TSLP (Thymic stromal lymphopoietin) variants and mutations
TSLP (also known as Thymic stromal lymphopoietin) is a human protein-coding gene encoding a thymic stromal lymphopoietin protein. When released from stressed barrier tissues, it activates dendritic cells and type 2 immune responses after allergen or tissue injury. Excess signaling is important in asthma and atopic dermatitis and is therapeutically targetable with TSLP-blocking antibodies. This analysis covers 399 TSLP variants and mutations. Of these, 81% have computational variant effect predictions. Disease context includes asthma, sinusitis, and chronic rhinosinusitis with nasal polyps. Example TSLP variants include F2I, F2L, and F2S.
Variant analysis overview
- Gene: TSLP
- Protein: Thymic stromal lymphopoietin
- UniProt accession: Q969D9
- Organism: Homo sapiens
- Variants analyzed: 399
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 229 unspecified-consequence records; 74 missense variants; 65 synonymous variants; 17 frameshift variants; 4 in-frame deletions; 4 splice-region variants; 5 stop-gained variants; 1 in-frame insertions
- Prediction scores: 322 variants have prediction scores (81% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: asthma, sinusitis, chronic rhinosinusitis with nasal polyps, nasal cavity polyp, allergic rhinitis, allergic disease, Wheezing, childhood onset asthma, upper respiratory tract disorder, Nasal polyposis, chronic rhinosinusitis, lower respiratory tract disorder.
Protein structure and variant hotspots
- Protein features: 2 post-translational modification sites.
- PTM context: 1 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 TSLP variants
Examples include F2I, F2L, F2S, F2F, P3R, F4C, F4L, A5G. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- F2I (p.Phe2Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F2L (p.Phe2Leu), ExAC rs750039970, gnomAD rs750039970, REVEL 0.03, CADD 2.50
- F2S (p.Phe2Ser), gnomAD rs1344868795, REVEL 0.03, CADD 14.40
- F2F (p.Phe2Phe), rs760433790, gnomAD 5-111071896-C-T, CADD 2.32
- P3R (p.Pro3Arg), NCI-TCGA Cosmic COSV6129, Variant assessed as somatic; moderate impact.
- F4C (p.Phe4Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F4L (p.Phe4Leu), gnomAD 5-111071902-T-A, REVEL 0.01, CADD 10.40
- A5G (p.Ala5Gly), TOPMed rs1175097184, gnomAD rs1175097184, REVEL 0.20, CADD 12.30
- A5T (p.Ala5Thr), ExAC rs766174320, TOPMed rs766174320, gnomAD rs766174320, REVEL 0.01, CADD 0.07
- A5Y (p.Ala5Tyr), rs776905212, gnomAD 5-111071901-TTGCC, CADD 21.20
- A5V (p.Ala5Val), gnomAD 5-111071904-C-T, REVEL 0.09, CADD 4.83
- L6* (p.Leu6Ter), gnomAD rs1752346154, CADD 33.00
- L6S (p.Leu6Ser), rs1752336991, gnomAD 5-111071494-T-C, CADD 6.21
- L6F (p.Leu6Phe), gnomAD 5-111071908-A-T, REVEL 0.09, CADD 18.90
- L7I (p.Leu7Ile), gnomAD rs1257910285, REVEL 0.10, CADD 16.40
- L7Q (p.Leu7Gln), TOPMed rs1752346246, gnomAD rs1752346246, REVEL 0.28, CADD 15.20, Uncertain significance, not specified
- L7V (p.Leu7Val), gnomAD 5-111071909-C-G, REVEL 0.12, CADD 19.10
- L7L (p.Leu7Leu), rs149732987, gnomAD 5-111071911-A-C, CADD 1.25
- Y8C (p.Tyr8Cys), 1000Genomes rs564641413, ExAC rs564641413, TOPMed rs564641413, gnomAD rs564641413, REVEL 0.04, CADD 10.80
- Y8N (p.Tyr8Asn), TOPMed rs1290698068
- Y8S (p.Tyr8Ser), gnomAD 5-111071913-A-C, REVEL 0.11, CADD 5.16
- V9I (p.Val9Ile), ESP rs145720113, ExAC rs145720113, gnomAD rs145720113, REVEL 0.07, CADD 11.30
- V9L (p.Val9Leu), ESP rs145720113, ExAC rs145720113, gnomAD rs145720113
- V9M (p.Val9Met), gnomAD 5-111071909-C-CTA, CADD 16.80
- L10M (p.Leu10Met), NCI-TCGA Cosmic COSV1007, Variant assessed as somatic; moderate impact.
- L10P (p.Leu10Pro), gnomAD rs1431494215, REVEL 0.30, CADD 22.90
- L10V (p.Leu10Val), gnomAD 5-111071916-TTC-T, CADD 20.90
- S11L (p.Ser11Leu), 1000Genomes rs200322626, ExAC rs200322626, TOPMed rs200322626, gnomAD rs200322626, REVEL 0.27, CADD 24.40
- S11K (p.Ser11Lys), gnomAD 5-111071502-AGC-A, CADD 2.79
- S11T (p.Ser11Thr), rs1307424791, gnomAD 5-111071503-G-C, CADD 3.73
- S11N (p.Ser11Asn), gnomAD 5-111071503-G-A, CADD 4.18
- S11R (p.Ser11Arg), rs1473796600, gnomAD 5-111071504-C-A, CADD 0.01
- S11S (p.Ser11Ser), rs1473796600, gnomAD 5-111071504-C-T, CADD 0.01
- V12D (p.Val12Asp), rs777564341, ClinGen CA3364870, ClinVar RCV004335757, ExAC rs777564341, REVEL 0.32, CADD 21.80, Uncertain significance, not specified
- V12I (p.Val12Ile), TOPMed rs1752347043
- V12L (p.Val12Leu), TOPMed rs1752347043
- S13A (p.Ser13Ala), gnomAD 5-111071927-T-G, REVEL 0.01, CADD 15.50
- F14L (p.Phe14Leu), ExAC rs769976695, gnomAD rs769976695, REVEL 0.13, CADD 18.90
- F14S (p.Phe14Ser), ExAC rs746052518, gnomAD rs746052518, REVEL 0.08, CADD 22.60
- F14G (p.Phe14Gly), rs760053269, gnomAD 5-111071924-GTTTC, CADD 24.70
- R15K (p.Arg15Lys), Ensembl rs1752347576
- R15W (p.Arg15Trp), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61292, Variant assessed as somatic; moderate impact.
- R15G (p.Arg15Gly), gnomAD 5-111071933-A-G, REVEL 0.38, CADD 23.90
- K16E (p.Lys16Glu), gnomAD rs1312955242, REVEL 0.03, CADD 19.20
- K16I (p.Lys16Ile), NCI-TCGA TCGA novel, REVEL 0.12, CADD 22.90, Variant assessed as somatic; moderate impact.
- K16R (p.Lys16Arg), gnomAD rs1275574034, REVEL 0.10, CADD 23.70
- K16M (p.Lys16Met), rs1452628128, gnomAD 5-111071488-A-T, CADD 2.73
- I17L (p.Ile17Leu), ExAC rs780307339, gnomAD rs780307339, REVEL 0.02, CADD 13.00
- I17V (p.Ile17Val), ExAC rs780307339, gnomAD rs780307339, REVEL 0.15, CADD 15.70
- I17T (p.Ile17Thr), gnomAD 5-111071940-T-C, REVEL 0.21, CADD 24.60
- I17N (p.Ile17Asn), gnomAD 5-111071940-T-A, REVEL 0.30, CADD 25.60
- F18del (p.Phe18del), gnomAD 5-111071939-ATCT-, CADD 17.30
- I19V (p.Ile19Val), TOPMed rs994023182, gnomAD rs994023182, REVEL 0.06, CADD 8.28
- I19T (p.Ile19Thr), gnomAD 5-111071946-T-C, REVEL 0.22, CADD 24.00
- I19M (p.Ile19Met), gnomAD 5-111071947-C-G, REVEL 0.14, CADD 21.90
- L20I (p.Leu20Ile), TOPMed rs759901388, gnomAD rs759901388, REVEL 0.27, CADD 23.20
- Q21K (p.Gln21Lys), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61291, REVEL 0.32, CADD 24.00, Variant assessed as somatic; moderate impact.
- Q21L (p.Gln21Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q21R (p.Gln21Arg), 1000Genomes rs144616951, ExAC rs144616951, TOPMed rs144616951, gnomAD rs144616951, REVEL 0.35, CADD 24.40
- Q21E (p.Gln21Glu), gnomAD 5-111071499-C-G, CADD 5.29
- L22F (p.Leu22Phe), ExAC rs768686022, TOPMed rs768686022, gnomAD rs768686022, REVEL 0.23, CADD 20.80
- L22P (p.Leu22Pro), ExAC rs774856310, TOPMed rs774856310, gnomAD rs774856310, REVEL 0.42, CADD 25.90, Uncertain significance, not specified
- L22V (p.Leu22Val), ExAC rs768686022, TOPMed rs768686022, gnomAD rs768686022, REVEL 0.05, CADD 8.59
- L22I (p.Leu22Ile), gnomAD 5-111071954-C-A, REVEL 0.11, CADD 19.10
- L22L (p.Leu22Leu), rs1461443658, gnomAD 5-111071956-T-G, CADD 7.13
- V23A (p.Val23Ala), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10078, TOPMed rs1752348603, Variant assessed as somatic; moderate impact.
- V23V (p.Val23Val), gnomAD 5-111071959-A-G, CADD 9.81
- G24R (p.Gly24Arg), rs1179899313, ClinGen CA360602522, ClinVar RCV004172194, TOPMed rs1179899313, REVEL 0.15, CADD 17.00, Uncertain significance, not specified
- G24V (p.Gly24Val), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10078, Variant assessed as somatic; moderate impact.
- G24K (p.Gly24Lys), gnomAD 5-111071495-AGGGC, CADD 4.61
- G24E (p.Gly24Glu), gnomAD 5-111071497-G-A, CADD 3.61
- G24A (p.Gly24Ala), rs1320964983, gnomAD 5-111071497-G-C, CADD 3.18
- G24G (p.Gly24Gly), gnomAD 5-111071498-G-A, CADD 2.77
- L25W (p.Leu25Trp), gnomAD 5-111071959-AG-A, CADD 23.80
- L25P (p.Leu25Pro), gnomAD 5-111071964-T-C, REVEL 0.38, CADD 26.00
- L25Q (p.Leu25Gln), gnomAD 5-111071964-T-A, REVEL 0.32, CADD 25.90
- L25L (p.Leu25Leu), rs1221209109, gnomAD 5-111071965-G-T, CADD 7.79
- V26L (p.Val26Leu), ExAC rs762242930, TOPMed rs762242930, gnomAD rs762242930, REVEL 0.15, CADD 25.30
- V26C (p.Val26Cys), rs1752348807, gnomAD 5-111071964-TG-T, CADD 24.50
- V26M (p.Val26Met), gnomAD 5-111071966-G-A, REVEL 0.19, CADD 25.80
- V26V (p.Val26Val), rs1240681324, gnomAD 5-111071968-G-A, CADD 9.00
- p.Leu27 Phe31del, rs1752349010, gnomAD 5-111071968-GTTAA, CADD 18.40
- T28I (p.Thr28Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y29* (p.Tyr29Ter), gnomAD rs1450834481, NCI-TCGA Cosmic COSV6129, cosmic curated COSV61291, CADD 28.80, Variant assessed as somatic; high impact.
- Y29H (p.Tyr29His), Ensembl rs1752349059
- Y29D (p.Tyr29Asp), gnomAD 5-111071975-T-G, REVEL 0.46, CADD 24.80
- Y29Y (p.Tyr29Tyr), rs772522358, gnomAD 5-111071977-C-T, CADD 8.42
- D30E (p.Asp30Glu), TOPMed rs1752349355
- D30G (p.Asp30Gly), Ensembl rs909988694, REVEL 0.20, CADD 23.50
- D30H (p.Asp30His), NCI-TCGA Cosmic COSV1007, cosmic curated COSV10078, NCI-TCGA Cosmic COSV6129, Variant assessed as somatic; moderate impact.
- D30N (p.Asp30Asn), rs765465942, NCI-TCGA Cosmic COSV1007, NCI-TCGA Cosmic COSV6129, cosmic curated COSV61291, REVEL 0.04, CADD 13.10, Variant assessed as somatic; moderate impact.
- D30Y (p.Asp30Tyr), ExAC rs765465942, TOPMed rs765465942, gnomAD rs765465942, REVEL 0.26, CADD 23.30
- D30D (p.Asp30Asp), gnomAD 5-111071980-C-T, CADD 10.00
- F31I (p.Phe31Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F31L (p.Phe31Leu), ExAC rs753025356, TOPMed rs753025356, gnomAD rs753025356, REVEL 0.41, CADD 27.40
- F31V (p.Phe31Val), ExAC rs753025356, TOPMed rs753025356, gnomAD rs753025356, REVEL 0.44, CADD 26.80, Uncertain significance, not specified
- F31F (p.Phe31Phe), rs148498768, gnomAD 5-111071983-C-T, CADD 9.38
- T32S (p.Thr32Ser), TOPMed rs1288648686, gnomAD rs1288648686, REVEL 0.02, CADD 8.88
- T32A (p.Thr32Ala), gnomAD 5-111071984-A-G, REVEL 0.05, CADD 20.80
- T32T (p.Thr32Thr), gnomAD 5-111071986-T-C, CADD 8.48
- N33V (p.Asn33Val), rs1752350324, gnomAD 5-111071983-CACTA, CADD 22.80
- N33N (p.Asn33Asn), rs1752350481, gnomAD 5-111071989-C-T, CADD 5.11
- C34* (p.Cys34Ter), Ensembl rs1752350646, CADD 29.50
- C34S (p.Cys34Ser), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61291, Variant assessed as somatic; moderate impact.
- C34Y (p.Cys34Tyr), TOPMed rs1359550993, gnomAD rs1359550993, REVEL 0.42, CADD 26.50
- C34R (p.Cys34Arg), gnomAD 5-111071490-T-C, CADD 0.02
- C34C (p.Cys34Cys), gnomAD 5-111071492-T-C, CADD 3.26
- D35G (p.Asp35Gly), ExAC rs759019000, gnomAD rs759019000
- D35N (p.Asp35Asn), rs753501114, ClinGen CA3364882, ClinVar RCV004309145, ExAC rs753501114, REVEL 0.04, CADD 14.40, Uncertain significance, not specified
- D35Y (p.Asp35Tyr), gnomAD 5-111071993-G-T, REVEL 0.21, CADD 22.60
- D35D (p.Asp35Asp), rs201436268, gnomAD 5-111071995-C-T, CADD 8.05
- F36L (p.Phe36Leu), rs1435982334, ClinGen CA360602603, ClinVar RCV004323388, gnomAD rs1435982334, REVEL 0.11, CADD 23.30, Uncertain significance, not specified
- F36* (p.Phe36Ter), gnomAD 5-111071995-CTT-C, CADD 24.40
- F36F (p.Phe36Phe), gnomAD 5-111071998-T-C, CADD 7.99
- E37* (p.Glu37Ter), TOPMed rs1330211729, gnomAD rs1330211729
- E37A (p.Glu37Ala), TOPMed rs1023195858, gnomAD rs1023195858, REVEL 0.02, CADD 0.00
- E37Q (p.Glu37Gln), TOPMed rs1330211729, gnomAD rs1330211729, REVEL 0.02, CADD 0.06
- E37R (p.Glu37Arg), rs1752337381, gnomAD 5-111071509-AG-A, CADD 5.56
- E37K (p.Glu37Lys), gnomAD 5-111071509-AGGAG, CADD 9.09
- E37E (p.Glu37Glu), rs1408210920, gnomAD 5-111071513-G-A, CADD 9.69
- E37G (p.Glu37Gly), gnomAD 5-111071515-A-G, CADD 12.70
- K38N (p.Lys38Asn), Ensembl rs1752351339
- I39L (p.Ile39Leu), ExAC rs758300677, gnomAD rs758300677, REVEL 0.27, CADD 15.80
- I39T (p.Ile39Thr), gnomAD 5-111072006-T-C, REVEL 0.27, CADD 23.00
- K40R (p.Lys40Arg), ExAC rs777729706, gnomAD rs777729706, REVEL 0.01, CADD 0.02
- K40E (p.Lys40Glu), gnomAD 5-111072008-A-G, REVEL 0.03, CADD 1.26
- A41S (p.Ala41Ser), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61291, Variant assessed as somatic; moderate impact.
- A41V (p.Ala41Val), TOPMed rs1323309760, gnomAD rs1323309760, REVEL 0.23, CADD 0.43
- A41T (p.Ala41Thr), gnomAD 5-111072011-G-A, REVEL 0.01, CADD 0.04
- A42T (p.Ala42Thr), cosmic curated COSV10943, Ensembl rs2112541744, REVEL 0.01, CADD 0.11
- A42V (p.Ala42Val), ExAC rs751334526, gnomAD rs751334526, REVEL 0.02, CADD 0.12
- A42A (p.Ala42Ala), rs142775283, gnomAD 5-111072016-C-T, CADD 0.15
- Y43Y (p.Tyr43Tyr), rs1329597723, gnomAD 5-111072019-T-C, CADD 1.40
- L44F (p.Leu44Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S45G (p.Ser45Gly), TOPMed rs1752351961, REVEL 0.05, CADD 0.00
- S45N (p.Ser45Asn), gnomAD rs1465847554, REVEL 0.13, CADD 0.77
- S45T (p.Ser45Thr), gnomAD rs1465847554, REVEL 0.20, CADD 2.98
- S45V (p.Ser45Val), gnomAD 5-111072022-CA-C, CADD 0.19
- S45R (p.Ser45Arg), gnomAD 5-111072025-T-A, REVEL 0.03, CADD 0.00
- T46I (p.Thr46Ile), ESP rs151075984, ExAC rs151075984, TOPMed rs151075984, gnomAD rs151075984, REVEL 0.04, CADD 0.40
- T46T (p.Thr46Thr), gnomAD 5-111072028-T-G, CADD 1.54
- I47L (p.Ile47Leu), gnomAD 5-111072029-A-C, REVEL 0.15, CADD 23.00
- S48F (p.Ser48Phe), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61292, Variant assessed as somatic; moderate impact.
- S48L (p.Ser48Leu), rs1752352319, gnomAD 5-111072029-AT-A, CADD 24.20
- S48S (p.Ser48Ser), rs1561690426, gnomAD 5-111072034-T-C, CADD 2.54
- K49E (p.Lys49Glu), ExAC rs749480146, TOPMed rs749480146, gnomAD rs749480146, REVEL 0.03, CADD 0.00
- D50E (p.Asp50Glu), gnomAD 5-111072040-C-G, REVEL 0.01, CADD 0.09
- D50D (p.Asp50Asp), rs755031052, gnomAD 5-111072040-C-T, CADD 1.01
- L51M (p.Leu51Met), NCI-TCGA Cosmic COSV6129, cosmic curated COSV61292, Variant assessed as somatic; moderate impact.
- L51P (p.Leu51Pro), NCI-TCGA TCGA novel, REVEL 0.35, CADD 23.60, Variant assessed as somatic; moderate impact.
- L51L (p.Leu51Leu), gnomAD 5-111072043-G-T, CADD 2.19
- I52T (p.Ile52Thr), Ensembl rs1156942975
- I52F (p.Ile52Phe), gnomAD 5-111072044-A-T, REVEL 0.03, CADD 0.01
- I52I (p.Ile52Ile), rs1752352861, gnomAD 5-111072046-T-A, CADD 0.29
- T53A (p.Thr53Ala), ExAC rs778884101, TOPMed rs778884101, gnomAD rs778884101, REVEL 0.02, CADD 0.01, Uncertain significance, not specified
- T53K (p.Thr53Lys), gnomAD 5-111072048-C-A, REVEL 0.03, CADD 0.00
- T53T (p.Thr53Thr), rs1043096650, gnomAD 5-111072049-A-T, CADD 0.10
- Y54* (p.Tyr54Ter), ExAC rs748296869, gnomAD rs748296869
- Y54C (p.Tyr54Cys), 1000Genomes rs2112541811, REVEL 0.10, CADD 17.40
- Y54N (p.Tyr54Asn), gnomAD 5-111072050-T-A, REVEL 0.08, CADD 22.50
- Y54Y (p.Tyr54Tyr), rs748296869, gnomAD 5-111072052-T-C, CADD 1.18
- M55I (p.Met55Ile), cosmic curated COSV10648, gnomAD rs781307526, REVEL 0.04, CADD 1.76
- M55T (p.Met55Thr), cosmic curated COSV61292, ExAC rs747370033, TOPMed rs747370033, gnomAD rs747370033, REVEL 0.02, CADD 8.26
- M55V (p.Met55Val), ExAC rs773909285, gnomAD rs773909285, REVEL 0.02, CADD 4.07
- S56G (p.Ser56Gly), gnomAD rs1343531295, REVEL 0.01, CADD 7.60
- S56R (p.Ser56Arg), ExAC rs771426130, gnomAD rs771426130, REVEL 0.04, CADD 0.13
- S56S (p.Ser56Ser), rs771426130, gnomAD 5-111072058-T-C, CADD 0.32
- G57R (p.Gly57Arg), gnomAD rs1345247368, REVEL 0.07, CADD 12.40
- G57A (p.Gly57Ala), gnomAD 5-111072060-G-C, REVEL 0.08, CADD 11.10
- G57G (p.Gly57Gly), rs1752353851, gnomAD 5-111072061-G-A, CADD 19.30
- T58I (p.Thr58Ile), ExAC rs763603107, TOPMed rs763603107, gnomAD rs763603107
- T58S (p.Thr58Ser), ExAC rs763603107, TOPMed rs763603107, gnomAD rs763603107, REVEL 0.03, CADD 11.90
- S60I (p.Ser60Ile), TOPMed rs889977306, gnomAD rs889977306, REVEL 0.07, CADD 21.20
- S60S (p.Ser60Ser), gnomAD 5-111072896-T-C, CADD 3.35
- T61A (p.Thr61Ala), rs199671638, ClinGen CA3364925, ClinVar RCV004211962, 1000Genomes rs199671638, REVEL 0.01, CADD 8.30, Uncertain significance, not specified
- T61N (p.Thr61Asn), ExAC rs761765403, gnomAD rs761765403, REVEL 0.09, CADD 16.10
- T61T (p.Thr61Thr), rs112048764, gnomAD 5-111072899-C-T, CADD 7.05
- E62K (p.Glu62Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E62* (p.Glu62Ter), gnomAD 5-111072900-G-T, CADD 32.00
- F63V (p.Phe63Val), gnomAD rs1397633322, REVEL 0.03, CADD 22.40
Public TSLP analysis runs
- TSLP analysis run — TSLP (399 variants) — completed 2026-08-21