NFKB1 (P19838) variants and mutations
NFKB1 (also known as P19838) is a human protein-coding gene encoding a nuclear factor NF-kappa-B p105 subunit protein. It produces p105 and the p50 NF-kappaB subunit, which regulate transcriptional responses to immune receptors, cytokines, and cellular stress. Haploinsufficiency can cause common-variable-immunodeficiency-like disease with recurrent infection, autoimmunity, and variable lymphoproliferation. This analysis covers 610 NFKB1 variants and mutations. Of these, 44% have computational variant effect predictions. Disease context includes common variable immunodeficiency, primary biliary cholangitis, and immunodeficiency disease. Example NFKB1 variants include M1V, E3K, and D4N.
Variant analysis overview
- Gene: NFKB1
- Protein: P19838
- UniProt accession: P19838
- Organism: Homo sapiens
- Variants analyzed: 610
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 427 unspecified-consequence records; 51 synonymous variants; 124 missense variants; 4 splice-region variants; 1 stop-gained variants; 3 frameshift variants
- Prediction scores: 271 variants have prediction scores (44% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: common variable immunodeficiency, primary biliary cholangitis, immunodeficiency disease, allergic rhinitis, Graves disease, systemic sclerosis, Eczematoid dermatitis, ulcerative colitis, hypothyroidism, upper respiratory tract disorder, tonsillitis, Abnormality of the skeletal system.
Protein structure and variant hotspots
- Protein features: 2 domains; 16 post-translational modification sites.
- Structural context: 301 variants have structural context.
- PTM context: 16 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 NFKB1 variants
Examples include M1V, E3K, D4N, D4E, D5Y, D5N, P6S, P6P. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1V (p.Met1Val), rs1223203083, ClinGen CA357957196, ClinVar RCV003322102, AlphaMissense 0.27, MetaLR 0.21, Uncertain significance, not provided
- E3K (p.Glu3Lys), rs1740854006, gnomAD 4-102525525-G-A, REVEL 0.11, CADD 24.60
- D4N (p.Asp4Asn), rs1740854197, gnomAD 4-102525528-G-A, REVEL 0.08, CADD 27.70
- D4E (p.Asp4Glu), rs754417859, gnomAD 4-102525530-T-G, REVEL 0.03, CADD 2.75
- D5Y (p.Asp5Tyr), cosmic curated COSV99897
- D5N (p.Asp5Asn), gnomAD 4-102525531-G-A, REVEL 0.08, CADD 25.10
- P6S (p.Pro6Ser), cosmic curated COSV56958, REVEL 0.01, CADD 12.30, Uncertain significance, Inborn genetic diseases
- P6P (p.Pro6Pro), gnomAD 4-102525536-A-G, CADD 4.57
- Y7H (p.Tyr7His), rs764715465, gnomAD 4-102525537-T-C, REVEL 0.16, CADD 26.00
- L8L (p.Leu8Leu), rs752031846, gnomAD 4-102525540-T-C, CADD 9.89
- L8M (p.Leu8Met), rs752031846, gnomAD 4-102525540-T-A, REVEL 0.06, CADD 18.60
- G9R (p.Gly9Arg), gnomAD 4-102525543-G-A, REVEL 0.11, CADD 17.20
- R10G (p.Arg10Gly), gnomAD 4-102510939-A-G, CADD 13.30
- R10K (p.Arg10Lys), rs1316353446, gnomAD 4-102510940-G-A, CADD 12.20
- R10R (p.Arg10Arg), rs1739737248, gnomAD 4-102510941-A-G, CADD 10.70
- R10S (p.Arg10Ser), rs1740855341, gnomAD 4-102525548-G-T, REVEL 0.09, CADD 4.71
- P11T (p.Pro11Thr), gnomAD 4-102525549-C-A, REVEL 0.11, CADD 8.47
- P11L (p.Pro11Leu), gnomAD 4-102525550-C-T, REVEL 0.12, CADD 12.70
- Q13E (p.Gln13Glu), rs1490669735, gnomAD 4-102525555-C-G, REVEL 0.06, CADD 18.40
- Q13R (p.Gln13Arg), rs1200938039, gnomAD 4-102525556-A-G, REVEL 0.05, CADD 24.00
- Q13H (p.Gln13His), gnomAD 4-102525557-A-C, REVEL 0.09, CADD 26.00
- Q13Q (p.Gln13Gln), rs746175553, gnomAD 4-102525557-A-G, CADD 15.20
- M14L (p.Met14Leu), rs2476157037, ClinGen CA357957300, ClinVar RCV002719040, Uncertain significance, Inborn genetic diseases
- M14I (p.Met14Ile), gnomAD 4-102529838-G-T, REVEL 0.04, CADD 16.80
- F15I (p.Phe15Ile), cosmic curated COSV10808, REVEL 0.10, CADD 23.20
- F15L (p.Phe15Leu), gnomAD 4-102525513-T-C, CADD 13.60
- F15S (p.Phe15Ser), gnomAD 4-102529840-T-C, REVEL 0.14, CADD 23.30
- H16N (p.His16Asn), rs1385709386, gnomAD 4-102529842-C-A, REVEL 0.07, CADD 16.20
- H16L (p.His16Leu), rs966015688, gnomAD 4-102529843-A-T, REVEL 0.09, CADD 10.40
- H16R (p.His16Arg), rs966015688, gnomAD 4-102529843-A-G, REVEL 0.04, CADD 7.64
- L17V (p.Leu17Val), rs2476157135, ClinGen CA357957325, ClinVar RCV002299969, Uncertain significance, not provided
- L17L (p.Leu17Leu), rs1161539912, gnomAD 4-102529847-G-A, CADD 10.40
- D18G (p.Asp18Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D18A (p.Asp18Ala), rs1364913100, gnomAD 4-102529849-A-C, REVEL 0.11, CADD 23.00
- D18E (p.Asp18Glu), gnomAD 4-102529850-T-A, REVEL 0.03, CADD 3.26
- P19T (p.Pro19Thr), gnomAD 4-102529851-C-A, REVEL 0.06, CADD 4.19
- P19H (p.Pro19His), gnomAD 4-102529852-C-A, REVEL 0.04, CADD 11.80
- P19L (p.Pro19Leu), rs750825184, gnomAD 4-102529852-C-T, REVEL 0.04, CADD 7.85
- P19P (p.Pro19Pro), gnomAD 4-102529853-T-G, CADD 6.23
- S20N (p.Ser20Asn), rs1214642839, gnomAD 4-102510949-G-A, CADD 21.50
- S20C (p.Ser20Cys), rs370685242, gnomAD 4-102529855-C-G, REVEL 0.03, CADD 15.00
- L21F (p.Leu21Phe), gnomAD 4-102529859-G-T, REVEL 0.03, CADD 17.40
- T22A (p.Thr22Ala), rs2476157260, ClinGen CA357957357, ClinVar RCV003042758, REVEL 0.03, CADD 5.71, Uncertain significance, not provided
- T22I (p.Thr22Ile), gnomAD 4-102510943-C-T, CADD 7.62
- T22T (p.Thr22Thr), gnomAD 4-102510944-C-A, CADD 2.24
- T22N (p.Thr22Asn), gnomAD 4-102510946-C-A, CADD 5.32
- H23D (p.His23Asp), rs1347167148, gnomAD 4-102529863-C-G, REVEL 0.03, CADD 13.60
- H23Y (p.His23Tyr), gnomAD 4-102529863-C-T, REVEL 0.02, CADD 8.21
- H23R (p.His23Arg), rs780417051, gnomAD 4-102529864-A-G, REVEL 0.02, CADD 8.77
- H23P (p.His23Pro), gnomAD 4-102529864-A-C, REVEL 0.07, CADD 10.60
- T24A (p.Thr24Ala), rs749502665, gnomAD 4-102529866-A-G, REVEL 0.03, CADD 2.65
- T24T (p.Thr24Thr), rs778127566, gnomAD 4-102529868-A-G, CADD 6.76
- I25V (p.Ile25Val), rs778867861, gnomAD 4-102529869-A-G, REVEL 0.03, CADD 14.00
- N27N (p.Asn27Asn), gnomAD 4-102529877-T-C, CADD 4.45
- P28S (p.Pro28Ser), cosmic curated COSV10505, TOPMed rs1485949241, REVEL 0.06, CADD 6.72, Uncertain significance
- P28Q (p.Pro28Gln), gnomAD 4-102529879-C-A, REVEL 0.03, CADD 20.50
- P28P (p.Pro28Pro), gnomAD 4-102529880-A-C, CADD 11.60
- E29E (p.Glu29Glu), gnomAD 4-102529883-A-G, CADD 11.30
- V30I (p.Val30Ile), rs899498254, gnomAD 4-102529884-G-A, REVEL 0.04, CADD 11.90
- V30G (p.Val30Gly), gnomAD 4-102529885-T-G, REVEL 0.12, CADD 21.30
- V30V (p.Val30Val), gnomAD 4-102529886-A-G, CADD 10.80
- P33L (p.Pro33Leu), rs1359408485, gnomAD 4-102529894-C-T, REVEL 0.08, CADD 19.30
- P33P (p.Pro33Pro), rs1223832583, gnomAD 4-102529895-A-G, CADD 10.20
- Q34* (p.Gln34Ter), gnomAD 4-102529896-C-T, CADD 35.00
- M35V (p.Met35Val), rs1285815126, gnomAD 4-102529899-A-G, REVEL 0.05, CADD 14.30
- M35T (p.Met35Thr), rs1382519896, gnomAD 4-102529900-T-C, REVEL 0.10, CADD 18.30
- M35I (p.Met35Ile), rs748222621, gnomAD 4-102529901-G-A, REVEL 0.07, CADD 20.20
- A36P (p.Ala36Pro), rs2476157704, ClinGen CA357957454, ClinVar RCV002713342, Likely benign, Inborn genetic diseases
- A36T (p.Ala36Thr), rs2476157704, ClinGen CA357957453, ClinVar RCV002731617, NCI-TCGA Cosmic COSV5695, REVEL 0.05, CADD 12.70, Uncertain significance, not provided
- A36V (p.Ala36Val), cosmic curated COSV10584, REVEL 0.11, CADD 15.80
- A36E (p.Ala36Glu), gnomAD 4-102529903-C-A, REVEL 0.11, CADD 15.60
- L37L (p.Leu37Leu), gnomAD 4-102529905-C-T, CADD 7.89
- L37M (p.Leu37Met), gnomAD 4-102529905-C-A, REVEL 0.05, CADD 11.90
- P38T (p.Pro38Thr), gnomAD 4-102529908-C-A, REVEL 0.03, CADD 10.20
- P38S (p.Pro38Ser), gnomAD 4-102529908-C-T, REVEL 0.03, CADD 10.40
- P38Q (p.Pro38Gln), gnomAD 4-102529909-C-A, REVEL 0.01, CADD 11.30
- T39A (p.Thr39Ala), rs572127952, gnomAD 4-102529911-A-G, REVEL 0.05, CADD 20.60
- T39I (p.Thr39Ile), gnomAD 4-102529912-C-T, REVEL 0.07, CADD 26.20
- T39T (p.Thr39Thr), gnomAD 4-102529913-A-G, CADD 15.20
- D40G (p.Asp40Gly), rs1183827374, gnomAD 4-102533848-A-G, REVEL 0.30, CADD 24.30
- G41G (p.Gly41Gly), gnomAD 4-102533852-C-T, CADD 10.40
- P42T (p.Pro42Thr), cosmic curated COSV10505
- P42A (p.Pro42Ala), rs201487209, gnomAD 4-102533853-C-G, REVEL 0.48, CADD 24.20
- P42P (p.Pro42Pro), gnomAD 4-102533855-A-G, CADD 12.90
- Y43C (p.Tyr43Cys), rs1741460789, gnomAD 4-102533857-A-G, REVEL 0.13, CADD 23.30
- Y43F (p.Tyr43Phe), rs1741460789, gnomAD 4-102533857-A-T, REVEL 0.06, CADD 19.80
- L44P (p.Leu44Pro), NCI-TCGA Cosmic COSV5695, cosmic curated COSV56958, Variant assessed as somatic; moderate impact.
- L44V (p.Leu44Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q45K (p.Gln45Lys), gnomAD 4-102533862-C-A, REVEL 0.14, CADD 22.70
- L47S (p.Leu47Ser), gnomAD 4-102533869-T-C, REVEL 0.26, CADD 24.90
- E48E (p.Glu48Glu), gnomAD 4-102533873-G-A, CADD 10.40
- Q49K (p.Gln49Lys), gnomAD 4-102533874-C-A, REVEL 0.45, CADD 25.40
- P50P (p.Pro50Pro), rs761203958, gnomAD 4-102533879-T-C, CADD 11.90
- K51K (p.Lys51Lys), rs1258525370, gnomAD 4-102510938-A-G, CADD 0.11
- R53I (p.Arg53Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R53K (p.Arg53Lys), gnomAD 4-102537859-G-A, REVEL 0.30, CADD 33.00
- R53R (p.Arg53Arg), gnomAD 4-102537860-A-G, CADD 19.40
- G54R (p.Gly54Arg), NCI-TCGA TCGA novel, Uncertain significance, Inborn genetic diseases
- G54G (p.Gly54Gly), gnomAD 4-102537863-A-G, CADD 17.50
- R56C (p.Arg56Cys), rs1040399901, ClinGen CA103124400, cosmic curated COSV10455, ClinVar RCV001368038, AlphaMissense 1.00, MetaLR 0.62, Uncertain significance, not provided
- R56H (p.Arg56His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R58H (p.Arg58His), cosmic curated COSV10960
- R58C (p.Arg58Cys), rs1377309694, gnomAD 4-102537873-C-T, REVEL 0.74, CADD 32.00
- R58P (p.Arg58Pro), gnomAD 4-102537874-G-C, REVEL 0.78, CADD 33.00
- R58R (p.Arg58Arg), rs1312917211, gnomAD 4-102537875-T-G, CADD 13.10
- Y59Y (p.Tyr59Tyr), rs1741746571, gnomAD 4-102537878-T-C, CADD 5.00
- V60A (p.Val60Ala), cosmic curated COSV56954
- V60I (p.Val60Ile), rs2476200201, ClinGen CA357957646, ClinVar RCV003321225, Uncertain significance, not provided
- V60V (p.Val60Val), rs1364504275, gnomAD 4-102537881-A-G, CADD 0.90
- C61R (p.Cys61Arg), gnomAD 4-102537882-T-C, REVEL 0.65, CADD 27.80
- E62G (p.Glu62Gly), rs2476200259, ClinGen CA357957664, ClinVar RCV003055832, Uncertain significance, not provided
- E62E (p.Glu62Glu), rs1462783079, gnomAD 4-102537887-A-G, CADD 15.20
- G63C (p.Gly63Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G63G (p.Gly63Gly), gnomAD 4-102537890-C-T, CADD 12.50
- P64L (p.Pro64Leu), gnomAD 4-102537892-C-T, REVEL 0.33, CADD 25.60
- S65F (p.Ser65Phe), cosmic curated COSV10505
- S65A (p.Ser65Ala), rs1170050395, gnomAD 4-102537894-T-G, REVEL 0.44, CADD 26.30
- S65S (p.Ser65Ser), rs1394947379, gnomAD 4-102537896-C-A, CADD 4.74
- H66R (p.His66Arg), rs2476200380, ClinGen CA357957690, ClinVar RCV002651835, Pathogenic, not provided
- H66Y (p.His66Tyr), cosmic curated COSV99896
- H66W (p.His66Trp), gnomAD 4-102537896-CCA-C, CADD 27.20
- H66H (p.His66His), rs1741747740, gnomAD 4-102537899-T-C, CADD 5.76
- G67R (p.Gly67Arg), rs2149127915, ClinGen CA357957695, ClinVar RCV002747233, AlphaMissense 1.00, MetaLR 0.58, Uncertain significance, Inborn genetic diseases
- G68R (p.Gly68Arg), rs2476200436, ClinGen CA357957701, ClinVar RCV003689173, Uncertain significance, not provided
- G68S (p.Gly68Ser), rs2149127915, gnomAD 4-102537900-G-A, REVEL 0.80, AlphaMissense 1.00
- G68G (p.Gly68Gly), rs1741747918, gnomAD 4-102537902-T-C, CADD 5.76
- L69Y (p.Leu69Tyr), gnomAD 4-102537904-GA-G, CADD 23.60
- L69L (p.Leu69Leu), gnomAD 4-102537906-C-T, CADD 11.60
- L69R (p.Leu69Arg), gnomAD 4-102537907-T-G, REVEL 0.60, CADD 27.70
- P70H (p.Pro70His), cosmic curated COSV99897
- G71C (p.Gly71Cys), cosmic curated COSV99897
- G71G (p.Gly71Gly), rs1270285030, gnomAD 4-102537914-T-G, CADD 10.10
- A72S (p.Ala72Ser), rs2149127937, ClinGen CA357957725, ClinVar RCV002001851, NCI-TCGA TCGA novel, AlphaMissense 0.45, MetaLR 0.24, Uncertain significance, not provided
- A72A (p.Ala72Ala), rs4648003, gnomAD 4-102537917-C-T, CADD 2.09
- S73C (p.Ser73Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S74R (p.Ser74Arg), rs2149127949, ClinGen CA357957741, ClinVar RCV003029742, Uncertain significance, not provided
- S74T (p.Ser74Thr), rs1304282431, gnomAD 4-102537918-T-A, REVEL 0.20, CADD 23.30
- N77D (p.Asn77Asp), gnomAD 4-102537930-A-G, REVEL 0.12, CADD 22.70
- N77S (p.Asn77Ser), rs1346783408, gnomAD 4-102537931-A-G, REVEL 0.08, CADD 22.20
- N77N (p.Asn77Asn), rs1443223050, gnomAD 4-102537932-C-T, CADD 11.60
- K78N (p.Lys78Asn), NCI-TCGA Cosmic COSV9989, cosmic curated COSV99897, Variant assessed as somatic; moderate impact.
- K79E (p.Lys79Glu), gnomAD 4-102537933-A-G, REVEL 0.11, CADD 23.80
- K79R (p.Lys79Arg), gnomAD 4-102537934-A-G, REVEL 0.07, CADD 21.40
- K79N (p.Lys79Asn), gnomAD 4-102537935-G-C, REVEL 0.12, CADD 23.70
- K79K (p.Lys79Lys), rs766892535, gnomAD 4-102537938-G-A, CADD 9.86
- S80Y (p.Ser80Tyr), cosmic curated COSV10731
- S80A (p.Ser80Ala), gnomAD 4-102537939-T-G, REVEL 0.15, CADD 25.20
- S80C (p.Ser80Cys), rs1300115442, gnomAD 4-102537940-C-G, REVEL 0.35, CADD 26.30
- Y81* (p.Tyr81Ter), rs1410266677, ClinGen CA357957795, ClinVar RCV003009492, Pathogenic
- Y81T (p.Tyr81Thr), gnomAD 4-102537940-CT-C, CADD 21.90
- Y81C (p.Tyr81Cys), gnomAD 4-102537943-A-G, REVEL 0.39, CADD 26.80
- Y81Y (p.Tyr81Tyr), rs1410266677, gnomAD 4-102537944-C-T, CADD 8.47
- P82H (p.Pro82His), cosmic curated COSV99897
- P82T (p.Pro82Thr), gnomAD 4-102537945-C-A, REVEL 0.68, CADD 25.10
- P82S (p.Pro82Ser), rs1326698146, gnomAD 4-102537945-C-T, REVEL 0.59, CADD 25.40
- P82P (p.Pro82Pro), rs754219657, gnomAD 4-102537947-T-C, CADD 8.95
- Q83E (p.Gln83Glu), gnomAD 4-102537948-C-G, REVEL 0.08, CADD 19.80
- Q83R (p.Gln83Arg), gnomAD 4-102537949-A-G, REVEL 0.12, CADD 23.60
- Q83H (p.Gln83His), gnomAD 4-102537950-G-T, REVEL 0.17, CADD 22.80
- V84V (p.Val84Val), gnomAD 4-102537953-C-A, CADD 15.40
- I86I (p.Ile86Ile), rs571739367, gnomAD 4-102566989-C-A, CADD 15.90
- C87F (p.Cys87Phe), rs1387606271, ClinGen CA357958706, ClinVar RCV003234817, AlphaMissense 0.28, MetaLR 0.15, Pathogenic, Primary ciliary dyskinesia 3
- C87R (p.Cys87Arg), rs1560679373, gnomAD 4-102566990-T-C, REVEL 0.26, CADD 22.90
- C87Y (p.Cys87Tyr), rs1387606271, gnomAD 4-102566991-G-A, REVEL 0.26, AlphaMissense 0.28
- C87C (p.Cys87Cys), rs1443388408, gnomAD 4-102566992-C-T, CADD 13.80
- N88S (p.Asn88Ser), rs763286279, ClinGen CA3025854, cosmic curated COSV10455, ClinVar RCV003870944, AlphaMissense 0.15, MetaLR 0.17, Uncertain significance, not provided
- Y89C (p.Tyr89Cys), rs764399130, ClinGen CA357958720, ClinVar RCV003055789, AlphaMissense 0.44, MetaLR 0.30, Uncertain significance, not provided
- Y89F (p.Tyr89Phe), rs764399130, gnomAD 4-102566997-A-T, REVEL 0.45, AlphaMissense 0.44
- V90L (p.Val90Leu), cosmic curated COSV56959
- V90M (p.Val90Met), gnomAD 4-102566999-G-A, REVEL 0.05, CADD 19.30
- G91V (p.Gly91Val), rs2149168137, gnomAD 4-102567003-G-T, REVEL 0.80, CADD 28.00
- P92S (p.Pro92Ser), rs751657227, gnomAD 4-102567005-C-T, REVEL 0.18, CADD 19.90
- P92Q (p.Pro92Gln), gnomAD 4-102567006-C-A, REVEL 0.14, CADD 22.20
- P92P (p.Pro92Pro), gnomAD 4-102567007-A-C, CADD 10.10
- A93T (p.Ala93Thr), cosmic curated COSV56954
- A93G (p.Ala93Gly), gnomAD 4-102567009-C-G, REVEL 0.25, CADD 25.00
- A93A (p.Ala93Ala), gnomAD 4-102567010-A-C, CADD 10.80
- K94Q (p.Lys94Gln), gnomAD 4-102567011-A-C, REVEL 0.13, CADD 23.50
- K94M (p.Lys94Met), gnomAD 4-102567012-A-T, REVEL 0.15, CADD 23.80
- K94K (p.Lys94Lys), rs139566935, gnomAD 4-102567013-G-A, CADD 8.21
Public NFKB1 analysis runs
- NFKB1 analysis run — NFKB1 (610 variants) — completed 2026-08-19