NFKBIA (NF-kappa-B inhibitor alpha) variants and mutations
NFKBIA (also known as NF-kappa-B inhibitor alpha) is a human protein-coding gene encoding a NF-kappa-B inhibitor alpha protein. It sequesters NF-kappaB transcription factors in the cytoplasm until immune or stress signals trigger its degradation. Dominant gain-of-function variants that resist degradation can cause severe immunodeficiency with ectodermal abnormalities. This analysis covers 815 NFKBIA variants and mutations. Of these, 86% have computational variant effect predictions. Disease context includes ectodermal dysplasia and immunodeficiency 2, Hypohidrotic ectodermal dysplasia with immunodeficiency, and psoriasis. Example NFKBIA variants include M1I, M1T, and Q3*.
Variant analysis overview
- Gene: NFKBIA
- Protein: NF-kappa-B inhibitor alpha
- UniProt accession: P25963
- Organism: Homo sapiens
- Variants analyzed: 815
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 615 unspecified-consequence records; 111 synonymous variants; 64 missense variants; 13 frameshift variants; 3 splice-region variants; 4 in-frame deletions; 2 stop-gained variants; 1 in-frame insertions; 2 substitution
- Prediction scores: 701 variants have prediction scores (86% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: ectodermal dysplasia and immunodeficiency 2, Hypohidrotic ectodermal dysplasia with immunodeficiency, psoriasis, asthma, Crohn disease, diffuse large B-cell lymphoma, inflammatory bowel disease, psoriasis vulgaris, hypohidrotic ectodermal dysplasia, childhood onset asthma, lymphoma, severe combined immunodeficiency.
Protein structure and variant hotspots
- Protein features: 10 post-translational modification sites.
- PTM context: 28 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 NFKBIA variants
Examples include M1I, M1T, Q3*, A4V, A5D, A5G, A5T, A5V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1I (p.Met1Ile), rs2502189029, ClinGen CA389455530, ClinVar RCV003419111, Uncertain significance, NFKBIA-related disorder
- M1T (p.Met1Thr), rs2138834467, ClinGen CA389455534, ClinVar RCV003630278, MetaLR 0.60, MetaSVM 0.39, Likely benign, Ectodermal dysplasia and immunodeficiency 2
- Q3* (p.Gln3Ter), TOPMed rs2052771254
- A4V (p.Ala4Val), rs1394403932, ClinGen CA389455508, ClinVar RCV001880981, TOPMed rs1394403932, REVEL 0.12, MetaLR 0.19, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- A5D (p.Ala5Asp), Ensembl rs2052771143, REVEL 0.17, MetaLR 0.24, Uncertain significance
- A5G (p.Ala5Gly), Ensembl rs2052771143, MetaLR 0.23, MetaSVM -0.86, Uncertain significance
- A5T (p.Ala5Thr), Ensembl rs2138834449, REVEL 0.06, MetaLR 0.24
- A5V (p.Ala5Val), rs2052771143, ClinGen CA389455504, ClinVar RCV001757189, Ensembl rs2052771143, REVEL 0.06, MetaLR 0.26, Uncertain significance, not provided
- E6A (p.Glu6Ala), Ensembl rs2138834428
- E6G (p.Glu6Gly), Ensembl rs2138834428, REVEL 0.12, MetaLR 0.20
- E6K (p.Glu6Lys), rs923187160, ClinGen CA258863095, cosmic curated COSV53753, ClinVar RCV000507514, REVEL 0.19, MetaLR 0.22, Uncertain significance, not specified; Ectodermal dysplasia and immunodeficiency 2
- E6Q (p.Glu6Gln), TOPMed rs923187160, gnomAD rs923187160, REVEL 0.14, MetaLR 0.23, Uncertain significance
- E6V (p.Glu6Val), Ensembl rs2138834428, MetaLR 0.23, MetaSVM -0.81
- R7C (p.Arg7Cys), rs1292103605, ClinGen CA389455492, ClinVar RCV003093139, TOPMed rs1292103605, REVEL 0.21, MetaLR 0.32, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P8H (p.Pro8His), TOPMed rs1269522219, gnomAD rs1269522219, REVEL 0.17, MetaLR 0.23
- P8S (p.Pro8Ser), gnomAD rs1356888768, REVEL 0.11, MetaLR 0.26
- Q9* (p.Gln9Ter), rs886041411, ClinGen CA10603205, ClinVar RCV000325290, ClinVar RCV005090329, Pathogenic
- Q9L (p.Gln9Leu), TOPMed rs1383874564, gnomAD rs1383874564, REVEL 0.34, MetaLR 0.26
- Q9R (p.Gln9Arg), TOPMed rs1383874564, gnomAD rs1383874564, REVEL 0.24, MetaLR 0.27
- Q9X, rs886041411, Pathogenic
- E10* (p.Glu10Ter), rs2502188897, ClinGen CA389455473, ClinVar RCV003325300, CADD 36.00, Pathogenic
- W11* (p.Trp11Ter), rs1555342918, ClinGen CA389455462, ClinVar RCV000519045, ClinVar RCV006463279, CADD 38.00, Pathogenic
- W11C (p.Trp11Cys), Ensembl rs1555342918, REVEL 0.40, MetaLR 0.34, Pathogenic
- W11G (p.Trp11Gly), TOPMed rs1306827115, gnomAD rs1306827115, MetaLR 0.21, MetaSVM -0.75
- W11R (p.Trp11Arg), TOPMed rs1306827115, gnomAD rs1306827115, REVEL 0.52, MetaLR 0.21
- A12T (p.Ala12Thr), Ensembl rs2138834385, REVEL 0.36, MetaLR 0.24
- A12V (p.Ala12Val), NCI-TCGA TCGA novel, REVEL 0.42, MetaLR 0.16, Variant assessed as somatic; moderate impact.
- M13R (p.Met13Arg), NCI-TCGA Cosmic COSV9939, cosmic curated COSV99395, MetaLR 0.29, MetaSVM -0.79, Variant assessed as somatic; moderate impact.
- E14* (p.Glu14Ter), rs121913665, ClinGen CA123696, ClinVar RCV000015042, Ensembl rs121913665, CADD 38.00, Pathogenic
- E14G (p.Glu14Gly), Ensembl rs2138834380, REVEL 0.40, MetaLR 0.37
- G15D (p.Gly15Asp), rs768610997, ClinGen CA7155604, ClinVar RCV002592119, ExAC rs768610997, REVEL 0.57, MetaLR 0.56, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P16A (p.Pro16Ala), rs1439671395, ClinGen CA389455431, ClinVar RCV002299047, AlphaMissense 0.08, MetaLR 0.23, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P16S (p.Pro16Ser), TOPMed rs1439671395, gnomAD rs1439671395, REVEL 0.14, AlphaMissense 0.08
- P16T (p.Pro16Thr), TOPMed rs1439671395, gnomAD rs1439671395, REVEL 0.36, AlphaMissense 0.08
- R17C (p.Arg17Cys), Ensembl rs2138834358, REVEL 0.51, MetaLR 0.31
- R17H (p.Arg17His), rs1347828578, ClinGen CA389455423, ClinVar RCV002741492, gnomAD rs1347828578, REVEL 0.39, MetaLR 0.29, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- D18E (p.Asp18Glu), Ensembl rs2138834337
- D18G (p.Asp18Gly), Ensembl rs2138834345, MetaLR 0.53, MetaSVM -0.19
- D18N (p.Asp18Asn), rs746636446, ClinGen CA7155603, cosmic curated COSV10586, ClinVar RCV001044340, REVEL 0.39, MetaLR 0.66, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- D18Y (p.Asp18Tyr), ExAC rs746636446, TOPMed rs746636446, gnomAD rs746636446, REVEL 0.60, MetaLR 0.74, Uncertain significance
- G19R (p.Gly19Arg), rs2138834333, ClinGen CA389455411, ClinVar RCV001924124, Ensembl rs2138834333, REVEL 0.36, MetaLR 0.36, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- L20Q (p.Leu20Gln), Ensembl rs2138834323
- L20V (p.Leu20Val), Ensembl rs2138834325
- K21N (p.Lys21Asn), ExAC rs779802553, TOPMed rs779802553, gnomAD rs779802553, REVEL 0.45, MetaLR 0.72, Likely benign
- K21R (p.Lys21Arg), TOPMed rs1256239793, gnomAD rs1256239793, REVEL 0.29, MetaLR 0.55
- K22Q (p.Lys22Gln), Ensembl rs1594427952, REVEL 0.41, MetaLR 0.62
- K22T (p.Lys22Thr), Ensembl rs2052770327, MetaLR 0.62, MetaSVM 0.05
- E23Q (p.Glu23Gln), NCI-TCGA TCGA novel, MetaLR 0.24, MetaSVM -0.95, Variant assessed as somatic; high impact.
- R24Q (p.Arg24Gln), TOPMed rs1193471162, gnomAD rs1193471162, REVEL 0.32, MetaLR 0.40, Uncertain significance, Inborn genetic diseases
- R24W (p.Arg24Trp), cosmic curated COSV53752, Ensembl rs2138834290, REVEL 0.61, MetaLR 0.57
- L25P (p.Leu25Pro), rs758102701, ClinGen CA7155600, ClinVar RCV003629373, ExAC rs758102701, REVEL 0.48, MetaLR 0.39, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- L25Q (p.Leu25Gln), ExAC rs758102701, TOPMed rs758102701, gnomAD rs758102701, REVEL 0.18, MetaLR 0.33, Uncertain significance
- L26M (p.Leu26Met), ExAC rs200033269, TOPMed rs200033269, gnomAD rs200033269, REVEL 0.17, MetaLR 0.34
- L26Q (p.Leu26Gln), TOPMed rs1222307946, gnomAD rs1222307946, REVEL 0.34, MetaLR 0.18, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- L26R (p.Leu26Arg), rs1222307946, ClinGen CA389455366, ClinVar RCV001968821, TOPMed rs1222307946, REVEL 0.45, MetaLR 0.26, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- L26V (p.Leu26Val), ExAC rs200033269, TOPMed rs200033269, gnomAD rs200033269, REVEL 0.17, MetaLR 0.22, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- D27E (p.Asp27Glu), 1000Genomes rs1957106, ESP rs1957106, ExAC rs1957106, TOPMed rs1957106, Benign
- D27H (p.Asp27His), NCI-TCGA Cosmic COSV9939, cosmic curated COSV99394, Variant assessed as somatic; moderate impact.
- D28A (p.Asp28Ala), Ensembl rs2138834246
- D28G (p.Asp28Gly), Ensembl rs2138834246
- D28V (p.Asp28Val), Ensembl rs2138834246, MetaLR 0.62, MetaSVM 0.32
- D28Y (p.Asp28Tyr), TOPMed rs2052769760, REVEL 0.53, MetaLR 0.65
- R29H (p.Arg29His), rs754412949, ClinGen CA389455345, ClinVar RCV001090524, ClinVar RCV003629146, REVEL 0.74, MetaLR 0.83, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2; not provided
- R29L (p.Arg29Leu), ExAC rs754412949, REVEL 0.78, MetaLR 0.83, Uncertain significance
- D31N (p.Asp31Asn), rs2052769679, ClinGen CA389455335, NCI-TCGA Cosmic COSV5375, cosmic curated COSV53754, AlphaMissense 0.91, MetaLR 0.83, Uncertain significance, Sterile multifocal osteomyelitis with periostitis and pustulosis
- S32G (p.Ser32Gly), rs1566591086, ClinGen CA389455326, ClinVar RCV000721150, Ensembl rs1566591086, REVEL 0.66, MetaLR 0.79, Pathogenic, Ectodermal dysplasia and immunodeficiency 2
- S32I (p.Ser32Ile), rs28933100, ClinGen CA123691, ClinVar RCV000015040, UniProt VAR 034871, AlphaMissense 0.95, MetaLR 0.80, Pathogenic, Ectodermal dysplasia and immunodeficiency 2
- S32N (p.Ser32Asn), rs28933100, ClinGen CA389455323, cosmic curated COSV53752, ClinVar RCV000721152, AlphaMissense 0.95, MetaLR 0.80, Pathogenic, not provided; Ectodermal dysplasia and immunodeficiency 2
- S32R (p.Ser32Arg), rs1566591082, ClinGen CA389455321, ClinVar RCV000721151, Ensembl rs1566591082, AlphaMissense 0.99, MetaLR 0.79, Pathogenic, Ectodermal dysplasia and immunodeficiency 2
- G33A (p.Gly33Ala), Ensembl rs2138834215, MetaLR 0.88, MetaSVM 0.92
- G33D (p.Gly33Asp), Ensembl rs2138834215, REVEL 0.71, MetaLR 0.87
- G33S (p.Gly33Ser), Ensembl rs2138834222, REVEL 0.72, MetaLR 0.88
- L34P (p.Leu34Pro), rs2502188602, ClinGen CA389455312, ClinVar RCV003330336, REVEL 0.81, MetaLR 0.79, Pathogenic
- D35Y (p.Asp35Tyr), Ensembl rs2138834209, REVEL 0.80, MetaLR 0.83
- S36F (p.Ser36Phe), Ensembl rs1566591076, REVEL 0.75, AlphaMissense 0.93, Pathogenic
- S36Y (p.Ser36Tyr), rs1566591076, ClinGen CA389455297, ClinVar RCV000721149, Ensembl rs1566591076, AlphaMissense 0.93, MetaLR 0.80, Pathogenic, Ectodermal dysplasia and immunodeficiency 2
- M37I (p.Met37Ile), rs764415243, ClinGen CA7155595, ClinVar RCV001203467, ExAC rs764415243, REVEL 0.38, MetaLR 0.53, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- M37K (p.Met37Lys), rs1566591073, ClinGen CA389455292, cosmic curated COSV53755, ClinVar RCV000721148, AlphaMissense 0.84, MetaLR 0.65, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- M37R (p.Met37Arg), rs1566591073, ClinGen CA389455290, ClinVar RCV000721147, Ensembl rs1566591073, AlphaMissense 0.84, MetaLR 0.65, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- K38Q (p.Lys38Gln), ESP rs373643552, ExAC rs373643552, gnomAD rs373643552, MetaLR 0.76, MetaSVM 0.43
- D39E (p.Asp39Glu), rs753085459, ClinGen CA7155593, ClinVar RCV001238140, ClinVar RCV005443280, REVEL 0.38, MetaLR 0.34, Uncertain significance, Inborn genetic diseases; Ectodermal dysplasia and immunodeficiency 2
- D39H (p.Asp39His), Ensembl rs2138834191
- E40* (p.Glu40Ter), NCI-TCGA TCGA novel, Ensembl rs2138834181, Variant assessed as somatic; high impact.
- E40G (p.Glu40Gly), TOPMed rs2052768256, REVEL 0.25, MetaLR 0.65
- E40K (p.Glu40Lys), rs2138834181, ClinGen CA389455273, ClinVar RCV002299978, REVEL 0.27, MetaLR 0.66, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- E41A (p.Glu41Ala), TOPMed rs1406848304, REVEL 0.23, MetaLR 0.41, Uncertain significance, Inborn genetic diseases
- E41D (p.Glu41Asp), cosmic curated COSV10605, Ensembl rs1566591059, REVEL 0.03, MetaLR 0.24
- Y42C (p.Tyr42Cys), NCI-TCGA Cosmic COSV5375, cosmic curated COSV53751, MetaLR 0.72, MetaSVM 0.46, Variant assessed as somatic; moderate impact.
- E43D (p.Glu43Asp), Ensembl rs2052768071, REVEL 0.07, MetaLR 0.30, Likely benign
- E43Q (p.Glu43Gln), cosmic curated COSV53752, TOPMed rs999467784, gnomAD rs999467784, REVEL 0.09, MetaLR 0.26
- Q44* (p.Gln44Ter), NCI-TCGA Cosmic COSV5375, cosmic curated COSV53751, CADD 39.00, Variant assessed as somatic; high impact.
- Q44H (p.Gln44His), Ensembl rs2052768011, REVEL 0.11, MetaLR 0.27
- Q44R (p.Gln44Arg), rs2052768045, ClinGen CA389455239, ClinVar RCV001111175, Ensembl rs2052768045, REVEL 0.05, MetaLR 0.21, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- V46A (p.Val46Ala), Ensembl rs2138834150
- V46D (p.Val46Asp), Ensembl rs2138834150
- V46I (p.Val46Ile), gnomAD rs1334636790
- K47R (p.Lys47Arg), rs1594427886, ClinGen CA389455208, ClinVar RCV000915244, Ensembl rs1594427886, REVEL 0.05, MetaLR 0.07, Benign, Ectodermal dysplasia and immunodeficiency 2
- K47E (p.Lys47Glu), rs774277544, []
- E48V (p.Glu48Val), Ensembl rs2138834141, MetaLR 0.25, MetaSVM -0.62
- Q50* (p.Gln50Ter), NCI-TCGA Cosmic COSV9939, cosmic curated COSV99395, Ensembl rs1566591053, CADD 35.00, Variant assessed as somatic; high impact.
- Q50E (p.Gln50Glu), Ensembl rs1566591053
- Q50R (p.Gln50Arg), Ensembl rs2052767815, REVEL 0.03, MetaLR 0.04
- E51G (p.Glu51Gly), Ensembl rs1043931157, REVEL 0.03, MetaLR 0.07
- E51K (p.Glu51Lys), rs774277544, ClinGen CA7155590, cosmic curated COSV10876, ClinVar RCV002913818, REVEL 0.06, MetaLR 0.07, Benign, Ectodermal dysplasia and immunodeficiency 2
- I52F (p.Ile52Phe), NCI-TCGA Cosmic COSV9939, cosmic curated COSV99395, Variant assessed as somatic; moderate impact.
- I52T (p.Ile52Thr), Ensembl rs2138834113, REVEL 0.14, MetaLR 0.12, Uncertain significance, not provided
- I52V (p.Ile52Val), gnomAD rs1432162067, REVEL 0.10, MetaLR 0.08
- R53C (p.Arg53Cys), Ensembl rs2138834102, REVEL 0.45, MetaLR 0.28, Uncertain significance
- R53G (p.Arg53Gly), Ensembl rs2138834102, Uncertain significance, Inborn genetic diseases
- R53H (p.Arg53His), rs761810172, ClinGen CA7155588, ClinVar RCV003628663, ExAC rs761810172, REVEL 0.22, MetaLR 0.30, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- R53L (p.Arg53Leu), ExAC rs761810172, gnomAD rs761810172, REVEL 0.31, MetaLR 0.31, Uncertain significance
- R53P (p.Arg53Pro), ExAC rs761810172, gnomAD rs761810172, MetaLR 0.31, MetaSVM -0.33, Uncertain significance
- L54F (p.Leu54Phe), TOPMed rs1211128367, gnomAD rs1211128367, REVEL 0.03, MetaLR 0.13
- L54P (p.Leu54Pro), Ensembl rs2138834090, REVEL 0.18, MetaLR 0.15
- L54R (p.Leu54Arg), NCI-TCGA TCGA novel, Ensembl rs2138834090, Variant assessed as somatic; high impact.
- E55D (p.Glu55Asp), rs2052767503, ClinGen CA389455087, ClinVar RCV003874383, TOPMed rs2052767503, REVEL 0.07, MetaLR 0.07, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P56S (p.Pro56Ser), TOPMed rs2052767477, REVEL 0.10, MetaLR 0.11
- Q57* (p.Gln57Ter), cosmic curated COSV10508, ExAC rs768735436, gnomAD rs768735436
- Q57H (p.Gln57His), Ensembl rs1300321511, REVEL 0.06, MetaLR 0.09
- V59A (p.Val59Ala), cosmic curated COSV53752, gnomAD rs2052767420, REVEL 0.01, MetaLR 0.03
- V59E (p.Val59Glu), gnomAD rs2052767420
- V59G (p.Val59Gly), gnomAD rs2052767420, MetaLR 0.06, MetaSVM -1.09
- P60L (p.Pro60Leu), rs371482940, ClinGen CA7155585, ClinVar RCV001043181, ClinVar RCV006455362, REVEL 0.04, MetaLR 0.07, Conflicting interpretations, not specified; Ectodermal dysplasia and immunodeficiency 2
- P60S (p.Pro60Ser), Ensembl rs2138834059, REVEL 0.03, MetaLR 0.08
- R61G (p.Arg61Gly), Ensembl rs2138834052
- G62D (p.Gly62Asp), rs1698098775, ClinGen CA389454997, ClinVar RCV003629306, TOPMed rs1698098775, REVEL 0.03, MetaLR 0.06, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- G62R (p.Gly62Arg), ExAC rs771568277, TOPMed rs771568277, gnomAD rs771568277, Uncertain significance
- G62S (p.Gly62Ser), rs771568277, ClinGen CA7155583, ClinVar RCV003825987, ExAC rs771568277, REVEL 0.02, MetaLR 0.05, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- G62V (p.Gly62Val), TOPMed rs1698098775, MetaLR 0.07, MetaSVM -1.08, Uncertain significance
- S63A (p.Ser63Ala), Ensembl rs2138834035
- S63L (p.Ser63Leu), rs376762724, ClinGen CA7155580, ClinVar RCV001223634, ClinVar RCV004960580, REVEL 0.11, MetaLR 0.06, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2; Inborn genetic diseases
- S63P (p.Ser63Pro), Ensembl rs2138834035, REVEL 0.05, MetaLR 0.03
- S63T (p.Ser63Thr), Ensembl rs2138834035
- S63W (p.Ser63Trp), 1000Genomes rs376762724, ESP rs376762724, ExAC rs376762724, TOPMed rs376762724, REVEL 0.09, MetaLR 0.08, Uncertain significance
- P65A (p.Pro65Ala), rs778206898, ClinGen CA7155578, ClinVar RCV001892947, ExAC rs778206898, REVEL 0.09, MetaLR 0.10, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P65L (p.Pro65Leu), rs756648390, ClinGen CA7155577, ClinVar RCV001351585, ExAC rs756648390, REVEL 0.13, MetaLR 0.13, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- P65R (p.Pro65Arg), ExAC rs756648390, TOPMed rs756648390, gnomAD rs756648390, MetaLR 0.20, MetaSVM -0.54, Uncertain significance
- P65S (p.Pro65Ser), cosmic curated COSV53751, ExAC rs778206898, TOPMed rs778206898, gnomAD rs778206898, REVEL 0.08, MetaLR 0.14, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- W66C (p.Trp66Cys), NCI-TCGA Cosmic COSV5375, NCI-TCGA Cosmic COSV9939, cosmic curated COSV99395, REVEL 0.37, MetaLR 0.29, Variant assessed as somatic; moderate impact.
- W66R (p.Trp66Arg), gnomAD rs1219414058, REVEL 0.24, MetaLR 0.23
- W66S (p.Trp66Ser), TOPMed rs2052766860, REVEL 0.31, MetaLR 0.19, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- Q68* (p.Gln68Ter), NCI-TCGA Cosmic COSV5375, cosmic curated COSV53751, Variant assessed as somatic; high impact.
- Q68P (p.Gln68Pro), TOPMed rs2052766835
- Q69* (p.Gln69Ter), cosmic curated COSV53752, 1000Genomes rs2138834009, CADD 40.00
- Q69H (p.Gln69His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q69L (p.Gln69Leu), ExAC rs781662093, gnomAD rs781662093, MetaLR 0.13, MetaSVM -0.98
- L70F (p.Leu70Phe), ExAC rs755146648, TOPMed rs755146648, gnomAD rs755146648, REVEL 0.07, MetaLR 0.31, Uncertain significance
- L70P (p.Leu70Pro), rs2052766731, ClinGen CA389454895, ClinVar RCV001047488, Ensembl rs2052766731, REVEL 0.31, MetaLR 0.35, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- L70V (p.Leu70Val), rs755146648, ClinGen CA7155574, ClinVar RCV003514163, ExAC rs755146648, REVEL 0.15, MetaLR 0.09, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- T71I (p.Thr71Ile), TOPMed rs1178195524, gnomAD rs1178195524, MetaLR 0.44, MetaSVM -0.06
- T71S (p.Thr71Ser), TOPMed rs1178195524, gnomAD rs1178195524, REVEL 0.08, MetaLR 0.32
- E72Q (p.Glu72Gln), NCI-TCGA Cosmic COSV9939, cosmic curated COSV99394, MetaLR 0.48, MetaSVM -0.27, Variant assessed as somatic; moderate impact.
- D73E (p.Asp73Glu), cosmic curated COSV10457, ESP rs371348054, ExAC rs371348054, gnomAD rs371348054, REVEL 0.23, MetaLR 0.50, Likely benign
- D73G (p.Asp73Gly), Ensembl rs2138833985
- D73V (p.Asp73Val), NCI-TCGA TCGA novel, MetaLR 0.66, MetaSVM 0.45, Variant assessed as somatic; moderate impact.
- G74A (p.Gly74Ala), rs763076696, ClinGen CA7155571, ClinVar RCV001111174, ClinVar RCV003918691, REVEL 0.63, MetaLR 0.78, Benign/Likely benign, Ectodermal dysplasia and immunodeficiency 2
- G74R (p.Gly74Arg), rs766345843, ClinGen CA7155572, ClinVar RCV001297368, ExAC rs766345843, REVEL 0.59, MetaLR 0.76, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- D75N (p.Asp75Asn), Ensembl rs2138833962, MetaLR 0.68, MetaSVM 0.34
- F77L (p.Phe77Leu), gnomAD rs1436082564, REVEL 0.14, MetaLR 0.21
- L80* (p.Leu80Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A81T (p.Ala81Thr), Ensembl rs2138832910, REVEL 0.67, MetaLR 0.81
- I82S (p.Ile82Ser), gnomAD rs1351502650, REVEL 0.82, MetaLR 0.78
- I82V (p.Ile82Val), TOPMed rs1459510148, gnomAD rs1459510148, REVEL 0.06, MetaLR 0.37
- I83V (p.Ile83Val), rs1165420329, ClinGen CA389454572, ClinVar RCV001299660, gnomAD rs1165420329, REVEL 0.52, MetaLR 0.78, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- H84Q (p.His84Gln), rs2502185825, ClinGen CA389454540, ClinVar RCV003629538, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- H84Y (p.His84Tyr), Ensembl rs2138832891
- E85* (p.Glu85Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E85K (p.Glu85Lys), TOPMed rs1448839061, gnomAD rs1448839061, REVEL 0.66, MetaLR 0.82
- E85Q (p.Glu85Gln), TOPMed rs1448839061, gnomAD rs1448839061, REVEL 0.48, MetaLR 0.76
- E85V (p.Glu85Val), NCI-TCGA TCGA novel, MetaLR 0.76, MetaSVM 0.57, Variant assessed as somatic; moderate impact.
- E86K (p.Glu86Lys), rs1388058525, ClinGen CA389454522, ClinVar RCV002023839, gnomAD rs1388058525, REVEL 0.32, MetaLR 0.55, Uncertain significance, Ectodermal dysplasia and immunodeficiency 2
- K87N (p.Lys87Asn), NCI-TCGA Cosmic COSV5375, cosmic curated COSV53754, REVEL 0.23, MetaLR 0.53, Variant assessed as somatic; moderate impact.
- A88T (p.Ala88Thr), 1000Genomes rs556918000, ExAC rs556918000, gnomAD rs556918000, REVEL 0.04, MetaLR 0.17
- A88V (p.Ala88Val), Ensembl rs2138832870, REVEL 0.08, MetaLR 0.32
- T90I (p.Thr90Ile), NCI-TCGA TCGA novel, MetaLR 0.20, MetaSVM -0.81, Variant assessed as somatic; moderate impact.
- T90N (p.Thr90Asn), TOPMed rs954063319, gnomAD rs954063319, REVEL 0.14, MetaLR 0.28
- T90S (p.Thr90Ser), TOPMed rs954063319, gnomAD rs954063319, REVEL 0.08, MetaLR 0.18, Uncertain significance, Inborn genetic diseases
- M91I (p.Met91Ile), cosmic curated COSV10457, TOPMed rs1249067323, gnomAD rs1249067323, Uncertain significance, not provided
- M91L (p.Met91Leu), ExAC rs758681852, gnomAD rs758681852
- M91R (p.Met91Arg), Ensembl rs1193290457
Public NFKBIA analysis runs
- NFKBIA analysis run — NFKBIA (815 variants) — completed 2026-08-19