TNFRSF4 (P43489) variants and mutations
TNFRSF4 (also known as P43489) is a human protein-coding gene encoding a tumor necrosis factor receptor superfamily member 4 protein. It provides a costimulatory signal that promotes survival and expansion of activated T cells while influencing regulatory T-cell function. Modulating OX40 signaling is being explored to enhance antitumor immunity or suppress inflammatory disease. This analysis covers 713 TNFRSF4 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes combined immunodeficiency due to OX40 deficiency, atopic eczema, and combined immunodeficiency. Example TNFRSF4 variants include M1L, C2*, and C2R.
Variant analysis overview
- Gene: TNFRSF4
- Protein: P43489
- UniProt accession: P43489
- Organism: Homo sapiens
- Variants analyzed: 713
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 385 unspecified-consequence records; 1 stop retained variant; 2 stop lost; 190 missense variants; 105 synonymous variants; 9 stop-gained variants; 16 frameshift variants; 4 splice-region variants; 2 in-frame deletions; 2 substitution
- Prediction scores: 659 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: combined immunodeficiency due to OX40 deficiency, atopic eczema, combined immunodeficiency, severe combined immunodeficiency, prurigo nodularis, neurodegenerative disease, neoplasm, asthma, acute myeloid leukemia, infection, hepatocellular carcinoma, ulcerative colitis.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 2 post-translational modification sites.
- Structural context: 95 variants have structural context.
- PTM context: 4 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable TNFRSF4 variants
Examples include M1L, C2*, C2R, C2W, C2Y, V3L, V3M, G4A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1L (p.Met1Leu), rs2100957059, ClinGen CA337803339, ClinVar RCV001970684, MutPred 0.98, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C2* (p.Cys2Ter), 1000Genomes rs202161001, ExAC rs202161001, TOPMed rs202161001, gnomAD rs202161001, CADD 26.90, Likely benign
- C2R (p.Cys2Arg), rs1206687241, ClinGen CA337803331, ClinVar RCV003009291, gnomAD rs1206687241, REVEL 0.04, CADD 11.70, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C2W (p.Cys2Trp), rs202161001, ClinGen CA337803303, ClinVar RCV001962229, ClinVar RCV004681274, REVEL 0.20, CADD 15.40, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- C2Y (p.Cys2Tyr), ExAC rs781743730, gnomAD rs781743730, REVEL 0.04, CADD 13.80
- V3L (p.Val3Leu), rs751046781, ClinGen CA512716, ClinVar RCV000907088, ExAC rs751046781, REVEL 0.10, CADD 14.20, Likely benign, Combined immunodeficiency due to OX40 deficiency
- V3M (p.Val3Met), rs751046781, ClinGen CA337803302, ClinVar RCV001308874, ExAC rs751046781, REVEL 0.08, CADD 19.50, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G4A (p.Gly4Ala), TOPMed rs1295347453, gnomAD rs1295347453, REVEL 0.05, CADD 15.10, Uncertain significance
- G4E (p.Gly4Glu), rs1295347453, ClinGen CA337803293, ClinVar RCV002046192, TOPMed rs1295347453, REVEL 0.03, CADD 11.60, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- A5D (p.Ala5Asp), rs979161075, ClinGen CA16734099, ClinVar RCV001212948, ClinVar RCV004877701, REVEL 0.24, CADD 9.28, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- A5S (p.Ala5Ser), Ensembl rs1649356524, REVEL 0.04, CADD 7.88
- A5T (p.Ala5Thr), Ensembl rs1649356524, REVEL 0.03, CADD 9.56
- A5V (p.Ala5Val), NCI-TCGA Cosmic COSV9976, TOPMed rs979161075, gnomAD rs979161075, Uncertain significance
- R6Q (p.Arg6Gln), TOPMed rs1020653313, gnomAD rs1020653313, REVEL 0.05, CADD 0.00, Conflicting interpretations, not specified; Combined immunodeficiency due to OX40 deficiency
- R6W (p.Arg6Trp), rs758084628, ClinGen CA512714, ClinVar RCV003052881, ClinVar RCV004070209, REVEL 0.07, CADD 16.40, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- R7G (p.Arg7Gly), 1000Genomes rs572497059, ExAC rs572497059, TOPMed rs572497059, gnomAD rs572497059, REVEL 0.11, CADD 12.40, Uncertain significance
- R7Q (p.Arg7Gln), rs555329852, ClinGen CA512710, ClinVar RCV001065495, 1000Genomes rs555329852, REVEL 0.14, CADD 2.04, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R7W (p.Arg7Trp), rs572497059, ClinGen CA512711, ClinVar RCV001992648, ClinVar RCV004043729, REVEL 0.12, CADD 16.90, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- L8M (p.Leu8Met), Ensembl rs2100956977, REVEL 0.10, CADD 10.40, Likely benign
- G9A (p.Gly9Ala), rs1162542365, ClinGen CA337803248, ClinVar RCV003743329, TOPMed rs1162542365, REVEL 0.04, CADD 0.08, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G9C (p.Gly9Cys), gnomAD rs1396484290, REVEL 0.16, CADD 4.47
- R10C (p.Arg10Cys), rs35304565, ClinGen CA512709, ClinVar RCV000559880, ClinVar RCV003915623, REVEL 0.12, CADD 15.10, Benign/Likely benign, not specified; Combined immunodeficiency due to OX40 deficiency; not provided
- R10H (p.Arg10His), rs774474644, NCI-TCGA Cosmic COSV9976, ExAC rs774474644, TOPMed rs774474644, REVEL 0.14, CADD 1.20, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R10L (p.Arg10Leu), rs774474644, ClinGen CA512707, ClinVar RCV001989804, ExAC rs774474644, REVEL 0.14, CADD 0.81, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R10P (p.Arg10Pro), ExAC rs774474644, TOPMed rs774474644, gnomAD rs774474644, REVEL 0.11, CADD 0.12, Uncertain significance
- G11R (p.Gly11Arg), rs376504072, ClinGen CA512703, ClinVar RCV000816564, ClinVar RCV004691312, REVEL 0.09, CADD 11.20, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency; not provided
- G11W (p.Gly11Trp), ESP rs376504072, ExAC rs376504072, TOPMed rs376504072, gnomAD rs376504072, REVEL 0.21, CADD 18.50, Uncertain significance
- P12L (p.Pro12Leu), rs771462465, ClinGen CA512700, ClinVar RCV001054037, 1000Genomes rs771462465, REVEL 0.25, CADD 16.60, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- P12R (p.Pro12Arg), rs771462465, ClinGen CA512701, ClinVar RCV001048845, ClinVar RCV004031529, REVEL 0.29, CADD 20.80, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- P12S (p.Pro12Ser), rs746209318, ClinGen CA512702, ClinVar RCV000810307, ExAC rs746209318, REVEL 0.16, CADD 21.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C13R (p.Cys13Arg), rs757810037, ClinGen CA512697, ClinVar RCV001223899, ExAC rs757810037, REVEL 0.14, CADD 4.67, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- A14E (p.Ala14Glu), 1000Genomes rs569590056, ExAC rs569590056, TOPMed rs569590056, gnomAD rs569590056, REVEL 0.15, CADD 3.99, Uncertain significance
- A14G (p.Ala14Gly), 1000Genomes rs569590056, ExAC rs569590056, TOPMed rs569590056, gnomAD rs569590056, REVEL 0.05, CADD 6.76, Uncertain significance
- A14T (p.Ala14Thr), rs2100956904, ClinGen CA337803155, ClinVar RCV001902760, Ensembl rs2100956904, REVEL 0.03, CADD 0.13, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- A14V (p.Ala14Val), rs569590056, ClinGen CA16734038, ClinVar RCV003745261, ClinVar RCV005515608, REVEL 0.04, CADD 1.59, Conflicting interpretations, Combined immunodeficiency due to OX40 deficiency; not specified
- A15G (p.Ala15Gly), ExAC rs754807989, TOPMed rs754807989, gnomAD rs754807989
- A15T (p.Ala15Thr), rs1269060561, NCI-TCGA Cosmic COSV5541, gnomAD rs1269060561, REVEL 0.26, CADD 22.70, Variant assessed as somatic; moderate impact.
- A15V (p.Ala15Val), ExAC rs754807989, TOPMed rs754807989, gnomAD rs754807989, REVEL 0.25, CADD 21.20
- L16V (p.Leu16Val), rs2521782178, ClinGen CA337803132, ClinVar RCV003583685, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- L18F (p.Leu18Phe), gnomAD rs1278868135, REVEL 0.13, CADD 16.10
- L19V (p.Leu19Val), rs931411183, ClinGen CA337803085, ClinVar RCV001968642, Ensembl rs931411183, MutPred 0.59, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G20R (p.Gly20Arg), ExAC rs753627787, gnomAD rs753627787, REVEL 0.30, CADD 21.30
- G20V (p.Gly20Val), Ensembl rs1293435510, REVEL 0.24, CADD 16.80
- T25N (p.Thr25Asn), TOPMed rs1649350178
- T25P (p.Thr25Pro), ExAC rs750259479, gnomAD rs750259479, REVEL 0.03, CADD 1.62
- V26A (p.Val26Ala), Ensembl rs2100956817
- V26M (p.Val26Met), rs1273445446, ClinGen CA337802938, ClinVar RCV001065548, TOPMed rs1273445446, REVEL 0.04, CADD 0.64, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T27K (p.Thr27Lys), ExAC rs775900244, TOPMed rs775900244, gnomAD rs775900244, REVEL 0.06, CADD 14.40, Uncertain significance
- T27M (p.Thr27Met), rs775900244, ClinGen CA512687, NCI-TCGA Cosmic COSV5541, ClinVar RCV000689630, REVEL 0.01, CADD 14.60, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- G28E (p.Gly28Glu), rs867902887, ClinGen CA337802915, ClinVar RCV003744456, TOPMed rs867902887, REVEL 0.05, CADD 0.00, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G28V (p.Gly28Val), TOPMed rs867902887, gnomAD rs867902887, Uncertain significance
- L29R (p.Leu29Arg), rs2521781835, ClinGen CA337802905, ClinVar RCV003583867, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- L29V (p.Leu29Val), TOPMed rs1649348975
- H30P (p.His30Pro), TOPMed rs1570468276, REVEL 0.06, CADD 0.01
- H30Y (p.His30Tyr), rs1649348844, ClinGen CA337802902, ClinVar RCV001940351, Ensembl rs1649348844, MutPred 0.42, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C31R (p.Cys31Arg), ESP rs145743320, ExAC rs145743320, TOPMed rs145743320, gnomAD rs145743320, REVEL 0.66, CADD 23.50
- G33R (p.Gly33Arg), ExAC rs771136814, TOPMed rs771136814, gnomAD rs771136814, REVEL 0.24, CADD 22.60
- T35I (p.Thr35Ile), rs915896849, ClinGen CA16733917, ClinVar RCV001996477, TOPMed rs915896849, REVEL 0.35, CADD 24.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T35P (p.Thr35Pro), Ensembl rs1570468252, REVEL 0.55, CADD 23.70
- T35S (p.Thr35Ser), TOPMed rs915896849, Uncertain significance
- Y36C (p.Tyr36Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P37A (p.Pro37Ala), ESP rs373434636, ExAC rs373434636, gnomAD rs373434636
- D40E (p.Asp40Glu), ExAC rs754613710, TOPMed rs754613710, gnomAD rs754613710, REVEL 0.23, CADD 3.35
- D40G (p.Asp40Gly), Ensembl rs1386674321, REVEL 0.20, CADD 0.79
- D40H (p.Asp40His), ESP rs368954253, ExAC rs368954253, TOPMed rs368954253, gnomAD rs368954253
- D40N (p.Asp40Asn), ESP rs368954253, ExAC rs368954253, TOPMed rs368954253, gnomAD rs368954253, REVEL 0.19, CADD 0.01, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R41Q (p.Arg41Gln), ExAC rs779828255, TOPMed rs779828255, gnomAD rs779828255, REVEL 0.32, CADD 5.42
- R41W (p.Arg41Trp), rs748879803, ClinGen CA512675, ClinVar RCV001364527, ExAC rs748879803, REVEL 0.25, CADD 22.90, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C42W (p.Cys42Trp), Ensembl rs1649346086
- C42Y (p.Cys42Tyr), rs2521781280, ClinGen CA337802612, ClinVar RCV003068633, REVEL 0.74, CADD 23.70, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C43S (p.Cys43Ser), rs2521781258, ClinGen CA337802592, ClinVar RCV003583898, REVEL 0.74, CADD 23.80, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- E45Q (p.Glu45Gln), gnomAD rs1365748174, REVEL 0.24, CADD 23.70
- N50S (p.Asn50Ser), ExAC rs768175804, gnomAD rs768175804, REVEL 0.10, CADD 7.67
- G51A (p.Gly51Ala), rs926489272, ClinGen CA16733604, ClinVar RCV000821371, ClinVar RCV005278676, REVEL 0.29, CADD 18.40, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- G51E (p.Gly51Glu), TOPMed rs926489272, gnomAD rs926489272, REVEL 0.33, CADD 19.20, Uncertain significance
- G51R (p.Gly51Arg), ExAC rs775248751, TOPMed rs775248751, gnomAD rs775248751, REVEL 0.23, CADD 14.30, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- M52T (p.Met52Thr), TOPMed rs1649327484
- M52V (p.Met52Val), rs2521779284, ClinGen CA337802353, ClinVar RCV003583714, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- V53A (p.Val53Ala), Ensembl rs1570467742, REVEL 0.18, CADD 14.00
- S54N (p.Ser54Asn), rs1649327062, ClinGen CA337802286, ClinVar RCV003745117, ClinVar RCV005291025, REVEL 0.35, CADD 14.90, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- R55C (p.Arg55Cys), rs769325973, ClinGen CA512639, ClinVar RCV001982154, ClinVar RCV004042078, REVEL 0.72, CADD 26.70, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- R55H (p.Arg55His), ExAC rs745731727, TOPMed rs745731727, gnomAD rs745731727, REVEL 0.53, CADD 25.20
- C56R (p.Cys56Arg), gnomAD rs1460774660, REVEL 0.83, CADD 25.40
- S57N (p.Ser57Asn), Ensembl rs865795160
- S57R (p.Ser57Arg), NCI-TCGA TCGA novel, gnomAD rs1373497203, REVEL 0.20, CADD 5.14, Variant assessed as somatic; moderate impact.
- R58C (p.Arg58Cys), rs780860323, ClinGen CA512637, NCI-TCGA Cosmic COSV9976, ClinVar RCV004267221, REVEL 0.36, CADD 8.12, Uncertain significance, not specified
- R58G (p.Arg58Gly), ExAC rs780860323, gnomAD rs780860323, REVEL 0.17, CADD 0.07, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- R58H (p.Arg58His), rs370340188, ClinGen CA337802241, ClinVar RCV003745741, ESP rs370340188, REVEL 0.21, CADD 0.04, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R58L (p.Arg58Leu), rs370340188, ClinGen CA512636, ClinVar RCV001239027, ESP rs370340188, REVEL 0.32, CADD 0.03, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- S59F (p.Ser59Phe), ExAC rs746967425, TOPMed rs746967425, gnomAD rs746967425, REVEL 0.35, CADD 6.49
- S59Y (p.Ser59Tyr), ExAC rs746967425, TOPMed rs746967425, gnomAD rs746967425, REVEL 0.35, CADD 4.72
- Q60H (p.Gln60His), gnomAD rs1419784742, REVEL 0.12, CADD 7.34
- Q60K (p.Gln60Lys), rs1187256575, ClinGen CA337802229, ClinVar RCV003743360, TOPMed rs1187256575, REVEL 0.18, CADD 0.51, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- Q60R (p.Gln60Arg), gnomAD rs1475763884, REVEL 0.16, CADD 0.23
- N61D (p.Asn61Asp), rs1649323945, ClinGen CA337802200, ClinVar RCV003583993, TOPMed rs1649323945, REVEL 0.19, CADD 12.80, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T62M (p.Thr62Met), rs368516876, ClinGen CA512633, ClinVar RCV001945004, ESP rs368516876, REVEL 0.37, CADD 23.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T62S (p.Thr62Ser), TOPMed rs1023569444, REVEL 0.23, CADD 12.50
- V63A (p.Val63Ala), TOPMed rs1649322551
- R65C (p.Arg65Cys), rs587777075, ClinGen CA149686, ClinVar RCV000082860, UniProt VAR 070942, REVEL 0.12, CADD 16.50, no classifications from unflagged records, Combined immunodeficiency due to OX40 deficiency
- R65H (p.Arg65His), rs767897638, ClinGen CA512629, ClinVar RCV001060936, ClinVar RCV004678938, REVEL 0.09, CADD 0.01, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- R65L (p.Arg65Leu), rs767897638, ClinGen CA512630, ClinVar RCV001975539, ExAC rs767897638, REVEL 0.06, CADD 0.01, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- P66L (p.Pro66Leu), rs370919067, ClinGen CA512628, ClinVar RCV000807184, ClinVar RCV004691305, REVEL 0.12, CADD 8.59, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not provided; not specified
- G68E (p.Gly68Glu), NCI-TCGA Cosmic COSV9902, Variant assessed as somatic; moderate impact.
- G68R (p.Gly68Arg), rs139254733, ESP rs139254733, ExAC rs139254733, TOPMed rs139254733, REVEL 0.31, CADD 0.46, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- P69L (p.Pro69Leu), rs199733493, ClinGen CA512624, ClinVar RCV001207182, ClinVar RCV004691387, REVEL 0.26, CADD 16.50, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not provided
- F71S (p.Phe71Ser), rs2521778866, ClinGen CA337802085, ClinVar RCV003871746, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- Y72H (p.Tyr72His), TOPMed rs1267039444, REVEL 0.73, CADD 24.80
- N73D (p.Asn73Asp), rs776299984, ClinGen CA512621, ClinVar RCV001913397, ExAC rs776299984, REVEL 0.38, CADD 24.00, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- N73K (p.Asn73Lys), ExAC rs746769533, TOPMed rs746769533, gnomAD rs746769533, REVEL 0.36, CADD 9.81, Likely benign
- N73S (p.Asn73Ser), ExAC rs770900616, gnomAD rs770900616, REVEL 0.18, CADD 14.80, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- D74N (p.Asp74Asn), rs1557508466, ClinGen CA337802054, ClinVar RCV002016618, TOPMed rs1557508466, REVEL 0.26, CADD 15.20, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- V75M (p.Val75Met), rs201012235, ClinGen CA512616, ClinVar RCV001212990, ClinVar RCV006327212, REVEL 0.23, CADD 17.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- V76I (p.Val76Ile), gnomAD rs1454373983, REVEL 0.16, CADD 2.43
- S77N (p.Ser77Asn), rs748063759, ClinGen CA512615, ClinVar RCV002617444, ExAC rs748063759, REVEL 0.17, CADD 5.83, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- S78F (p.Ser78Phe), ExAC rs750629113, TOPMed rs750629113, gnomAD rs750629113, REVEL 0.29, CADD 21.00
- S78T (p.Ser78Thr), ExAC rs756177147, TOPMed rs756177147, gnomAD rs756177147, REVEL 0.27, CADD 13.80
- P80L (p.Pro80Leu), rs757655414, ClinGen CA512611, ClinVar RCV001299889, ClinVar RCV004036155, REVEL 0.32, CADD 5.39, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- P80Q (p.Pro80Gln), rs757655414, NCI-TCGA Cosmic COSV5542, 1000Genomes rs757655414, ExAC rs757655414, REVEL 0.32, CADD 10.60, Uncertain significance
- P80T (p.Pro80Thr), gnomAD rs1467008668, REVEL 0.24, CADD 0.02
- P83S (p.Pro83Ser), Ensembl rs1570467435, REVEL 0.36, CADD 1.61
- C84Y (p.Cys84Tyr), gnomAD rs1352399688, REVEL 0.82, CADD 25.30
- T85A (p.Thr85Ala), rs367654407, ClinGen CA512608, ClinVar RCV001881418, ClinVar RCV004041386, REVEL 0.46, CADD 24.70, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- T85M (p.Thr85Met), rs758841991, ClinGen CA512607, ClinVar RCV003583804, ClinVar RCV004369383, REVEL 0.57, CADD 24.30, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- C87Y (p.Cys87Tyr), Ensembl rs1649313708, REVEL 0.77, CADD 25.00
- N88D (p.Asn88Asp), TOPMed rs1649313437, gnomAD rs1649313437, REVEL 0.26, CADD 21.90
- N88K (p.Asn88Lys), rs975694220, ClinGen CA16733399, ClinVar RCV001052159, TOPMed rs975694220, REVEL 0.28, CADD 22.20, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R90S (p.Arg90Ser), TOPMed rs1649255846, REVEL 0.22, CADD 21.80
- S91R (p.Ser91Arg), rs762686787, ClinGen CA512542, ClinVar RCV001993494, ClinVar RCV004044631, REVEL 0.20, CADD 20.60, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- G92A (p.Gly92Ala), rs1649255349, ClinGen CA337801729, ClinVar RCV002802122, MutPred 0.77, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G92E (p.Gly92Glu), Ensembl rs1649255349
- G92V (p.Gly92Val), NCI-TCGA Cosmic COSV5541, REVEL 0.84, CADD 23.90, Variant assessed as somatic; moderate impact.
- G92W (p.Gly92Trp), TOPMed rs1264090634, REVEL 0.78, CADD 25.00
- E94V (p.Glu94Val), gnomAD rs1326996565
- R95P (p.Arg95Pro), 1000Genomes rs552133296, ExAC rs552133296, TOPMed rs552133296, gnomAD rs552133296, REVEL 0.14, CADD 2.09
- R95Q (p.Arg95Gln), 1000Genomes rs552133296, ExAC rs552133296, TOPMed rs552133296, gnomAD rs552133296, REVEL 0.11, CADD 0.95, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R95W (p.Arg95Trp), ExAC rs752672557, gnomAD rs752672557, REVEL 0.31, CADD 16.20, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- L98P (p.Leu98Pro), rs150516264, ClinGen CA512539, ClinVar RCV000531541, 1000Genomes rs150516264, REVEL 0.18, CADD 1.17, Likely benign, Combined immunodeficiency due to OX40 deficiency
- T100M (p.Thr100Met), rs762131334, ClinGen CA512536, ClinVar RCV001902243, ClinVar RCV005278920, REVEL 0.53, CADD 23.30, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- Q103* (p.Gln103Ter), TOPMed rs952685421, gnomAD rs952685421, CADD 34.00
- Q103E (p.Gln103Glu), TOPMed rs952685421, gnomAD rs952685421, REVEL 0.17, CADD 4.44
- Q103K (p.Gln103Lys), TOPMed rs952685421, gnomAD rs952685421, REVEL 0.18, CADD 5.12
- Q103R (p.Gln103Arg), rs769195529, ClinGen CA512534, ClinVar RCV001893505, ExAC rs769195529, REVEL 0.14, CADD 3.34, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T105I (p.Thr105Ile), ExAC rs749636810, gnomAD rs749636810, REVEL 0.57, CADD 24.10
- V106F (p.Val106Phe), ExAC rs745432631, TOPMed rs745432631, REVEL 0.46, CADD 17.40, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C107* (p.Cys107Ter), TOPMed rs1649251279, CADD 36.00
- C107Y (p.Cys107Tyr), gnomAD rs1486595167, REVEL 0.73, CADD 23.60
- R108C (p.Arg108Cys), rs527845865, ClinGen CA512530, ClinVar RCV001873887, ClinVar RCV004038964, REVEL 0.05, CADD 14.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- R108H (p.Arg108His), rs1402392323, ClinGen CA337801491, ClinVar RCV001246435, TOPMed rs1402392323, REVEL 0.03, CADD 7.09, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R108L (p.Arg108Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- C109G (p.Cys109Gly), rs780756664, ClinGen CA512529, ClinVar RCV002968084, ClinVar RCV004065103, REVEL 0.39, CADD 24.10, Uncertain significance, not specified; Combined immunodeficiency due to OX40 deficiency
- R110P (p.Arg110Pro), rs371978650, ClinGen CA337801479, ClinVar RCV003744158, ExAC rs371978650, REVEL 0.17, CADD 22.30, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- R110Q (p.Arg110Gln), rs371978650, ClinGen CA512527, ClinVar RCV002004886, ClinVar RCV004877723, REVEL 0.04, CADD 14.40, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- R110W (p.Arg110Trp), rs756682107, ClinGen CA512528, ClinVar RCV003084428, ClinVar RCV004073137, REVEL 0.18, CADD 17.30, Uncertain significance, Combined immunodeficiency due to OX40 deficiency; not specified
- A111E (p.Ala111Glu), rs777266991, ClinGen CA337801464, ClinVar RCV001359682, ExAC rs777266991, MutPred 0.15, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- A111G (p.Ala111Gly), ExAC rs777266991, TOPMed rs777266991, gnomAD rs777266991, REVEL 0.03, CADD 21.60, Uncertain significance
- A111T (p.Ala111Thr), rs1423127792, NCI-TCGA Cosmic COSV9976, TOPMed rs1423127792, gnomAD rs1423127792, REVEL 0.05, CADD 18.60, Variant assessed as somatic; moderate impact.
- A111V (p.Ala111Val), rs777266991, ClinGen CA512526, ClinVar RCV001316210, ExAC rs777266991, REVEL 0.06, CADD 21.10, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- G112C (p.Gly112Cys), TOPMed rs1649249051
- G112D (p.Gly112Asp), TOPMed rs1209627925, gnomAD rs1209627925, REVEL 0.32, CADD 23.50
- T113I (p.Thr113Ile), ExAC rs764954719, TOPMed rs764954719, gnomAD rs764954719, REVEL 0.09, CADD 15.80, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- T113S (p.Thr113Ser), ExAC rs764954719, TOPMed rs764954719, gnomAD rs764954719, REVEL 0.03, CADD 14.20
- P115A (p.Pro115Ala), gnomAD rs1296437763, REVEL 0.15, CADD 19.40
- P115S (p.Pro115Ser), gnomAD rs1296437763, REVEL 0.14, CADD 21.10
- L116Q (p.Leu116Gln), ExAC rs753682470, TOPMed rs753682470, gnomAD rs753682470, REVEL 0.01, CADD 1.87
- D117E (p.Asp117Glu), ESP rs146733335, ExAC rs146733335, TOPMed rs146733335, gnomAD rs146733335, REVEL 0.02, CADD 0.00, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- D117N (p.Asp117Asn), gnomAD rs1174077781
- S118R (p.Ser118Arg), rs1376702819, ClinGen CA337801366, ClinVar RCV003583482, gnomAD rs1376702819, REVEL 0.06, CADD 23.40, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- Y119* (p.Tyr119Ter), gnomAD rs1193540239, CADD 36.00
- K120E (p.Lys120Glu), rs1056773421, ClinGen CA16732688, ClinVar RCV004137857, gnomAD rs1056773421, REVEL 0.07, CADD 19.20, Uncertain significance, not specified
- K120Q (p.Lys120Gln), gnomAD rs1056773421, REVEL 0.07, CADD 22.10, Uncertain significance
- K120T (p.Lys120Thr), Ensembl rs1649246320
- G122R (p.Gly122Arg), TOPMed rs1316722005
- G122V (p.Gly122Val), TOPMed rs1283414773, REVEL 0.24, CADD 24.30
- V123L (p.Val123Leu), TOPMed rs1649245303, REVEL 0.09, CADD 16.70
- D124E (p.Asp124Glu), Ensembl rs1649224253, REVEL 0.13, CADD 17.30
- D124G (p.Asp124Gly), rs1448767765, ClinGen CA337801181, ClinVar RCV001300620, gnomAD rs1448767765, REVEL 0.14, CADD 24.40, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- D124H (p.Asp124His), rs761778989, ClinGen CA512519, ClinVar RCV001903039, ExAC rs761778989, REVEL 0.08, CADD 33.00, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- D124Y (p.Asp124Tyr), rs761778989, ClinGen CA16732680, ClinVar RCV001977698, ExAC rs761778989, REVEL 0.19, CADD 33.00, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
- C125R (p.Cys125Arg), gnomAD rs1397660394, REVEL 0.79, CADD 24.90
- A126D (p.Ala126Asp), TOPMed rs1649223718, REVEL 0.07, CADD 6.67, Uncertain significance, Combined immunodeficiency due to OX40 deficiency
Public TNFRSF4 analysis runs
- TNFRSF4 analysis run — TNFRSF4 (713 variants) — completed 2026-08-21