RARA (Retinoic acid receptor alpha) variants and mutations
RARA (also known as Retinoic acid receptor alpha) is a human protein-coding gene encoding a retinoic acid receptor alpha protein. It converts retinoic-acid binding into transcriptional programs that promote differentiation and development. The PML::RARA fusion blocks myeloid maturation in acute promyelocytic leukemia, a mechanism directly reversed by all-trans retinoic acid and arsenic-based therapy. This analysis covers 1,148 RARA variants and mutations. Of these, 48% have computational variant effect predictions. Disease context includes acne, acute promyelocytic leukemia, and psoriasis. Example RARA variants include M1?, M1V, and M1T.
Variant analysis overview
- Gene: RARA
- Protein: Retinoic acid receptor alpha
- UniProt accession: P10276
- Organism: Homo sapiens
- Variants analyzed: 1148
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 951 unspecified-consequence records; 114 missense variants; 53 synonymous variants; 14 frameshift variants; 7 stop-gained variants; 5 in-frame deletions; 2 splice-region variants; 1 in-frame insertions; 4 substitution
- Prediction scores: 555 variants have prediction scores (48% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: acne, acute promyelocytic leukemia, psoriasis, psoriasis vulgaris, hyperpigmentation of the skin, freckles, acute myeloid leukemia, neoplasm, Kaposi's sarcoma, Eczematoid dermatitis, myelodysplastic syndrome, neurodegenerative disease.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 binding sites; 4 post-translational modification sites.
- Structural context: 577 variants have structural context.
- PTM context: 11 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 RARA variants
Examples include M1?, M1V, M1T, M1I, M1L, A2T, A2S, A2V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10583
- M1V (p.Met1Val), rs776437326, gnomAD 17-40341393-A-G, CADD 21.70
- M1T (p.Met1Thr), gnomAD 17-40341394-T-C, CADD 22.30
- M1I (p.Met1Ile), rs1254576226, gnomAD 17-40341395-G-A, CADD 21.10
- M1L (p.Met1Leu), gnomAD 17-40341405-A-T, CADD 20.90
- A2T (p.Ala2Thr), Ensembl rs2143276642, REVEL 0.28, CADD 22.00
- A2S (p.Ala2Ser), gnomAD 17-40331222-G-T, REVEL 0.29, CADD 21.70
- A2V (p.Ala2Val), gnomAD 17-40331223-C-T, REVEL 0.41, CADD 23.50
- A2D (p.Ala2Asp), gnomAD 17-40341415-C-A, CADD 19.20
- A2A (p.Ala2Ala), rs1567756390, gnomAD 17-40341416-C-T, CADD 20.50
- S3N (p.Ser3Asn), gnomAD rs1403940287, REVEL 0.41, CADD 23.60
- S3I (p.Ser3Ile), gnomAD 17-40331226-G-T, REVEL 0.38, CADD 24.30
- S3S (p.Ser3Ser), rs545841176, gnomAD 17-40331227-C-T, CADD 12.00
- S3R (p.Ser3Arg), gnomAD 17-40331227-C-A, REVEL 0.36, CADD 22.70
- S3P (p.Ser3Pro), gnomAD 17-40341396-T-C, CADD 22.40
- S3T (p.Ser3Thr), gnomAD 17-40341396-T-A, CADD 22.10
- S3L (p.Ser3Leu), gnomAD 17-40341397-C-T, CADD 21.20
- S3* (p.Ser3Ter), rs963045699, gnomAD 17-40341397-C-A, CADD 20.90
- N4H (p.Asn4His), ExAC rs759886628, gnomAD rs759886628, REVEL 0.42, CADD 23.60
- N4K (p.Asn4Lys), rs1290843078, gnomAD 17-40331227-C-CA, CADD 27.80
- N4N (p.Asn4Asn), rs2033681765, gnomAD 17-40331230-C-T, CADD 9.77
- S5N (p.Ser5Asn), NCI-TCGA Cosmic COSV9956, cosmic curated COSV99565, REVEL 0.30, CADD 22.00, Variant assessed as somatic; moderate impact.
- S5R (p.Ser5Arg), cosmic curated COSV54198, REVEL 0.27, CADD 19.30
- S5G (p.Ser5Gly), gnomAD 17-40331231-A-G, REVEL 0.32, CADD 21.80
- S5S (p.Ser5Ser), rs2143276845, gnomAD 17-40331233-C-T, CADD 11.50
- S6G (p.Ser6Gly), gnomAD rs1229353893
- S6N (p.Ser6Asn), TOPMed rs1173565250, gnomAD rs1173565250, REVEL 0.25, CADD 19.80
- S6T (p.Ser6Thr), cosmic curated COSV10583
- S6R (p.Ser6Arg), gnomAD 17-40331234-A-C, REVEL 0.33, CADD 22.00
- S6I (p.Ser6Ile), gnomAD 17-40331235-G-T, REVEL 0.38, CADD 22.60
- S6S (p.Ser6Ser), rs770268838, gnomAD 17-40331236-C-T, CADD 8.85
- S7C (p.Ser7Cys), cosmic curated COSV54196, ESP rs150291626, ExAC rs150291626, TOPMed rs150291626, REVEL 0.39, CADD 23.30, Uncertain significance, Familial meningioma
- S7F (p.Ser7Phe), ESP rs150291626, ExAC rs150291626, TOPMed rs150291626, gnomAD rs150291626
- S7Y (p.Ser7Tyr), ESP rs150291626, ExAC rs150291626, TOPMed rs150291626, gnomAD rs150291626
- S7T (p.Ser7Thr), gnomAD 17-40341423-T-A, CADD 22.10
- S7P (p.Ser7Pro), gnomAD 17-40341423-T-C, CADD 22.30
- S7L (p.Ser7Leu), gnomAD 17-40341424-C-T, CADD 20.10
- S7* (p.Ser7Ter), gnomAD 17-40341424-C-A, CADD 19.80
- S7S (p.Ser7Ser), rs775402747, gnomAD 17-40341425-A-C, CADD 18.20
- S7G (p.Ser7Gly), gnomAD 17-40341435-A-G, CADD 12.20
- S7R (p.Ser7Arg), gnomAD 17-40341435-A-C, CADD 11.80
- S7I (p.Ser7Ile), gnomAD 17-40341436-G-T, CADD 14.00
- S7N (p.Ser7Asn), gnomAD 17-40341436-G-A, CADD 14.40
- C8R (p.Cys8Arg), Ensembl rs1598550551, REVEL 0.54, CADD 22.70
- C8D (p.Cys8Asp), rs777315412, gnomAD 17-40331237-TCCTG, CADD 27.60
- C8* (p.Cys8Ter), gnomAD 17-40331242-C-A, CADD 34.00
- p.Cys22 His23insArgValArgAlaAlaG, gnomAD 17-40341435-A-AGC, CADD 14.80
- C8Y (p.Cys8Tyr), rs1184715821, gnomAD 17-40341454-G-A, CADD 21.50
- C8F (p.Cys8Phe), gnomAD 17-40341454-G-T, CADD 21.20
- C8C (p.Cys8Cys), gnomAD 17-40341455-T-C, CADD 22.00
- P9L (p.Pro9Leu), cosmic curated COSV54196, ExAC rs762408148, TOPMed rs762408148, gnomAD rs762408148, REVEL 0.52, CADD 22.30, Uncertain significance, Familial meningioma
- P9Q (p.Pro9Gln), gnomAD 17-40331244-C-A, REVEL 0.47, CADD 22.10
- P9P (p.Pro9Pro), rs563927918, gnomAD 17-40331245-G-A, CADD 5.51
- T10A (p.Thr10Ala), TOPMed rs1419067649, gnomAD rs1419067649, REVEL 0.29, CADD 17.10
- T10I (p.Thr10Ile), TOPMed rs2033682611, REVEL 0.29, CADD 20.90
- T10P (p.Thr10Pro), TOPMed rs1419067649, gnomAD rs1419067649
- T10K (p.Thr10Lys), gnomAD 17-40331247-C-A, REVEL 0.27, CADD 20.40
- p.Thr5 Gln8del, rs2034031588, gnomAD 17-40341396-TCACA, CADD 20.10
- T10* (p.Thr10Ter), rs2034031697, gnomAD 17-40341397-CACAG, CADD 19.30
- T10T (p.Thr10Thr), gnomAD 17-40341404-A-G, CADD 21.20
- T10S (p.Thr10Ser), gnomAD 17-40341408-A-T, CADD 22.10
- T10R (p.Thr10Arg), rs1281234713, gnomAD 17-40341409-C-G, CADD 19.40
- T10N (p.Thr10Asn), gnomAD 17-40341460-C-A, CADD 18.10
- P11A (p.Pro11Ala), gnomAD 17-40331249-C-G, REVEL 0.31, CADD 16.20
- P11S (p.Pro11Ser), gnomAD 17-40331249-C-T, REVEL 0.30, CADD 22.20
- P11P (p.Pro11Pro), gnomAD 17-40331251-T-G, CADD 10.20
- G12A (p.Gly12Ala), rs137929765, ClinGen CA8542236, ClinVar RCV004259539, ESP rs137929765, REVEL 0.44, CADD 20.20, Uncertain significance, not specified
- G12E (p.Gly12Glu), cosmic curated COSV54197, ESP rs137929765, ExAC rs137929765, TOPMed rs137929765, REVEL 0.42, CADD 23.40, Uncertain significance
- G12V (p.Gly12Val), ESP rs137929765, ExAC rs137929765, TOPMed rs137929765, gnomAD rs137929765, REVEL 0.42, CADD 23.30, Uncertain significance
- G12W (p.Gly12Trp), NCI-TCGA Cosmic COSV9956, cosmic curated COSV99564, Variant assessed as somatic; moderate impact.
- G12G (p.Gly12Gly), gnomAD 17-40331254-G-T, CADD 10.10
- G12S (p.Gly12Ser), rs867198424, gnomAD 17-40341417-G-A, CADD 20.20
- G12C (p.Gly12Cys), gnomAD 17-40341417-G-T, CADD 19.70
- G12D (p.Gly12Asp), gnomAD 17-40341418-G-A, CADD 18.90
- G13A (p.Gly13Ala), ExAC rs761512575, gnomAD rs761512575
- G13C (p.Gly13Cys), TOPMed rs2033682871
- G13D (p.Gly13Asp), ExAC rs761512575, gnomAD rs761512575, REVEL 0.27, CADD 19.00
- G13S (p.Gly13Ser), gnomAD 17-40331255-G-A, REVEL 0.29, CADD 20.40
- G13G (p.Gly13Gly), rs767138451, gnomAD 17-40331257-C-T, CADD 4.95
- G14E (p.Gly14Glu), Ensembl rs1567751373, REVEL 0.62, CADD 25.50
- G14R (p.Gly14Arg), cosmic curated COSV54194, Ensembl rs1567751372, REVEL 0.58, CADD 25.80
- G14W (p.Gly14Trp), cosmic curated COSV54196
- G14G (p.Gly14Gly), rs2143277329, gnomAD 17-40331260-G-A, CADD 11.10
- H15N (p.His15Asn), ExAC rs750162967, gnomAD rs750162967, CADD 16.80
- H15Y (p.His15Tyr), ExAC rs750162967, gnomAD rs750162967, REVEL 0.43, CADD 23.00
- H15H (p.His15His), rs1022636786, gnomAD 17-40331263-C-T, CADD 9.99
- H15Q (p.His15Gln), gnomAD 17-40341430-GAC-G, CADD 16.00
- H15R (p.His15Arg), gnomAD 17-40341433-A-G, CADD 16.60
- H15L (p.His15Leu), gnomAD 17-40341433-A-T, CADD 16.30
- H15D (p.His15Asp), gnomAD 17-40341456-C-G, CADD 21.30
- L16L (p.Leu16Leu), gnomAD 17-40331266-C-T, CADD 9.78
- N17S (p.Asn17Ser), rs368040095, ClinGen CA8542240, ClinVar RCV004339263, ESP rs368040095, REVEL 0.23, CADD 15.50, Uncertain significance, not specified
- N17T (p.Asn17Thr), gnomAD 17-40341469-CA-C, CADD 8.02
- N17D (p.Asn17Asp), gnomAD 17-40341471-A-G, CADD 12.40
- N17Y (p.Asn17Tyr), gnomAD 17-40341471-A-T, CADD 11.90
- N17K (p.Asn17Lys), rs972734651, gnomAD 17-40341473-C-A, CADD 13.00
- G18G (p.Gly18Gly), rs2143277388, gnomAD 17-40331272-G-A, CADD 7.58
- Y19* (p.Tyr19Ter), Ensembl rs2143277434
- Y19D (p.Tyr19Asp), Ensembl rs2143277421
- P20A (p.Pro20Ala), rs201015843, ClinGen CA8542241, cosmic curated COSV54198, ClinVar RCV004205446, REVEL 0.42, CADD 20.80, Uncertain significance, not specified
- P20L (p.Pro20Leu), Ensembl rs773378786, REVEL 0.61, CADD 23.40
- P20S (p.Pro20Ser), NCI-TCGA Cosmic COSV5419, cosmic curated COSV54194, Variant assessed as somatic; moderate impact.
- P20P (p.Pro20Pro), rs753861488, gnomAD 17-40331278-G-C, CADD 4.38
- V21L (p.Val21Leu), Ensembl rs2143277533
- V21M (p.Val21Met), gnomAD 17-40331279-G-A, REVEL 0.28, CADD 22.50
- V21E (p.Val21Glu), gnomAD 17-40331280-T-A, REVEL 0.53, CADD 23.10
- V21V (p.Val21Val), rs2143277557, gnomAD 17-40331281-G-A, CADD 8.85
- V21I (p.Val21Ile), gnomAD 17-40341420-G-A, CADD 22.10
- V21F (p.Val21Phe), gnomAD 17-40341420-G-T, CADD 21.80
- V21A (p.Val21Ala), gnomAD 17-40341421-T-C, CADD 22.00
- P22S (p.Pro22Ser), Ensembl rs2143277587, REVEL 0.51, CADD 23.30
- P22T (p.Pro22Thr), Ensembl rs2143277587
- P23L (p.Pro23Leu), cosmic curated COSV10728, Ensembl rs956087235
- P23T (p.Pro23Thr), cosmic curated COSV99564
- P23P (p.Pro23Pro), gnomAD 17-40331287-C-T, CADD 12.90
- Y24F (p.Tyr24Phe), TOPMed rs2033683761, gnomAD rs2033683761, REVEL 0.64, CADD 23.80
- Y24Y (p.Tyr24Tyr), rs148576098, gnomAD 17-40331290-C-T, CADD 8.53
- Y24N (p.Tyr24Asn), gnomAD 17-40341498-T-A, CADD 13.10
- Y24H (p.Tyr24His), rs755230002, gnomAD 17-40341498-T-C, CADD 13.50
- Y24C (p.Tyr24Cys), gnomAD 17-40341499-A-G, CADD 9.56
- Y24* (p.Tyr24Ter), rs902525648, gnomAD 17-40341500-C-G, CADD 5.21
- A25P (p.Ala25Pro), 1000Genomes rs371882393, ESP rs371882393, ExAC rs371882393, TOPMed rs371882393
- A25S (p.Ala25Ser), 1000Genomes rs371882393, ESP rs371882393, ExAC rs371882393, TOPMed rs371882393, REVEL 0.27, CADD 21.80
- A25T (p.Ala25Thr), rs371882393, NCI-TCGA Cosmic COSV1043, cosmic curated COSV10439, 1000Genomes rs371882393, REVEL 0.34, CADD 23.60, Variant assessed as somatic; moderate impact.
- A25V (p.Ala25Val), Ensembl rs2033683969, REVEL 0.40, CADD 23.40
- A25A (p.Ala25Ala), rs781275602, gnomAD 17-40331293-C-T, CADD 13.20
- A25D (p.Ala25Asp), gnomAD 17-40341445-C-A, CADD 16.30
- A25G (p.Ala25Gly), gnomAD 17-40341445-C-G, CADD 16.40
- A25E (p.Ala25Glu), gnomAD 17-40341448-C-A, CADD 19.90
- F26L (p.Phe26Leu), ExAC rs746187167, gnomAD rs746187167, REVEL 0.31, CADD 20.30
- F26F (p.Phe26Phe), rs746187167, gnomAD 17-40331296-C-T, CADD 11.80
- F26Y (p.Phe26Tyr), gnomAD 17-40341427-T-A, CADD 19.20
- F26S (p.Phe26Ser), gnomAD 17-40341427-T-C, CADD 19.40
- F27V (p.Phe27Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- F27F (p.Phe27Phe), rs2033684316, gnomAD 17-40331299-C-T, CADD 11.90
- F28L (p.Phe28Leu), TOPMed rs2033684389
- F28F (p.Phe28Phe), rs2033684389, gnomAD 17-40331302-C-T, CADD 10.60
- P29A (p.Pro29Ala), Ensembl rs2143277969
- P29H (p.Pro29His), TOPMed rs1297897531, gnomAD rs1297897531, REVEL 0.59, CADD 25.50
- P29S (p.Pro29Ser), NCI-TCGA Cosmic COSV5419, cosmic curated COSV54190, Ensembl rs2143277969, Variant assessed as somatic; moderate impact.
- P29T (p.Pro29Thr), cosmic curated COSV54191, Ensembl rs2143277969
- P29L (p.Pro29Leu), gnomAD 17-40331304-C-T, REVEL 0.68, CADD 26.00
- P29Q (p.Pro29Gln), gnomAD 17-40341469-C-A, CADD 8.84
- P29P (p.Pro29Pro), gnomAD 17-40341470-A-G, CADD 11.40
- P30A (p.Pro30Ala), TOPMed rs1371891710, gnomAD rs1371891710, REVEL 0.31, CADD 17.40
- P30H (p.Pro30His), cosmic curated COSV99565
- P30L (p.Pro30Leu), cosmic curated COSV54189, NCI-TCGA Cosmic COSV9956, Variant assessed as somatic; high impact.
- P30S (p.Pro30Ser), TOPMed rs1371891710, gnomAD rs1371891710, REVEL 0.30, CADD 17.50
- P30T (p.Pro30Thr), TOPMed rs1371891710, gnomAD rs1371891710, REVEL 0.31, CADD 18.90
- P30P (p.Pro30Pro), rs770175416, gnomAD 17-40331308-T-C, CADD 9.29
- P30R (p.Pro30Arg), rs750435578, gnomAD 17-40341481-C-G, CADD 11.30
- M31I (p.Met31Ile), Ensembl rs1334285485
- M31L (p.Met31Leu), TOPMed rs1313589879, gnomAD rs1313589879, REVEL 0.39, CADD 16.90
- M31V (p.Met31Val), cosmic curated COSV99564, TOPMed rs1313589879, gnomAD rs1313589879, REVEL 0.28, CADD 15.40
- L32M (p.Leu32Met), ExAC rs775872347, TOPMed rs775872347, gnomAD rs775872347, REVEL 0.38, CADD 16.90
- L32R (p.Leu32Arg), TOPMed rs1402282746, REVEL 0.68, CADD 24.10
- L32del (p.Leu32del), gnomAD 17-40331309-ATGC-, CADD 19.70
- L32L (p.Leu32Leu), rs775872347, gnomAD 17-40331312-C-T, CADD 8.22
- G33S (p.Gly33Ser), gnomAD 17-40331315-G-A, REVEL 0.56, CADD 24.30
- G33D (p.Gly33Asp), gnomAD 17-40331316-G-A, REVEL 0.63, CADD 24.30
- G33G (p.Gly33Gly), rs769208251, gnomAD 17-40331317-T-G, CADD 8.67
- G34R (p.Gly34Arg), Ensembl rs2143278293
- G34A (p.Gly34Ala), gnomAD 17-40331319-G-C, REVEL 0.45, CADD 22.60
- L35F (p.Leu35Phe), Ensembl rs2143278309, REVEL 0.32, CADD 21.10
- L35H (p.Leu35His), gnomAD 17-40331322-T-A, REVEL 0.62, CADD 25.80
- L35P (p.Leu35Pro), gnomAD 17-40331322-T-C, REVEL 0.66, CADD 26.30
- L35L (p.Leu35Leu), gnomAD 17-40331323-C-T, CADD 1.99
- S36F (p.Ser36Phe), gnomAD 17-40331325-C-T, REVEL 0.60, CADD 23.50
- S36S (p.Ser36Ser), rs2033685560, gnomAD 17-40331326-C-T, CADD 2.24
- S36P (p.Ser36Pro), gnomAD 17-40341504-T-C, CADD 5.78
- S36Y (p.Ser36Tyr), gnomAD 17-40341505-C-A, CADD 6.10
- S36A (p.Ser36Ala), gnomAD 17-40341516-T-G, CADD 4.36
- P37L (p.Pro37Leu), 1000Genomes rs561629991, ExAC rs561629991, TOPMed rs561629991, gnomAD rs561629991, REVEL 0.56, CADD 23.10, Uncertain significance, not specified
- P37T (p.Pro37Thr), Ensembl rs2143278370
- P37P (p.Pro37Pro), rs376736940, gnomAD 17-40331329-G-T, CADD 0.64
- P37S (p.Pro37Ser), gnomAD 17-40341495-C-T, CADD 6.86
- P38S (p.Pro38Ser), cosmic curated COSV54195
- P38P (p.Pro38Pro), rs1232082912, gnomAD 17-40331332-A-G, CADD 2.95
- G39V (p.Gly39Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- G39G (p.Gly39Gly), rs767135725, gnomAD 17-40331335-C-T, CADD 8.68
Public RARA analysis runs
- RARA analysis run — RARA (1,148 variants) — completed 2026-08-21