motor neuron disease (Orphanet:275872), Amyotrophic lateral sclerosis (Orphanet:803), Primary progressive aphasia (Orphanet:95432), Early-onset autosomal dominant Alzheimer disease (Orphanet:1020), NON RARE IN EUROPE: Alzheimer disease (Orphanet:238616)

HPO phenotypes

83 total (30 of 83 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000474	Thickened nuchal skin fold
HP:0000505	Visual impairment
HP:0000556	Retinal dystrophy
HP:0000648	Optic atrophy
HP:0000708	Atypical behavior
HP:0000709	Psychosis
HP:0000710	Hyperorality
HP:0000711	Restlessness
HP:0000713	Agitation
HP:0000716	Depression
HP:0000718	Aggressive behavior
HP:0000719	Inappropriate behavior
HP:0000723	Restrictive behavior
HP:0000726	Dementia
HP:0000733	Motor stereotypy
HP:0000734	Disinhibition
HP:0000737	Irritability
HP:0000738	Hallucinations
HP:0000739	Anxiety
HP:0000741	Apathy
HP:0000751	Personality changes
HP:0000757	Lack of insight
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001268	Mental deterioration
HP:0001272	Cerebellar atrophy
HP:0001288	Gait disturbance
HP:0001297	Stroke

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001483_2	Intracranial volume	8.000000e-15
GCST002756_10	Subcortical brain region volumes	1.000000e-08
GCST005109_3	Progranulin levels	5.000000e-14
GCST006585_2773	Blood protein levels	5.000000e-08
GCST010703_292	Brain morphology (MOSTest)	1.000000e-14
GCST90026416_21	Mild age-related type 2 diabetes	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004886	intracranial volume measurement
EFO:0004625	progranulin measurement
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000544	Alzheimer Disease	C10.228.140.380.100; C10.574.945.249; F03.615.400.100
D018888	Aphasia, Primary Progressive	C10.228.140.380.132; C10.597.606.150.500.800.100.155; C23.888.592.604.150.500.800.100.155; F03.615.400.125
D057180	Frontotemporal Dementia	C10.228.140.380.266.299; C10.574.950.300.299; C18.452.845.800.300.299; F03.615.400.380.299
D020734	Parkinsonian Disorders	C10.228.140.079.862; C10.228.662.600
C567429	Amyotrophic Lateral Sclerosis 10 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4680051 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

27 potent at pChembl≥5 of 33 total, top 27 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.70	IC50	20	nM	CHEMBL4752312
7.19	IC50	65	nM	CHEMBL4751985
7.05	IC50	90	nM	CHEMBL4751566
6.92	IC50	120	nM	CHEMBL4752312
6.77	IC50	170	nM	CHEMBL4741088
6.54	IC50	290	nM	CHEMBL4751566
6.46	IC50	350	nM	CHEMBL4759392
6.31	IC50	490	nM	CHEMBL4791749
6.19	IC50	650	nM	CHEMBL4741088
5.82	IC50	1500	nM	CHEMBL4750083
5.70	IC50	2000	nM	CHEMBL4748685
5.68	IC50	2100	nM	CHEMBL4781044
5.68	IC50	2100	nM	CHEMBL4777461
5.64	IC50	2300	nM	CHEMBL4757228
5.57	IC50	2700	nM	CHEMBL4789084
5.52	IC50	3000	nM	CHEMBL4789976
5.37	IC50	4300	nM	CHEMBL4786857
5.35	IC50	4500	nM	CHEMBL4757916
5.28	IC50	5300	nM	CHEMBL4764009
5.28	IC50	5300	nM	CHEMBL4753027
5.20	IC50	6300	nM	CHEMBL3930223
5.18	IC50	6600	nM	CHEMBL4792809
5.17	IC50	6800	nM	CHEMBL135435
5.17	IC50	6800	nM	CHEMBL4763573
5.16	IC50	6900	nM	CHEMBL4799607
5.11	IC50	7800	nM	CHEMBL4743518
5.08	IC50	8300	nM	CHEMBL1359408

PubChem BioAssay actives

27 with measured affinity, of 37 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(2S)-5,5-dimethyl-2-[(6-phenoxypyridine-3-carbonyl)amino]hexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0200	uM
(2S)-4,4-dimethyl-2-[(6-phenoxypyridine-3-carbonyl)amino]pentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0650	uM
(2S)-2-[(4-chloro-1H-pyrrole-2-carbonyl)amino]-5,5-dimethylhexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.0900	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-5,5-dimethylhexanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.1700	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-4,4-dimethylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.3500	uM
3-tert-butyl-1-[(5-phenyl-1,3,4-oxadiazol-2-yl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	0.4900	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-3-[(2-methylpropan-2-yl)oxy]propanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	1.5000	uM
1-benzyl-3-tert-butylpyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.0000	uM
3-tert-butyl-1-[(6-phenoxy-3-pyridinyl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.1000	uM
3-tert-butyl-1-[(3,5-dichlorophenyl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.1000	uM
(2S)-3-cyclohexyl-2-[(3,5-dichlorobenzoyl)amino]propanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.3000	uM
(2S)-2-[(3,5-dichlorobenzoyl)amino]-4-methylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	2.7000	uM
3-tert-butyl-1-[(6-pyrazol-1-yl-3-pyridinyl)methyl]pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	3.0000	uM
(2S)-2-[(3,4-dichlorobenzoyl)amino]-4-methylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	4.3000	uM
(2S)-2-[(3-chlorobenzoyl)amino]-4-methylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	4.5000	uM
(2S)-4-methyl-2-[(1-methylpyrazole-4-carbonyl)amino]pentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	5.3000	uM
3-tert-butyl-1-(2-phenylethyl)pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	5.3000	uM
(2S)-4-methyl-2-(quinoxaline-2-carbonylamino)pentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	6.3000	uM
1-benzyl-3-(2,2-dimethylpropyl)pyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	6.6000	uM
(2S)-2-[[3-(4-chlorophenyl)-2,2-dimethylpropanoyl]amino]-4-methylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	6.8000	uM
(2S)-2-[(3-methoxybenzoyl)amino]-4-methylpentanoic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	6.8000	uM
3,5-dichloro-N-[3,3-dimethyl-1-(2H-tetrazol-5-yl)butyl]benzamide	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	6.9000	uM
3-tert-butyl-1-phenylpyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	7.8000	uM
3-tert-butyl-1-methylpyrazole-5-carboxylic acid	1674949: Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	ic50	8.3000	uM

CTD chemical–gene interactions

82 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	6
sodium arsenite	affects methylation, decreases expression, increases abundance, increases expression	4
Tretinoin	affects expression, increases expression	4
Cisplatin	increases expression, decreases expression, decreases reaction, affects cotreatment	3
Ozone	affects cotreatment, increases oxidation, increases abundance, affects expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
bisphenol A	increases expression	2
cobaltous chloride	decreases secretion, increases expression	2
perfluorooctanoic acid	decreases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
chloropicrin	decreases expression	2
Resveratrol	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	increases expression	2
Acrolein	increases abundance, affects cotreatment, increases oxidation	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, affects expression	2
Dimethyl Sulfoxide	increases expression	2
Cyclosporine	decreases expression, increases expression	2
afuresertib	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	decreases expression	1
beta-lapachone	decreases expression	1
sulindac sulfide	decreases expression	1
cupric oxide	increases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	increases expression	1
tamibarotene	increases expression	1
deguelin	decreases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4669365	Binding	Inhibition of SORT1 (unknown origin)-GRN (unknown origin) protein-protein interaction by HTRF assay	Identification of potent inhibitors of the sortilin-progranulin interaction. — Bioorg Med Chem Lett

Cellosaurus cell lines

46 cell lines: 36 induced pluripotent stem cell, 4 finite cell line, 3 cancer cell line, 2 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A9RN	NH50293	Induced pluripotent stem cell	Female
CVCL_A9T4	ND42499	Finite cell line	Male
CVCL_B2Y9	Abcam HEK293T GRN KO	Transformed cell line	Female
CVCL_B6HK	NH50327	Induced pluripotent stem cell	Female
CVCL_B6HL	NH50328	Induced pluripotent stem cell	Female
CVCL_C0P2	NCBL2.c11	Induced pluripotent stem cell	Male
CVCL_C0P3	NCBL2.c46	Induced pluripotent stem cell	Male
CVCL_C0P4	NCBL3.c2	Induced pluripotent stem cell	Male
CVCL_C0P5	NCBL3.c6	Induced pluripotent stem cell	Male
CVCL_C0P6	NCBL4.c27	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

230 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01818661	PHASE4	RECRUITING	Longitudinal Multi-Modality Imaging in Progressive Apraxia of Speech
NCT00376051	PHASE4	COMPLETED	Serotonergic Function and Behavioural and Psychological Symptoms of Frontotemporal Dementia
NCT00950430	PHASE4	ENROLLING_BY_INVITATION	Imaging of Brain Amyloid Plaques in the Aging Population
NCT06093126	PHASE4	RECRUITING	Lemborexant for Insomnia in a Patient With Dementia: An N-of-1 Trial
NCT01662414	PHASE4	COMPLETED	Effect of Undenatured Cysteine-Rich Whey Protein Isolate (HMS 90®) in Patients With Parkinson’s Disease
NCT04871464	PHASE4	UNKNOWN	Role and Mechanism of Probiotics in Improving Motor Symptoms in Mild to Moderate Parkinson’s Disease
NCT00594737	PHASE3	COMPLETED	Open Label Pilot Study of the Effects of Memantine on FDG-PET in Frontotemporal Dementia
NCT03682185	PHASE3	COMPLETED	The Healthy Patterns Sleep Study
NCT04374136	PHASE3	TERMINATED	A Phase 3 Study to Evaluate Efficacy and Safety of AL001 in Frontotemporal Dementia (INFRONT-3)
NCT04046991	PHASE2	COMPLETED	Treating Primary Progressive Aphasia (PPA) Using High-definition tDCS
NCT05386394	PHASE2	RECRUITING	Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia
NCT05615922	PHASE2	COMPLETED	Remotely Supervised Transcranial Direct Current Stimulation (tDCS) for Primary Progressive Aphasia (PPA)
NCT05742698	PHASE2	RECRUITING	Nabilone for Agitation in Frontotemporal Dementia
NCT06191198	PHASE2	RECRUITING	Communication Bridge 3 Study
NCT00416169	PHASE2	COMPLETED	A Pilot Study to Explore the Safety and Tolerability of Galantamine HBr in the Treatment of Pick Complex/Frontotemporal Dementia
NCT01890343	PHASE2	COMPLETED	Imaging Characteristics of Florbetapir 18F in Patients With Frontotemporal Dementia, Alzheimer’s Disease and Normal Controls.
NCT01937013	PHASE2	COMPLETED	Impact of Emotional Mimicry and Oxytocin on Frontotemporal Dementia
NCT02676843	PHASE2	COMPLETED	Tau PET Imaging With 18F-AV-1451 in Subjects With MAPT Mutations
NCT02862210	PHASE2	COMPLETED	Low-Dose Lithium for the Treatment of Behavioral Symptoms in Frontotemporal Dementia
NCT03260920	PHASE2	UNKNOWN	Intranasal Oxytocin for Frontotemporal Dementia
NCT03987295	PHASE2	COMPLETED	A Phase 2 Study to Evaluate Safety of Long-term AL001 Dosing in Frontotemporal Dementia (FTD) Patients (INFRONT-2)
NCT04220021	PHASE2	ACTIVE_NOT_RECRUITING	Safety and Therapeutic Potential of the FDA-approved Drug Metformin for C9orf72 ALS/FTD
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