PRF1

Summary

PRF1 (perforin 1, HGNC:9360) is a protein-coding gene on chromosome 10q22.1, encoding Perforin-1 (P14222). Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells.

This gene encodes a protein with structural similarities to complement component C9 that is important in immunity. This protein forms membrane pores that allow the release of granzymes and subsequent cytolysis of target cells. Whether pore formation occurs in the plasma membrane of target cells or in an endosomal membrane inside target cells is subject to debate. Mutations in this gene are associated with a variety of human disease including diabetes, multiple sclerosis, lymphomas, autoimmune lymphoproliferative syndrome (ALPS), aplastic anemia, and familial hemophagocytic lymphohistiocytosis type 2 (FHL2), a rare and lethal autosomal recessive disorder of early childhood.

Source: NCBI Gene 5551 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial hemophagocytic lymphohistiocytosis 2 (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 766 total — 62 pathogenic, 43 likely-pathogenic
• Phenotypes (HPO): 79
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001083116

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9360
Approved symbol	PRF1
Name	perforin 1
Location	10q22.1
Locus type	gene with protein product
Status	Approved
Aliases	PFP, P1, HPLH2
Ensembl gene	ENSG00000180644
Ensembl biotype	protein_coding
OMIM	170280
Entrez	5551

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000373209, ENST00000441259, ENST00000638674, ENST00000639390, ENST00000862973, ENST00000862974, ENST00000945922

RefSeq mRNA: 2 — MANE Select: NM_001083116 NM_001083116, NM_005041

CCDS: CCDS7305

Canonical transcript exons

ENST00000441259 — 3 exons

Exon	Start	End
ENSE00001614299	70600364	70600932
ENSE00003808924	70602645	70602741
ENSE00003890218	70597348	70599181

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 99.56.

FANTOM5 (CAGE): breadth broad, TPM avg 7.2886 / max 1348.6780, expressed in 315 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109848	2.9407	179
109849	2.4759	187
109850	1.2408	165
109845	0.4076	79
109851	0.1374	59
109846	0.0541	29
109847	0.0321	18

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.56	gold quality
blood	UBERON:0000178	96.47	gold quality
spleen	UBERON:0002106	93.48	gold quality
decidua	UBERON:0002450	91.89	gold quality
bone marrow cell	CL:0002092	87.21	gold quality
buccal mucosa cell	CL:0002336	86.41	gold quality
bone marrow	UBERON:0002371	86.04	gold quality
apex of heart	UBERON:0002098	85.54	gold quality
lymph node	UBERON:0000029	84.82	gold quality
superficial temporal artery	UBERON:0001614	84.10	gold quality
upper lobe of left lung	UBERON:0008952	83.78	gold quality
upper lobe of lung	UBERON:0008948	82.95	gold quality
right lung	UBERON:0002167	82.28	gold quality
lung	UBERON:0002048	81.46	gold quality
leukocyte	CL:0000738	81.28	gold quality
lower lobe of lung	UBERON:0008949	80.42	gold quality
colonic epithelium	UBERON:0000397	80.00	gold quality
mononuclear cell	CL:0000842	79.55	gold quality
periodontal ligament	UBERON:0008266	79.32	gold quality
palpebral conjunctiva	UBERON:0001812	79.21	gold quality
monocyte	CL:0000576	78.91	gold quality
jejunal mucosa	UBERON:0000399	78.35	gold quality
adult organism	UBERON:0007023	78.34	gold quality
vermiform appendix	UBERON:0001154	78.12	gold quality
mammary duct	UBERON:0001765	77.57	silver quality
thymus	UBERON:0002370	77.34	gold quality
vena cava	UBERON:0004087	77.29	silver quality
trabecular bone tissue	UBERON:0002483	77.26	gold quality
right lobe of liver	UBERON:0001114	77.04	gold quality
caecum	UBERON:0001153	76.89	gold quality

Single-cell (SCXA)

Detected in 38 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-6505	yes	3062.39
E-GEOD-106540	yes	2969.99
E-MTAB-6653	yes	2967.98
E-GEOD-150728	yes	2775.94
E-GEOD-149689	yes	2773.47
E-HCAD-1	yes	2661.11
E-MTAB-6678	yes	2532.69
E-MTAB-10553	yes	2228.29
E-CURD-122	yes	2213.71
E-CURD-55	yes	2196.21
E-HCAD-15	yes	2176.27
E-MTAB-10287	yes	2091.70
E-MTAB-6701	yes	2053.68
E-GEOD-139324	yes	1989.70
E-MTAB-9467	yes	1899.37

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, ELF4, EOMES, ETS1, MITF, NFKB1, NFKB, RELA, RUNX3, SPIC, STAT1, STAT3, STAT4, STAT5A, STAT5B, ZNF395

miRNA regulators (miRDB)

34 targeting PRF1, 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-3120-5P	100.00	65.56	965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-4520-3P	98.75	66.55	963
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-4640-5P	97.42	66.33	1543
HSA-MIR-7855-5P	97.39	67.18	925
HSA-MIR-4726-5P	97.24	65.67	1299
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-610	96.84	67.98	905
HSA-MIR-6508-3P	96.73	65.48	576
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-4265	96.18	64.68	557

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• six novel mutations in children with haemophagocytic lymphohistiocytosis (PMID:11565555)
• expressed during acute cellular rejection episodes after kidney transplantation (PMID:12009596)
• The fraction of perforin-expressing HIV-specific CD8 T cells is a marker for disease progression in HIV infection (PMID:12131187)
• detection of transcript levels of this gene in peripheral blood lymphocytes in patients with renal allografts (PMID:12270380)
• Although high frequencies of HIV-specific CD8+ T cells were present in nonprogressors and progressors, only those of nonprogressors maintained a high proliferative capacity. This proliferation was coupled to increases in perforin expression. (PMID:12368910)
• IL-12-induced expression of the perforin gene in NK cells is directly regulated by STAT4 (PMID:12372421)
• A study using a combination of hereditary perforin-deficient effector cells and Fas-deficient target cells reveals the essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4+ as well as CD8+ cytotoxic T lymphocytes. (PMID:12574394)
• Perforin positive cells may participate in the acute phase of RA by maintaining and perpetuating inflammation and contributing to tissue destruction. (PMID:12672182)
• Expressed in blood as a marker of kidney transplantation rejection. (PMID:12919092)
• PMNs contain perforin and granzyme B, the 2 molecules known as the cytotoxic entity of natural killer cells and of cytotoxic T lymphocytes (PMID:14512315)
• A decrease in perforin expression by cytotoxic cells could be a major factor in explaining the physiopathologic mechanisms of several alcohol-associated diseases. (PMID:14634500)
• Levels predict acute rejection in small intestine transplants. (PMID:14697980)
• Hemophagocytic lymphohistiocytosis patients with PRF1 mutations demonstrated absent or markedly decreased natural killer cell function. (PMID:14757862)
• examined the correlation between injury of the hepatocytes and mRNA expression of FasL and perforin/granzyme B in liver tissue to investigate the roles of both the FasL and the perforin/granzyme B pathways in chronic hepatitis B (PMID:14996347)
• perforin has a role in a granzyme M- mediated cell death pathway that plays a significant role in death mediated by NK cells (PMID:15028722)
• Ligand-induced LFA-1 clustering facilitated perforin release, demonstrating LFA-1 could regulate degranulation mechanisms (PMID:15113754)
• role of polymorphism in the familial hemophagocytic lymphohistiocytosis phenotype (PMID:15342365)
• the perforin C2 domain regulates calcium-dependent plasma membrane binding and cell lysis (PMID:15576364)
• Patients with disease flares were characterized by higher proportions of perforin- and/or granzyme B-positive lymphocytes with a differentiated effector phenotype (CCR7- and CD45RA+). (PMID:15641052)
• findings suggest that perforin also plays a key role in the mechanisms of immune surveillance that prevent tumor growth and/or development (PMID:15728124)
• etiologic agent of Kawasaki Disease interferes with expression of this cytotoxic protein by CD8 T lymphocytes, prolonging inflammation in the arterial wall and leading to coronary artery aneurysm formation. (PMID:15818305)
• A91V is a novel and frequent predisposing factor for childhood ALL. (PMID:15921391)
• polymorphonuclear leukocytes from mice and humans lack the 3 cytotoxic effector molecules, granzyme A, gzmB, and perf, generally associated with natural killer and cytotoxic T lymphocytes (PMID:15998831)
• A large group of 63 unrelated patients with Familial hemophagocytic lymphohistiocytosis (FHL) was analysed for mutations in STX11, PRF1, and UNC13D. (PMID:16278825)
• Perforin missense mutations lead to absent perforin detection and impaired cytotoxicity and underly the diversity of hemophagocytic lymphohistiocytosis. (PMID:16374518)
• UV-B induces GrB and PFN expression in keratinocytes, and these cells acquire acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets. (PMID:16524880)
• Although the 1012T genotype appears to influence perforin expression, it is not conclusively associated with disease progression in HIV infection. (PMID:16611250)
• The frequency of the A91V variant in familial haemophagocytic lymphohistiocytosis patients is much higher than that observed in controls and suggests that the alteration is an important genetic susceptibility factor. (PMID:16611257)
• data suggest that perforin variations are a susceptibility factor for ALPS/DALD development in subjects with defective Fas function and may influence disease expression (PMID:16720836)
• NK cells express perforin more efficiently than CD8+ T cells, CD8+ T cells expressed perforin higher than that of healthy controls, but NK cells expressed lower perforin than that of healthy controls, both were not correlated with HIV disease progression (PMID:16770700)
• We found that all identified infants with HLH of African descent (17 from USA, 4 from Europe) have 50delT-PRF1 (16 homozygotes, 5 compound heterozygotes), accounting for the most frequently observed PRF1 mutation. (PMID:16860143)
• PCR analysis for Granzyme B/perforin up-regulation might play a role along with clinical criteria for detection of presymptomatic acute rejection episodes in intestinal recipients. (PMID:16908262)
• cathepsin B is not essential for protection of cytotoxic lymphocytes from the toxic effects of their secreted perforin (PMID:16914553)
• Results suggest that perforin and granzyme-B gene expressions are accurate in detecting both cellular and antibody-mediated rejection. (PMID:17055354)
• The mRNA and protein expression of perforin significantly increases in CD4(+) and CD8(+) T cells treated with 5-azaC, which is associated with DNA hypomethylation of perforin promoter in T cells. (PMID:17213580)
• we identified the locus-wide ensemble of cis-acting sequences that drives PRF1 transcription physiologically (PMID:17222571)
• nonsense perforin gene mutations yield early onset and missense mutations late onset in familial hemophagocytic lymphohistiocytosis cases (PMID:17266056)
• PRF1 genetic alterations may represent genetic risk factors for bone marrow failure (PMID:17311987)
• Polymorphism in PRF1 is associated with presynaptic and postsynaptic defects in function (PMID:17475905)
• Germline mutations of the perforin gene are a frequent occurrence in childhood anaplastic large cell lymphoma (PMID:17477373)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prf1.2	ENSDARG00000021444
danio_rerio	prf1.8	ENSDARG00000109428
danio_rerio	prf1.7	ENSDARG00000110781
mus_musculus	Prf1	ENSMUSG00000037202
rattus_norvegicus	Prf1	ENSRNOG00000000562

Paralogs (39): CFH (ENSG00000000971), SELE (ENSG00000007908), C8B (ENSG00000021852), C6 (ENSG00000039537), SEZ6 (ENSG00000063015), CFHR2 (ENSG00000080910), APOH (ENSG00000091583), SEZ6L (ENSG00000100095), SUSD6 (ENSG00000100647), SRPX (ENSG00000101955), SRPX2 (ENSG00000102359), C7 (ENSG00000112936), C9 (ENSG00000113600), PAPPA2 (ENSG00000116183), CFHR3 (ENSG00000116785), CR2 (ENSG00000117322), CD46 (ENSG00000117335), CSMD2 (ENSG00000121904), C4BPA (ENSG00000123838), C4BPB (ENSG00000123843), CFHR4 (ENSG00000134365), CFHR5 (ENSG00000134389), F13B (ENSG00000143278), SUSD4 (ENSG00000143502), C8A (ENSG00000157131), SUSD3 (ENSG00000157303), CSMD3 (ENSG00000164796), SVEP1 (ENSG00000165124), C2 (ENSG00000166278), SELP (ENSG00000174175), SEZ6L2 (ENSG00000174938), PAPPA (ENSG00000182752), CSMD1 (ENSG00000183117), SELL (ENSG00000188404), CD55 (ENSG00000196352), CR1L (ENSG00000197721), CR1 (ENSG00000203710), CFB (ENSG00000243649), CFHR1 (ENSG00000244414)

Protein

Protein identifiers

Perforin-1 — P14222 (reviewed: P14222)

Alternative names: Cytolysin, Lymphocyte pore-forming protein

All UniProt accessions (2): A0A1W2PR25, P14222

UniProt curated annotations — full annotation on UniProt →

Function. Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells. Plays an important role in killing other cells that are recognized as non-self by the immune system, e.g. in transplant rejection or some forms of autoimmune disease. Can insert into the membrane of target cells in its calcium-bound form, oligomerize and form large pores. Promotes cytolysis and apoptosis of target cells by mediating the passage and uptake of cytotoxic granzymes. Facilitates the delivery of cationic cargo protein, while anionic or neural proteins are not delivered efficiently. Perforin pores allow the release of mature caspase-7 (CASP7) into the extracellular milieu.

Subunit / interactions. Monomer, as soluble protein. Homooligomer; homooligomerizes to form a pore-forming ring.

Subcellular location. Cytolytic granule. Secreted. Cell membrane. Endosome lumen.

Post-translational modifications. N-glycosylated.

Disease relevance. Hemophagocytic lymphohistiocytosis, familial, 2 (FHL2) [MIM:603553] A rare disorder characterized by immune dysregulation with hypercytokinemia, defective function of natural killer cell, and massive infiltration of several organs by activated lymphocytes and macrophages. The clinical features of the disease include fever, hepatosplenomegaly, cytopenia, and less frequently neurological abnormalities ranging from irritability and hypotonia to seizures, cranial nerve deficits and ataxia. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Perforin consists of three domains: (1) the MACPF domain, which includes the central machinery of pore formation, (2) the EGF-like domain, which forms a ‘shelf-like’ assembly connecting the MACPF and C2 domains, and (3) the C2 domain, which mediates calcium-dependent binding to lipid membranes. The C2 domain is critical for initial calcium-dependent interaction with lipid membranes of the target cell: calcium-binding causes a significant structural rearrangement, leading to oligomerization and deployment of the two transmembrane beta-strands (named CH1/TMH1 and CH2/TMH2) that enter the membrane as amphipathic beta-hairpins. The third calcium-binding site (Ca(2+) 3), which constitutes the weakest affinity site, triggers structural rearrangements in the C2 domain that facilitate its interaction with lipid membranes.

Induction. Repressed by contact with target cells.

Similarity. Belongs to the complement C6/C7/C8/C9 family.

RefSeq proteins (2): NP_001076585, NP_005032 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR020863	MACPF_CS	Conserved_site
IPR020864	MACPF	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037300	Perforin-1_C2	Domain
IPR052784	Perforin-1_pore-forming	Family

Pfam: PF00168, PF01823

UniProt features (53 total): binding site 18, sequence variant 13, disulfide bond 9, domain 3, transmembrane region 2, site 2, glycosylation site 2, sequence conflict 2, signal peptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14222-F1	91.01	0.78

Functional residue map

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

Catalytic / active sites (2): 214 (important for oligomerization); 344 (important for oligomerization)

Ligand- & substrate-binding residues (18): 430; 433; 434; 436; 436; 484; 484; 486; 486; 486; 486; 490 …

Disulfide bonds (9): 23–76, 31–73, 102–176, 242–408, 377–393, 381–395, 397–407, 497–510, 525–534

Glycosylation sites (2): 205, 549

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer

MSigDB gene sets: 444 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, WALLACE_PROSTATE_CANCER_RACE_UP, MODULE_45, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_PROTEIN_IMPORT, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, GOLDRATH_ANTIGEN_RESPONSE, KEGG_VIRAL_MYOCARDITIS, RICKMAN_METASTASIS_DN, MODULE_75, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, CHEOK_RESPONSE_TO_MERCAPTOPURINE_DN

GO Biological Process (20): immunological synapse formation (GO:0001771), plasma membrane repair (GO:0001778), T cell mediated cytotoxicity (GO:0001913), defense response to tumor cell (GO:0002357), immune response to tumor cell (GO:0002418), apoptotic process (GO:0006915), cellular defense response (GO:0006968), protein secretion (GO:0009306), protein import (GO:0017038), killing of cells of another organism (GO:0031640), ceramide biosynthetic process (GO:0046513), protein homooligomerization (GO:0051260), protein maturation (GO:0051604), defense response to virus (GO:0051607), positive regulation of killing of cells of another organism (GO:0051712), protein transmembrane transport (GO:0071806), granzyme-mediated programmed cell death signaling pathway (GO:0140507), leukocyte mediated cytotoxicity (GO:0001909), positive regulation of immune response to tumor cell (GO:0002839), pyroptotic cell death (GO:0141201)

GO Molecular Function (6): calcium ion binding (GO:0005509), wide pore channel activity (GO:0022829), identical protein binding (GO:0042802), pore-forming activity (GO:0140911), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (11): immunological synapse (GO:0001772), extracellular region (GO:0005576), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), endosome lumen (GO:0031904), cytolytic granule (GO:0044194), cytolytic granule lumen (GO:1904856), lysosome (GO:0005764), endosome (GO:0005768), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Signaling by ALK fusions and activated point mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
defense response	3
programmed cell death	3
protein transport	3
response to tumor cell	2
cell killing	2
cytoplasm	2
cell-cell recognition	1
lymphocyte activation	1
plasma membrane organization	1
wound healing	1
leukocyte mediated cytotoxicity	1
T cell mediated immunity	1
immune response	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
secretion by cell	1
establishment of protein localization to extracellular region	1
protein localization to extracellular region	1
disruption of cell in another organism	1
ceramide metabolic process	1
sphingolipid biosynthetic process	1
protein complex oligomerization	1
gene expression	1
protein metabolic process	1
response to virus	1
positive regulation of cell killing	1
killing of cells of another organism	1
positive regulation of programmed cell death	1
regulation of killing of cells of another organism	1
transmembrane transport	1
signal transduction	1
leukocyte mediated immunity	1
immune response to tumor cell	1
positive regulation of response to tumor cell	1
regulation of immune response to tumor cell	1
positive regulation of immune response	1
pyroptotic inflammatory response	1
metal ion binding	1
channel activity	1

Protein interactions and networks

STRING

3190 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRF1	GZMB	P10144	999
PRF1	GNLY	P09325	998
PRF1	GZMA	P12544	991
PRF1	FASLG	P48023	979
PRF1	CD8A	P01732	947
PRF1	SRGN	P10124	935
PRF1	IFNG	P01579	929
PRF1	CD4	P01730	927
PRF1	NCAM1	P13591	916
PRF1	UNC13D	Q70J99	902
PRF1	IL2	P01585	898
PRF1	KLRK1	P26718	884
PRF1	NCR1	O76036	880
PRF1	NCR3	O14931	876
PRF1	NCR2	O95944	867

IntAct

58 interactions, top by confidence:

A	B	Type	Score
KRT31	PRF1	psi-mi:“MI:0915”(physical association)	0.720
PRF1	KRT31	psi-mi:“MI:0915”(physical association)	0.720
PRF1	PRF1	psi-mi:“MI:0407”(direct interaction)	0.630
PRF1	PRF1	psi-mi:“MI:0915”(physical association)	0.630
CYSRT1	PRF1	psi-mi:“MI:0915”(physical association)	0.560
NOTCH2NLC	PRF1	psi-mi:“MI:0915”(physical association)	0.560
OGFOD3	CLGN	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
SRGN	PRF1	psi-mi:“MI:0915”(physical association)	0.400
GZMB	PRF1	psi-mi:“MI:0915”(physical association)	0.400
PRF1	GZMB	psi-mi:“MI:0915”(physical association)	0.400
TMEM106A	QSOX1	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350
KLRD1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
SFTPC	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BRICD5	TMEM131L	psi-mi:“MI:0914”(association)	0.350
LY86	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-DRB1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
PTCH1	TMEM131L	psi-mi:“MI:0914”(association)	0.350
ASIC4	TMEM131L	psi-mi:“MI:0914”(association)	0.350
NCR3	POTEF	psi-mi:“MI:0914”(association)	0.350
DNAJB9	POTEF	psi-mi:“MI:0914”(association)	0.350
LDLRAD1	ZNF316	psi-mi:“MI:0914”(association)	0.350
MFAP4	QSOX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (51): PRF1 (Two-hybrid), PRF1 (Two-hybrid), CYSRT1 (Two-hybrid), NOTCH2NL (Two-hybrid), NBPF19 (Two-hybrid), PRF1 (Affinity Capture-Western), PRF1 (Reconstituted Complex), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS), PRF1 (Affinity Capture-MS)

ESM2 similar proteins: O00115, O08590, O15547, O46406, O62855, O70423, O95897, P10820, P14222, P34387, P35763, P36633, P56541, P56542, Q04912, Q16853, Q17778, Q24K15, Q29437, Q2KJC3, Q2T8B0, Q3JJK4, Q3V5L5, Q4R9E0, Q5R9I0, Q5SSH8, Q62190, Q63IT3, Q6AX53, Q6NUS6, Q6TMA8, Q71SY6, Q75WF2, Q765H6, Q812C9, Q8JZQ5, Q8R2Q6, Q8WZ79, Q91ZV7, Q93086

Diamond homologs: A2AR95, A2ARV4, A2AVA0, A4IHY6, A7MBS7, B3EWY9, B3EWZ3, C0HL12, C5IAW9, D3YXF5, D3YXG0, D3ZTD8, E9Q6D8, F1LW30, O08721, O08722, O14514, O15072, O60241, O60242, O75074, O88307, P07357, P07358, P07996, P0C6B8, P0DSP1, P10643, P13671, P14222, P35441, P35446, P35447, P35763, P55314, P61134, P61135, P79331, P98136, P98137

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
STAT4	“up-regulates quantity by expression”	PRF1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 58 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
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	6	15.4×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of T cell mediated cytotoxicity	5	47.3×	3e-05
immune response	7	6.1×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	43
Uncertain significance	287
Likely benign	246
Benign	14

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1069592	NM_001083116.3(PRF1):c.1168C>T (p.Arg390Ter)	Pathogenic
1069593	NM_001083116.3(PRF1):c.185_195del (p.Asp62fs)	Pathogenic
1072304	NM_001083116.3(PRF1):c.1103_1110dup (p.Arg371Ter)	Pathogenic
1192232	NM_001083116.3(PRF1):c.91T>G (p.Cys31Gly)	Pathogenic
1342127	NM_001083116.3(PRF1):c.943_949del (p.Leu315fs)	Pathogenic
13709	NM_001083116.3(PRF1):c.1122G>A (p.Trp374Ter)	Pathogenic
13710	NM_001083116.3(PRF1):c.190C>T (p.Gln64Ter)	Pathogenic
13711	NM_001083116.3(PRF1):c.673C>T (p.Arg225Trp)	Pathogenic
13715	NM_001083116.3(PRF1):c.548T>G (p.Val183Gly)	Pathogenic
13721	NM_001083116.3(PRF1):c.1090_1091del (p.Leu364fs)	Pathogenic
13722	NM_001083116.3(PRF1):c.207del (p.Asp70fs)	Pathogenic
13723	NM_001083116.3(PRF1):c.1246C>T (p.Gln416Ter)	Pathogenic
1393918	NM_001083116.3(PRF1):c.501C>G (p.Tyr167Ter)	Pathogenic
1427863	NM_001083116.3(PRF1):c.2T>C (p.Met1Thr)	Pathogenic
1457555	NM_001083116.3(PRF1):c.808_812del (p.Gly270fs)	Pathogenic
1686096	NM_001083116.3(PRF1):c.1016T>G (p.Val339Gly)	Pathogenic
2005802	NM_001083116.3(PRF1):c.1406_1428del (p.Asp469fs)	Pathogenic
2029973	NM_001083116.3(PRF1):c.1126del (p.Asp376fs)	Pathogenic
2032770	NM_001083116.3(PRF1):c.329_330del (p.Lys110fs)	Pathogenic
2055336	NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)	Pathogenic
2088310	NM_001083116.3(PRF1):c.1428dup (p.Pro477fs)	Pathogenic
2111112	NM_001083116.3(PRF1):c.858del (p.His286fs)	Pathogenic
2124154	NM_001083116.3(PRF1):c.285G>A (p.Trp95Ter)	Pathogenic
2136868	NM_001083116.3(PRF1):c.1428del (p.Pro477_Leu478insTer)	Pathogenic
2442794	NM_001083116.3(PRF1):c.65del (p.Pro22fs)	Pathogenic
2498463	NM_001083116.3(PRF1):c.150del (p.Thr51fs)	Pathogenic
2501794	NM_001083116.3(PRF1):c.880del (p.Gln294fs)	Pathogenic
2516257	NM_001083116.3(PRF1):c.1432del (p.Pro477_Leu478insTer)	Pathogenic
2678060	NM_001083116.3(PRF1):c.916G>T (p.Gly306Cys)	Pathogenic
2678061	NM_001083116.3(PRF1):c.1519G>T (p.Glu507Ter)	Pathogenic

SpliceAI

319 predictions. Top by Δscore:

Variant	Effect	Δscore
10:70599177:GGAAA:G	acceptor_gain	1.0000
10:70599178:GAAA:G	acceptor_gain	1.0000
10:70599179:AAA:A	acceptor_gain	1.0000
10:70599180:AA:A	acceptor_gain	1.0000
10:70599181:AC:A	acceptor_loss	1.0000
10:70599182:C:CC	acceptor_gain	1.0000
10:70600359:CTCAC:C	donor_loss	1.0000
10:70600360:TCA:T	donor_loss	1.0000
10:70600361:CA:C	donor_loss	1.0000
10:70600379:TC:T	donor_gain	1.0000
10:70600380:CC:C	donor_gain	1.0000
10:70602639:CCTTA:C	donor_loss	1.0000
10:70602640:CTTAC:C	donor_loss	1.0000
10:70602641:TTA:T	donor_loss	1.0000
10:70602642:TACCT:T	donor_loss	1.0000
10:70602643:ACCTG:A	donor_loss	1.0000
10:70600362:A:AC	donor_gain	0.9900
10:70600363:C:CC	donor_gain	0.9900
10:70602643:A:AC	donor_gain	0.9900
10:70602644:C:CC	donor_gain	0.9900
10:70599185:C:CT	acceptor_gain	0.9800
10:70600362:AC:A	donor_gain	0.9800
10:70600363:CC:C	donor_gain	0.9800
10:70602643:AC:A	donor_gain	0.9800
10:70602644:CC:C	donor_gain	0.9800
10:70599186:G:T	acceptor_gain	0.9700
10:70602644:CCT:C	donor_gain	0.9700
10:70600378:CT:C	donor_gain	0.9500
10:70600907:C:CC	acceptor_gain	0.9400
10:70602644:CCTGG:C	donor_gain	0.9400

AlphaMissense

3596 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:70598737:C:A	W328C	0.986
10:70598737:C:G	W328C	0.986
10:70600516:C:A	W129C	0.986
10:70600516:C:G	W129C	0.986
10:70600618:C:A	W95C	0.983
10:70600618:C:G	W95C	0.983
10:70600811:C:G	C31S	0.983
10:70600812:A:T	C31S	0.983
10:70600396:G:C	F169L	0.981
10:70600396:G:T	F169L	0.981
10:70600398:A:G	F169L	0.981
10:70600518:A:G	W129R	0.978
10:70600518:A:T	W129R	0.978
10:70600685:C:G	C73S	0.978
10:70600686:A:T	C73S	0.978
10:70598845:G:C	F292L	0.973
10:70598845:G:T	F292L	0.973
10:70598847:A:G	F292L	0.973
10:70599062:C:A	G220V	0.971
10:70598846:A:C	F292C	0.970
10:70599055:G:C	H222Q	0.966
10:70599055:G:T	H222Q	0.966
10:70598338:C:A	W461C	0.965
10:70598338:C:G	W461C	0.965
10:70600676:C:G	C76S	0.965
10:70600677:A:T	C76S	0.965
10:70598147:C:G	C525S	0.964
10:70598148:A:T	C525S	0.964
10:70600397:A:C	F169C	0.964
10:70600685:C:T	C73Y	0.964

dbSNP variants (sampled 300 via entrez): RS1000260035 (10:70602919 G>A,C), RS1000832913 (10:70604060 A>G), RS1000868256 (10:70604066 C>T), RS1002554205 (10:70601541 C>T), RS1002586298 (10:70602262 C>T), RS1003916811 (10:70601453 T>C), RS1004324371 (10:70602974 C>A,T), RS1004782861 (10:70603129 G>C,T), RS1004925635 (10:70600165 A>G), RS1005535592 (10:70597065 A>C), RS1006046517 (10:70602121 G>A), RS1006111570 (10:70596881 T>C), RS1006712868 (10:70599713 C>G,T), RS1007029174 (10:70599476 G>A), RS1008178961 (10:70603513 C>T)

Disease associations

OMIM: gene MIM:170280 | disease phenotypes: MIM:603553, MIM:605027, MIM:267700, MIM:609135, MIM:312080

GenCC curated gene-disease

Disease	Classification	Inheritance
familial hemophagocytic lymphohistiocytosis 2	Strong	Autosomal recessive
aplastic anemia	Strong	Autosomal recessive
fatal post-viral neurodegenerative disorder	Supportive	Autosomal recessive
hereditary hemophagocytic lymphohistiocytosis	Supportive	Autosomal recessive
lymphoma, non-Hodgkin, familial	Limited	Unknown

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
familial hemophagocytic lymphohistiocytosis 2	Definitive	AR

Mondo (8): familial hemophagocytic lymphohistiocytosis 2 (MONDO:0011337), lymphoma, non-Hodgkin, familial (MONDO:0011508), hereditary hemophagocytic lymphohistiocytosis (MONDO:0015541), aplastic anemia (MONDO:0015909), autoinflammatory syndrome (MONDO:0019751), familial hemophagocytic lymphohistiocytosis type 1 (MONDO:0009974), Pelizaeus-Merzbacher spectrum disorder (MONDO:0010714), fatal post-viral neurodegenerative disorder (MONDO:0018316)

Orphanet (6): Familial hemophagocytic lymphohistiocytosis (Orphanet:540), Primary hemophagocytic lymphohistiocytosis (Orphanet:158038), Rare aplastic anemia (Orphanet:182040), Idiopathic aplastic anemia (Orphanet:88), Autoinflammatory syndrome (Orphanet:93665), Pelizaeus-Merzbacher disease (Orphanet:702)

HPO phenotypes

79 total (30 of 79 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000225	Gingival bleeding
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000573	Retinal hemorrhage
HP:0000707	Abnormality of the nervous system
HP:0000737	Irritability
HP:0000952	Jaundice
HP:0000967	Petechiae
HP:0000969	Edema
HP:0000978	Bruising susceptibility
HP:0000979	Purpura
HP:0000988	Skin rash
HP:0001019	Erythroderma
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001259	Coma
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001287	Meningitis
HP:0001290	Generalized hypotonia
HP:0001410	Decreased liver function
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001882	Decreased total leukocyte count

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000426_11	Obesity (extreme)	5.000000e-06
GCST004134_10	Multiple keratinocyte cancers	3.000000e-06
GCST90002388_561	Lymphocyte count	1.000000e-27
GCST90014023_30	Type 1 diabetes	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D000741	Anemia, Aplastic	C15.378.050.085; C15.378.190.223.250
D020371	Pelizaeus-Merzbacher Disease	C10.228.140.163.100.362.775; C10.228.140.695.625.775; C10.314.400.775; C16.320.322.906; C16.320.565.189.362.775; C18.452.132.100.362.775; C18.452.648.189.362.775
C537250	Hemophagocytic lymphohistiocytosis, familial, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5480 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs885821	PRF1		0.00	0

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Cytolytic pore-forming proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 16 [PMID: 31525966]	Inhibition	5.35	pIC50

ChEMBL bioactivities

225 potent at pChembl≥5 of 267 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.75	IC50	180	nM	CHEMBL3754633
6.47	IC50	340	nM	CHEMBL1934375
6.44	IC50	360	nM	CHEMBL1934381
6.44	IC50	360	nM	CHEMBL1934383
6.43	IC50	370	nM	CHEMBL1934370
6.40	IC50	400	nM	CHEMBL3103651
6.40	IC50	400	nM	CHEMBL1934397
6.33	IC50	470	nM	CHEMBL1934386
6.31	IC50	490	nM	CHEMBL1934380
6.29	IC50	510	nM	CHEMBL3103907
6.29	IC50	510	nM	CHEMBL1934382
6.28	IC50	530	nM	CHEMBL3103914
6.26	IC50	550	nM	CHEMBL3103917
6.22	IC50	600	nM	CHEMBL3103908
6.20	IC50	630	nM	CHEMBL3103655
6.19	IC50	640	nM	CHEMBL3103647
6.17	IC50	670	nM	CHEMBL3754407
6.12	IC50	750	nM	CHEMBL4169732
6.11	IC50	780	nM	CHEMBL3103913
6.11	IC50	780	nM	CHEMBL4453871
6.11	IC50	780	nM	CHEMBL1934364
6.10	IC50	790	nM	CHEMBL3102870
6.10	IC50	800	nM	CHEMBL1934396
6.09	IC50	820	nM	CHEMBL1934384
6.05	IC50	900	nM	CHEMBL3753587
6.04	IC50	920	nM	CHEMBL3753271
6.03	IC50	930	nM	CHEMBL3103916
6.01	IC50	970	nM	CHEMBL463187
5.99	IC50	1030	nM	CHEMBL4171638
5.98	IC50	1040	nM	CHEMBL1795754
5.98	IC50	1050	nM	CHEMBL1934365
5.97	IC50	1070	nM	CHEMBL4175880
5.97	IC50	1070	nM	CHEMBL4165670
5.96	IC50	1090	nM	CHEMBL3752189
5.95	IC50	1120	nM	CHEMBL1934395
5.94	IC50	1140	nM	CHEMBL3103646
5.94	IC50	1150	nM	CHEMBL3104019
5.93	IC50	1170	nM	CHEMBL3103912
5.93	IC50	1180	nM	CHEMBL3103910
5.93	IC50	1170	nM	CHEMBL4090472
5.92	IC50	1200	nM	CHEMBL3752776
5.92	IC50	1190	nM	CHEMBL1934393
5.91	IC50	1220	nM	CHEMBL4162248
5.90	IC50	1260	nM	CHEMBL3103915
5.89	IC50	1300	nM	CHEMBL456668
5.89	IC50	1300	nM	CHEMBL1934376
5.88	IC50	1320	nM	CHEMBL4159529
5.86	IC50	1380	nM	CHEMBL3103644
5.86	IC50	1380	nM	CHEMBL4536876
5.85	IC50	1420	nM	CHEMBL4166108

PubChem BioAssay actives

224 with measured affinity, of 570 total; 50 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
4-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]benzamide	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	0.1800	uM
(5E)-5-[[2-(1-oxo-3H-2-benzofuran-5-yl)-1,3-thiazol-4-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.3400	uM
5-[(2Z)-2-[(5-hydroxy-2-sulfanylidene-1,3-dihydroimidazol-4-yl)methylidene]indol-6-yl]-3H-2-benzofuran-1-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.3600	uM
(5E)-5-[[6-(1-oxo-3H-2-benzofuran-5-yl)-1-benzothiophen-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.3600	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)-2-pyridinyl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.3700	uM
(5E)-5-[[5-(1-oxo-2,3-dihydroisoindol-5-yl)thiophen-2-yl]methylidene]imidazolidine-2,4-dione	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.4000	uM
5-[[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]-2-sulfanylidene-1,3-diazinane-4,6-dione	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.4000	uM
(5E)-5-[[6-(1-oxo-3H-2-benzofuran-5-yl)quinolin-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.4700	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)-1-benzothiophen-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.4900	uM
2-methyl-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.5100	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)-1-benzofuran-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.5100	uM
2-(3-hydroxypropyl)-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.5300	uM
ethyl 3-oxo-6-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-1H-isoindole-2-carboxylate	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.5500	uM
2-ethyl-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.6000	uM
5-[6-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]-3-pyridinyl]-2,3-dihydroisoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.6300	uM
7-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3,4-dihydro-2H-isoquinolin-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.6400	uM
2-hydroxy-4-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]benzamide	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	0.6700	uM
4-[[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]sulfamoyl]benzoic acid	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	0.7500	uM
N-[2-methoxy-5-[5-(6-methyl-7-oxo-5H-pyrrolo[3,4-b]pyridin-3-yl)thiophen-2-yl]-3-pyridinyl]-2-(trifluoromethyl)benzenesulfonamide	1545726: Inhibition of perforin (unknown origin) assessed as reduction in perforin-mediated cell lysis in human Jurkat T cells incubated for 30 mins by 51Cr release based gamma counting method	ic50	0.7800	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.7800	uM
2-(2-hydroxyethyl)-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.7800	uM
3-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]benzamide	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.7900	uM
5-[[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]-1,3-diazinane-2,4,6-trione	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.8000	uM
5-[(2Z)-2-[(5-hydroxy-2-sulfanylidene-1,3-dihydroimidazol-4-yl)methylidene]indol-5-yl]-3H-2-benzofuran-1-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	0.8200	uM
5-[5-[4-(hydroxymethyl)phenyl]thiophen-2-yl]-3H-2-benzofuran-1-one	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	0.9000	uM
5-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]pyridine-2-carboxamide	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	0.9200	uM
2-acetyl-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	0.9300	uM
(1Z)-1-(1-benzothiophen-3-ylmethylidene)-6-methyl-4-sulfanylidene-5H-furo[3,4-c]pyridin-3-one	347593: Inhibition of recombinant perforin-mediated lysis of human Jurkat T cells by 51Cr release assay	ic50	0.9700	uM
N-[2-chloro-5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	1.0300	uM
4-(1-amino-2,4-dicyanopyrido[1,2-a]benzimidazol-3-yl)-N-methylbenzamide	604395: Inhibition of recombinant perforin mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs in presence of 0.1% BSA by [51Cr] release assay	ic50	1.0400	uM
(5E)-5-[[4-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	1.0500	uM
N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]pyridine-2-sulfonamide	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	1.0700	uM
N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]thiophene-2-sulfonamide	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	1.0700	uM
N-[4-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]phenyl]methanesulfonamide	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	1.0900	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]-1,3-thiazolidine-2,4-dione	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	1.1200	uM
6-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3,4-dihydro-2H-isoquinolin-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.1400	uM
(5E)-5-[[5-(4-methylsulfanylphenyl)thiophen-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.1500	uM
2-[3-oxo-6-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-1H-isoindol-2-yl]ethyl acetate	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.1700	uM
2,4-difluoro-N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]benzenesulfonamide	1436946: Inhibition of recombinant perforin (unknown origin) assessed as decrease in lysis of 51Cr-labelled human Jurkat cells by measuring 51Cr release preincubated for 30 mins followed by cell line addition measured after 4 hrs in presence of 0.1% BSA by gamma counting method	ic50	1.1700	uM
2-butyl-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.1800	uM
(5E)-5-[[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]methylidene]imidazolidine-2,4-dione	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	1.1900	uM
2-amino-4-[5-(1-oxo-3H-2-benzofuran-5-yl)thiophen-2-yl]benzamide	1272060: Inhibition of recombinant perforin (unknown origin) mediated lysis of human Jurkat cells pre-incubated for 30 mins with perforin followed by incubation with Jurkat cells at 37 degC for 4 hrs assessed as 51Cr release by gamma counting analysis	ic50	1.2000	uM
N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]-3-(trifluoromethyl)benzenesulfonamide	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	1.2200	uM
2-(2,3-dihydroxypropyl)-5-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-3H-isoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.2600	uM
(5E)-5-[[3-(1-oxo-3H-2-benzofuran-5-yl)-1,2-oxazol-5-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	1.3000	uM
(1Z)-1-(1H-indol-2-ylmethylidene)-6-methyl-4-sulfanylidene-5H-furo[3,4-c]pyridin-3-one	347593: Inhibition of recombinant perforin-mediated lysis of human Jurkat T cells by 51Cr release assay	ic50	1.3000	uM
3,4-dichloro-N-[5-[5-(2-methyl-1-oxo-3H-isoindol-5-yl)thiophen-2-yl]-3-pyridinyl]benzenesulfonamide	1499120: Inhibition of perforin (unknown origin)-mediated 51Cr-labelled human Jurkat cell lysis preincubated with protein for 30 mins followed by cell addition measured after 4 hrs by gamma counting method	ic50	1.3200	uM
N-[5-[5-(6-methyl-7-oxo-5H-pyrrolo[3,4-b]pyridin-3-yl)thiophen-2-yl]-3-pyridinyl]-2-(trifluoromethyl)benzenesulfonamide	1545726: Inhibition of perforin (unknown origin) assessed as reduction in perforin-mediated cell lysis in human Jurkat T cells incubated for 30 mins by 51Cr release based gamma counting method	ic50	1.3800	uM
6-[5-[(E)-(5-oxo-2-sulfanylideneimidazolidin-4-ylidene)methyl]thiophen-2-yl]-2,3-dihydroisoindol-1-one	1062400: Inhibition of recombinant perforin (unknown origin)-mediated lysis of human [51Cr]-labelled Jurkat cells assessed as release of [51Cr] preincubated for 30 mins followed by addition of cells measured after 4 hrs by gamma counting analysis	ic50	1.3800	uM
(5E)-5-[[4-(1-oxo-3H-2-benzofuran-5-yl)-1,3-thiazol-2-yl]methylidene]-2-sulfanylideneimidazolidin-4-one	637077: Inhibition of recombinant perforin-mediated lysis of Jurkat cells assessed as [51Cr] release preincubated with perforin for 30 mins followed by incubation with [51Cr]-labeled Jurkat cells by gamma counting	ic50	1.4100	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic	affects expression, increases expression, affects cotreatment	2
Nickel	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Ziram	decreases expression	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
trichostatin A	affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
pyrazolanthrone	decreases reaction, increases expression	1
3-(4-dimethylamino-naphthalen-1-ylmethylene)-1,3-dihydro-indol-2-one	increases expression	1
(+)-JQ1 compound	decreases expression	1
Bortezomib	decreases expression	1
Resveratrol	decreases reaction, increases expression, affects reaction	1
Fulvestrant	decreases expression, increases expression	1
Air Pollutants, Occupational	decreases expression	1
Vehicle Emissions	decreases reaction, increases expression	1
Azacitidine	decreases reaction, increases secretion	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Dichlorvos	decreases expression	1
Menthol	decreases expression	1
Pentoxifylline	decreases secretion	1
Poly I-C	decreases reaction, increases expression	1
Tamoxifen	decreases expression, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	decreases expression	1

ChEMBL screening assays

34 unique, capped per target: 34 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000314	Binding	Inhibition of recombinant perforin-mediated lysis of human Jurkat T cells by 51Cr release assay	Dihydrofuro[3,4-c]pyridinones as inhibitors of the cytolytic effects of the pore-forming glycoprotein perforin. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8N0	Abcam HCT 116 PRF1 KO	Cancer cell line	Male
CVCL_B9AL	Abcam MCF-7 PRF1 KO	Cancer cell line	Female
CVCL_B9Q9	Abcam A-549 PRF1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00114348	PHASE4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00168727	PHASE4	COMPLETED	Zevalin® Followed by Rituxan® Maintenance in Previously Treated Low Grade Non-Hodgkin’s Lymphoma
NCT03229200	PHASE4	ACTIVE_NOT_RECRUITING	Extended Treatment Protocol for Subjects Continuing to Benefit From Ibrutinib.
NCT04083079	PHASE4	UNKNOWN	Cost-Effectiveness Study of PEG-rhG-CSF in Prophylactic Treatment of Neutropenia After Chemotherapy in Lymphoma
NCT04460235	PHASE4	RECRUITING	Clinical Trial Assessing the Immunogenicity of an Anti-pneumococcal Vaccination Strategy (PCV13+PPV23 Versus PREVENAR20) in Adult Patients Treated for a Lymphoma
NCT00000658	PHASE3	COMPLETED	A Phase III Randomized Trial of Low-Dose Versus Standard-Dose mBACOD Chemotherapy With rGM-CSF for Treatment of AIDS-Associated Non-Hodgkin’s Lymphoma
NCT00006434	PHASE3	COMPLETED	Tumor Lysate Pulsed-Dendritic Cell Vaccines After High-Dose Chemotherapy for Non-Hodgkin’s Lymphoma
NCT00088530	PHASE3	COMPLETED	BBR 2778 for Relapsed, Aggressive Non-Hodgkin’s Lymphoma (NHL)
NCT00103610	PHASE3	COMPLETED	Mobilization of Stem Cells With AMD3100 (Plerixafor) in Non-Hodgkin’s Lymphoma Patients
NCT00154440	PHASE3	UNKNOWN	Helicobacter - Lymphoma - Radiation Part I: Eradication, Part II: Radiation
NCT00185393	PHASE3	COMPLETED	Treatment With [90]Y-Ibritumomab Tiuxetan Versus no Treatment in Patients With Follicular Non Hodgkin Lymphoma (Stage III or IV) Having Achieved a Partial or Complete Remission After First Line Chemotherapy
NCT00186823	PHASE3	COMPLETED	Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00261677	PHASE3	COMPLETED	A Study to Evaluate the Effect of Weekly PROCRIT (Epoetin Alfa) or Placebo on Anemia and Quality of Life in Children With Cancer Undergoing Chemotherapy
NCT00268983	PHASE3	COMPLETED	Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
NCT00319332	PHASE3	WITHDRAWN	A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen
NCT00329030	PHASE3	COMPLETED	Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin’s Lymphoma (BMTCTN0401)
NCT01232556	PHASE3	TERMINATED	A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy
NCT01938001	PHASE3	COMPLETED	Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin’s Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
NCT01987505	PHASE3	COMPLETED	MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma
NCT01996865	PHASE3	COMPLETED	Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.
NCT02369016	PHASE3	COMPLETED	Phase III Copanlisib in Rituximab-refractory iNHL
NCT02417129	PHASE3	TERMINATED	BI 695500 vs Rituxan First Line Treatment in Patients With Low Tumor Burden Follicular Lymphoma
NCT02626455	PHASE3	TERMINATED	Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin’s Lymphoma (iNHL)
NCT02703272	PHASE3	TERMINATED	A Safety and Efficacy Study of Ibrutinib in Pediatric and Young Adult Participants With Relapsed or Refractory Mature B-cell Non-Hodgkin Lymphoma
NCT02747043	PHASE3	COMPLETED	Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab
NCT03480360	PHASE3	ACTIVE_NOT_RECRUITING	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03575351	PHASE3	COMPLETED	A Study to Compare the Efficacy and Safety of JCAR017 to Standard of Care in Adult Subjects With High-risk, Transplant-eligible Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphomas
NCT05431179	PHASE3	WITHDRAWN	A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
NCT05556720	PHASE3	ACTIVE_NOT_RECRUITING	Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
NCT00000801	PHASE2	COMPLETED	Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
NCT00002003	PHASE2	COMPLETED	Phase II Study of Novantrone(R) (Mitoxantrone) and Etoposide in Patients With HIV Associated Large Cell and Immunoblastic Lymphomas
NCT00002221	PHASE2	COMPLETED	Gene Therapy in HIV-Positive Patients With Non-Hodgkin’s Lymphoma
NCT00002348	PHASE2	COMPLETED	A Study of Mitoguazone Dihydrochloride in Patients With AIDS-Related Non-Hodgkin’s Lymphoma
NCT00025662	PHASE2	COMPLETED	Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS
NCT00044551	PHASE2	COMPLETED	Evaluation of Bay 59-8862 in Patients With Aggressive, Refractory Non-Hodgkin’s Lymphoma
NCT00045864	PHASE2	COMPLETED	Proleukin in Combination With Rituxan in Patients With Intermediate and High-Grade Non-Hodgkin’s Lymphoma.
NCT00061672	PHASE2	COMPLETED	Study Evaluating the Safety and Effectiveness of ABT-510 in Subjects With Refractory Lymphoma
NCT00067002	PHASE2	COMPLETED	Randomized Double Cord Blood Transplant Study
NCT00067288	PHASE2	COMPLETED	Meaning-Centered Psychotherapy in Advanced Cancer
NCT00094848	PHASE2	COMPLETED	Study of TRM-1 (TRAIL-R1 Monoclonal Antibody) in Subjects With Relapsed or Refractory Non-Hodgkin’s Lymphoma (NHL)