PADI4 (Q9UM07) variants and mutations
PADI4 (also known as Q9UM07) is a human protein-coding gene encoding a protein-arginine deiminase type-4 protein. It converts arginine residues in proteins to citrulline, altering charge and protein interactions during processes such as neutrophil extracellular-trap formation. Genetic variation and excessive citrullination are strongly linked to rheumatoid arthritis and autoantibody formation. This analysis covers 1,083 PADI4 variants and mutations. Of these, 78% have computational variant effect predictions. Disease context includes rheumatoid arthritis, Abnormal pulmonary interstitial morphology, and neurodegenerative disease. Example PADI4 variants include A2T, A2G, and A2V.
Variant analysis overview
- Gene: PADI4
- Protein: Q9UM07
- UniProt accession: Q9UM07
- Organism: Homo sapiens
- Variants analyzed: 1083
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 864 unspecified-consequence records; 110 missense variants; 73 synonymous variants; 8 stop-gained variants; 23 frameshift variants; 2 in-frame deletions; 2 in-frame insertions; 2 splice-region variants; 2 stop lost; 1 stop retained variant; 1 substitution
- Prediction scores: 850 variants have prediction scores (78% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: rheumatoid arthritis, Abnormal pulmonary interstitial morphology, neurodegenerative disease, ulcerative colitis, stroke disorder, alcohol drinking, skin neoplasm, cancer, basal cell carcinoma, hair color, neoplasm, hepatocellular carcinoma.
Protein structure and variant hotspots
- Protein features: 24 binding sites; 6 post-translational modification sites.
- PTM context: 10 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 PADI4 variants
Examples include A2T, A2G, A2V, A2A, Q3*, Q3L, Q3Q, G4E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2T (p.Ala2Thr), gnomAD 1-17308226-G-A, REVEL 0.23, CADD 22.90
- A2G (p.Ala2Gly), gnomAD 1-17308227-C-G, REVEL 0.23, CADD 23.00
- A2V (p.Ala2Val), gnomAD 1-17308227-C-T, REVEL 0.24, CADD 21.20
- A2A (p.Ala2Ala), rs1264401208, gnomAD 1-17308228-C-T, CADD 3.80
- Q3* (p.Gln3Ter), gnomAD 1-17308229-C-T, CADD 37.00
- Q3L (p.Gln3Leu), gnomAD 1-17308230-A-T, REVEL 0.08, CADD 14.40
- Q3Q (p.Gln3Gln), rs531814225, gnomAD 1-17308231-G-A, CADD 2.21
- G4E (p.Gly4Glu), Ensembl rs2073705618
- G4R (p.Gly4Arg), ESP rs377643304, ExAC rs377643304, TOPMed rs377643304, gnomAD rs377643304, REVEL 0.12, CADD 22.20
- G4G (p.Gly4Gly), rs1179792965, gnomAD 1-17308234-G-T, CADD 0.51
- T5I (p.Thr5Ile), TOPMed rs2073705829
- T5P (p.Thr5Pro), ExAC rs761415467, TOPMed rs761415467, gnomAD rs761415467, REVEL 0.02, CADD 8.76
- T5H (p.Thr5His), gnomAD 1-17308230-AG-A, CADD 22.10
- T5S (p.Thr5Ser), gnomAD 1-17308234-G-GTC, CADD 12.90
- T5A (p.Thr5Ala), gnomAD 1-17308235-A-G, REVEL 0.02, CADD 2.47
- L6F (p.Leu6Phe), gnomAD rs1465113059, REVEL 0.04, CADD 20.00
- L6L (p.Leu6Leu), gnomAD 1-17308238-T-C, CADD 3.23
- L6W (p.Leu6Trp), gnomAD 1-17308239-T-G, REVEL 0.04, CADD 17.10
- I7T (p.Ile7Thr), gnomAD rs1172726333, REVEL 0.25, CADD 23.80
- I7V (p.Ile7Val), gnomAD 1-17308241-A-G, REVEL 0.03, CADD 8.15
- R8C (p.Arg8Cys), ExAC rs572732935, TOPMed rs572732935, gnomAD rs572732935, REVEL 0.04, CADD 22.90
- R8H (p.Arg8His), rs35381732, 1000Genomes rs35381732, ESP rs35381732, ExAC rs35381732, REVEL 0.03, CADD 14.60, Benign, not provided
- R8L (p.Arg8Leu), 1000Genomes rs35381732, ESP rs35381732, ExAC rs35381732, TOPMed rs35381732, REVEL 0.05, CADD 22.90, Benign
- R8S (p.Arg8Ser), ExAC rs572732935, TOPMed rs572732935, gnomAD rs572732935, REVEL 0.07, CADD 22.90
- V9A (p.Val9Ala), gnomAD rs1317156822
- V9M (p.Val9Met), gnomAD 1-17308247-G-A, REVEL 0.14, CADD 19.80
- V9V (p.Val9Val), rs766332674, gnomAD 1-17308249-G-C, CADD 5.14
- T10A (p.Thr10Ala), Ensembl rs2100633941
- T10N (p.Thr10Asn), 1000Genomes rs201885629, ExAC rs201885629, TOPMed rs201885629, gnomAD rs201885629, REVEL 0.08, CADD 12.70
- P11R (p.Pro11Arg), gnomAD rs2073706411, REVEL 0.11, CADD 16.80
- P11T (p.Pro11Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P11P (p.Pro11Pro), rs1281308165, gnomAD 1-17308255-A-G, CADD 0.33
- E12E (p.Glu12Glu), gnomAD 1-17308258-G-A, CADD 5.51
- Q13E (p.Gln13Glu), 1000Genomes rs201070994, ExAC rs201070994, gnomAD rs201070994
- Q13K (p.Gln13Lys), gnomAD 1-17308259-C-A, REVEL 0.06, CADD 1.63
- P14S (p.Pro14Ser), Ensembl rs2100633996, REVEL 0.10, CADD 19.20
- T15S (p.Thr15Ser), ESP rs148054220, TOPMed rs148054220, gnomAD rs148054220, REVEL 0.23, CADD 21.40
- T15I (p.Thr15Ile), gnomAD 1-17308266-C-T, REVEL 0.28, CADD 22.20
- H16D (p.His16Asp), gnomAD rs1233872154, REVEL 0.09, CADD 14.80
- H16R (p.His16Arg), rs370820749, ESP rs370820749, ExAC rs370820749, TOPMed rs370820749, REVEL 0.03, CADD 5.49, Uncertain significance, not specified
- H16Q (p.His16Gln), gnomAD 1-17308270-T-G, REVEL 0.03, CADD 6.92
- A17D (p.Ala17Asp), Ensembl rs112918821, REVEL 0.32, CADD 23.30
- A17A (p.Ala17Ala), rs752860727, gnomAD 1-17308273-C-T, CADD 1.15
- V18A (p.Val18Ala), TOPMed rs894020390, gnomAD rs894020390, REVEL 0.28, CADD 25.40
- V18M (p.Val18Met), rs371193672, 1000Genomes rs371193672, ESP rs371193672, ExAC rs371193672, REVEL 0.26, CADD 24.20, Uncertain significance, not specified
- V18L (p.Val18Leu), gnomAD 1-17308274-G-C, REVEL 0.26, CADD 22.80
- V18V (p.Val18Val), rs2073707132, gnomAD 1-17308276-G-A, CADD 8.40
- C19G (p.Cys19Gly), ExAC rs778157610, gnomAD rs778157610, REVEL 0.44, CADD 26.30
- C19Y (p.Cys19Tyr), gnomAD 1-17308278-G-A, REVEL 0.34, CADD 24.10
- C19C (p.Cys19Cys), gnomAD 1-17308279-T-C, CADD 9.35
- V20M (p.Val20Met), TOPMed rs2073707263, gnomAD rs2073707263, REVEL 0.32, CADD 25.60
- V20A (p.Val20Ala), gnomAD 1-17308273-CGT-C, CADD 25.50
- V20V (p.Val20Val), rs1326506581, gnomAD 1-17308282-G-T, CADD 8.81
- L21P (p.Leu21Pro), 1000Genomes rs547720396, ExAC rs547720396, gnomAD rs547720396, REVEL 0.42, CADD 26.30
- L21C (p.Leu21Cys), gnomAD 1-17308273-C-CGT, CADD 24.80
- G22D (p.Gly22Asp), Ensembl rs2100634141, REVEL 0.43, CADD 23.80
- G22S (p.Gly22Ser), ESP rs367980085, ExAC rs367980085, TOPMed rs367980085, gnomAD rs367980085, REVEL 0.43, CADD 25.70
- G22R (p.Gly22Arg), gnomAD 1-17308286-G-C, REVEL 0.49, CADD 25.90
- G22A (p.Gly22Ala), gnomAD 1-17308287-G-C, REVEL 0.39, CADD 23.50
- G22G (p.Gly22Gly), rs150078026, gnomAD 1-17308288-C-T, CADD 8.56
- T23I (p.Thr23Ile), TOPMed rs528959988, REVEL 0.34, CADD 23.40
- T23P (p.Thr23Pro), 1000Genomes rs567560287, ExAC rs567560287, TOPMed rs567560287, gnomAD rs567560287, REVEL 0.35, CADD 24.70
- T23S (p.Thr23Ser), 1000Genomes rs567560287, ExAC rs567560287, TOPMed rs567560287, gnomAD rs567560287, REVEL 0.25, CADD 22.60
- T23T (p.Thr23Thr), gnomAD 1-17308291-C-T, CADD 1.73
- L24W (p.Leu24Trp), gnomAD 1-17308293-T-G, REVEL 0.08, CADD 19.50
- L24F (p.Leu24Phe), gnomAD 1-17308294-G-T, REVEL 0.01, CADD 14.60
- L24L (p.Leu24Leu), gnomAD 1-17308294-G-A, CADD 3.04
- T25T (p.Thr25Thr), rs142726269, gnomAD 1-17308297-T-G, CADD 2.31
- Q26R (p.Gln26Arg), gnomAD rs1378897693, REVEL 0.06, CADD 13.50
- Q26* (p.Gln26Ter), gnomAD 1-17308298-C-T, CADD 37.00
- Q26Q (p.Gln26Gln), rs2073708049, gnomAD 1-17308300-G-A, CADD 4.86
- L27F (p.Leu27Phe), gnomAD rs1468120978, REVEL 0.10, CADD 23.50
- L27P (p.Leu27Pro), ExAC rs776068449, TOPMed rs776068449, gnomAD rs776068449, REVEL 0.34, CADD 25.40
- D28A (p.Asp28Ala), Ensembl rs2073708235, REVEL 0.30, CADD 25.00
- D28H (p.Asp28His), NCI-TCGA Cosmic COSV6492, cosmic curated COSV64924, Variant assessed as somatic; moderate impact.
- D28D (p.Asp28Asp), rs189976928, gnomAD 1-17308306-C-T, CADD 0.88
- I29N (p.Ile29Asn), ExAC rs769365946, gnomAD rs769365946, REVEL 0.17, CADD 23.50
- I29S (p.Ile29Ser), gnomAD 1-17308306-CA-C, CADD 16.10
- I29I (p.Ile29Ile), rs1342714878, gnomAD 1-17308309-C-T, CADD 5.58
- C30W (p.Cys30Trp), gnomAD rs1301130261, REVEL 0.07, CADD 12.00
- C30Y (p.Cys30Tyr), Ensembl rs1042169383
- C30F (p.Cys30Phe), gnomAD 1-17308311-G-T, REVEL 0.01, CADD 1.27
- S31G (p.Ser31Gly), ExAC rs772912664, gnomAD rs772912664, REVEL 0.12, CADD 1.55
- S31R (p.Ser31Arg), gnomAD 1-17330969-C-A, REVEL 0.21, CADD 22.10
- S32F (p.Ser32Phe), gnomAD 1-17330971-C-T, REVEL 0.16, CADD 23.50
- A33G (p.Ala33Gly), gnomAD rs1199802826, REVEL 0.24, CADD 23.30
- A33T (p.Ala33Thr), gnomAD 1-17330973-G-A, REVEL 0.20, CADD 24.30
- A33D (p.Ala33Asp), gnomAD 1-17330974-C-A, REVEL 0.34, CADD 25.50
- A33A (p.Ala33Ala), rs1238305168, gnomAD 1-17330975-C-T, CADD 9.38
- E35K (p.Glu35Lys), gnomAD 1-17330979-G-A, REVEL 0.01, CADD 1.92
- E35E (p.Glu35Glu), gnomAD 1-17330981-G-A, CADD 2.52
- D36Y (p.Asp36Tyr), gnomAD 1-17330982-G-T, REVEL 0.04, CADD 22.40
- D36N (p.Asp36Asn), gnomAD 1-17330982-G-A, REVEL 0.01, CADD 18.40
- D36D (p.Asp36Asp), rs1458689956, gnomAD 1-17330984-C-T, CADD 7.13
- C37Y (p.Cys37Tyr), ExAC rs772896628, gnomAD rs772896628, REVEL 0.03, CADD 7.00
- C37S (p.Cys37Ser), gnomAD 1-17330985-T-A, REVEL 0.06, CADD 18.10
- C37* (p.Cys37Ter), gnomAD 1-17330987-C-A, CADD 39.00
- T38M (p.Thr38Met), ExAC rs748929537, TOPMed rs748929537, gnomAD rs748929537, REVEL 0.07, CADD 24.10
- T38K (p.Thr38Lys), gnomAD 1-17330989-C-A, REVEL 0.05, CADD 16.90
- T38T (p.Thr38Thr), rs199525421, gnomAD 1-17330990-G-A, CADD 0.16
- S39T (p.Ser39Thr), gnomAD 1-17330991-T-A, REVEL 0.04, CADD 8.90
- S39Y (p.Ser39Tyr), gnomAD 1-17330992-C-A, REVEL 0.12, CADD 20.60
- S39S (p.Ser39Ser), gnomAD 1-17330993-C-T, CADD 8.79
- F40L (p.Phe40Leu), gnomAD 1-17330994-T-C, REVEL 0.35, CADD 24.50
- F40S (p.Phe40Ser), gnomAD 1-17330995-T-C, REVEL 0.34, CADD 25.80
- S41N (p.Ser41Asn), gnomAD rs1226569388, REVEL 0.07, CADD 19.00
- S41G (p.Ser41Gly), gnomAD 1-17330997-A-G, REVEL 0.04, CADD 10.20
- S41S (p.Ser41Ser), rs746424344, gnomAD 1-17330999-C-T, CADD 7.37
- I42T (p.Ile42Thr), TOPMed rs2074200505
- I42V (p.Ile42Val), TOPMed rs1371117096, gnomAD rs1371117096, REVEL 0.02, CADD 1.38
- I42N (p.Ile42Asn), gnomAD 1-17331001-T-A, REVEL 0.20, CADD 24.60
- I42I (p.Ile42Ile), gnomAD 1-17331002-C-T, CADD 5.93
- N43I (p.Asn43Ile), gnomAD 1-17331004-A-T, REVEL 0.06, CADD 0.03
- N43S (p.Asn43Ser), gnomAD 1-17331004-A-G, REVEL 0.11, CADD 0.00
- N43N (p.Asn43Asn), rs138052968, gnomAD 1-17331005-C-T, CADD 0.08
- A44D (p.Ala44Asp), ExAC rs775636673, TOPMed rs775636673, gnomAD rs775636673, REVEL 0.18, CADD 21.70
- A44T (p.Ala44Thr), rs767499070, ExAC rs767499070, TOPMed rs767499070, gnomAD rs767499070, REVEL 0.03, CADD 8.75, Variant assessed as somatic; moderate impact.
- A44V (p.Ala44Val), ExAC rs775636673, TOPMed rs775636673, gnomAD rs775636673, REVEL 0.13, CADD 14.00
- A44S (p.Ala44Ser), gnomAD 1-17331006-G-T, REVEL 0.05, CADD 8.25
- A44A (p.Ala44Ala), rs760824369, gnomAD 1-17331008-C-T, CADD 1.23
- S45T (p.Ser45Thr), TOPMed rs2074200805, gnomAD rs2074200805, REVEL 0.07, CADD 6.96
- S45S (p.Ser45Ser), gnomAD 1-17331011-C-T, CADD 1.19
- P46S (p.Pro46Ser), Ensembl rs2074200858, REVEL 0.05, CADD 8.26
- P46Q (p.Pro46Gln), gnomAD 1-17331009-TC-T, CADD 22.60
- P46P (p.Pro46Pro), gnomAD 1-17331014-A-T, CADD 3.17
- G47E (p.Gly47Glu), cosmic curated COSV10748, ExAC rs764319833, TOPMed rs764319833, gnomAD rs764319833, REVEL 0.04, CADD 5.03
- G47R (p.Gly47Arg), TOPMed rs1017936326, gnomAD rs1017936326, REVEL 0.28, CADD 22.40
- G47V (p.Gly47Val), gnomAD 1-17331016-G-T, REVEL 0.09, CADD 16.20
- G47G (p.Gly47Gly), rs2074201071, gnomAD 1-17331017-G-A, CADD 0.29
- V48W (p.Val48Trp), gnomAD 1-17331014-AG-A, CADD 23.50
- V48L (p.Val48Leu), gnomAD 1-17331018-G-C, REVEL 0.29, CADD 22.00
- V48M (p.Val48Met), gnomAD 1-17331018-G-A, REVEL 0.31, CADD 23.90
- V48E (p.Val48Glu), gnomAD 1-17331019-T-A, REVEL 0.39, CADD 24.20
- V49I (p.Val49Ile), Ensembl rs2074201148
- V49A (p.Val49Ala), gnomAD 1-17331021-GT-G, CADD 9.43
- V49V (p.Val49Val), rs754061682, gnomAD 1-17331023-C-G, CADD 0.06
- V50M (p.Val50Met), rs757370203, ClinGen CA640360, cosmic curated COSV10096, ClinVar RCV004252260, REVEL 0.18, CADD 19.60, Uncertain significance, not specified
- V50V (p.Val50Val), gnomAD 1-17331026-G-T, CADD 0.54
- D51N (p.Asp51Asn), NCI-TCGA TCGA novel, REVEL 0.03, CADD 1.55, Variant assessed as somatic; moderate impact.
- D51V (p.Asp51Val), TOPMed rs1236437368, gnomAD rs1236437368, REVEL 0.10, CADD 10.70
- D51Y (p.Asp51Tyr), gnomAD 1-17331027-G-T, REVEL 0.05, CADD 0.22
- D51D (p.Asp51Asp), rs1471587854, gnomAD 1-17331029-T-C, CADD 1.25
- I52S (p.Ile52Ser), gnomAD 1-17331031-T-G, REVEL 0.17, CADD 17.80
- A53S (p.Ala53Ser), gnomAD 1-17331033-G-T, REVEL 0.06, CADD 1.43
- A53V (p.Ala53Val), gnomAD 1-17331034-C-T, REVEL 0.05, CADD 2.46
- H54Y (p.His54Tyr), gnomAD 1-17331036-C-T, REVEL 0.04, CADD 10.50
- H54H (p.His54His), rs765510547, gnomAD 1-17331038-C-T, CADD 0.57
- H54Q (p.His54Gln), gnomAD 1-17331038-C-A, REVEL 0.04, CADD 7.20
- G55C (p.Gly55Cys), 1000Genomes rs11203366, ESP rs11203366, ExAC rs11203366, TOPMed rs11203366, Benign
- G55D (p.Gly55Asp), TOPMed rs2074201780, cosmic curated COSV10530, REVEL 0.02, CADD 1.82
- G55S (p.Gly55Ser), rs11203366, ClinGen CA640362, cosmic curated COSV64923, ClinVar RCV001249179, REVEL 0.03, CADD 0.00, Benign; association, Rheumatoid arthritis; Abnormal pulmonary interstitial morphology; PADI4-related
- G55R (p.Gly55Arg), gnomAD 1-17331039-G-C, REVEL 0.01, CADD 0.00
- G55G (p.Gly55Gly), gnomAD 1-17331041-C-A, CADD 2.37
- P56S (p.Pro56Ser), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10096, Variant assessed as somatic; moderate impact.
- P56R (p.Pro56Arg), gnomAD 1-17331043-C-G, REVEL 0.04, CADD 7.09
- P56P (p.Pro56Pro), rs758826242, gnomAD 1-17331044-T-A, CADD 5.96
- P57A (p.Pro57Ala), TOPMed rs868374114, gnomAD rs868374114, REVEL 0.13, CADD 15.80, Uncertain significance, not specified
- P57S (p.Pro57Ser), TOPMed rs868374114, gnomAD rs868374114
- A58D (p.Ala58Asp), ExAC rs780521824, gnomAD rs780521824, REVEL 0.06, CADD 18.10
- A58V (p.Ala58Val), ExAC rs780521824, gnomAD rs780521824, REVEL 0.02, CADD 13.50, Uncertain significance, not specified
- A58A (p.Ala58Ala), gnomAD 1-17331050-C-T, CADD 7.27
- K59N (p.Lys59Asn), gnomAD rs1254902955, REVEL 0.10, CADD 20.50
- K59Q (p.Lys59Gln), NCI-TCGA Cosmic COSV6492, cosmic curated COSV64923, Variant assessed as somatic; moderate impact.
- K59R (p.Lys59Arg), gnomAD rs1201164120, REVEL 0.09, CADD 21.70
- K60E (p.Lys60Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- K60R (p.Lys60Arg), gnomAD rs1483406409, REVEL 0.07, CADD 22.60
- K60T (p.Lys60Thr), NCI-TCGA Cosmic COSV6492, cosmic curated COSV64922, REVEL 0.10, CADD 22.80, Variant assessed as somatic; moderate impact.
- K61K (p.Lys61Lys), rs1260048721, gnomAD 1-17331059-A-G, CADD 0.08
- S62Y (p.Ser62Tyr), gnomAD rs1183220061, REVEL 0.06, CADD 18.90
- S62S (p.Ser62Ser), rs1259451839, gnomAD 1-17331062-C-T, CADD 5.76
- T63S (p.Thr63Ser), Ensembl rs2100702630
- T63A (p.Thr63Ala), gnomAD 1-17331063-A-G, REVEL 0.06, CADD 11.20
- G64A (p.Gly64Ala), ExAC rs777111314, gnomAD rs777111314, REVEL 0.14, CADD 17.90
- G64C (p.Gly64Cys), NCI-TCGA TCGA novel, REVEL 0.11, CADD 23.30, Variant assessed as somatic; moderate impact.
- G64S (p.Gly64Ser), ExAC rs755587116, gnomAD rs755587116, REVEL 0.10, CADD 20.90
- G64V (p.Gly64Val), gnomAD 1-17331067-G-T, REVEL 0.17, CADD 22.50
- G64D (p.Gly64Asp), gnomAD 1-17331067-G-A, REVEL 0.15, CADD 18.70
- S65F (p.Ser65Phe), NCI-TCGA Cosmic COSV1009, cosmic curated COSV10096, NCI-TCGA Cosmic COSV6492, REVEL 0.04, CADD 14.60, Variant assessed as somatic; moderate impact.
- S65S (p.Ser65Ser), gnomAD 1-17331071-C-T, CADD 3.40
- S66Y (p.Ser66Tyr), gnomAD 1-17331073-C-A, REVEL 0.05, CADD 17.40
Public PADI4 analysis runs
- PADI4 analysis run — PADI4 (1,083 variants) — completed 2026-08-21