HLA-DRA (P01903) variants and mutations
HLA-DRA (also known as P01903) is a human protein-coding gene encoding a HLA class II histocompatibility antigen, DR alpha chain protein. It provides the relatively conserved alpha chain of HLA-DR antigen-presenting complexes, which activate CD4 T cells by displaying peptides from extracellular proteins. Variation in its partner beta chains largely determines peptide specificity and many HLA-DR-associated disease risks. This analysis covers 611 HLA-DRA variants and mutations. Of these, 85% have computational variant effect predictions. Disease context includes Graham Little-Piccardi-Lassueur syndrome, lichen planopilaris, and Sepsis. Example HLA-DRA variants include M1?, A2G, and A2T.
Variant analysis overview
- Gene: HLA-DRA
- Protein: P01903
- UniProt accession: P01903
- Organism: Homo sapiens
- Variants analyzed: 611
- Variant scope: all variants
- Completed: 2026-08-19
Variant and mutation evidence
- Variant composition: 334 unspecified-consequence records; 139 missense variants; 110 synonymous variants; 4 stop-gained variants; 4 in-frame deletions; 2 splice-region variants; 14 frameshift variants; 2 in-frame insertions; 1 stop lost; 1 stop retained variant
- Prediction scores: 522 variants have prediction scores (85% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Graham Little-Piccardi-Lassueur syndrome, lichen planopilaris, Sepsis, nonpapillary renal cell carcinoma, diffuse large B-cell lymphoma, COVID-19, amyotrophic lateral sclerosis, non-small cell lung carcinoma, sarcopenia, gastric cancer, neoplasm, cancer.
Protein structure and variant hotspots
- Protein features: 1 transmembrane segments; 1 domains; 2 post-translational modification sites.
- Structural context: 280 variants have structural context.
- PTM context: 6 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 HLA-DRA variants
Examples include M1?, A2G, A2T, A2V, I3K, I3T, I3V, I3M. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- A2G (p.Ala2Gly), gnomAD rs1776144393
- A2T (p.Ala2Thr), rs765347014, NCI-TCGA Cosmic COSV6662, cosmic curated COSV66622, ExAC rs765347014, REVEL 0.03, CADD 8.18, Variant assessed as somatic; moderate impact.
- A2V (p.Ala2Val), ExAC rs752785871, gnomAD rs752785871, MetaLR 0.00, MetaSVM -0.91
- I3K (p.Ile3Lys), 1000Genomes rs3129952, TOPMed rs3129952
- I3T (p.Ile3Thr), ExAC rs755760382, gnomAD rs755760382, REVEL 0.02, CADD 1.35
- I3V (p.Ile3Val), ExAC rs763131341, TOPMed rs763131341, gnomAD rs763131341, REVEL 0.01, CADD 0.02
- I3M (p.Ile3Met), gnomAD 6-32439959-A-G, REVEL 0.06, CADD 4.65
- S4N (p.Ser4Asn), TOPMed rs1386047724, gnomAD rs1386047724, cosmic curated COSV66622, REVEL 0.07, CADD 0.00
- S4T (p.Ser4Thr), Ensembl rs984464072, MetaLR 0.00, MetaSVM -0.89
- G5R (p.Gly5Arg), 1000Genomes rs138394438, ESP rs138394438, ExAC rs138394438, TOPMed rs138394438, REVEL 0.08, CADD 10.20
- G5V (p.Gly5Val), Ensembl rs1762510699, MetaLR 0.00, MetaSVM -0.88
- G5E (p.Gly5Glu), gnomAD 6-32439964-G-A, REVEL 0.07, CADD 9.89
- G5A (p.Gly5Ala), gnomAD 6-32439964-G-C, REVEL 0.05, CADD 15.90
- V6I (p.Val6Ile), TOPMed rs982803944, MetaLR 0.00, MetaSVM -0.91
- V6V (p.Val6Val), gnomAD 6-32439968-C-T, CADD 5.37
- P7A (p.Pro7Ala), Ensembl rs2127699358
- P7S (p.Pro7Ser), NCI-TCGA Cosmic COSV6662, cosmic curated COSV66622, MetaLR 0.00, MetaSVM -0.92, Variant assessed as somatic; moderate impact.
- P7R (p.Pro7Arg), gnomAD 6-32439970-C-G, REVEL 0.10, CADD 13.50
- V8A (p.Val8Ala), Ensembl rs756294427, MetaLR 0.00, MetaSVM -0.92
- V8M (p.Val8Met), gnomAD 6-32439972-G-A, REVEL 0.01, CADD 8.54
- L9I (p.Leu9Ile), TOPMed rs1776141702, MetaLR 0.00, MetaSVM -0.93
- L9L (p.Leu9Leu), rs1762510884, gnomAD 6-32439975-C-T, CADD 6.87
- G10R (p.Gly10Arg), 1000Genomes rs199928204, REVEL 0.06, CADD 17.50
- G10E (p.Gly10Glu), gnomAD 6-32439979-G-A, REVEL 0.07, CADD 18.30
- F12L (p.Phe12Leu), gnomAD rs1776141510, MetaLR 0.00, MetaSVM -0.95
- I13V (p.Ile13Val), TOPMed rs1776141324, REVEL 0.02, CADD 0.24
- I13I (p.Ile13Ile), rs781412925, gnomAD 6-32439989-C-T, CADD 8.93
- I14T (p.Ile14Thr), TOPMed rs1762511966, gnomAD rs1762511966, REVEL 0.06, CADD 14.10
- I14V (p.Ile14Val), ExAC rs750880721, TOPMed rs750880721, gnomAD rs750880721, REVEL 0.04, CADD 11.20
- I14I (p.Ile14Ile), rs756633767, gnomAD 6-32439992-A-T, CADD 0.94
- A15G (p.Ala15Gly), TOPMed rs1029783855, gnomAD rs1029783855, MetaLR 0.00, MetaSVM -0.91
- A15A (p.Ala15Ala), gnomAD 6-32439995-T-C, CADD 8.77
- V16L (p.Val16Leu), rs16822586, cosmic curated COSV66622, UniProt VAR 035241, 1000Genomes rs16822586, REVEL 0.01, CADD 1.16
- M18I (p.Met18Ile), ESP rs143284297, ExAC rs143284297, TOPMed rs143284297, gnomAD rs143284297, REVEL 0.05, CADD 21.60
- M18K (p.Met18Lys), Ensembl rs1583321989, REVEL 0.16, CADD 22.60
- M18L (p.Met18Leu), TOPMed rs1033174290, gnomAD rs1033174290, REVEL 0.07, CADD 9.05
- M18T (p.Met18Thr), 1000Genomes rs2127699318, MetaLR 0.00, MetaSVM -0.95
- S19G (p.Ser19Gly), gnomAD rs1259929692, REVEL 0.02, CADD 6.58
- S19R (p.Ser19Arg), ESP rs371443293, ExAC rs371443293, gnomAD rs371443293, REVEL 0.04, CADD 1.59
- S19N (p.Ser19Asn), gnomAD 6-32440006-G-A, REVEL 0.03, CADD 9.97
- S19S (p.Ser19Ser), rs371443293, gnomAD 6-32440007-C-T, CADD 1.35
- A20S (p.Ala20Ser), 1000Genomes rs142154804, ESP rs142154804, ExAC rs142154804, TOPMed rs142154804, REVEL 0.01, CADD 0.73
- A20T (p.Ala20Thr), 1000Genomes rs142154804, ESP rs142154804, ExAC rs142154804, TOPMed rs142154804, REVEL 0.01, CADD 1.67
- A20V (p.Ala20Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A20P (p.Ala20Pro), gnomAD 6-32440008-G-C, REVEL 0.01, CADD 0.56
- A20G (p.Ala20Gly), gnomAD 6-32440009-C-G, REVEL 0.04, CADD 10.20
- A20A (p.Ala20Ala), gnomAD 6-32440010-T-C, CADD 8.75
- E22D (p.Glu22Asp), TOPMed rs1171560943
- E22Q (p.Glu22Gln), TOPMed rs1415256386, MetaLR 0.00, MetaSVM -0.96
- E22K (p.Glu22Lys), gnomAD 6-32440014-G-A, REVEL 0.02, CADD 12.10
- E22G (p.Glu22Gly), gnomAD 6-32440015-A-G, REVEL 0.02, CADD 13.80
- S23A (p.Ser23Ala), Ensembl rs13194146, MetaLR 0.00, MetaSVM -0.88
- S23L (p.Ser23Leu), ExAC rs771937138, TOPMed rs771937138, gnomAD rs771937138, REVEL 0.12, CADD 19.10
- S23S (p.Ser23Ser), rs772938215, gnomAD 6-32440019-A-G, CADD 4.49
- W24* (p.Trp24Ter), 1000Genomes rs182203129, TOPMed rs182203129
- W24C (p.Trp24Cys), 1000Genomes rs182203129, TOPMed rs182203129, REVEL 0.19, CADD 24.40
- W24K (p.Trp24Lys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- W24R (p.Trp24Arg), TOPMed rs1000738756, gnomAD rs1000738756, REVEL 0.02, CADD 4.83
- W24S (p.Trp24Ser), 1000Genomes rs187703080, TOPMed rs187703080, MetaLR 0.00, MetaSVM -0.91
- A25P (p.Ala25Pro), gnomAD rs542202057, REVEL 0.23, CADD 27.40
- A25V (p.Ala25Val), gnomAD 6-32440024-C-T, REVEL 0.20, CADD 26.60
- A25A (p.Ala25Ala), rs2150369736, gnomAD 6-32440025-T-C, CADD 13.30
- I26N (p.Ile26Asn), ExAC rs770813718, TOPMed rs770813718, gnomAD rs770813718, REVEL 0.20, CADD 29.00
- I26V (p.Ile26Val), ExAC rs760658180, gnomAD rs760658180, REVEL 0.05, CADD 18.80
- K27R (p.Lys27Arg), ExAC rs775617318, gnomAD rs775617318, MetaLR 0.01, MetaSVM -0.90
- E28V (p.Glu28Val), TOPMed rs1419539410, gnomAD rs1419539410
- E29* (p.Glu29Ter), Ensembl rs1583239421
- H30R (p.His30Arg), Ensembl rs1762679435
- H30Y (p.His30Tyr), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, MetaLR 0.01, MetaSVM -1.02, Variant assessed as somatic; moderate impact.
- V31M (p.Val31Met), gnomAD rs1305664191, REVEL 0.10, CADD 17.40
- V31V (p.Val31Val), gnomAD 6-32442458-G-T, CADD 6.57
- I32I (p.Ile32Ile), rs1226822679, gnomAD 6-32442461-C-T, CADD 12.00
- I33V (p.Ile33Val), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, MetaLR 0.00, MetaSVM -0.98, Variant assessed as somatic; moderate impact.
- I33M (p.Ile33Met), gnomAD 6-32442464-C-G, REVEL 0.23, CADD 22.50
- I33I (p.Ile33Ile), gnomAD 6-32442464-C-T, CADD 10.70
- A35V (p.Ala35Val), ExAC rs767685919, gnomAD rs767685919, REVEL 0.10, CADD 22.50
- A35S (p.Ala35Ser), gnomAD 6-32442468-G-T, REVEL 0.10, CADD 22.20
- A35A (p.Ala35Ala), rs773509597, gnomAD 6-32442470-C-T, CADD 0.90
- E36K (p.Glu36Lys), NCI-TCGA TCGA novel, REVEL 0.24, CADD 24.00, Variant assessed as somatic; moderate impact.
- F37L (p.Phe37Leu), gnomAD rs1234552316, REVEL 0.14, CADD 23.60
- Y38C (p.Tyr38Cys), TOPMed rs1471176855, gnomAD rs1471176855, REVEL 0.11, CADD 23.20
- L39M (p.Leu39Met), Ensembl rs2150373966
- L39P (p.Leu39Pro), rs1257068252, TOPMed rs1257068252, gnomAD rs1257068252, REVEL 0.18, CADD 24.50, Variant assessed as somatic; moderate impact.
- L39R (p.Leu39Arg), TOPMed rs1257068252, gnomAD rs1257068252
- L39L (p.Leu39Leu), gnomAD 6-32442480-C-T, CADD 5.84
- N40I (p.Asn40Ile), 1000Genomes rs146003878, TOPMed rs146003878
- N40S (p.Asn40Ser), Ensembl rs2150373982, MetaLR 0.00, MetaSVM -0.91
- P41H (p.Pro41His), cosmic curated COSV66622, TOPMed rs1183939426, gnomAD rs1183939426, REVEL 0.08, CADD 20.50
- P41S (p.Pro41Ser), TOPMed rs1486234672, gnomAD rs1486234672, REVEL 0.07, CADD 21.10
- P41T (p.Pro41Thr), TOPMed rs1486234672, gnomAD rs1486234672, REVEL 0.10, CADD 15.70
- D42E (p.Asp42Glu), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, MetaLR 0.00, MetaSVM -0.93, Variant assessed as somatic; moderate impact.
- D42N (p.Asp42Asn), ExAC rs760911515, gnomAD rs760911515, REVEL 0.06, CADD 18.80
- D42Y (p.Asp42Tyr), gnomAD 6-32442489-G-T, REVEL 0.12, CADD 22.50
- D42D (p.Asp42Asp), rs2150374001, gnomAD 6-32442491-C-T, CADD 2.16
- Q43P (p.Gln43Pro), TOPMed rs947855152, gnomAD rs947855152
- Q43Q (p.Gln43Gln), rs766774047, gnomAD 6-32442494-A-G, CADD 2.17
- S44* (p.Ser44Ter), TOPMed rs1775957419, gnomAD rs1775957419
- S44L (p.Ser44Leu), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, MetaLR 0.01, MetaSVM -1.00, Variant assessed as somatic; moderate impact.
- G45A (p.Gly45Ala), TOPMed rs1775957061, MetaLR 0.00, MetaSVM -0.95
- G45G (p.Gly45Gly), rs754340783, gnomAD 6-32442500-C-T, CADD 7.16
- E46K (p.Glu46Lys), rs1429185771, TOPMed rs1429185771, cosmic curated COSV10469, REVEL 0.25, CADD 31.00, Variant assessed as somatic; moderate impact.
- E46* (p.Glu46Ter), gnomAD 6-32442501-G-T, CADD 45.00
- E46E (p.Glu46Glu), gnomAD 6-32442503-G-A, CADD 11.20
- F47L (p.Phe47Leu), 1000Genomes rs555417043, TOPMed rs555417043, REVEL 0.17, CADD 25.00
- M48I (p.Met48Ile), gnomAD 6-32442509-G-A, REVEL 0.19, CADD 24.40
- F49S (p.Phe49Ser), gnomAD 6-32442511-T-C, REVEL 0.29, CADD 31.00
- F51F (p.Phe51Phe), gnomAD 6-32442518-T-C, CADD 11.50
- D52A (p.Asp52Ala), 1000Genomes rs142547860, TOPMed rs142547860
- D52Y (p.Asp52Tyr), TOPMed rs1353014177, MetaLR 0.06, MetaSVM -0.96
- D52G (p.Asp52Gly), gnomAD 6-32442520-A-G, REVEL 0.36, CADD 32.00
- D52D (p.Asp52Asp), gnomAD 6-32442521-T-C, CADD 9.58
- G53S (p.Gly53Ser), gnomAD 6-32442522-G-A, REVEL 0.26, CADD 32.00
- D54E (p.Asp54Glu), ExAC rs758045784, gnomAD rs758045784, REVEL 0.17, CADD 22.80
- D54G (p.Asp54Gly), ExAC rs752296773, gnomAD rs752296773, REVEL 0.20, CADD 32.00
- D54N (p.Asp54Asn), ExAC rs764836598, gnomAD rs764836598, REVEL 0.21, CADD 26.80
- D54Y (p.Asp54Tyr), TOPMed rs946216536
- D54D (p.Asp54Asp), gnomAD 6-32442527-T-C, CADD 12.70
- I56N (p.Ile56Asn), NCI-TCGA TCGA novel, MetaLR 0.01, MetaSVM -0.95, Variant assessed as somatic; moderate impact.
- F57L (p.Phe57Leu), TOPMed rs1374452743, gnomAD rs1374452743, REVEL 0.19, CADD 23.70
- F57Y (p.Phe57Tyr), TOPMed rs1396961473
- F57F (p.Phe57Phe), gnomAD 6-32442536-C-T, CADD 13.00
- H58H (p.His58His), rs777242292, gnomAD 6-32442539-T-C, CADD 3.06
- V59A (p.Val59Ala), TOPMed rs1172099910, gnomAD rs1172099910, cosmic curated COSV66622, REVEL 0.25, CADD 28.00
- V59L (p.Val59Leu), TOPMed rs1775955519
- D60N (p.Asp60Asn), Ensembl rs1762684097, MetaLR 0.01, MetaSVM -1.14
- D60D (p.Asp60Asp), rs1304331656, gnomAD 6-32442545-T-C, CADD 10.20
- M61I (p.Met61Ile), Ensembl rs572981937, REVEL 0.07, CADD 21.50
- M61V (p.Met61Val), gnomAD 6-32442546-A-G, REVEL 0.05, CADD 3.79
- A62E (p.Ala62Glu), gnomAD rs1359806648, REVEL 0.03, CADD 1.69
- A62S (p.Ala62Ser), ExAC rs779773110, gnomAD rs779773110, REVEL 0.03, CADD 6.51
- A62T (p.Ala62Thr), ExAC rs779773110, gnomAD rs779773110, REVEL 0.02, CADD 8.31
- A62V (p.Ala62Val), gnomAD 6-32442550-C-T, REVEL 0.03, CADD 14.60
- K63N (p.Lys63Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K63E (p.Lys63Glu), gnomAD 6-32442552-A-G, REVEL 0.16, CADD 23.30
- K64N (p.Lys64Asn), TOPMed rs1162776272
- K64del (p.Lys64del), gnomAD 6-32442551-AAAG-A, CADD 15.80
- K64E (p.Lys64Glu), gnomAD 6-32442555-A-G, REVEL 0.08, CADD 17.70
- E65A (p.Glu65Ala), Ensembl rs1386507650, REVEL 0.22, CADD 28.20
- E65G (p.Glu65Gly), TOPMed rs968253546, gnomAD rs968253546
- E65K (p.Glu65Lys), NCI-TCGA Cosmic COSV6662, cosmic curated COSV66622, MetaLR 0.03, MetaSVM -1.13, Variant assessed as somatic; moderate impact.
- E65D (p.Glu65Asp), gnomAD 6-32442560-G-T, REVEL 0.20, CADD 24.10
- T66A (p.Thr66Ala), gnomAD rs1381520023, REVEL 0.18, CADD 24.50
- T66K (p.Thr66Lys), 1000Genomes rs536514150, ExAC rs536514150, gnomAD rs536514150, REVEL 0.18, CADD 26.70
- T66M (p.Thr66Met), rs536514150, 1000Genomes rs536514150, ExAC rs536514150, gnomAD rs536514150, REVEL 0.14, CADD 26.40, Variant assessed as somatic; moderate impact.
- T66T (p.Thr66Thr), gnomAD 6-32442563-G-T, CADD 1.95
- V67I (p.Val67Ile), rs745789724, ExAC rs745789724, gnomAD rs745789724, REVEL 0.08, CADD 21.20, Variant assessed as somatic; moderate impact.
- W68* (p.Trp68Ter), Ensembl rs1019237675
- W68R (p.Trp68Arg), Ensembl rs1775954309
- R69Q (p.Arg69Gln), TOPMed rs1348828850, gnomAD rs1348828850, cosmic curated COSV10531, REVEL 0.19, CADD 26.40
- R69W (p.Arg69Trp), rs751526731, NCI-TCGA Cosmic COSV6662, cosmic curated COSV66622, ExAC rs751526731, REVEL 0.18, CADD 23.50, Variant assessed as somatic; moderate impact.
- R69R (p.Arg69Arg), rs748180734, gnomAD 6-32442572-G-A, CADD 10.10
- L70P (p.Leu70Pro), TOPMed rs1775954101, gnomAD rs1775954101, REVEL 0.28, CADD 31.00
- E71A (p.Glu71Ala), ESP rs375252283, ExAC rs375252283, TOPMed rs375252283, gnomAD rs375252283, REVEL 0.04, CADD 22.00
- E71K (p.Glu71Lys), Ensembl rs2127696531, REVEL 0.04, CADD 12.20
- E71E (p.Glu71Glu), rs1250433057, gnomAD 6-32442578-A-G, CADD 9.43
- E72* (p.Glu72Ter), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, Variant assessed as somatic; high impact.
- E72E (p.Glu72Glu), rs1450847117, gnomAD 6-32442581-A-G, CADD 10.90
- F73S (p.Phe73Ser), ExAC rs760968091, TOPMed rs760968091, gnomAD rs760968091, REVEL 0.36, CADD 25.90
- G74R (p.Gly74Arg), NCI-TCGA Cosmic COSV1008, cosmic curated COSV10089, MetaLR 0.00, MetaSVM -0.91, Variant assessed as somatic; moderate impact.
- R75* (p.Arg75Ter), rs754420534, ExAC rs754420534, TOPMed rs754420534, gnomAD rs754420534, CADD 34.00, Variant assessed as somatic; high impact.
- R75Q (p.Arg75Gln), TOPMed rs1762688265, gnomAD rs1762688265, NCI-TCGA Cosmic COSV6662, cosmic curated COSV66622, REVEL 0.01, CADD 0.27, Variant assessed as somatic; moderate impact.
- R75R (p.Arg75Arg), gnomAD 6-32442588-C-A, CADD 5.47
- R75G (p.Arg75Gly), gnomAD 6-32442588-C-G, REVEL 0.01, CADD 9.87
- A77S (p.Ala77Ser), TOPMed rs1762688467
- A77A (p.Ala77Ala), gnomAD 6-32442596-C-A, CADD 10.20
- S78I (p.Ser78Ile), gnomAD rs1762688867, REVEL 0.15, CADD 24.70
- S78R (p.Ser78Arg), TOPMed rs1459855639
- S78G (p.Ser78Gly), gnomAD 6-32442597-A-G, REVEL 0.12, CADD 17.30
- F79I (p.Phe79Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F79L (p.Phe79Leu), TOPMed rs778823096, gnomAD rs778823096
- F79S (p.Phe79Ser), TOPMed rs925035815, gnomAD rs925035815, MetaLR 0.01, MetaSVM -1.22
- E80A (p.Glu80Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E80V (p.Glu80Val), gnomAD 6-32442604-A-T, REVEL 0.18, CADD 29.20
- A81T (p.Ala81Thr), 1000Genomes rs530162371, TOPMed rs530162371, gnomAD rs530162371, MetaLR 0.01, MetaSVM -1.13
- Q82H (p.Gln82His), gnomAD rs1177981886, REVEL 0.12, CADD 22.90
- Q82* (p.Gln82Ter), gnomAD 6-32442609-C-T, CADD 38.00
- Q82Q (p.Gln82Gln), rs1177981886, gnomAD 6-32442611-A-G, CADD 7.69
- A84S (p.Ala84Ser), TOPMed rs1257735350
- L85S (p.Leu85Ser), TOPMed rs1219191287, gnomAD rs1219191287, REVEL 0.24, CADD 26.20
Public HLA-DRA analysis runs
- HLA-DRA analysis run — HLA-DRA (611 variants) — completed 2026-08-19