PRF1 (perforin 1)

Gene

• Entrez ID: 5551
• Gene name: Perforin 1
• Gene symbol: PRF1
• Synonyms (NCBI Gene): HPLH2, P1, PFP
• Chromosome: 10
• Chromosome location: 10q22.1
• Summary: 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 occur

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28933374	G>A,T	Pathogenic	Missense variant, coding sequence variant
rs28933375	T>C	Conflicting-interpretations-of-pathogenicity, uncertain-significance, likely-benign	Missense variant, coding sequence variant
rs28933376	G>A	Pathogenic	Missense variant, coding sequence variant
rs28933973	G>A	Pathogenic	Missense variant, coding sequence variant
rs35418374	C>T	Pathogenic, benign, likely-benign	Missense variant, coding sequence variant
rs35947132	G>A	Conflicting-interpretations-of-pathogenicity, uncertain-significance, benign, likely-benign	Missense variant, coding sequence variant
rs104894176	C>T	Pathogenic	Stop gained, coding sequence variant
rs104894180	G>A,C	Pathogenic	Stop gained, missense variant, coding sequence variant
rs104894181	C>T	Pathogenic	Missense variant, coding sequence variant
rs104894182	C>T	Pathogenic	Missense variant, coding sequence variant
rs104894183	A>C	Pathogenic	Missense variant, coding sequence variant
rs138126912	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs141660796	G>A	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs142012387	G>C,T	Likely-pathogenic	Missense variant, coding sequence variant
rs147035858	A>-	Pathogenic	Coding sequence variant, frameshift variant
rs147462227	C>T	Pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs189650890	G>A	Pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs193302875	C>A	Pathogenic	Coding sequence variant, missense variant
rs193302876	G>A	Pathogenic	Coding sequence variant, stop gained
rs200430442	G>A	Pathogenic	Coding sequence variant, missense variant
rs202217604	C>T	Likely-pathogenic	Coding sequence variant, missense variant
rs751161742	T>G	Likely-pathogenic	Coding sequence variant, missense variant
rs751247865	G>T	Pathogenic	Coding sequence variant, missense variant
rs752858869	T>A	Pathogenic	Coding sequence variant, missense variant
rs768849283	C>G	Likely-pathogenic	Coding sequence variant, missense variant
rs771552960	AG>-	Pathogenic	Coding sequence variant, frameshift variant
rs776299562	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs786205093	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1060499556	A>C,G	Likely-pathogenic	Missense variant, coding sequence variant
rs1554867753	G>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1564723653	G>T	Pathogenic	Stop gained, coding sequence variant
rs1589233357	G>A	Likely-pathogenic	Coding sequence variant, stop gained

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT755480	hsa-miR-221-5p	Luciferase reporter assay, Western blotting, qRT-PCR	36499501
MIRT1261237	hsa-miR-124	CLIP-seq
MIRT1261238	hsa-miR-145	CLIP-seq
MIRT1261239	hsa-miR-219-2-3p	CLIP-seq
MIRT1261240	hsa-miR-2682	CLIP-seq
MIRT1261241	hsa-miR-3147	CLIP-seq
MIRT1261242	hsa-miR-3185	CLIP-seq
MIRT1261243	hsa-miR-3675-5p	CLIP-seq
MIRT1261244	hsa-miR-3714	CLIP-seq
MIRT1261245	hsa-miR-3910	CLIP-seq
MIRT1261246	hsa-miR-3925-3p	CLIP-seq
MIRT1261247	hsa-miR-4283	CLIP-seq
MIRT1261248	hsa-miR-4423-3p	CLIP-seq
MIRT1261249	hsa-miR-4425	CLIP-seq
MIRT1261250	hsa-miR-4489	CLIP-seq
MIRT1261251	hsa-miR-4493	CLIP-seq
MIRT1261252	hsa-miR-449c	CLIP-seq
MIRT1261253	hsa-miR-4520a-3p	CLIP-seq
MIRT1261254	hsa-miR-4520b-3p	CLIP-seq
MIRT1261255	hsa-miR-4529-3p	CLIP-seq
MIRT1261256	hsa-miR-4640-5p	CLIP-seq
MIRT1261257	hsa-miR-4726-5p	CLIP-seq
MIRT1261258	hsa-miR-506	CLIP-seq
MIRT1261259	hsa-miR-7	CLIP-seq
MIRT1261260	hsa-miR-940	CLIP-seq
MIRT2076838	hsa-miR-127-5p	CLIP-seq
MIRT2076839	hsa-miR-3064-5p	CLIP-seq
MIRT2076840	hsa-miR-4679	CLIP-seq
MIRT2076838	hsa-miR-127-5p	CLIP-seq
MIRT2076839	hsa-miR-3064-5p	CLIP-seq
MIRT2076840	hsa-miR-4679	CLIP-seq
MIRT2457142	hsa-miR-1237	CLIP-seq
MIRT2457143	hsa-miR-1913	CLIP-seq
MIRT2457144	hsa-miR-324-3p	CLIP-seq
MIRT2457145	hsa-miR-4267	CLIP-seq
MIRT2457146	hsa-miR-4727-5p	CLIP-seq
MIRT2457142	hsa-miR-1237	CLIP-seq
MIRT2457143	hsa-miR-1913	CLIP-seq
MIRT2457144	hsa-miR-324-3p	CLIP-seq
MIRT2457145	hsa-miR-4267	CLIP-seq
MIRT2457146	hsa-miR-4727-5p	CLIP-seq
MIRT2688562	hsa-miR-556-5p	CLIP-seq
MIRT2688563	hsa-miR-610	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
STAT4	Activation	12372421

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001771	Process	Immunological synapse formation	IDA	21438968
GO:0001913	Process	T cell mediated cytotoxicity	IEA
GO:0002357	Process	Defense response to tumor cell	ISS
GO:0002418	Process	Immune response to tumor cell	ISS
GO:0005509	Function	Calcium ion binding	ISS
GO:0005515	Function	Protein binding	IPI	11911826, 25416956, 32296183
GO:0005576	Component	Extracellular region	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0006915	Process	Apoptotic process	TAS	10779745
GO:0006968	Process	Cellular defense response	TAS	10779745
GO:0016020	Component	Membrane	HDA	19946888
GO:0016021	Component	Integral component of membrane	IDA	20889983
GO:0019835	Process	Cytolysis	IEA
GO:0022829	Function	Wide pore channel activity	IDA	20889983
GO:0031904	Component	Endosome lumen	IEA
GO:0042802	Function	Identical protein binding	IPI	21037563, 21685908
GO:0044194	Component	Cytolytic granule	IDA	9756476
GO:0044194	Component	Cytolytic granule	ISS
GO:0051260	Process	Protein homooligomerization	IDA	20889983
GO:0051607	Process	Defense response to virus	ISS
GO:0051712	Process	Positive regulation of killing of cells of other organism	IDA	9756476
GO:0055085	Process	Transmembrane transport	IEA

Other IDs

• MIM: 170280
• HGNC: 9360
• e!Ensembl: ENSG00000180644

Protein

• UniProt ID: P14222
• Protein name: Perforin-1 (P1) (Cytolysin) (Lymphocyte pore-forming protein) (PFP)
• Protein function: Pore-forming protein that plays a key role in granzyme-mediated programmed cell death, and in defense against virus-infected or neoplastic cells (PubMed:20889983, PubMed:21037563, PubMed:24558045, PubMed:9058810, PubMed:9164947). Plays an import
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01823	MACPF	147 → 367	MAC/Perforin domain	Domain
  PF00168	C2	415 → 508	C2 domain	Domain

• Sequence:

  MAARLLLLGILLLLLPLPVPAPCHTAARSECKRSHKFVPGAWLAGEGVDVTSLRRSGSFP
  VDTQRFLRPDGTCTLCENALQEGTLQRLPLALTNWRAQGSGCQRHVTRAKVSSTEAVARD
  AARSIRNDWKVGLDVTPKPTSNVHVSVAGSHSQAANFAAQKTHQDQYSFSTDTVECRFYS
  FHVVHTPPLHPDFKRALGDLPHHFNASTQPAYLRLISNYGTHFIRAVELGGRISALTALR
  TCELALEGLTDNEVEDCLTVEAQVNIGIHGSISAEAKACEEKKKKHKMTASFHQTYRERH
  SEVVGGHHTSINDLLFGIQAGPEQYSAWVNSLPGSPGLVDYTLEPLHVLLDSQDPRREAL
  RRALSQYLTDRARWRDCSRPCPPGRQKSPRDPCQCVCHGSAVTTQDCCPRQRGLAQLEVT
  FIQAWGLWGDWFTATDAYVKLFFGGQELRTSTVWDNNNPIWSVRLDFGDVLLATGGPLRL
  QVWDQDSGRDDDLLGTCDQAPKSGSHEVRCNLNHGHLKFRYHARCLPHLGGGTCLDYVPQ
  MLLGEPPGNRSGAVW

• Sequence length: 555

Pathways

KEGG:

Apoptosis
Natural killer cell mediated cytotoxicity
Type I diabetes mellitus
Autoimmune thyroid disease
Allograft rejection
Graft-versus-host disease
Viral myocarditis

Associated diseases

Causal
Disease term	Disease name	dbSNP ID	References
Anemia	Anemia, Aplastic anemia, idiopathic	rs118204044, rs118204045, rs118204046, rs121918330, rs869320719, rs869312029, rs121918332, rs869320724, rs767094129, rs786205058, rs786205059, rs137853119, rs137853120, rs137853121, rs1384933966, rs137853122, rs137853123, rs786205060, rs267607121, rs121908584, rs80338697, rs80338699, rs120074166, rs120074167, rs1050828, rs74575103, rs137852314, rs5030868, rs137852316, rs137852317, rs137852318, rs137852319, rs137852320, rs137852321, rs137852322, rs137852323, rs137852324, rs72554665, rs387906468, rs5030872, rs137852326, rs137852333, rs137852327, rs137852328, rs137852329, rs137852330, rs137852331, rs137852332, rs137852334, rs137852335, rs137852336, rs137852339, rs76645461, rs137852340, rs137852341, rs78478128, rs137852343, rs137852344, rs137852345, rs587776730, rs137852346, rs137852347, rs137852349, rs2070404412, rs2070350038, rs2070350009, rs137852303, rs137852304, rs33946267, rs34378160, rs33933298, rs11549407, rs35724775, rs34598529, rs41469945, rs267607201, rs80338694, rs80338696, rs387907018, rs398123546, rs78365220, rs587777100, rs587777101, rs483352840, rs869312752, rs765487627, rs1557229599, rs1557230040, rs1555524842, rs782090947, rs1358275550, rs1557229736, rs1557230573, rs1556323334, rs1233124208, rs1293528130, rs146864395, rs1595503440, rs1603411214, rs137852325, rs1575247302, rs1603411177, rs1336651679, rs782322505	17311987
Aplastic anemia	Aplastic Anemia, Idiopathic aplastic anemia	rs113993991, rs113993993, rs864309668, rs121908974, rs199422265, rs199422270, rs104894176, rs104894180, rs28933973, rs104894182, rs28933376, rs771552960, rs786205093, rs193302876, rs113993992, rs113993994, rs113993998, rs199422298, rs199422305, rs199422273, rs199422275, rs199422276, rs199422259, rs199422279, rs199422280, rs199422281, rs199422283, rs587780100, rs587781305, rs587781891, rs587781969, rs587782130, rs587782545, rs730881864, rs730881857, rs730881850, rs730881839, rs142301194, rs786201745, rs764884516, rs786202490, rs768378152, rs574673404, rs767215758, rs786205135, rs762664474, rs751161742, rs373730800, rs864622143, rs864622090, rs864622511, rs864622253, rs786201965, rs756363734, rs766044684, rs876659521, rs876659592, rs113993990, rs751247865, rs1057517262, rs1057516668, rs1057516611, rs1057516320, rs1057516772, rs931715719, rs767454740, rs1057519587, rs1060503483, rs1060503467, rs1064795816, rs1064793210, rs1131691842, rs772797192, rs751567476, rs780235686, rs1554562083, rs578092914, rs147035858, rs189650890, rs759232053, rs1554558613, rs1554567892, rs1554564297, rs1554558472, rs1554559083, rs1349928568, rs1178384498, rs1198614767, rs1554558449, rs1554568427, rs752858869, rs147462227, rs748513310, rs1238152597, rs760237820, rs1554562110, rs750375741, rs758708229, rs768849283, rs1563578540, rs1563526747, rs1563559078, rs772005832, rs1563539146, rs778306619, rs771475965, rs1586052851, rs1554559094, rs776571416, rs200430442, rs776299562, rs1584439050, rs1586075907, rs1586101154, rs1586059584, rs1586088924, rs1810540992, rs772411713, rs1812023981
Autism	Autistic Disorder	rs121964908, rs62643608, rs181327458, rs797046134, rs869312704, rs1555013332, rs876657679, rs1057518999, rs1057518658, rs771827120, rs1555187899, rs773080572, rs753871454, rs1684130791, rs1684180699, rs1553510219, rs1684182454, rs1559060428, rs1553510677, rs1576352885, rs1574152522, rs1574152672, rs1696658542	18762240
Developmental delay	Global developmental delay	rs28941770, rs199469464, rs281865469, rs143747297, rs398123009, rs587777428, rs786205133, rs606231459, rs797044854, rs797045027, rs864309504, rs878853160, rs886039902, rs886042046, rs886041291, rs886041382, rs1057518991, rs1057518699, rs753254213, rs748294403, rs762552974, rs1135401795, rs1553121073, rs1553122926, rs1364690005, rs1554086554, rs1554210415, rs1554168326, rs1554776342, rs1553873247, rs1567860112, rs779009256, rs1557447255, rs1564568350, rs780011005, rs1597464953, rs1200336864, rs1569513017, rs1587459606, rs1570332505, rs748888652, rs1575155995, rs2087029320, rs1589669105, rs1601769604, rs1184981709, rs749201074
Diffuse lymphoma	Diffuse Mixed-Cell Lymphoma	rs121912651, rs121913289, rs121913293, rs878854402, rs869025340, rs1349928568, rs1569115687, rs121913291
Hemophagocytic lymphohistiocytosis	HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS, FAMILIAL, 2, Familial hemophagocytic lymphohistiocytosis	rs796065024, rs796065025, rs796065026, rs777759523, rs121434352, rs201908137, rs121434353, rs121434354, rs483352901, rs104893996, rs121918540, rs1599398298, rs121918541, rs1599395085, rs2146217813, rs104894176, rs104894180, rs28933973, rs104894181, rs104894182, rs104894183, rs28933376, rs771552960, rs786205093, rs193302876, rs61736587, rs431905512, rs794729649, rs751161742, rs751247865, rs766657895, rs140148806, rs747169857, rs1060499556, rs764196809, rs1555601863, rs1555600214, rs754621494, rs1555768979, rs578092914, rs147035858, rs189650890, rs752858869, rs147462227, rs1554867753, rs754882266, rs959968589, rs1555601754, rs1555769166, rs773360200, rs768849283, rs1564723653, rs763117746, rs1567818774, rs1567816070, rs1278701043, rs1567818219, rs1568463402, rs1564724291, rs1274685768, rs776571416, rs201032696, rs1157287613, rs141717050, rs1165696705, rs1388957809, rs765034513, rs1589233357, rs910650073, rs933702160, rs1584062332, rs200430442, rs776299562, rs1599414759, rs1848204643, rs1442964152, rs2064936948, rs1041960684, rs921624651, rs2064960126, rs143184345	23443029, 15365097, 18074390, 19487666, 22437823, 21959744, 14757862, 10583959, 17873118, 21234777, 27271812, 16278825, 26903364, 26684649, 25233452, 11565555, 25937001, 16374518, 17266056, 23255033, 20092789, 25297583, 2618478, 24916509, 15728124, 11179007, 15632205, 16860143, 25845254, 21881043, 21152410
Hypofibrinogenemia	Hypofibrinogenemia	rs121913087, rs121913088, rs587776837, rs121909616, rs121909625, rs121909608, rs121909607, rs146387238, rs1578795296, rs1214070111, rs776817952, rs762964798, rs121909606, rs1414035000, rs1310452604
Leukemia	leukemia	rs121909646, rs121913488, rs587776834, rs752746786, rs869312821, rs767454740, rs1554564297
Lymphoma	Lymphoma, Lymphoma, Mixed-Cell, Lymphoma, Undifferentiated, Lymphoma, Small Noncleaved-Cell, Lymphoma, Diffuse, Lymphoma, Non-Hodgkin, Familial	rs11540652, rs1592119138, rs1592123162, rs1599367044
Non-hodgkin lymphoma	Lymphoma, Non-Hodgkin	rs121908689, rs28936699, rs121909775, rs398122800, rs121913357, rs121913355, rs398122820
Multiple congenital anomalies	Multiple congenital anomalies	rs1057517732	23690113, 15755897, 21303357, 26605207, 17266056, 23443029, 18710388, 16937360
Neutropenia	Neutropenia	rs879253882
Pancytopenia	Pancytopenia	rs869312883, rs770551610, rs1131690788, rs530073586, rs374333820

Unknown
Disease term	Disease name	Evidence	References	Source
Hemophagocytic Lymphohistiocytosis	hereditary hemophagocytic lymphohistiocytosis, familial hemophagocytic lymphohistiocytosis 2			GenCC
Neurodegenerative Disorders	fatal post-viral neurodegenerative disorder			GenCC

Associations from Text Mining
Disease Name	Relationship Type	References
Adenocarcinoma of Lung	Associate	35733175
Alcoholism	Stimulate	21121937
Anemia Aplastic	Associate	17311987
Arthritis Rheumatoid	Associate	29388193
Asthma	Associate	37730635
Ataxia	Associate	23443029, 37390248
Ataxia Telangiectasia	Associate	30009527
Autoimmune Diseases	Associate	33566725, 38149249
Autoimmune Lymphoproliferative Syndrome	Associate	15459303, 18198357
Bone Marrow Failure Disorders	Associate	17311987
Brain Diseases	Associate	37390248
Breast Neoplasms	Associate	39363164
Carcinoma Ductal	Associate	39363164
Carcinoma Hepatocellular	Associate	35902905
Carcinoma Pancreatic Ductal	Associate	27768182
Carcinoma Renal Cell	Associate	35739510
Cardiomyopathies	Associate	39294340
Central Nervous System Diseases	Associate	37390248
Colorectal Neoplasms	Associate	1892750, 29770915, 35937946
Common Variable Immunodeficiency	Associate	33838017
Coronary Artery Disease	Associate	34777632
COVID 19	Associate	34975885, 35733175, 36016321
Cranial Nerve Injuries	Associate	37390248
Crohn Disease	Associate	31191543
Death	Associate	33224420, 38149249
Demyelinating Diseases	Associate	38149249
Dengue	Associate	35267010
Diabetes Mellitus	Associate	29216683
Diabetes Mellitus Type 1	Associate	18198357, 33566725, 35626661
Drug Related Side Effects and Adverse Reactions	Associate	20529823, 27383371, 30333226, 39405653
Epstein Barr Virus Infections	Associate	25947952
Genetic Diseases Inborn	Associate	17606450
Glioma	Associate	36325335
Heart Failure Diastolic	Associate	36266995
Hematologic Diseases	Associate	31562900, 32098966
Hemophagocytic lymphohistiocytosis familial 2	Associate	22186995, 25104007, 29216683, 30045285, 30658162, 32259894, 33566725, 38149249, 40090000
Hemorrhage	Associate	37203300
Hereditary Autoinflammatory Diseases	Associate	36263058
Hypertension	Associate	37675573
Immune Reconstitution Inflammatory Syndrome	Stimulate	25589068
Immune System Diseases	Associate	33838017, 37325673
Immunologic Deficiency Syndromes	Associate	25569260, 30658162, 31562900
Immunologic Deficiency Syndromes	Inhibit	30658162
Inflammation	Associate	23734059, 27383371, 33566725
Leukemia	Associate	37919606
Leukemia Lymphocytic Chronic B Cell	Associate	19897574
Leukemia Lymphoid	Associate	29599780
Leukemia Myelogenous Chronic BCR ABL Positive	Associate	37919606
Leukemia Myeloid Acute	Associate	32098966
Lupus Erythematosus Systemic	Stimulate	23029299
Lupus Erythematosus Systemic	Associate	25986394
Lymphohistiocytosis Hemophagocytic	Associate	12358924, 15632205, 16778144, 16791263, 17606450, 17652853, 18198357, 18240215, 18311812, 18710388, 19884660, 20015888, 21152410, 21881043, 22186995, 22796692, 23443029, 24632576, 24916509, 25104007, 25233452, 25312756, 25845254, 26342526, 26597256, 26903364, 27209435, 28270454, 28468610, 29157204, 29357941, 29649976, 29783935, 30045285, 30295794, 31562900, 32076423, 32375849, 32542393, 33224420, 33658321, 33746956, 34677667, 35078966, 35902954, 37390248, 38149249
Lymphoma	Associate	15459303, 17477373, 18198357
Lymphoma B Cell	Associate	15459303
Lymphoma Large Cell Anaplastic	Associate	17477373
Lymphoma T Cell	Associate	24632576, 37781365
Macrophage Activation Syndrome	Associate	26597256
Melanoma	Associate	25944800, 39222576
Meningism	Associate	12952922
Microsatellite Instability	Associate	34181673
Multiple Sclerosis	Associate	33566725, 36755464
Myelodysplastic Syndromes	Associate	32098966
Narcolepsy	Associate	37188663
Neoplasms	Inhibit	1892750, 35201851
Neoplasms	Associate	19897574, 22735807, 22829880, 24632576, 26625258, 29770915, 30009527, 30504371, 30963401, 36271373, 38017109, 39376571
Neuroblastoma	Associate	26161395
Non alcoholic Fatty Liver Disease	Associate	36266995
Nose Diseases	Associate	24632576
Paralysis	Associate	37390248
Paraparesis Tropical Spastic	Stimulate	24041428
Phyllodes Tumor	Associate	36271373
Polyradiculoneuropathy Chronic Inflammatory Demyelinating	Associate	38149249
Precursor Cell Lymphoblastic Leukemia Lymphoma	Associate	16791263
Primary Immunodeficiency Diseases	Associate	38644452
Pulmonary Fibrosis	Associate	35558069
Purpura Thrombocytopenic Idiopathic	Associate	27391055
Respiratory Syncytial Virus Infections	Associate	28253869
Respiratory Tract Infections	Associate	25569648
Retinitis Pigmentosa	Associate	34070492
Seizures	Associate	37390248
Spinocerebellar Degenerations	Stimulate	35937946
Stomach Neoplasms	Associate	33312758, 34181673, 35741779
Tn Syndrome	Inhibit	29892290