EP300 (Histone acetyltransferase p300) variants and mutations
EP300 (also known as Histone acetyltransferase p300) is a human protein-coding gene encoding a histone acetyltransferase p300 protein. It acetylates histones and transcription factors and acts as a central coactivator for developmental and stress-responsive transcription. Germline loss-of-function variants cause Rubinstein-Taybi syndrome type 2, while acquired alterations occur in several cancers. This analysis covers 6,833 EP300 variants and mutations. Of these, 39% have computational variant effect predictions. Disease context includes Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, Menke-Hennekam syndrome 2, and cancer. Example EP300 variants include M1?, A2G, and A2V.
Variant analysis overview
- Gene: EP300
- Protein: Histone acetyltransferase p300
- UniProt accession: Q09472
- Organism: Homo sapiens
- Variants analyzed: 6833
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 6,583 unspecified-consequence records; 146 synonymous variants; 96 missense variants; 5 in-frame deletions; 2 splice-region variants; 1 in-frame insertions
- Prediction scores: 2,674 variants have prediction scores (39% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, Menke-Hennekam syndrome 2, cancer, Rubinstein-Taybi syndrome, hereditary disease, head and neck squamous cell carcinoma, urinary bladder cancer, Rubinstein-Taybi syndrome due to CREBBP mutations, cervical squamous cell carcinoma, neurodegenerative disease, colorectal cancer, Intellectual disability.
Protein structure and variant hotspots
- Protein features: 3 domains; 25 binding sites; 30 post-translational modification sites.
- Structural context: 1,749 variants have structural context.
- PTM context: 55 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, ClinGen, MaveDB, LitVar.
Notable EP300 variants
Examples include M1?, A2G, A2V, A2A, E3*, E3D, E3K, E3Q. 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), Ensembl rs2145665423
- A2V (p.Ala2Val), Ensembl rs2145665423
- A2A (p.Ala2Ala), rs1292335705, gnomAD 22-41093010-C-A, CADD 14.50
- E3* (p.Glu3Ter), NCI-TCGA Cosmic COSV9960, Variant assessed as somatic; high impact.
- E3D (p.Glu3Asp), rs2058682150, ClinGen CA411679375, NCI-TCGA Cosmic COSV9960, ClinVar RCV003527257, AlphaMissense 0.15, MetaLR 0.43, Uncertain significance, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- E3K (p.Glu3Lys), rs181951278, ClinGen CA324525050, ClinVar RCV001198506, 1000Genomes rs181951278, REVEL 0.51, CADD 32.00, Uncertain significance, Menke-Hennekam syndrome 2
- E3Q (p.Glu3Gln), 1000Genomes rs181951278, Uncertain significance
- E3E (p.Glu3Glu), rs2058682150, gnomAD 22-41093013-G-A, AlphaMissense 0.15, MetaLR 0.43
- N4I (p.Asn4Ile), Ensembl rs2145665445
- N4K (p.Asn4Lys), rs758604225, ClinGen CA411679382, ClinVar RCV003147059, Uncertain significance, not provided
- N4Y (p.Asn4Tyr), Ensembl rs2145665440
- N4N (p.Asn4Asn), rs758604225, gnomAD 22-41093016-T-C, CADD 14.30
- V5M (p.Val5Met), gnomAD 22-41093017-G-A, REVEL 0.39, CADD 28.70
- V5V (p.Val5Val), rs1400876948, gnomAD 22-41093019-G-A, CADD 11.70
- V6G (p.Val6Gly), Ensembl rs2145665458, REVEL 0.54, CADD 29.70
- V6L (p.Val6Leu), Ensembl rs2145665455
- V6M (p.Val6Met), Ensembl rs2145665455
- E7A (p.Glu7Ala), Ensembl rs2145665463
- E7G (p.Glu7Gly), Ensembl rs2145665463
- E7Q (p.Glu7Gln), Ensembl rs2145665461, Uncertain significance, Rubinstein-Taybi syndrome due to CREBBP mutations; Colorectal cancer; Rubinstein
- E7V (p.Glu7Val), Ensembl rs2145665463
- E7D (p.Glu7Asp), gnomAD 22-41093025-A-T, REVEL 0.29, CADD 19.60
- P8A (p.Pro8Ala), Ensembl rs1601582416, Uncertain significance
- P8L (p.Pro8Leu), ExAC rs760995545, TOPMed rs760995545, gnomAD rs760995545, REVEL 0.33, CADD 24.20, Likely benign, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- P8R (p.Pro8Arg), ExAC rs760995545, TOPMed rs760995545, gnomAD rs760995545, REVEL 0.32, CADD 24.60
- P8S (p.Pro8Ser), Ensembl rs1601582416, REVEL 0.19, CADD 21.80, Uncertain significance, EP300-related disorder
- G9A (p.Gly9Ala), Ensembl rs2145665484
- G9R (p.Gly9Arg), gnomAD rs1264361255
- G9W (p.Gly9Trp), gnomAD rs1264361255, REVEL 0.72, CADD 32.00
- P10A (p.Pro10Ala), Ensembl rs2145665490, Uncertain significance
- P10L (p.Pro10Leu), ExAC rs764405219, TOPMed rs764405219, gnomAD rs764405219, REVEL 0.53, CADD 27.80, Likely benign
- P10Q (p.Pro10Gln), NCI-TCGA Cosmic COSV5434, Variant assessed as somatic; moderate impact.
- P10R (p.Pro10Arg), rs764405219, ClinGen CA10252139, ClinVar RCV003919744, ExAC rs764405219, REVEL 0.62, CADD 27.00, Likely benign, EP300-related disorder
- P10S (p.Pro10Ser), rs2145665490, ClinGen CA411679417, ClinVar RCV002592674, ClinVar RCV004779238, AlphaMissense 0.31, MetaLR 0.78, Uncertain significance, not provided; Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- P10T (p.Pro10Thr), Ensembl rs2145665490, Uncertain significance
- P10P (p.Pro10Pro), rs754309936, gnomAD 22-41093034-G-A, CADD 14.10
- P11A (p.Pro11Ala), ExAC rs762278198, TOPMed rs762278198, gnomAD rs762278198, Benign
- P11H (p.Pro11His), ExAC rs765627133, gnomAD rs765627133
- P11L (p.Pro11Leu), ExAC rs765627133, gnomAD rs765627133, REVEL 0.45, CADD 27.80
- P11R (p.Pro11Arg), ExAC rs765627133, gnomAD rs765627133
- P11S (p.Pro11Ser), rs762278198, ClinGen CA10252141, ClinVar RCV002637526, ClinVar RCV003404118, REVEL 0.40, CADD 24.00, Conflicting interpretations, EP300-related disorder; Rubinstein-Taybi syndrome due to EP300 haploinsufficienc
- P11T (p.Pro11Thr), ExAC rs762278198, TOPMed rs762278198, gnomAD rs762278198, Benign
- P11P (p.Pro11Pro), rs750974943, gnomAD 22-41093037-T-A, CADD 14.80
- S12* (p.Ser12Ter), ExAC rs758786824, TOPMed rs758786824, gnomAD rs758786824, CADD 28.40
- S12L (p.Ser12Leu), ExAC rs758786824, TOPMed rs758786824, gnomAD rs758786824, REVEL 0.42, CADD 25.40
- S12P (p.Ser12Pro), Ensembl rs2145665525
- S12T (p.Ser12Thr), Ensembl rs2145665525
- S12S (p.Ser12Ser), rs2145665538, gnomAD 22-41093040-A-G, CADD 14.60
- A13D (p.Ala13Asp), ExAC rs767107086, TOPMed rs767107086, gnomAD rs767107086
- A13G (p.Ala13Gly), ExAC rs767107086, TOPMed rs767107086, gnomAD rs767107086, REVEL 0.30, CADD 27.10, Uncertain significance, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- A13P (p.Ala13Pro), Ensembl rs2145665545
- A13V (p.Ala13Val), ExAC rs767107086, TOPMed rs767107086, gnomAD rs767107086
- A13S (p.Ala13Ser), gnomAD 22-41093041-G-T, REVEL 0.27, CADD 23.50
- A13A (p.Ala13Ala), rs2145665558, gnomAD 22-41093043-C-G, CADD 14.40
- K14* (p.Lys14Ter), Ensembl rs2145665564
- K14E (p.Lys14Glu), Ensembl rs2145665564
- K14M (p.Lys14Met), Ensembl rs2145665571
- K14N (p.Lys14Asn), rs2145665576, Ensembl rs2145665576, ClinGen CA411679441, ClinVar RCV003194454, AlphaMissense 0.99, MetaLR 0.81, Uncertain significance, Inborn genetic diseases
- K14Q (p.Lys14Gln), NCI-TCGA Cosmic COSV5432, Variant assessed as somatic; moderate impact.
- K14R (p.Lys14Arg), Ensembl rs2145665571
- K14K (p.Lys14Lys), gnomAD 22-41093046-G-A, CADD 13.40
- R15P (p.Arg15Pro), Ensembl rs2145665582
- R15Q (p.Arg15Gln), Ensembl rs2145665582
- R15R (p.Arg15Arg), rs752119517, gnomAD 22-41093049-G-C, CADD 14.40
- P16A (p.Pro16Ala), ExAC rs757059831, gnomAD rs757059831
- P16H (p.Pro16His), Ensembl rs2145665599, Uncertain significance
- P16L (p.Pro16Leu), Ensembl rs2145665599, REVEL 0.51, AlphaMissense 0.92, Uncertain significance
- P16R (p.Pro16Arg), rs2145665599, ClinGen CA411679450, ClinVar RCV002834199, Ensembl rs2145665599, AlphaMissense 0.92, MetaLR 0.73, Uncertain significance, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- P16S (p.Pro16Ser), ExAC rs757059831, gnomAD rs757059831
- P16T (p.Pro16Thr), ExAC rs757059831, gnomAD rs757059831
- P16P (p.Pro16Pro), rs2058682349, gnomAD 22-41093052-T-C, CADD 15.40
- K17* (p.Lys17Ter), Ensembl rs2145665611
- K17E (p.Lys17Glu), NCI-TCGA Cosmic COSV5432, Ensembl rs2145665611, Variant assessed as somatic; moderate impact.
- K17I (p.Lys17Ile), Ensembl rs2145665617
- K17N (p.Lys17Asn), Ensembl rs2145665622
- K17Q (p.Lys17Gln), Ensembl rs2145665611
- K17R (p.Lys17Arg), Ensembl rs2145665617
- K17T (p.Lys17Thr), Ensembl rs2145665617
- K17K (p.Lys17Lys), gnomAD 22-41093055-A-G, CADD 14.60
- L18F (p.Leu18Phe), ExAC rs777392825, TOPMed rs777392825, gnomAD rs777392825, REVEL 0.43, CADD 27.10
- L18I (p.Leu18Ile), ExAC rs777392825, TOPMed rs777392825, gnomAD rs777392825
- L18T (p.Leu18Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L18V (p.Leu18Val), ExAC rs777392825, TOPMed rs777392825, gnomAD rs777392825, REVEL 0.38, CADD 25.80, Likely benign, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- L18R (p.Leu18Arg), gnomAD 22-41093057-T-G, REVEL 0.64, CADD 31.00
- L18L (p.Leu18Leu), rs748882006, gnomAD 22-41093058-C-G, CADD 13.50
- S19* (p.Ser19Ter), NCI-TCGA Cosmic COSV5433, TOPMed rs2058682377, Variant assessed as somatic; high impact.
- S19L (p.Ser19Leu), TOPMed rs2058682377
- S19P (p.Ser19Pro), Ensembl rs2145665635
- S19S (p.Ser19Ser), gnomAD 22-41093061-A-C, CADD 11.00
- S20C (p.Ser20Cys), TOPMed rs1340956941, gnomAD rs1340956941
- S20F (p.Ser20Phe), TOPMed rs1340956941, gnomAD rs1340956941, REVEL 0.62, CADD 28.70
- S20T (p.Ser20Thr), Ensembl rs2145665649
- S20Y (p.Ser20Tyr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- S20S (p.Ser20Ser), rs2145665664, gnomAD 22-41093064-T-C, CADD 14.70
- P21A (p.Pro21Ala), NCI-TCGA Cosmic COSV5433, Variant assessed as somatic; moderate impact.
- P21L (p.Pro21Leu), Ensembl rs2145665670, REVEL 0.66, CADD 28.30
- P21Q (p.Pro21Gln), Ensembl rs2145665670
- P21R (p.Pro21Arg), Ensembl rs2145665670, REVEL 0.68, CADD 27.40
- P21P (p.Pro21Pro), rs757050695, gnomAD 22-41093067-G-C, CADD 14.00
- A22P (p.Ala22Pro), Ensembl rs2058682425
- A22S (p.Ala22Ser), Ensembl rs2058682425
- A22T (p.Ala22Thr), Ensembl rs2058682425
- A22V (p.Ala22Val), TOPMed rs755558514, gnomAD rs755558514, REVEL 0.38, CADD 27.40, Uncertain significance, EP300-related disorder
- A22A (p.Ala22Ala), gnomAD 22-41093070-C-A, CADD 14.50
- L23F (p.Leu23Phe), ExAC rs778522586, TOPMed rs778522586, gnomAD rs778522586, REVEL 0.26, CADD 24.40
- L23H (p.Leu23His), Ensembl rs2145665700
- L23I (p.Leu23Ile), ExAC rs778522586, TOPMed rs778522586, gnomAD rs778522586
- L23P (p.Leu23Pro), Ensembl rs2145665700
- L23L (p.Leu23Leu), rs543993838, gnomAD 22-41093073-C-T, CADD 10.30
- S24* (p.Ser24Ter), ESP rs373061594, ExAC rs373061594, gnomAD rs373061594
- S24L (p.Ser24Leu), ESP rs373061594, ExAC rs373061594, gnomAD rs373061594, REVEL 0.50, CADD 28.60
- S24P (p.Ser24Pro), TOPMed rs1478987595
- S24T (p.Ser24Thr), TOPMed rs1478987595
- S24W (p.Ser24Trp), ESP rs373061594, ExAC rs373061594, gnomAD rs373061594
- S24S (p.Ser24Ser), rs1485139574, gnomAD 22-41093076-G-A, CADD 14.30
- A25G (p.Ala25Gly), Ensembl rs2145665733
- A25P (p.Ala25Pro), rs775703248, NCI-TCGA Cosmic COSV9960, ExAC rs775703248, TOPMed rs775703248, REVEL 0.34, CADD 31.00, Variant assessed as somatic; moderate impact.
- A25S (p.Ala25Ser), ExAC rs775703248, TOPMed rs775703248, gnomAD rs775703248
- A25T (p.Ala25Thr), ExAC rs775703248, TOPMed rs775703248, gnomAD rs775703248
- A25V (p.Ala25Val), Ensembl rs2145665733, REVEL 0.28, CADD 22.20
- A25A (p.Ala25Ala), rs2058682567, gnomAD 22-41093079-G-A, CADD 14.00
- S26A (p.Ser26Ala), Ensembl rs2145665745
- S26C (p.Ser26Cys), Ensembl rs2145665751
- S26F (p.Ser26Phe), Ensembl rs2145665751
- S26P (p.Ser26Pro), Ensembl rs2145665745
- S26T (p.Ser26Thr), Ensembl rs2145665745
- S26Y (p.Ser26Tyr), Ensembl rs2145665751
- S26S (p.Ser26Ser), rs747042929, gnomAD 22-41093082-C-G, CADD 12.80
- A27D (p.Ala27Asp), ExAC rs776993553, TOPMed rs776993553, gnomAD rs776993553
- A27G (p.Ala27Gly), ExAC rs776993553, TOPMed rs776993553, gnomAD rs776993553
- A27P (p.Ala27Pro), ExAC rs768794905, gnomAD rs768794905
- A27T (p.Ala27Thr), ExAC rs768794905, gnomAD rs768794905, REVEL 0.25, CADD 26.60
- A27V (p.Ala27Val), ExAC rs776993553, TOPMed rs776993553, gnomAD rs776993553, REVEL 0.33, CADD 25.60, Benign, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- A27A (p.Ala27Ala), rs2145665783, gnomAD 22-41093085-C-A, CADD 14.90
- S28C (p.Ser28Cys), ExAC rs762091919, gnomAD rs762091919
- S28G (p.Ser28Gly), ExAC rs762091919, gnomAD rs762091919, REVEL 0.37, CADD 29.70
- S28I (p.Ser28Ile), TOPMed rs1382860268, gnomAD rs1382860268, REVEL 0.47, CADD 32.00
- S28N (p.Ser28Asn), TOPMed rs1382860268, gnomAD rs1382860268
- S28R (p.Ser28Arg), ExAC rs762091919, gnomAD rs762091919, REVEL 0.42, CADD 27.40
- S28T (p.Ser28Thr), TOPMed rs1382860268, gnomAD rs1382860268
- D29E (p.Asp29Glu), gnomAD rs1180540617
- D29G (p.Asp29Gly), Ensembl rs2145665807
- D29N (p.Asp29Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D29del (p.Asp29del), gnomAD 22-41093088-CGAT-, CADD 22.60
- D29D (p.Asp29Asp), rs1180540617, gnomAD 22-41093091-T-C, CADD 9.68
- G30A (p.Gly30Ala), Ensembl rs2145665820, REVEL 0.26, CADD 25.20
- G30C (p.Gly30Cys), Ensembl rs2145665814, Uncertain significance
- G30D (p.Gly30Asp), Ensembl rs2145665820
- G30S (p.Gly30Ser), rs2145665814, ClinGen CA411679526, ClinVar RCV003427760, ClinVar RCV003525397, AlphaMissense 0.30, MetaLR 0.65, Uncertain significance, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency; EP300-related disorde
- G30G (p.Gly30Gly), rs2145665827, gnomAD 22-41093094-C-G, CADD 14.40
- T31A (p.Thr31Ala), Ensembl rs2145665831, REVEL 0.21, CADD 23.10
- T31I (p.Thr31Ile), Ensembl rs2145665839, REVEL 0.43, CADD 27.80
- T31K (p.Thr31Lys), Ensembl rs2145665839
- T31P (p.Thr31Pro), Ensembl rs2145665831
- T31R (p.Thr31Arg), Ensembl rs2145665839
- T31S (p.Thr31Ser), Ensembl rs2145665831
- T31T (p.Thr31Thr), rs2145665847, gnomAD 22-41093097-A-G, CADD 23.00
- D32H (p.Asp32His), TOPMed rs1198218045, gnomAD rs1198218045
- D32N (p.Asp32Asn), TOPMed rs1198218045, gnomAD rs1198218045
- D32Y (p.Asp32Tyr), TOPMed rs1198218045, gnomAD rs1198218045, REVEL 0.77, CADD 35.00
- D32G (p.Asp32Gly), gnomAD 22-41117187-A-G, REVEL 0.56, CADD 32.00
- F33V (p.Phe33Val), NCI-TCGA Cosmic COSV5433, Variant assessed as somatic; moderate impact.
- F33L (p.Phe33Leu), gnomAD 22-41117189-T-C, REVEL 0.58, CADD 24.30
- G34D (p.Gly34Asp), ExAC rs764782074, gnomAD rs764782074, REVEL 0.61, CADD 27.40
- G34V (p.Gly34Val), ExAC rs764782074, gnomAD rs764782074
- G34R (p.Gly34Arg), gnomAD 22-41117192-G-C, REVEL 0.64, CADD 27.20
- G34G (p.Gly34Gly), rs750031887, gnomAD 22-41117194-C-G, CADD 9.42
- S35A (p.Ser35Ala), rs546292445, ClinGen CA10252190, ClinVar RCV000598410, ClinVar RCV006463494, REVEL 0.54, CADD 26.00, Conflicting interpretations, not provided; Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- S35C (p.Ser35Cys), rs2145696235, ClinGen CA411679576, ClinVar RCV002554127, Ensembl rs2145696235, REVEL 0.54, CADD 25.30, Uncertain significance, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency
- L36R (p.Leu36Arg), NCI-TCGA Cosmic COSV5434, Variant assessed as somatic; moderate impact.
- L36L (p.Leu36Leu), gnomAD 22-41117198-C-T, CADD 8.11
- F37L (p.Phe37Leu), gnomAD 22-41117201-T-C, REVEL 0.52, CADD 24.00
- D38V (p.Asp38Val), Ensembl rs2145696247
- D38Y (p.Asp38Tyr), gnomAD 22-41117204-G-T, REVEL 0.67, CADD 32.00
- L39L (p.Leu39Leu), gnomAD 22-41117209-G-A, CADD 15.60
- E40* (p.Glu40Ter), Ensembl rs2145696261
- E40V (p.Glu40Val), Ensembl rs2145696267
- E40E (p.Glu40Glu), rs564574458, gnomAD 22-41117212-G-A, CADD 8.73
- H41D (p.His41Asp), Ensembl rs2145696274
Public EP300 analysis runs
- EP300 analysis run — EP300 (6,833 variants) — completed 2026-08-18