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): 783 total — 62 pathogenic, 47 likely-pathogenic (top 4% of genes corpus-wide)
• GTEx eGene: eQTL in 5 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 79
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.44 (unconstrained)
• MANE Select transcript: NM_001083116
• Interaction hub: 2,730 STRING partners (top 3% of genes corpus-wide)

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: 8 — 7 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000441259

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 5: 3

ENST00000441259, ENST00000373209, ENST00000638674, ENST00000639390, ENST00000862973, ENST00000862974, ENST00000945922, ENST00001143163

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.

Highest expression (Bgee): granulocyte, blood, spleen, decidua, bone marrow cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PRF1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 5 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

5 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	eqtl	4.9e-03	+0.55	10:70526229:T:C
Artery Coronary	eqtl	5.9e-03	+0.24	10:70928993:T:C
Brain Nucleus accumbens basal ganglia	eqtl	7.1e-03	+1.76	10:70874555:C:T
Pituitary	eqtl	2.4e-02	-0.27	10:71552579:G:A
Minor Salivary Gland	eqtl	2.5e-02	+1.02	10:70252664:T:C

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

showing 100 of 283 tissues 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
endometrium epithelium	UBERON:0004811	76.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	76.16	gold quality
mucosa of paranasal sinus	UBERON:0005030	76.15	silver quality
epithelium of mammary gland	UBERON:0003244	75.68	silver quality
amniotic fluid	UBERON:0000173	75.44	gold quality
mucosa of transverse colon	UBERON:0004991	75.24	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.84	gold quality
omental fat pad	UBERON:0010414	74.74	gold quality
peritoneum	UBERON:0002358	74.72	gold quality
jejunum	UBERON:0002115	74.47	gold quality
liver	UBERON:0002107	74.46	gold quality
gall bladder	UBERON:0002110	74.24	gold quality
oral cavity	UBERON:0000167	73.36	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.73	gold quality
adipose tissue	UBERON:0001013	72.72	gold quality
thoracic mammary gland	UBERON:0005200	72.64	gold quality
mammary gland	UBERON:0001911	72.61	gold quality
pylorus	UBERON:0001166	72.49	gold quality
connective tissue	UBERON:0002384	72.21	gold quality
subcutaneous adipose tissue	UBERON:0002190	72.18	gold quality
esophagus squamous epithelium	UBERON:0006920	72.15	gold quality
small intestine	UBERON:0002108	72.02	gold quality
body of stomach	UBERON:0001161	71.74	gold quality
endometrium	UBERON:0001295	71.70	gold quality
pericardium	UBERON:0002407	71.55	silver quality
nasal cavity mucosa	UBERON:0001826	71.46	gold quality
placenta	UBERON:0001987	71.44	gold quality
nasal cavity epithelium	UBERON:0005384	71.43	silver quality
biceps brachii	UBERON:0001507	71.24	silver quality
olfactory segment of nasal mucosa	UBERON:0005386	70.88	gold quality
trachea	UBERON:0003126	70.44	gold quality
mammalian vulva	UBERON:0000997	70.31	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	70.28	silver quality
cardia of stomach	UBERON:0001162	70.15	gold quality
trigeminal ganglion	UBERON:0001675	70.13	silver quality
mucosa of urinary bladder	UBERON:0001259	69.88	silver quality
rectum	UBERON:0001052	69.72	gold quality
pleura	UBERON:0000977	69.42	silver quality
fundus of stomach	UBERON:0001160	69.41	gold quality
stomach	UBERON:0000945	69.38	gold quality
parietal pleura	UBERON:0002400	69.27	gold quality
bronchus	UBERON:0002185	69.26	gold quality
bronchial epithelial cell	CL:0002328	69.25	gold quality
ileal mucosa	UBERON:0000331	69.18	gold quality
epithelium of bronchus	UBERON:0002031	69.12	gold quality
pharyngeal mucosa	UBERON:0000355	68.94	silver quality
oviduct epithelium	UBERON:0004804	68.90	silver quality
epithelium of esophagus	UBERON:0001976	68.86	silver quality
smooth muscle tissue	UBERON:0001135	68.85	gold quality
superior surface of tongue	UBERON:0007371	68.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	68.80	gold quality
duodenum	UBERON:0002114	68.65	gold quality
visceral pleura	UBERON:0002401	68.64	gold quality
penis	UBERON:0000989	68.58	gold quality
urinary bladder	UBERON:0001255	68.48	gold quality
uterus	UBERON:0000995	68.46	gold quality
tonsil	UBERON:0002372	68.34	gold quality
myometrium	UBERON:0001296	68.28	gold quality
colonic mucosa	UBERON:0000317	68.12	gold quality
fallopian tube	UBERON:0003889	67.92	gold quality
germinal epithelium of ovary	UBERON:0001304	67.85	gold quality
squamous epithelium	UBERON:0006914	67.61	silver quality
subthalamic nucleus	UBERON:0001906	67.41	gold quality
right lobe of thyroid gland	UBERON:0001119	67.33	gold quality
inferior vagus X ganglion	UBERON:0005363	67.26	gold quality
saphenous vein	UBERON:0007318	67.17	silver quality
mucosa of sigmoid colon	UBERON:0004993	67.05	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.03	gold quality
right coronary artery	UBERON:0001625	66.92	gold quality
deltoid	UBERON:0001476	66.90	silver 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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 74 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spleen	tissue	36.5	high
Bone marrow	tissue	26.9	not detected
Lymph node	tissue	19.0	medium
Lung	tissue	12.0	not detected
Appendix	tissue	7.2	not detected
Thymus	tissue	5.4
Tonsil	tissue	4.6	medium
Stomach 1	tissue	4.4	not detected
Small intestine	tissue	4.4	not detected
Adipose tissue	tissue	4.2	not detected
Liver	tissue	4.1	not detected
Gallbladder	tissue	3.9	not detected
Urinary bladder	tissue	3.5	not detected
Amygdala	tissue	3.4
Endometrium 1	tissue	3.3	medium
Periaqueductal gray	tissue	3.3
Corpus callosum	tissue	3.2
Cerebral cortex	tissue	3.1	not detected
Septum	tissue	3.1
Insular cortex	tissue	3.1
Hypothalamus	tissue	3.0
Substantia nigra	tissue	3.0
Spinal cord	tissue	3.0
Ventral forebrain	tissue	2.9
Olfactory bulb	tissue	2.9
Choroid plexus	tissue	2.8
Retrosplenial cortex	tissue	2.8
Basal ganglia	tissue	2.7	not detected
Medulla oblongata	tissue	2.7
Placenta	tissue	2.6	not detected
Cerebellum	tissue	2.6	not detected
Hippocampal formation	tissue	2.6
Retrosplenial and cingulate cortex	tissue	2.6
Temporal cortex	tissue	2.6
Prefrontal cortex	tissue	2.5
Putamen	tissue	2.5
Entorhinal cortex	tissue	2.5
Skeletal muscle	tissue	2.4	not detected
Midbrain	tissue	2.4
Pons	tissue	2.2
Motor cortex	tissue	2.2
Salivary gland	tissue	2.1	not detected
Colon	tissue	2.1	not detected
Thalamus	tissue	2.1
Duodenum	tissue	2.1	not detected
Occipital cortex	tissue	2.1
Somatosensory cortex	tissue	2.0
Smooth muscle	tissue	1.9	not detected
Superior colliculi	tissue	1.9
Adrenal gland	tissue	1.9	not detected
Vagina	tissue	1.8	low
Esophagus	tissue	1.8	medium
Fallopian tube	tissue	1.8	not detected
Rectum	tissue	1.4	not detected
Tongue	tissue	1.4
Breast	tissue	1.3	not detected
Locus coeruleus	tissue	1.3
Cervix	tissue	1.2	not detected
Heart muscle	tissue	1.2	not detected
Seminal vesicle	tissue	1.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — White matter (3.2), Area postrema (3.0), Ventral spinal cord (3.0), Cervical spinal cord, ventral horn (2.9), Nucleus gracilis (2.9).

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)

Targeting PRF1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 34 miRNAs:

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

gnomAD constraint: pLI 0.00029, LOEUF 1.44, missense Z 0.695 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000441259 — one region, missense o/e 0.97. 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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:97551) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 84 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased susceptibility to Riboviria infection	5
impaired natural killer cell mediated cytotoxicity	4
decreased cytotoxic T cell cytolysis	4
hunched posture	2
brain inflammation	2
decreased susceptibility to autoimmune diabetes	2
pancytopenia	2
increased circulating tumor necrosis factor level	2
increased circulating interferon-gamma level	2
increased circulating interleukin-6 level	2
increased susceptibility to induced morbidity/mortality	2
abnormal NK cell physiology	2
abnormal circulating glucose level	1
decreased leukocyte cell number	1
decreased neutrophil cell number	1
decreased bone marrow cell number	1
ruffled hair	1
demyelination	1
weight loss	1
decreased locomotor activity	1
increased circulating triglyceride level	1
abnormal body temperature homeostasis	1
abnormal T cell activation	1
increased activated T cell number	1
abnormal inflammatory response	1

+59 more (showing top 25).

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ADAMTS14	protein-coding	140766
EIF4EBP2	protein-coding	1979
PALD1	protein-coding	27143
NODAL	protein-coding	4838
TBATA	protein-coding	219793
SGPL1	protein-coding	8879

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted intracellular proteins, Cancer-related genes, Disease related genes, Potential drug targets, Human disease related genes, Primary immunodeficiency

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
214	important for oligomerization
344	important for oligomerization

Ligand- & substrate-binding residues (18)

Position	Role
430	Ca(2+)
433	Ca(2+)
434	Ca(2+)
436	Ca(2+)
484	Ca(2+)
486	Ca(2+)
490	Ca(2+)
491	Ca(2+)
492	Ca(2+)
429	Ca(2+)

Disulfide bonds (9)

Type	Positions
Disulfide bond	23–76, 31–73, 102–176, 242–408, 377–393, 381–395, 397–407, 497–510, 525–534

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	205, 549

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 5 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer ⚕	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	—
R-HSA-9700206	Signaling by ALK 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 (15): immunological synapse formation (GO:0001771), 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), protein homooligomerization (GO:0051260), 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)

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 (8): immunological synapse (GO:0001772), extracellular region (GO:0005576), plasma membrane (GO:0005886), membrane (GO:0016020), endosome lumen (GO:0031904), cytolytic granule (GO:0044194), cytolytic granule lumen (GO:1904856), cytoplasmic vesicle (GO:0031410)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Signaling by ALK fusions and activated point mutants	1
Disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signaling by ALK in cancer	1

GO top-level categories

43 GO namespaces:

Category	Terms
defense response	3
protein transport	3
cellular anatomical structure	3
response to tumor cell	2
programmed cell death	2
cell killing	2
cell-cell recognition	1
lymphocyte activation	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
protein complex oligomerization	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
metal ion binding	1
channel activity	1
protein binding	1
molecular_function	1
binding	1
cation binding	1
plasma membrane	1
membrane	1
cell periphery	1
endosome	1
intracellular organelle lumen	1
lysosome	1
vacuolar lumen	1
cytolytic granule	1
cytoplasmic vesicle lumen	1
cytoplasm	1
intracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 29 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
immunological synapse formation	BP	direct assay
positive regulation of killing of cells of another organism	BP	direct assay
protein homooligomerization	BP	direct assay
protein import	BP	direct assay
protein transmembrane transport	BP	direct assay
cytolytic granule	CC	direct assay
membrane	CC	direct assay
plasma membrane	CC	direct assay
identical protein binding	MF	physical interaction
wide pore channel activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 2,730 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRF1	GZMB	P10144	970
PRF1	CD8A	P01732	945
PRF1	IFNG	P01579	929
PRF1	CD4	P01730	928
PRF1	GZMA	P12544	928
PRF1	UNC13D	Q70J99	900
PRF1	GNLY	P09325	895
PRF1	IL2	P01585	881
PRF1	NCR3	O14931	881
PRF1	NCR1	O76036	873
PRF1	NCR2	O95944	868
PRF1	FASLG	P48023	859
PRF1	FCGR3A	P08637	856
PRF1	NCAM1	P13591	856
PRF1	FCGR3B	O75015	850

IntAct

Human interaction partners of PRF1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

7 partners by confidence:

Partner	Interaction type	MIscore	Records
KRT31	physical association	0.720	6
CYSRT1	physical association	0.560	3
NOTCH2NLC	physical association	0.560	3
GZMB	physical association	0.400	3
SRGN	physical association	0.400	1
HLA-E	association	0.350	1
DDX24	physical association	0.000	1

BioGRID (51 interactions; top human partners by supporting records): CALR (Affinity Capture-Western; 2 records), KRT31 (Two-hybrid; 2 records), TRIM54 (Affinity Capture-Western; 2 records), ADAM30 (Affinity Capture-MS), ASIC4 (Affinity Capture-MS), BRICD5 (Affinity Capture-MS), BTF3 (Affinity Capture-MS), BTNL2 (Affinity Capture-MS), C12orf49 (Affinity Capture-MS), C1orf54 (Affinity Capture-MS), CA6 (Affinity Capture-MS), CD1A (Affinity Capture-MS), CLEC2B (Affinity Capture-MS), CRISP2 (Affinity Capture-MS), CST11 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

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

Disease & clinical

Genetic variants

Variant evidence for PRF1: 783 ClinVar records (109 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	62
Likely pathogenic	47
Uncertain significance	291
Likely benign	249
Benign	8

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 109 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
468305	NM_001083116.3(PRF1):c.50del (p.Leu17fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	23
13709	NM_001083116.3(PRF1):c.1122G>A (p.Trp374Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	20
520942	NM_001083116.3(PRF1):c.445G>A (p.Gly149Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
971288	NM_001083116.3(PRF1):c.844AAG[3] (p.Lys285del)	Pathogenic	criteria provided, multiple submitters, no conflicts	13
13711	NM_001083116.3(PRF1):c.673C>T (p.Arg225Trp)	Pathogenic	criteria provided, multiple submitters, no conflicts	11
13721	NM_001083116.3(PRF1):c.1090_1091del (p.Leu364fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
2498463	NM_001083116.3(PRF1):c.150del (p.Thr51fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
468300	NM_001083116.3(PRF1):c.133G>A (p.Gly45Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
961631	NM_001083116.3(PRF1):c.658G>A (p.Gly220Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
645064	NM_001083116.3(PRF1):c.658G>C (p.Gly220Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1069592	NM_001083116.3(PRF1):c.1168C>T (p.Arg390Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2442794	NM_001083116.3(PRF1):c.65del (p.Pro22fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2692425	NM_001083116.3(PRF1):c.218_224del (p.Cys73fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
2055336	NM_001083116.3(PRF1):c.449C>A (p.Ser150Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2678060	NM_001083116.3(PRF1):c.916G>T (p.Gly306Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	3

Per-variant reference — Sugi Variant

Explore PRF1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 25 predictions of 124):

Position(s)	Effect	Δscore	Sites
10:70599182–70599183	acceptor_loss	1.0000	4
10:70600362–70600363	donor_loss	1.0000	5
10:70599182–70599183	acceptor_loss	0.9900	2
10:70602643–70602644	donor_loss	0.9900	3
10:70599186	acceptor_gain	0.9700
10:70602643	donor_loss	0.9700
10:70602644	donor_loss	0.9500
10:70600907–70600908	acceptor_loss	0.9000	5
10:70600907–70600909	acceptor_loss	0.8900	2
10:70600917	acceptor_loss	0.8800

AlphaMissense

682 missense substitutions predicted likely pathogenic (of 3,596 scored), across 201 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
H222	8	0.906	0.966
D484	8	0.803	0.910
F193	8	0.792	0.948
D165	8	0.774	0.885
C73	7	0.954	0.978
C31	7	0.928	0.983
C257	7	0.927	0.961
F169	7	0.918	0.981
W129	7	0.915	0.986
C525	7	0.913	0.964
C76	7	0.911	0.965
C534	7	0.908	0.941
W95	7	0.905	0.983
W328	7	0.902	0.986
C279	7	0.895	0.947
C23	7	0.893	0.943
C242	7	0.885	0.922
C408	7	0.883	0.936
F316	7	0.878	0.957
C176	7	0.877	0.952

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Head and Neck Squamous Cell Carcinoma (TCGA)	favorable	0.000455

Disease associations

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

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
familial hemophagocytic lymphohistiocytosis 2	Strong	Autosomal recessive	2
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

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

1 validity classifications:

Disease	Classification	Inheritance
familial hemophagocytic lymphohistiocytosis 2	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
COVID-19 research	green
Fetal anomalies	green
Haematological malignancies cancer susceptibility	green
Haematological malignancies for rare disease	green
Haemophagocytic syndrome with absent perforin expression	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Autoinflammatory disorders	amber

Mondo (7): 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), fatal post-viral neurodegenerative disorder (MONDO:0018316)

Orphanet (5): Familial hemophagocytic lymphohistiocytosis (Orphanet:540), Primary hemophagocytic lymphohistiocytosis (Orphanet:158038), Rare aplastic anemia (Orphanet:182040), Idiopathic aplastic anemia (Orphanet:88), Autoinflammatory syndrome (Orphanet:93665)

HPO phenotypes

showing 60 of 79 phenotypes (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
HP:0001896	Reticulocytopenia
HP:0001903	Anemia
HP:0001915	Aplastic anemia
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0002086	Abnormality of the respiratory system
HP:0002155	Hypertriglyceridemia
HP:0002240	Hepatomegaly
HP:0002301	Hemiplegia
HP:0002383	Infectious encephalitis
HP:0002445	Tetraplegia
HP:0002500	Abnormal cerebral white matter morphology
HP:0002516	Increased intracranial pressure
HP:0002583	Colitis
HP:0002611	Cholestatic liver disease
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002902	Hyponatremia
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002922	Increased CSF protein concentration
HP:0002958	Immune dysregulation
HP:0003073	Hypoalbuminemia
HP:0003075	Hypoproteinemia
HP:0003256	Abnormality of the coagulation cascade
HP:0003281	Increased circulating ferritin concentration
HP:0003573	Increased total bilirubin
HP:0003593	Infantile onset
HP:0004302	Functional motor deficit
HP:0004313	Decreased circulating immunoglobulin concentration

GWAS associations

4 associations:

Study	Trait	p-value
GCST90002388_203	Lymphocyte count	1e-27
GCST90014023_22	Type 1 diabetes	2e-11
GCST004134_10	Multiple keratinocyte cancers	3e-6
GCST000426_11	Obesity (extreme)	5e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004587	lymphocyte count

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
D000741	Anemia, Aplastic	C15.378.050.085; C15.378.190.223.250
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 (CPIC guideline: no)

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

Binding affinities (BindingDB)

259 measured of 356 human assays (356 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3754633	IC50	180 nM
CHEMBL1934375	IC50	340 nM
CHEMBL1934381	IC50	360 nM
CHEMBL1934383	IC50	360 nM
CHEMBL1934370	IC50	370 nM
CHEMBL1934397	IC50	400 nM
CHEMBL3103651	IC50	400 nM
CHEMBL1934386	IC50	470 nM
CHEMBL1934380	IC50	490 nM
CHEMBL1934382	IC50	510 nM
CHEMBL3103907	IC50	510 nM
CHEMBL3103914	IC50	530 nM
CHEMBL3103917	IC50	550 nM
CHEMBL3103908	IC50	600 nM
CHEMBL3103655	IC50	630 nM
CHEMBL3103647	IC50	640 nM
CHEMBL3754407	IC50	670 nM
CHEMBL4169732	IC50	750 nM
CHEMBL1934364	IC50	780 nM
CHEMBL3103913	IC50	780 nM
CHEMBL3102870	IC50	790 nM
CHEMBL1934396	IC50	800 nM
CHEMBL1934384	IC50	820 nM
CHEMBL3753271	IC50	920 nM
CHEMBL3103916	IC50	930 nM
(Z)-1-(Benzo[b]thiophen-3-ylmethylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one	IC50	970 nM
CHEMBL4171638	IC50	1030 nM
CHEMBL1795754	IC50	1040 nM
CHEMBL1934365	IC50	1050 nM
CHEMBL4175880	IC50	1070 nM
CHEMBL4165670	IC50	1070 nM
CHEMBL3752189	IC50	1090 nM
CHEMBL1934395	IC50	1120 nM
CHEMBL3103646	IC50	1140 nM
CHEMBL3104019	IC50	1150 nM
CHEMBL4090472	IC50	1170 nM
CHEMBL3103912	IC50	1170 nM
CHEMBL3103910	IC50	1180 nM
CHEMBL1934393	IC50	1190 nM
CHEMBL3752776	IC50	1200 nM
CHEMBL4162248	IC50	1220 nM
CHEMBL3103915	IC50	1260 nM
(Z)-1-((1H-Indol-2-yl)methylene)-6-methyl-4-thioxo-4,5-dihydrofuro[3,4-c]pyridin-3(1H)-one	IC50	1300 nM
CHEMBL1934376	IC50	1300 nM
CHEMBL4159529	IC50	1320 nM
CHEMBL3103644	IC50	1380 nM
CHEMBL4536876	IC50	1380 nM
CHEMBL1934374	IC50	1410 nM
CHEMBL4166108	IC50	1420 nM
CHEMBL1934378	IC50	1440 nM

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

35 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 methylation, increases expression	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
Omeprazole	increases secretion	1
Pentoxifylline	decreases secretion	1
Poly I-C	decreases reaction, increases expression	1
Tamoxifen	increases expression, decreases expression	1
Tobacco Smoke Pollution	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00114348	Phase 4	COMPLETED	ALL-REZ BFM 2002: Multi-Center Study for Children With Relapsed Acute Lymphoblastic Leukemia
NCT00168727	Phase 4	COMPLETED	Zevalin® Followed by Rituxan® Maintenance in Previously Treated Low Grade Non-Hodgkin’s Lymphoma
NCT03229200	Phase 4	ACTIVE_NOT_RECRUITING	Extended Treatment Protocol for Subjects Continuing to Benefit From Ibrutinib.
NCT04083079	Phase 4	UNKNOWN	Cost-Effectiveness Study of PEG-rhG-CSF in Prophylactic Treatment of Neutropenia After Chemotherapy in Lymphoma
NCT04460235	Phase 4	RECRUITING	Clinical Trial Assessing the Immunogenicity of an Anti-pneumococcal Vaccination Strategy (PCV13+PPV23 Versus PREVENAR20) in Adult Patients Treated for a Lymphoma
NCT00000658	Phase 3	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	Phase 3	COMPLETED	Tumor Lysate Pulsed-Dendritic Cell Vaccines After High-Dose Chemotherapy for Non-Hodgkin’s Lymphoma
NCT00088530	Phase 3	COMPLETED	BBR 2778 for Relapsed, Aggressive Non-Hodgkin’s Lymphoma (NHL)
NCT00103610	Phase 3	COMPLETED	Mobilization of Stem Cells With AMD3100 (Plerixafor) in Non-Hodgkin’s Lymphoma Patients
NCT00154440	Phase 3	UNKNOWN	Helicobacter - Lymphoma - Radiation Part I: Eradication, Part II: Radiation
NCT00185393	Phase 3	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	Phase 3	COMPLETED	Haploidentical Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00261677	Phase 3	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	Phase 3	COMPLETED	Comparison Of Rituximab Versus Tositumomab and Iodine I 131 Tositumomab (BEXXAR® Therapeutic Regimen) For Patients With Relapsed Follicular Non-Hodgkins Lymphoma
NCT00319332	Phase 3	WITHDRAWN	A Comparative Study Of Iodine I 131 Tositumomab Therapeutic Regimen Versus Ibritumomab Tiuxetan Therapeutic Regimen
NCT00329030	Phase 3	COMPLETED	Rituxan/BEAM vs Bexxar/BEAM in Autologous Hematopoietic Stem Cell Transplant for Non-Hodgkin’s Lymphoma (BMTCTN0401)
NCT01232556	Phase 3	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	Phase 3	COMPLETED	Rituximab Plus Lenalidomide for Patients With Relapsed / Refractory Indolent Non-Hodgkin’s Lymphoma (Follicular Lymphoma and Marginal Zone Lymphoma)
NCT01987505	Phase 3	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	Phase 3	COMPLETED	Lenalidomide Plus Rituximab Followed by Lenalidomide Versus Rituximab Maintenance for Relapsed/Refractory Follicular, Marginal Zone or Mantle Cell Lymphoma.
NCT02369016	Phase 3	COMPLETED	Phase III Copanlisib in Rituximab-refractory iNHL
NCT02417129	Phase 3	TERMINATED	BI 695500 vs Rituxan First Line Treatment in Patients With Low Tumor Burden Follicular Lymphoma
NCT02626455	Phase 3	TERMINATED	Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin’s Lymphoma (iNHL)
NCT02703272	Phase 3	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	Phase 3	COMPLETED	Study to Assess if ABP798 is Safe & Effective in Treating Non Hodgkin Lymphoma Compared to Rituximab
NCT03480360	Phase 3	COMPLETED	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03575351	Phase 3	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	Phase 3	WITHDRAWN	A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
NCT05556720	Phase 3	ACTIVE_NOT_RECRUITING	Bringing Optimised COVID-19 Vaccine Schedules To ImmunoCompromised Populations (BOOST-IC): an Adaptive Randomised Controlled Clinical Trial
NCT00000801	Phase 2	COMPLETED	Phase II Trial of Sequential Chemotherapy and Radiotherapy for AIDS-Related Primary Central Nervous System Lymphoma
NCT00002003	Phase 2	COMPLETED	Phase II Study of Novantrone(R) (Mitoxantrone) and Etoposide in Patients With HIV Associated Large Cell and Immunoblastic Lymphomas
NCT00002221	Phase 2	COMPLETED	Gene Therapy in HIV-Positive Patients With Non-Hodgkin’s Lymphoma
NCT00002348	Phase 2	COMPLETED	A Study of Mitoguazone Dihydrochloride in Patients With AIDS-Related Non-Hodgkin’s Lymphoma
NCT00025662	Phase 2	COMPLETED	Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS
NCT00044551	Phase 2	COMPLETED	Evaluation of Bay 59-8862 in Patients With Aggressive, Refractory Non-Hodgkin’s Lymphoma
NCT00045864	Phase 2	COMPLETED	Proleukin in Combination With Rituxan in Patients With Intermediate and High-Grade Non-Hodgkin’s Lymphoma.
NCT00061672	Phase 2	COMPLETED	Study Evaluating the Safety and Effectiveness of ABT-510 in Subjects With Refractory Lymphoma
NCT00067002	Phase 2	COMPLETED	Randomized Double Cord Blood Transplant Study
NCT00067288	Phase 2	COMPLETED	Meaning-Centered Psychotherapy in Advanced Cancer
NCT00094848	Phase 2	COMPLETED	Study of TRM-1 (TRAIL-R1 Monoclonal Antibody) in Subjects With Relapsed or Refractory Non-Hodgkin’s Lymphoma (NHL)
NCT00117156	Phase 2	COMPLETED	Fludarabine and Rituximab for the Treatment of Marginal Zone Non-Hodgkin’s Lymphoma
NCT00145613	Phase 2	COMPLETED	Haploidentical Stem Cell Transplant for Treatment Refractory Hematological Malignancies
NCT00185731	Phase 2	COMPLETED	Phase 2 Study of Atorvastatin Safety and Antitumor Effects in Non-Hodgkin’s Lymphoma
NCT00186394	Phase 2	COMPLETED	High Dose Chemotherapy and Allogeneic Hematopoietic Cell Transplant for Non-Hodgkin’s Lymphoma
NCT00188370	Phase 2	COMPLETED	Ultrasound Biomicroscopy - Apoptosis
NCT00188929	Phase 2	COMPLETED	Assessment of Treatment Response Using PET/CT Scanner - Non Hodgkin’s Lymphoma
NCT00240565	Phase 2	COMPLETED	Tositumomab And Iodine I 131-Tositumomab In Patients With Relapsed Indolent Non-Hodgkin’s Lymphoma
NCT00268203	Phase 2	COMPLETED	Expanded Access Study Of BEXXAR® For Low Grade And Transformed Low-Grade Non-Hodgkin’s Lymphoma
NCT00275262	Phase 2	TERMINATED	A Study to Evaluate the Ability of Lupron Depot to Enhance Immune Function Following Bone Marrow Transplantation
NCT00283985	Phase 2	COMPLETED	Association of L-asparaginase-Methotrexate-Dexamethasone for Nasal and Nasal-type Natural Killer (NK)-T-cell Lymphoma
NCT00322387	Phase 2	COMPLETED	Mobilization of Stem Cells With Plerixafor, Chemotherapy and G-CSF in Multiple Myeloma or Non-Hodgkin’s Lymphoma Patients
NCT00322491	Phase 2	COMPLETED	Mobilization of Stem Cells With AMD3100 (Plerixafor) and G-CSF in Non-Hodgkin’s Lymphoma and Multiple Myeloma Patients
NCT00322842	Phase 2	COMPLETED	Treatment With AMD3100 (Plerixafor) in Non-Hodgkin’s Lymphoma and Multiple Myeloma Patients
NCT00324467	Phase 2	UNKNOWN	Tailoring Treatment for B Cell Non-hodgkin’s Lymphoma Based on PET Scan Results Mid Treatment
NCT00333008	Phase 2	UNKNOWN	A Dose Study of Doxil in a Dose Dense, 14 Day CDOP/Rituximab Regimen for Patients With Diffuse Large B-Cell Non-Hodgkin Lymphoma (NHL)> 60 Years or With Compromised Cardiac Status.
NCT00350181	Phase 2	COMPLETED	Sirolimus & Mycophenolate Mofetil as GVHD Prophylaxis in Myeloablative, Matched Related Donor HCT
NCT00354822	Phase 2	TERMINATED	Fludarabine,Cyclophosphamide and Rituximab Followed by Zevalin for Non-Follicular Indolent Lymphomas.
NCT00367497	Phase 2	TERMINATED	Safety and Efficacy Study of Salvage Chemotherapy (R-ESHAP) to Treat Relapsed and Refractory Aggressive Non-Hodgkin’s Lymphoma
NCT00396266	Phase 2	COMPLETED	AMD3100 (Plerixafor) Given to NHL and MM Patients to Increase the Number of PBSCs When Given a Mobilizing Regimen of G-CSF
NCT00413959	Phase 2	TERMINATED	VELCADE,Rituximab,Cyclophosphamide and Decadron

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PRF1 across ~30M SureChEMBL compounds — explore on Sugi Predict.