TFR2 (transferrin receptor 2)

Gene

• Entrez ID: 7036
• Gene name: Transferrin receptor 2
• Gene symbol: TFR2
• Synonyms (NCBI Gene): HFE3, TFRC2
• Chromosome: 7
• Chromosome location: 7q22.1
• Summary: This gene encodes a single-pass type II membrane protein, which is a member of the transferrin receptor-like family. This protein mediates cellular uptake of transferrin-bound iron, and may be involved in iron metabolism, hepatocyte function and erythrocy

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs41295912	G>A,C	Conflicting-interpretations-of-pathogenicity, likely-benign	Intron variant
rs41303495	G>T	Conflicting-interpretations-of-pathogenicity	Missense variant, coding sequence variant
rs41303501	C>T	Benign, likely-benign, risk-factor	Missense variant, coding sequence variant
rs80338876	C>T	Pathogenic	Missense variant, coding sequence variant, genic upstream transcript variant
rs80338877	->G	Pathogenic	Coding sequence variant, genic upstream transcript variant, frameshift variant
rs80338878	G>A	Pathogenic	Coding sequence variant, genic upstream transcript variant, stop gained
rs80338879	A>T	Pathogenic	Missense variant, initiator codon variant, coding sequence variant
rs80338880	G>C	Pathogenic	Coding sequence variant, stop gained
rs80338881	G>A	Pathogenic	Coding sequence variant, stop gained
rs80338882	G>A	Pathogenic	Coding sequence variant, stop gained
rs80338883	TTG>-	Pathogenic	Inframe deletion, coding sequence variant
rs80338884	C>T	Pathogenic	Missense variant, coding sequence variant
rs80338885	C>T	Uncertain-significance, pathogenic	Missense variant, coding sequence variant
rs80338886	A>C	Pathogenic	Missense variant, coding sequence variant
rs80338887	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs80338888	CTGGGCCACGGC>-,CTGGGCCACGGCCTGGGCCACGGC	Pathogenic	Inframe deletion, coding sequence variant, inframe insertion
rs80338889	T>C,G	Pathogenic	Missense variant, coding sequence variant
rs80338890	C>T	Pathogenic	Splice acceptor variant
rs80338891	C>T	Pathogenic, likely-pathogenic	Missense variant, coding sequence variant
rs139178017	C>T	Conflicting-interpretations-of-pathogenicity	Synonymous variant, coding sequence variant
rs148902192	A>T	Conflicting-interpretations-of-pathogenicity	Intron variant, genic upstream transcript variant
rs184812195	C>T	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, missense variant
rs750609759	T>C	Likely-pathogenic	Splice acceptor variant
rs772104483	C>A	Pathogenic	Coding sequence variant, missense variant
rs773050231	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs786204108	C>G,T	Likely-pathogenic	Coding sequence variant, missense variant
rs946552921	G>A,T	Pathogenic	Stop gained, synonymous variant, coding sequence variant
rs1051249273	G>A,T	Uncertain-significance, pathogenic	Stop gained, missense variant, coding sequence variant
rs1220336558	G>A	Pathogenic	Coding sequence variant, stop gained
rs1388444100	->CT	Pathogenic	Coding sequence variant, genic upstream transcript variant, frameshift variant
rs1426704853	G>-	Pathogenic	Coding sequence variant, frameshift variant, genic upstream transcript variant
rs1562838535	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1584460907	C>G	Likely-pathogenic	Splice donor variant

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004998	Function	Transferrin receptor activity	IDA	18353247
GO:0004998	Function	Transferrin receptor activity	IEA
GO:0004998	Function	Transferrin receptor activity	NAS	10409623
GO:0005515	Function	Protein binding	IPI	18353247, 22728873, 25635054, 29388418, 32296183
GO:0005737	Component	Cytoplasm	IEA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	IGI	18353247
GO:0005886	Component	Plasma membrane	NAS	10409623
GO:0005886	Component	Plasma membrane	TAS
GO:0006826	Process	Iron ion transport	NAS	10409623
GO:0006879	Process	Intracellular iron ion homeostasis	IDA	18353247
GO:0006879	Process	Intracellular iron ion homeostasis	TAS	15319276
GO:0006898	Process	Receptor-mediated endocytosis	IEA
GO:0006898	Process	Receptor-mediated endocytosis	IGI	18353247
GO:0009897	Component	External side of plasma membrane	IBA
GO:0009897	Component	External side of plasma membrane	IEA
GO:0009897	Component	External side of plasma membrane	IGI	18353247
GO:0010039	Process	Response to iron ion	IMP	21173098
GO:0016020	Component	Membrane	IEA
GO:0031410	Component	Cytoplasmic vesicle	IDA	12704209
GO:0033572	Process	Transferrin transport	IDA	18353247
GO:0033572	Process	Transferrin transport	IEA
GO:0033572	Process	Transferrin transport	IGI	18353247
GO:0039706	Function	Co-receptor binding	IPI	22728873
GO:0045807	Process	Positive regulation of endocytosis	IGI	18353247
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IGI	25635054
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IEA
GO:0060586	Process	Multicellular organismal-level iron ion homeostasis	IMP	21173098
GO:0071281	Process	Cellular response to iron ion	IGI	18353247
GO:0090277	Process	Positive regulation of peptide hormone secretion	IMP	21173098
GO:0140298	Process	Endocytic iron import into cell	IBA
GO:0140298	Process	Endocytic iron import into cell	IGI	18353247
GO:1903319	Process	Positive regulation of protein maturation	IGI	18353247
GO:1990712	Component	HFE-transferrin receptor complex	IDA	12704209, 22728873
GO:1990712	Component	HFE-transferrin receptor complex	IEA

Other IDs

• MIM: 604720
• HGNC: 11762
• e!Ensembl: ENSG00000106327

Protein

• UniProt ID: Q9UP52
• Protein name: Transferrin receptor protein 2 (TfR2)
• Protein function: Mediates cellular uptake of transferrin-bound iron in a non-iron dependent manner. May be involved in iron metabolism, hepatocyte function and erythrocyte differentiation.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF02225	PA	241 → 329	PA domain	Family
  PF04389	Peptidase_M28	412 → 624	Peptidase family M28	Family

• Tissue specificity: TISSUE SPECIFICITY: Predominantly expressed in liver. While the alpha form is also expressed in spleen, lung, muscle, prostate and peripheral blood mononuclear cells, the beta form is expressed in all tissues tested, albeit weakly.
• Sequence:

  MERLWGLFQRAQQLSPRSSQTVYQRVEGPRKGHLEEEEEDGEEGAETLAHFCPMELRGPE
  PLGSRPRQPNLIPWAAAGRRAAPYLVLTALLIFTGAFLLGYVAFRGSCQACGDSVLVVSE
  DVNYEPDLDFHQGRLYWSDLQAMFLQFLGEGRLEDTIRQTSLRERVAGSAGMAALTQDIR
  AALSRQKLDHVWTDTHYVGLQFPDPAHPNTLHWVDEAGKVGEQLPLEDPDVYCPYSAIGN
  VTGELVYAHYGRPEDLQDLRARGVDPVGRLLLVRVGVISFAQKVTNAQDFGAQGVLIYPE
  PADFSQDPPKPSLSSQQAVYGHVHLGTGDPYTPGFPSFNQTQFPPVASSGLPSIPAQPIS
  ADIASRLLRKLKGPVAPQEWQGSLLGSPYHLGPGPRLRLVVNNHRTSTPINNIFGCIEGR
  SEPDHYVVIGAQRDAWGPGAAKSAVGTAILLELVRTFSSMVSNGFRPRRSLLFISWDGGD
  FGSVGSTEWLEGYLSVLHLKAVVYVSLDNAVLGDDKFHAKTSPLLTSLIESVLKQVDSPN
  HSGQTLYEQVVFTNPSWDAEVIRPLPMDSSAYSFTAFVGVPAVEFSFMEDDQAYPFLHTK
  EDTYENLHKVLQGRLPAVAQAVAQLAGQLLIRLSHDRLLPLDFGRYGDVVLRHIGNLNEF
  SGDLKARGLTLQWVYSARGDYIRAAEKLRQEIYSSEERDERLTRMYNVRIMRVEFYFLSQ
  YVSPADSPFRHIFMGRGDHTLGALLDHLRLLRSNSSGTPGATSSTGFQESRFRRQLALLT
  WTLQGAANALSGDVWNIDNNF

• Sequence length: 801

Pathways

KEGG:

TGF-beta signaling pathway

Reactome:

Transferrin endocytosis and recycling

Associated diseases

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Hemochromatosis type 1	Likely pathogenic; Pathogenic	rs946552921	RCV000987937
Hemochromatosis type 3	Likely pathogenic; Pathogenic	rs2131312371, rs756989018, rs777027788, rs1562837561, rs1398396879, rs763292953, rs868823304, rs2131312223, rs1463281712, rs1803699632, rs2131328001, rs781427471, rs786204108, rs1803510959, rs931476373, rs2486128874, rs2131313576, rs80338880, rs80338877, rs80338879, rs80338889, rs2486147926, rs2131311231, rs2486116981, rs2486134386, rs2486128952, rs779594895, rs2486147890, rs2486115109, rs2486118586, rs774862156, rs2486102241, rs2486114662, rs1803445521, rs2486133745, rs2486148819, rs2486117732, rs2486118857, rs2486146890, rs2486147617, rs2486102603, rs1803693127, rs1803359971, rs2486117269, rs1803324863, rs2486114850, rs1224612016, rs2486146809, rs556553563, rs2486147571, rs2486123194, rs1320849993, rs2486129744, rs2486133638, rs2486133805, rs2486123093, rs80338882, rs80338883, rs80338888, rs80338891, rs80338878, rs773050231, rs1220336558, rs750609759, rs772104483, rs1051249273, rs946552921, rs768907730, rs1562837669, rs1405776096, rs1803297757, rs1422733588, rs1803502704, rs1803316071, rs1803096138, rs765525417	RCV003473897 RCV005040242 RCV003473958 RCV003473987 RCV003473971 RCV003473996 RCV003473959 RCV001785060 RCV003475193 RCV003475145 RCV004571645 RCV003475159 RCV001831985 RCV003475501 RCV003475516 RCV003475527 RCV003475403 RCV000005711 RCV000005712 RCV000005713 RCV000005715 RCV003475423 RCV003139229 RCV003132883 RCV003474062 RCV003474063 RCV003474064 RCV003474065 RCV003474066 RCV003474068 RCV003474069 RCV003474070 RCV003474071 RCV003474072 RCV003474073 RCV003474074 RCV003474075 RCV003474076 RCV003474077 RCV003474078 RCV003474079 RCV003474080 RCV003474081 RCV003474082 RCV003474083 RCV003474084 RCV005040541 RCV004573717 RCV004573718 RCV004573719 RCV004573720 RCV004573721 RCV004573722 RCV004573723 RCV004573724 RCV004573725 RCV004573726 RCV004573727 RCV000020534 RCV000020535 RCV000020543 RCV000020547 RCV000020548 RCV003476250 RCV003472250 RCV003472202 RCV005431893 RCV000779521 RCV003473533 RCV001827421 RCV003473667 RCV003473623 RCV003473683 RCV005047258 RCV001250718 RCV001250719 RCV003473763 RCV003473807
Hereditary hemochromatosis	Likely pathogenic; Pathogenic	rs1562845204, rs2131304244, rs2131312371, rs1803316195, rs2131318652, rs756989018, rs777027788, rs1562837561, rs1188426077, rs1803309728, rs1398396879, rs763292953, rs868823304, rs2131313564, rs1324815806, rs1463281712, rs1584459683, rs1803699632, rs1478674823, rs2131320006, rs2131320223, rs2131328001, rs2131327975, rs2131320933, rs2131318647, rs1411667989, rs2131320942, rs781427471, rs2131327564, rs786204108, rs1803510959, rs1803363753, rs931476373, rs2486128874, rs2131313576, rs2486148789, rs80338877, rs1389208146, rs1034968542, rs2486147926, rs776441721, rs774862156, rs2486147898, rs2486126656, rs2486102360, rs2486147622, rs1414730937, rs1803693127, rs1803324863, rs2486146751, rs2486134236, rs2486114991, rs762648897, rs2486129782, rs2486117611, rs2486133665, rs2486131876, rs2486147767, rs1020301245, rs147286030, rs2486114892, rs2486120240, rs1803700065, rs2486133707, rs2486147588, rs2486133812, rs2486114850, rs2486147879, rs773320398, rs753747243, rs780902940, rs2486117181, rs80338882, rs80338888, rs80338891, rs80338878, rs773050231, rs1426704853, rs1220336558, rs750609759, rs1562838535, rs772104483, rs1051249273, rs1388444100, rs1584460907, rs946552921, rs768907730, rs1562837669, rs1405776096, rs1803297757, rs749211542, rs1422733588, rs1803411479, rs1803096138, rs1803418157, rs765525417	RCV001379277 RCV001377637 RCV001376871 RCV001377806 RCV001378951 RCV001379150 RCV001385287 RCV001388574 RCV001386233 RCV001387375 RCV001386715 RCV001390139 RCV001385290 RCV003752072 RCV002002104 RCV001967760 RCV001994589 RCV001898123 RCV001938609 RCV001975864 RCV001925261 RCV001940897 RCV001899385 RCV001924337 RCV002011622 RCV001941550 RCV002000942 RCV001903601 RCV001888051 RCV000168040 RCV003051332 RCV003074867 RCV002637506 RCV003118146 RCV002630749 RCV002766353 RCV001381389 RCV002750888 RCV002820228 RCV002806718 RCV002842569 RCV002863094 RCV002880402 RCV003007471 RCV003017294 RCV003040231 RCV003027763 RCV005100232 RCV003750975 RCV003589630 RCV003589784 RCV003588932 RCV003589962 RCV003589343 RCV003588484 RCV003589410 RCV003590266 RCV003751079 RCV003750996 RCV003751237 RCV003751815 RCV003751811 RCV003751750 RCV003752169 RCV003752112 RCV003752352 RCV003750415 RCV003832884 RCV003864170 RCV003854524 RCV003873330 RCV003879508 RCV003875081 RCV003877390 RCV001237605 RCV001390238 RCV001219293 RCV001851971 RCV000551640 RCV000527640 RCV000706048 RCV000691270 RCV000705183 RCV000700023 RCV000812711 RCV000807770 RCV000813654 RCV001068810 RCV001065051 RCV001059109 RCV001041067 RCV001062633 RCV001035774 RCV001055157 RCV001048748 RCV001214976 RCV001218623 RCV001234936
Ovarian serous cystadenocarcinoma	Likely pathogenic	rs1320849993	RCV005939490
TFR2-related disorder	Pathogenic	rs1051249273	RCV003411720

Unknown
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession
Cervical cancer	Conflicting classifications of pathogenicity; Benign	rs139178017, rs41295899, rs200816061	RCV005895270 RCV005892639 RCV005906969
Chronic lymphocytic leukemia/small lymphocytic lymphoma	Conflicting classifications of pathogenicity	rs200816061	RCV005906971
Clear cell carcinoma of kidney	Conflicting classifications of pathogenicity	rs780902940	RCV005912268
Colon adenocarcinoma	Conflicting classifications of pathogenicity	rs139178017	RCV005895268
Colorectal cancer	Conflicting classifications of pathogenicity	rs139178017	RCV005895273
Familial cancer of breast	Conflicting classifications of pathogenicity	rs139178017	RCV005895267
Gastric cancer	Conflicting classifications of pathogenicity; Uncertain significance	rs139178017, rs756044574	RCV005895275 RCV005914001
Hemochromatosis, type 1, modifier of	Conflicting classifications of pathogenicity	rs41303501	RCV000005714
Hepatocellular carcinoma	Benign	rs41295899, rs41303468	RCV005892638 RCV005899148
Hereditary hemochromatosis type 4	Benign	rs2075674	RCV001272113
Hereditary hemochromatosis type 5	Likely benign	rs147286030	RCV001272114
Lymphoma	Conflicting classifications of pathogenicity	rs139178017, rs200816061	RCV005895276 RCV005906970
Malignant lymphoma, large B-cell, diffuse	Conflicting classifications of pathogenicity	rs139178017	RCV005895272
Malignant tumor of esophagus	Benign	rs41303468	RCV005899149
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity; Uncertain significance	rs139178017, rs763004927	RCV005895269 RCV005914007
Melanoma	Conflicting classifications of pathogenicity	rs139178017	RCV005895280
Ovarian cancer	Conflicting classifications of pathogenicity	rs139178017	RCV005895271
Sarcoma	Conflicting classifications of pathogenicity; Benign; Uncertain significance	rs139178017, rs41295899, rs201483480, rs578087339	RCV005895274 RCV005892640 RCV005899147 RCV005913997
Thymoma	Conflicting classifications of pathogenicity	rs139178017	RCV005895279
Uterine carcinosarcoma	Conflicting classifications of pathogenicity	rs139178017	RCV005895278
Uterine corpus endometrial carcinoma	Conflicting classifications of pathogenicity; Benign; Likely benign	rs139178017, rs111760099	RCV005895281 RCV005900159

Associations from Text Mining
Disease Name	Relationship Type	References
Arthralgia	Associate	28276324
Arthritis	Associate	15319290
Autism Spectrum Disorder	Associate	31936202
beta Thalassemia	Associate	35355750
Carcinoma Hepatocellular	Associate	11675342, 17956864, 19828835, 20576915
Carcinoma Pancreatic Ductal	Associate	34258619
Colorectal Neoplasms	Associate	32375704
Crohn Disease	Associate	40527798
Diabetes Mellitus	Associate	15319290
Drug Related Side Effects and Adverse Reactions	Associate	20220060
Dysautonomia Familial	Associate	28276324
Fibrocartilaginous embolism	Associate	37480032
Ganglioneuroblastoma	Associate	31698611
Ganglioneuroma	Associate	31698611
Heart Failure	Associate	15319290
Hemochromatosis	Associate	11313241, 12091366, 12130528, 12406888, 15084147, 15147384, 15317665, 15319290, 15486069, 15521925, 16838333, 17202145, 17847004, 17956864, 18245657, 19759876, 19819738, 21173098, 21770687, 23556518, 25152992, 25352340, 25635054, 26633544, 26799139, 28276324, 29388418, 29743178, 33787609, 34048062, 34583728, 34946929, 35355750
Hemochromatosis type 2	Associate	15147384
Hemochromatosis type 3	Associate	11313241, 17298224, 19144662
Hepatitis C Chronic	Associate	37632052
Hyperferritinemia	Associate	34828384
Idiopathic Noncirrhotic Portal Hypertension	Associate	19307463
Immunologic Deficiency Syndromes	Associate	15671438
Intervertebral Disc Degeneration	Associate	37480032
Iron Deficiencies	Associate	25637053
Iron Overload	Associate	11313241, 12130528, 15147384, 16838333, 17202145, 18245657, 19819738, 20027482, 21770687, 23556518, 25635054, 25637053, 26633544, 26799139, 34048062, 35355750
Liver Cirrhosis	Associate	15319290
Macular Degeneration	Associate	24648608
Melanoma Cutaneous Malignant	Associate	32199022
Mitochondrial Diseases	Associate	24121126
Multiple Sclerosis	Associate	35682458
Neoplasms	Associate	19307463, 24338397, 31698611
Neoplastic Syndromes Hereditary	Associate	15521925, 28276324
Neuroblastoma	Associate	31698611
Non alcoholic Fatty Liver Disease	Stimulate	29065180
Obesity	Associate	24648608
Osteogenesis imperfecta type 3	Associate	29388418
Parkinson Disease	Associate	24121126
Porphyria Cutanea Tarda	Associate	17298224
Precursor T Cell Lymphoblastic Leukemia Lymphoma	Associate	15015967, 20220060
Prostatic Neoplasms	Associate	25080433
Stomach Neoplasms	Associate	32705773
Thyroid Cancer Papillary	Associate	37361050