TNFRSF1B (P20333) variants and mutations
TNFRSF1B (also known as P20333) is a human protein-coding gene encoding a tumor necrosis factor receptor superfamily member 1B protein. It responds preferentially to membrane-bound TNF and modulates survival, proliferation, and immune regulation in selected lymphocyte and vascular populations. Rare variants can disturb immune homeostasis, while the receptor is being explored as a therapeutic target in autoimmunity and cancer. This analysis covers 747 TNFRSF1B variants and mutations. Of these, 96% have computational variant effect predictions. Disease context includes hypothyroidism, thyroid gland disorder, and neurodegenerative disease. Example TNFRSF1B variants include A2T, A2S, and A2P.
Variant analysis overview
- Gene: TNFRSF1B
- Protein: P20333
- UniProt accession: P20333
- Organism: Homo sapiens
- Variants analyzed: 747
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 527 unspecified-consequence records; 134 missense variants; 62 synonymous variants; 10 frameshift variants; 7 stop-gained variants; 1 in-frame deletions; 4 splice-region variants; 2 substitution
- Prediction scores: 719 variants have prediction scores (96% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: hypothyroidism, thyroid gland disorder, neurodegenerative disease, childhood onset asthma, neoplasm, rheumatoid arthritis, cancer, breast cancer, esophageal squamous cell carcinoma, nonpapillary renal cell carcinoma, colorectal carcinoma, pancreatic neoplasm.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 7 post-translational modification sites.
- Structural context: 36 variants have structural context.
- PTM context: 9 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable TNFRSF1B variants
Examples include A2T, A2S, A2P, A2G, A2E, A2V, A2A, P3A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD 1-12167095-G-A, REVEL 0.33, MetaLR 0.76
- A2S (p.Ala2Ser), gnomAD 1-12167095-G-T, REVEL 0.31, MetaLR 0.74
- A2P (p.Ala2Pro), gnomAD 1-12167095-G-C, REVEL 0.36, MetaLR 0.80
- A2G (p.Ala2Gly), gnomAD 1-12167096-C-G, REVEL 0.25, MetaLR 0.77
- A2E (p.Ala2Glu), gnomAD 1-12167096-C-A, REVEL 0.28, MetaLR 0.79
- A2V (p.Ala2Val), gnomAD 1-12167096-C-T, REVEL 0.21, MetaLR 0.55
- A2A (p.Ala2Ala), gnomAD 1-12167097-G-T, CADD 12.10
- P3A (p.Pro3Ala), gnomAD 1-12167098-C-G, REVEL 0.16, MetaLR 0.66
- P3T (p.Pro3Thr), gnomAD 1-12167098-C-A, REVEL 0.23, MetaLR 0.67
- P3S (p.Pro3Ser), gnomAD 1-12167098-C-T, REVEL 0.18, MetaLR 0.65
- P3L (p.Pro3Leu), gnomAD 1-12167099-C-T, REVEL 0.21, MetaLR 0.64
- P3H (p.Pro3His), gnomAD 1-12167099-C-A, REVEL 0.24, MetaLR 0.74
- P3R (p.Pro3Arg), gnomAD 1-12167099-C-G, REVEL 0.28, MetaLR 0.71
- P3P (p.Pro3Pro), gnomAD 1-12167100-C-A, CADD 12.20
- V4L (p.Val4Leu), gnomAD 1-12167101-G-C, REVEL 0.17, MetaLR 0.60
- V4I (p.Val4Ile), gnomAD 1-12167101-G-A, REVEL 0.15, MetaLR 0.60
- V4F (p.Val4Phe), gnomAD 1-12167101-G-T, REVEL 0.21, MetaLR 0.62
- V4A (p.Val4Ala), gnomAD 1-12167102-T-C, REVEL 0.18, MetaLR 0.46
- V4D (p.Val4Asp), gnomAD 1-12167102-T-A, REVEL 0.17, MetaLR 0.60
- V4V (p.Val4Val), gnomAD 1-12167103-C-A, CADD 9.82
- A5S (p.Ala5Ser), gnomAD 1-12167104-G-T, REVEL 0.23, MetaLR 0.63
- A5T (p.Ala5Thr), gnomAD 1-12167104-G-A, REVEL 0.17, MetaLR 0.64
- A5P (p.Ala5Pro), gnomAD 1-12167104-G-C, REVEL 0.35, MetaLR 0.75
- A5D (p.Ala5Asp), gnomAD 1-12167105-C-A, REVEL 0.27, MetaLR 0.70
- A5G (p.Ala5Gly), gnomAD 1-12167105-C-G, REVEL 0.21, MetaLR 0.67
- A5V (p.Ala5Val), gnomAD 1-12167105-C-T, REVEL 0.16, MetaLR 0.68
- A5A (p.Ala5Ala), gnomAD 1-12167106-C-G, CADD 10.50
- V6A (p.Val6Ala), gnomAD rs1333138678, REVEL 0.18, MetaLR 0.58
- V6F (p.Val6Phe), 1000Genomes rs543515279, ExAC rs543515279, TOPMed rs543515279, gnomAD rs543515279, REVEL 0.21, MetaLR 0.54
- V6I (p.Val6Ile), 1000Genomes rs543515279, ExAC rs543515279, TOPMed rs543515279, gnomAD rs543515279, REVEL 0.12, MetaLR 0.57
- V6L (p.Val6Leu), gnomAD 1-12167107-G-C, REVEL 0.26, MetaLR 0.45
- V6V (p.Val6Val), gnomAD 1-12167109-C-A, CADD 10.60
- W7R (p.Trp7Arg), gnomAD 1-12167110-T-C, REVEL 0.55, MetaLR 0.87
- W7G (p.Trp7Gly), gnomAD 1-12167110-T-G, REVEL 0.59, MetaLR 0.87
- W7L (p.Trp7Leu), gnomAD 1-12167111-G-T, REVEL 0.51, MetaLR 0.85
- W7* (p.Trp7Ter), gnomAD 1-12167111-G-A, CADD 36.00
- W7C (p.Trp7Cys), gnomAD 1-12167112-G-T, REVEL 0.69, MetaLR 0.88
- A8P (p.Ala8Pro), gnomAD 1-12167110-TG-T, CADD 24.50
- A8S (p.Ala8Ser), gnomAD 1-12167113-G-T, REVEL 0.34, MetaLR 0.72
- A8T (p.Ala8Thr), gnomAD 1-12167113-G-A, REVEL 0.33, MetaLR 0.74
- A8V (p.Ala8Val), gnomAD 1-12167114-C-T, REVEL 0.14, MetaLR 0.57
- A8G (p.Ala8Gly), gnomAD 1-12167114-C-G, REVEL 0.27, MetaLR 0.68
- A8D (p.Ala8Asp), gnomAD 1-12167114-C-A, REVEL 0.51, MetaLR 0.78
- A8A (p.Ala8Ala), rs886255288, gnomAD 1-12167115-C-T, CADD 13.10
- A9S (p.Ala9Ser), TOPMed rs1638406704, REVEL 0.34, MetaLR 0.81
- A9V (p.Ala9Val), TOPMed rs1277388576, gnomAD rs1277388576, REVEL 0.28, MetaLR 0.62
- A9P (p.Ala9Pro), gnomAD 1-12167116-G-C, REVEL 0.54, MetaLR 0.82
- A9T (p.Ala9Thr), gnomAD 1-12167116-G-A, REVEL 0.35, MetaLR 0.81
- A9G (p.Ala9Gly), gnomAD 1-12167117-C-G, REVEL 0.35, MetaLR 0.80
- A9E (p.Ala9Glu), gnomAD 1-12167117-C-A, REVEL 0.54, MetaLR 0.81
- A9A (p.Ala9Ala), rs1256653355, gnomAD 1-12167118-G-A, CADD 13.20
- L10R (p.Leu10Arg), Ensembl rs1570114167, MetaLR 0.86, MetaSVM 0.31
- L10M (p.Leu10Met), gnomAD 1-12167119-C-A, REVEL 0.43, MetaLR 0.88
- L10V (p.Leu10Val), gnomAD 1-12167119-C-G, REVEL 0.44, MetaLR 0.86
- L10L (p.Leu10Leu), gnomAD 1-12167119-C-T, CADD 13.80
- L10P (p.Leu10Pro), gnomAD 1-12167120-T-C, REVEL 0.72, MetaLR 0.88
- L10Q (p.Leu10Gln), gnomAD 1-12167120-T-A, REVEL 0.62, MetaLR 0.88
- A11T (p.Ala11Thr), Ensembl rs113538181, REVEL 0.23, MetaLR 0.65
- A11V (p.Ala11Val), gnomAD rs1446199331, REVEL 0.22, MetaLR 0.45
- A11P (p.Ala11Pro), gnomAD 1-12167120-TG-T, CADD 24.80
- A11del (p.Ala11del), gnomAD 1-12167121-GGCC-G, CADD 21.00
- A11S (p.Ala11Ser), gnomAD 1-12167122-G-T, REVEL 0.27, MetaLR 0.67
- A11D (p.Ala11Asp), gnomAD 1-12167123-C-A, REVEL 0.33, MetaLR 0.61
- A11G (p.Ala11Gly), gnomAD 1-12167123-C-G, REVEL 0.27, MetaLR 0.60
- A11A (p.Ala11Ala), gnomAD 1-12167124-C-T, CADD 13.70
- V12F (p.Val12Phe), gnomAD 1-12167125-G-T, REVEL 0.27, MetaLR 0.60
- V12L (p.Val12Leu), gnomAD 1-12167125-G-C, REVEL 0.24, MetaLR 0.58
- V12I (p.Val12Ile), gnomAD 1-12167125-G-A, REVEL 0.24, MetaLR 0.57
- V12A (p.Val12Ala), gnomAD 1-12167126-T-C, REVEL 0.19, MetaLR 0.65
- V12V (p.Val12Val), gnomAD 1-12167127-C-A, CADD 11.80
- G13* (p.Gly13Ter), gnomAD 1-12167128-G-T, CADD 36.00
- G13R (p.Gly13Arg), gnomAD 1-12167128-G-A, REVEL 0.53, MetaLR 0.78
- G13E (p.Gly13Glu), gnomAD 1-12167129-G-A, REVEL 0.23, MetaLR 0.55
- G13A (p.Gly13Ala), gnomAD 1-12167129-G-C, REVEL 0.30, MetaLR 0.61
- G13V (p.Gly13Val), gnomAD 1-12167129-G-T, REVEL 0.44, MetaLR 0.75
- G13G (p.Gly13Gly), gnomAD 1-12167130-A-G, CADD 15.80
- L14M (p.Leu14Met), gnomAD 1-12167131-C-A, REVEL 0.37, MetaLR 0.76
- L14L (p.Leu14Leu), gnomAD 1-12167131-C-T, CADD 13.70
- L14P (p.Leu14Pro), gnomAD 1-12167132-T-C, REVEL 0.66, MetaLR 0.79
- L14Q (p.Leu14Gln), gnomAD 1-12167132-T-A, REVEL 0.53, MetaLR 0.79
- E15S (p.Glu15Ser), gnomAD 1-12167132-TG-T, CADD 24.20
- E15* (p.Glu15Ter), gnomAD 1-12167134-G-T, CADD 35.00
- E15K (p.Glu15Lys), gnomAD 1-12167134-G-A, REVEL 0.26, MetaLR 0.62
- E15A (p.Glu15Ala), gnomAD 1-12167135-A-C, REVEL 0.24, MetaLR 0.59
- E15G (p.Glu15Gly), gnomAD 1-12167135-A-G, REVEL 0.21, MetaLR 0.60
- E15D (p.Glu15Asp), gnomAD 1-12167136-G-T, REVEL 0.24, MetaLR 0.63
- E15E (p.Glu15Glu), rs2101070191, gnomAD 1-12167136-G-A, CADD 14.20
- L16V (p.Leu16Val), gnomAD 1-12167137-C-G, REVEL 0.30, MetaLR 0.59
- L16F (p.Leu16Phe), gnomAD 1-12167137-C-T, REVEL 0.24, MetaLR 0.61
- L16I (p.Leu16Ile), gnomAD 1-12167137-C-A, REVEL 0.31, MetaLR 0.60
- L16P (p.Leu16Pro), gnomAD 1-12167138-T-C, REVEL 0.66, MetaLR 0.72
- L16L (p.Leu16Leu), gnomAD 1-12167139-C-G, CADD 10.70
- W17R (p.Trp17Arg), TOPMed rs1464781369, REVEL 0.52, MetaLR 0.76
- W17* (p.Trp17Ter), gnomAD 1-12167141-G-A, CADD 36.00
- W17S (p.Trp17Ser), gnomAD 1-12167141-G-C, REVEL 0.55, MetaLR 0.76
- W17L (p.Trp17Leu), gnomAD 1-12167141-G-T, REVEL 0.30, MetaLR 0.63
- W17C (p.Trp17Cys), gnomAD 1-12167142-G-T, REVEL 0.42, MetaLR 0.78
- A18T (p.Ala18Thr), Ensembl rs1039748824, REVEL 0.29, MetaLR 0.63
- A18L (p.Ala18Leu), gnomAD 1-12167140-TG-T, CADD 24.90
- A18P (p.Ala18Pro), gnomAD 1-12167143-G-C, REVEL 0.60, MetaLR 0.66
- A18S (p.Ala18Ser), gnomAD 1-12167143-G-T, REVEL 0.28, MetaLR 0.62
- A18D (p.Ala18Asp), gnomAD 1-12167144-C-A, REVEL 0.55, MetaLR 0.63
- A18G (p.Ala18Gly), gnomAD 1-12167144-C-G, REVEL 0.19, MetaLR 0.60
- A18V (p.Ala18Val), gnomAD 1-12167144-C-T, REVEL 0.19, MetaLR 0.61
- A18A (p.Ala18Ala), gnomAD 1-12167145-T-A, CADD 8.53
- A19V (p.Ala19Val), gnomAD rs1421760930, REVEL 0.26, MetaLR 0.58
- A19T (p.Ala19Thr), gnomAD 1-12167146-G-A, REVEL 0.20, MetaLR 0.53
- A19P (p.Ala19Pro), gnomAD 1-12167146-G-C, REVEL 0.57, MetaLR 0.62
- A19S (p.Ala19Ser), gnomAD 1-12167146-G-T, REVEL 0.20, MetaLR 0.61
- A19E (p.Ala19Glu), gnomAD 1-12167147-C-A, REVEL 0.45, MetaLR 0.62
- A19A (p.Ala19Ala), rs557129960, gnomAD 1-12167148-G-A, CADD 10.40
- A20S (p.Ala20Ser), gnomAD rs1171501277, REVEL 0.20, MetaLR 0.59
- A20V (p.Ala20Val), TOPMed rs1638407667, REVEL 0.23, MetaLR 0.59, Uncertain significance, Meniere disease
- A20T (p.Ala20Thr), gnomAD 1-12167149-G-A, REVEL 0.28, MetaLR 0.58
- A20G (p.Ala20Gly), gnomAD 1-12167150-C-G, REVEL 0.22, MetaLR 0.47
- A20E (p.Ala20Glu), gnomAD 1-12167150-C-A, REVEL 0.41, MetaLR 0.57
- A20A (p.Ala20Ala), rs1428640704, gnomAD 1-12167151-G-A, CADD 7.95
- H21R (p.His21Arg), TOPMed rs1016755763, gnomAD rs1016755763, REVEL 0.24, MetaLR 0.50
- H21N (p.His21Asn), gnomAD 1-12167152-C-A, REVEL 0.18, MetaLR 0.63
- H21D (p.His21Asp), gnomAD 1-12167152-C-G, REVEL 0.45, MetaLR 0.64
- H21Y (p.His21Tyr), gnomAD 1-12167152-C-T, REVEL 0.29, MetaLR 0.59
- H21L (p.His21Leu), gnomAD 1-12167153-A-T, REVEL 0.39, MetaLR 0.55
- H21H (p.His21His), gnomAD 1-12167154-C-T, CADD 9.37
- H21Q (p.His21Gln), gnomAD 1-12167154-C-A, REVEL 0.22, MetaLR 0.59
- A22S (p.Ala22Ser), TOPMed rs1638407880, REVEL 0.21, MetaLR 0.60
- A22T (p.Ala22Thr), gnomAD 1-12167155-G-A, REVEL 0.23, MetaLR 0.52
- A22P (p.Ala22Pro), gnomAD 1-12167155-G-C, REVEL 0.41, MetaLR 0.59
- A22V (p.Ala22Val), gnomAD 1-12167156-C-T, REVEL 0.20, MetaLR 0.64
- A22D (p.Ala22Asp), gnomAD 1-12167156-C-A, REVEL 0.38, MetaLR 0.63
- A22A (p.Ala22Ala), rs998708768, gnomAD 1-12167157-C-T, CADD 9.77
- L23C (p.Leu23Cys), gnomAD 1-12167157-CT-C, CADD 20.60
- L23M (p.Leu23Met), gnomAD 1-12167158-T-A, REVEL 0.27, MetaLR 0.54
- L23V (p.Leu23Val), gnomAD 1-12167158-T-G, REVEL 0.20, MetaLR 0.46
- L23L (p.Leu23Leu), rs1305090896, gnomAD 1-12167158-T-C, CADD 9.69
- L23S (p.Leu23Ser), gnomAD 1-12167159-T-C, REVEL 0.28, MetaLR 0.60
- L23F (p.Leu23Phe), gnomAD 1-12167160-G-T, REVEL 0.22, MetaLR 0.63
- P24S (p.Pro24Ser), gnomAD rs1403431276, REVEL 0.26, MetaLR 0.65
- P24A (p.Pro24Ala), gnomAD 1-12167161-C-G, REVEL 0.29, MetaLR 0.61
- P24T (p.Pro24Thr), gnomAD 1-12167161-C-A, REVEL 0.25, MetaLR 0.68
- P24H (p.Pro24His), gnomAD 1-12167162-C-A, REVEL 0.34, MetaLR 0.78
- P24R (p.Pro24Arg), gnomAD 1-12167162-C-G, REVEL 0.48, MetaLR 0.75
- P24L (p.Pro24Leu), gnomAD 1-12167162-C-T, REVEL 0.30, MetaLR 0.64
- P24P (p.Pro24Pro), gnomAD 1-12167163-C-A, CADD 10.10
- A25P (p.Ala25Pro), gnomAD rs1382008273, REVEL 0.36, MetaLR 0.54
- A25T (p.Ala25Thr), gnomAD rs1382008273, REVEL 0.23, MetaLR 0.54
- A25S (p.Ala25Ser), gnomAD 1-12167164-G-T, REVEL 0.22, MetaLR 0.53
- A25D (p.Ala25Asp), gnomAD 1-12167165-C-A, REVEL 0.51, MetaLR 0.65
- A25G (p.Ala25Gly), gnomAD 1-12167165-C-G, REVEL 0.23, MetaLR 0.65
- A25V (p.Ala25Val), gnomAD 1-12167165-C-T, REVEL 0.26, MetaLR 0.65
- A25A (p.Ala25Ala), gnomAD 1-12167166-C-G, CADD 13.30
- Q26R (p.Gln26Arg), gnomAD 1-12167164-GC-G, CADD 23.40
- Q26G (p.Gln26Gly), gnomAD 1-12167164-GCC-G, CADD 23.50
- Q26K (p.Gln26Lys), gnomAD 1-12167167-C-A, REVEL 0.29, MetaLR 0.55
- Q26E (p.Gln26Glu), gnomAD 1-12167167-C-G, REVEL 0.27, MetaLR 0.61
- Q26* (p.Gln26Ter), gnomAD 1-12167167-C-T, CADD 33.00
- Q26L (p.Gln26Leu), gnomAD 1-12167168-A-T, REVEL 0.28, MetaLR 0.65
- Q26Q (p.Gln26Gln), gnomAD 1-12167169-G-A, CADD 22.90
- Q26H (p.Gln26His), gnomAD 1-12167169-G-T, REVEL 0.30, MetaLR 0.64
- V27A (p.Val27Ala), rs1420687244, ClinGen CA338467925, ClinVar RCV004473168, TOPMed rs1420687244, REVEL 0.13, MetaLR 0.51, Uncertain significance
- V27V (p.Val27Val), rs558237743, gnomAD 1-12188798-G-C, CADD 0.05
- A28S (p.Ala28Ser), Ensembl rs1570150813, REVEL 0.25, MetaLR 0.57
- A28V (p.Ala28Val), ESP rs142907823, REVEL 0.19, MetaLR 0.43
- A28T (p.Ala28Thr), gnomAD 1-12188799-G-A, REVEL 0.23, MetaLR 0.52
- A28A (p.Ala28Ala), gnomAD 1-12188801-A-T, CADD 1.05
- F29F (p.Phe29Phe), gnomAD 1-12188804-T-C, CADD 0.82
- T30I (p.Thr30Ile), 1000Genomes rs183755458, ExAC rs183755458, TOPMed rs183755458, gnomAD rs183755458, REVEL 0.14, MetaLR 0.60
- T30T (p.Thr30Thr), gnomAD 1-12188807-A-G, CADD 3.96
- P31S (p.Pro31Ser), gnomAD 1-12188808-C-T, REVEL 0.33, MetaLR 0.73
- P31P (p.Pro31Pro), gnomAD 1-12188810-C-T, CADD 6.25
- Y32F (p.Tyr32Phe), gnomAD 1-12188812-A-T, REVEL 0.31, MetaLR 0.72
- Y32Y (p.Tyr32Tyr), rs761386236, gnomAD 1-12188813-C-T, CADD 0.13
- A33S (p.Ala33Ser), 1000Genomes rs540459773, ExAC rs540459773, TOPMed rs540459773, gnomAD rs540459773, MetaLR 0.50, MetaSVM -0.31
- A33T (p.Ala33Thr), 1000Genomes rs540459773, ExAC rs540459773, TOPMed rs540459773, gnomAD rs540459773, REVEL 0.08, MetaLR 0.50
- A33V (p.Ala33Val), ExAC rs750041133, TOPMed rs750041133, gnomAD rs750041133, REVEL 0.10, MetaLR 0.55
- A33D (p.Ala33Asp), gnomAD 1-12188815-C-A, REVEL 0.20, MetaLR 0.52
- A33A (p.Ala33Ala), gnomAD 1-12188816-C-T, CADD 1.57
- P34L (p.Pro34Leu), cosmic curated COSV66164, ExAC rs760020939, TOPMed rs760020939, gnomAD rs760020939, REVEL 0.12, MetaLR 0.63
- P34R (p.Pro34Arg), ExAC rs760020939, TOPMed rs760020939, gnomAD rs760020939, REVEL 0.27, MetaLR 0.77
- P34P (p.Pro34Pro), rs373387104, gnomAD 1-12188819-G-A, CADD 0.25
- E35Q (p.Glu35Gln), TOPMed rs1639043827, gnomAD rs1639043827, REVEL 0.18, MetaLR 0.58
Public TNFRSF1B analysis runs
- TNFRSF1B analysis run — TNFRSF1B (747 variants) — completed 2026-08-20