POLR1D (P0DPB6) variants and mutations
POLR1D (also known as P0DPB6) is a human protein-coding gene encoding a DNA-directed RNA polymerases I and III subunit RPAC2 protein. Its annotated function is DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I and III which synthesize ribosomal RNA precursors and short…. It is annotated at the nucleus. This analysis covers 346 POLR1D variants and mutations. Of these, 99% have computational variant effect predictions. Disease context includes Treacher Collins syndrome 2, Treacher-Collins syndrome, and hereditary disease. Example POLR1D variants include E2D, E2G, and E2*.
Variant analysis overview
- Gene: POLR1D
- Protein: P0DPB6
- UniProt accession: P0DPB6
- Organism: Homo sapiens
- Variants analyzed: 346
- Variant scope: all variants
- Completed: 2026-09-13
Variant and mutation evidence
- Variant composition: 164 unspecified-consequence records; 8 stop-gained variants; 107 missense variants; 62 synonymous variants; 11 frameshift variants; 3 splice-region variants; 2 in-frame deletions; 1 in-frame insertions; 1 stop retained variant; 2 stop lost; 1 substitution
- Prediction scores: 343 variants have prediction scores (99% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Treacher Collins syndrome 2, Treacher-Collins syndrome, hereditary disease, neurodegenerative disease, Hearing impairment, ovarian neoplasm, colorectal carcinoma, exostosis, lung cancer, lung carcinoma, trauma complication, central nervous system cancer.
Protein structure and variant hotspots
- Protein features: 1 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 POLR1D variants
Examples include E2D, E2G, E2*, E2K, E2E, E3D, E3K, E3V. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- E2D (p.Glu2Asp), 1000Genomes rs376051642, ExAC rs376051642, TOPMed rs376051642, gnomAD rs376051642, REVEL 0.32, CADD 21.20
- E2G (p.Glu2Gly), Ensembl rs1955936711, REVEL 0.44, CADD 28.60
- E2* (p.Glu2Ter), gnomAD 13-27621987-G-T, CADD 50.00
- E2K (p.Glu2Lys), gnomAD 13-27621987-G-A, REVEL 0.35, CADD 26.40
- E2E (p.Glu2Glu), rs376051642, gnomAD 13-27621989-A-G, CADD 13.80
- E3D (p.Glu3Asp), Ensembl rs2138515151, REVEL 0.35, CADD 19.40
- E3K (p.Glu3Lys), gnomAD rs1207392749, MetaLR 0.54, MetaSVM -0.30
- E3V (p.Glu3Val), gnomAD 13-27621991-A-T, REVEL 0.40, CADD 26.20
- E3G (p.Glu3Gly), gnomAD 13-27621991-A-G, REVEL 0.34, CADD 32.00
- D4G (p.Asp4Gly), gnomAD rs1248020853, MetaLR 0.55, MetaSVM 0.24
- D4N (p.Asp4Asn), gnomAD 13-27621993-G-A, REVEL 0.34, CADD 26.40
- D4Y (p.Asp4Tyr), gnomAD 13-27621993-G-T, REVEL 0.42, CADD 32.00
- Q5* (p.Gln5Ter), TOPMed rs1347269621, gnomAD rs1347269621, CADD 44.00
- Q5R (p.Gln5Arg), gnomAD 13-27621995-TC-T, CADD 33.00
- Q5K (p.Gln5Lys), gnomAD 13-27621996-C-A, REVEL 0.26, CADD 23.80
- Q5E (p.Gln5Glu), gnomAD 13-27621996-C-G, REVEL 0.23, CADD 22.60
- Q5P (p.Gln5Pro), gnomAD 13-27621997-A-C, REVEL 0.45, CADD 24.40
- Q5L (p.Gln5Leu), gnomAD 13-27621997-A-T, REVEL 0.34, CADD 24.60
- Q5Q (p.Gln5Gln), gnomAD 13-27621998-G-A, CADD 12.70
- E6K (p.Glu6Lys), TOPMed rs1450614909, gnomAD rs1450614909, REVEL 0.42, CADD 26.20
- E6Q (p.Glu6Gln), TOPMed rs1450614909, gnomAD rs1450614909, REVEL 0.28, CADD 27.90
- E6* (p.Glu6Ter), gnomAD 13-27621999-G-T, CADD 49.00
- E6E (p.Glu6Glu), gnomAD 13-27622001-G-A, CADD 11.90
- E6D (p.Glu6Asp), gnomAD 13-27622001-G-T, REVEL 0.23, CADD 18.70
- L7L (p.Leu7Leu), gnomAD 13-27622002-C-T, CADD 14.40
- L7M (p.Leu7Met), gnomAD 13-27622002-C-A, REVEL 0.25, CADD 23.20
- L7P (p.Leu7Pro), gnomAD 13-27622003-T-C, REVEL 0.59, CADD 24.70
- L7Q (p.Leu7Gln), gnomAD 13-27622003-T-A, REVEL 0.38, CADD 25.50
- E8* (p.Glu8Ter), gnomAD 13-27622005-G-T, CADD 49.00
- E8K (p.Glu8Lys), gnomAD 13-27622005-G-A, REVEL 0.48, CADD 32.00
- E8V (p.Glu8Val), gnomAD 13-27622006-A-T, REVEL 0.45, CADD 34.00
- E8G (p.Glu8Gly), gnomAD 13-27622006-A-G, REVEL 0.47, CADD 33.00
- E8D (p.Glu8Asp), gnomAD 13-27622007-G-T, REVEL 0.31, CADD 26.20
- E8E (p.Glu8Glu), rs1190644767, gnomAD 13-27622007-G-A, CADD 17.00
- R9K (p.Arg9Lys), Ensembl rs1593274191, REVEL 0.32, CADD 33.00
- R9G (p.Arg9Gly), gnomAD 13-27622008-A-G, REVEL 0.47, CADD 34.00
- R9I (p.Arg9Ile), gnomAD 13-27622009-G-T, REVEL 0.41, CADD 36.00
- R9S (p.Arg9Ser), gnomAD 13-27648379-G-C, CADD 25.80
- R9R (p.Arg9Arg), rs200478683, gnomAD 13-27648379-G-A, CADD 20.40
- K10E (p.Lys10Glu), gnomAD 13-27622876-A-G, REVEL 0.40, CADD 24.40
- K10Q (p.Lys10Gln), rs1448031546, gnomAD 13-27648380-A-C, CADD 27.00
- K10R (p.Lys10Arg), rs748142776, gnomAD 13-27648381-A-G, CADD 23.60
- K10K (p.Lys10Lys), gnomAD 13-27648382-A-G, CADD 9.99
- I11M (p.Ile11Met), gnomAD rs1955962901, REVEL 0.23, CADD 14.70
- I11Y (p.Ile11Tyr), gnomAD 13-27622874-GA-G, CADD 35.00
- I11V (p.Ile11Val), rs758252910, gnomAD 13-27648386-A-G, CADD 17.20
- I11T (p.Ile11Thr), gnomAD 13-27648387-T-C, CADD 24.20
- I11I (p.Ile11Ile), rs777776296, gnomAD 13-27648388-A-T, CADD 10.70
- S12P (p.Ser12Pro), TOPMed rs1013753456, gnomAD rs1013753456, REVEL 0.26, CADD 21.80, Uncertain significance, not provided; Inborn genetic diseases
- S12Y (p.Ser12Tyr), gnomAD 13-27622883-C-A, REVEL 0.22, CADD 23.80
- G13K (p.Gly13Lys), gnomAD 13-27622009-G-GAA, CADD 32.00
- G13R (p.Gly13Arg), gnomAD 13-27622885-G-A, REVEL 0.37, CADD 34.00
- G13A (p.Gly13Ala), gnomAD 13-27622886-G-C, REVEL 0.33, CADD 27.00
- G13G (p.Gly13Gly), gnomAD 13-27622887-A-G, CADD 19.40
- L14M (p.Leu14Met), cosmic curated COSV10026, TOPMed rs1286517710, MetaLR 0.53, MetaSVM -0.40
- L14F (p.Leu14Phe), gnomAD 13-27622890-G-C, REVEL 0.24, CADD 23.00
- L14L (p.Leu14Leu), rs139003194, gnomAD 13-27648397-G-A, CADD 8.73
- K15M (p.Lys15Met), Ensembl rs1955963043, MetaLR 0.73, MetaSVM 0.42
- K15del (p.Lys15del), rs752153066, gnomAD 13-27622889-TGAA-, CADD 23.10
- K15E (p.Lys15Glu), gnomAD 13-27622891-A-G, REVEL 0.39, CADD 24.30
- K15K (p.Lys15Lys), rs1206684244, gnomAD 13-27622893-G-A, CADD 15.90
- K15T (p.Lys15Thr), gnomAD 13-27648402-A-C, CADD 22.70
- T16I (p.Thr16Ile), TOPMed rs921178811, gnomAD rs921178811, REVEL 0.21, CADD 23.70
- T16S (p.Thr16Ser), TOPMed rs921178811, gnomAD rs921178811, REVEL 0.24, CADD 22.70
- T16N (p.Thr16Asn), gnomAD 13-27622895-C-A, REVEL 0.23, CADD 22.60
- T16T (p.Thr16Thr), gnomAD 13-27622896-C-T, CADD 12.40
- S17L (p.Ser17Leu), gnomAD 13-27622898-C-T, REVEL 0.41, CADD 26.60
- M18I (p.Met18Ile), 1000Genomes rs529013502, ExAC rs529013502, gnomAD rs529013502
- M18T (p.Met18Thr), gnomAD rs1181663977
- M18V (p.Met18Val), TOPMed rs1482213619, gnomAD rs1482213619, MetaLR 0.43, MetaSVM -0.63, Uncertain significance, Inborn genetic diseases
- A19G (p.Ala19Gly), TOPMed rs1555271293, gnomAD rs1555271293, REVEL 0.18, CADD 23.60, Uncertain significance
- A19V (p.Ala19Val), rs1555271293, ClinGen CA387634742, ClinVar RCV000497583, TOPMed rs1555271293, AlphaMissense 0.11, MetaLR 0.54, Uncertain significance, not provided
- A19A (p.Ala19Ala), rs776525888, gnomAD 13-27622905-T-C, CADD 11.30
- A19T (p.Ala19Thr), rs1956238400, gnomAD 13-27648383-G-A, CADD 27.60
- A19E (p.Ala19Glu), gnomAD 13-27648384-C-A, CADD 25.60
- E20K (p.Glu20Lys), gnomAD 13-27622009-G-GAA, CADD 32.00
- E20E (p.Glu20Glu), rs1296188944, gnomAD 13-27648406-G-A, CADD 9.28
- G21D (p.Gly21Asp), Ensembl rs1361719344, MetaLR 0.52, MetaSVM 0.13
- G21S (p.Gly21Ser), ExAC rs759527489, gnomAD rs759527489, REVEL 0.28, CADD 22.90
- G21G (p.Gly21Gly), rs932578285, gnomAD 13-27622911-C-T, CADD 14.90
- E22K (p.Glu22Lys), ExAC rs765011144, TOPMed rs765011144, gnomAD rs765011144, REVEL 0.41, CADD 23.20, Uncertain significance, not provided
- E22* (p.Glu22Ter), gnomAD 13-27622912-G-T, CADD 38.00
- E22E (p.Glu22Glu), rs151041219, gnomAD 13-27622914-G-A, CADD 11.20
- R23G (p.Arg23Gly), gnomAD rs1368109089, REVEL 0.39, CADD 23.00
- R23K (p.Arg23Lys), gnomAD 13-27622916-G-A, REVEL 0.24, CADD 22.10
- R23R (p.Arg23Arg), gnomAD 13-27622917-G-A, CADD 14.30
- R23C (p.Arg23Cys), rs770558990, gnomAD 13-27648413-C-T, CADD 31.00
- R23P (p.Arg23Pro), rs1215916836, gnomAD 13-27648414-G-C, CADD 29.00
- R23H (p.Arg23His), rs1215916836, gnomAD 13-27648414-G-A, CADD 29.20
- R23T (p.Arg23Thr), gnomAD 13-27648426-G-C, CADD 25.60
- K24R (p.Lys24Arg), gnomAD 13-27622919-A-G, REVEL 0.34, CADD 23.20
- K24N (p.Lys24Asn), gnomAD 13-27622920-G-C, REVEL 0.30, CADD 23.20
- K24T (p.Lys24Thr), rs1956238781, gnomAD 13-27648420-A-C, CADD 25.60
- T25I (p.Thr25Ile), TOPMed rs777412814, gnomAD rs777412814, REVEL 0.37, CADD 21.50
- T25T (p.Thr25Thr), gnomAD 13-27648424-T-C, CADD 2.52
- A26P (p.Ala26Pro), gnomAD rs1308191452, REVEL 0.45, CADD 22.90
- A26T (p.Ala26Thr), gnomAD 13-27622924-G-A, REVEL 0.22, CADD 22.30
- A26D (p.Ala26Asp), gnomAD 13-27622925-C-A, REVEL 0.50, CADD 18.30
- A26A (p.Ala26Ala), rs372189960, gnomAD 13-27622926-C-T, CADD 13.60
- A26V (p.Ala26Val), rs1956238897, gnomAD 13-27648429-C-T, CADD 26.60
- L27L (p.Leu27Leu), rs763616303, gnomAD 13-27622927-C-T, CADD 11.60
- p.Glu28 Gln31del, gnomAD 13-27622928-TGGAA, CADD 21.20
- E28A (p.Glu28Ala), gnomAD 13-27622931-A-C, REVEL 0.28, CADD 21.70
- E28K (p.Glu28Lys), rs1209845490, gnomAD 13-27648431-G-A, CADD 26.60
- E28Q (p.Glu28Gln), rs1209845490, gnomAD 13-27648431-G-C, CADD 27.50
- E28V (p.Glu28Val), gnomAD 13-27648432-A-T, CADD 29.60
- E28E (p.Glu28Glu), gnomAD 13-27648433-A-G, CADD 9.01
- M29V (p.Met29Val), gnomAD 13-27622933-A-G, REVEL 0.26, CADD 21.60
- M29T (p.Met29Thr), gnomAD 13-27648447-T-C, CADD 22.60
- V30K (p.Val30Lys), gnomAD 13-27622008-A-AGA, CADD 32.00
- V30F (p.Val30Phe), gnomAD 13-27622936-G-T, REVEL 0.52, CADD 27.70
- Q31* (p.Gln31Ter), gnomAD 13-27650049-C-T, CADD 11.70
- Q31R (p.Gln31Arg), gnomAD 13-27650049-CA-C, CADD 7.47
- Q31K (p.Gln31Lys), gnomAD 13-27650055-C-A, CADD 6.00
- Q31Q (p.Gln31Gln), gnomAD 13-27650057-A-G, CADD 6.93
- A32T (p.Ala32Thr), gnomAD rs1311004441, REVEL 0.30, CADD 23.20
- A32A (p.Ala32Ala), rs1340438966, gnomAD 13-27622944-A-C, CADD 11.90
- A33P (p.Ala33Pro), rs751267443, ClinGen CA6927257, ClinVar RCV002901983, ExAC rs751267443, REVEL 0.29, CADD 23.30, Uncertain significance, Inborn genetic diseases
- A33V (p.Ala33Val), gnomAD rs1294065662, REVEL 0.24, CADD 22.60
- A33S (p.Ala33Ser), gnomAD 13-27622945-G-T, REVEL 0.31, CADD 22.10
- G34A (p.Gly34Ala), Ensembl rs1955964392, MetaLR 0.51, MetaSVM -0.19
- G34R (p.Gly34Arg), gnomAD 13-27622948-G-A, REVEL 0.53, CADD 31.00
- G34G (p.Gly34Gly), gnomAD 13-27622950-A-T, CADD 11.80
- G34D (p.Gly34Asp), gnomAD 13-27648438-TG-T, CADD 31.00
- G34V (p.Gly34Val), rs769345066, gnomAD 13-27648441-G-T, CADD 28.50
- G34* (p.Gly34Ter), gnomAD 13-27648449-G-T, CADD 34.00
- T35I (p.Thr35Ile), rs1053573832, ClinGen CA387634957, ClinVar RCV003577479, REVEL 0.39, CADD 22.80, Uncertain significance, not provided
- T35R (p.Thr35Arg), TOPMed rs1053573832, gnomAD rs1053573832, REVEL 0.36, CADD 22.60, Uncertain significance, Inborn genetic diseases
- D36G (p.Asp36Gly), TOPMed rs1399388625, REVEL 0.52, CADD 25.10
- D36N (p.Asp36Asn), ExAC rs756808529, gnomAD rs756808529, REVEL 0.37, CADD 24.80, Uncertain significance, Inborn genetic diseases
- p.Asp36 Arg37insVal, gnomAD 13-27622956-T-TGT, CADD 20.50
- D36E (p.Asp36Glu), gnomAD 13-27622956-T-G, REVEL 0.31, CADD 23.80
- D36D (p.Asp36Asp), rs1193305939, gnomAD 13-27650060-T-C, CADD 7.82
- R37K (p.Arg37Lys), TOPMed rs1955964638
- p.Arg37delinsThrValTer, gnomAD 13-27622957-A-ACT, CADD 34.00
- R37T (p.Arg37Thr), gnomAD 13-27622958-G-C, REVEL 0.38, CADD 22.70
- H38P (p.His38Pro), gnomAD rs1204708589, REVEL 0.47, CADD 22.40
- H38R (p.His38Arg), gnomAD rs1204708589, REVEL 0.22, CADD 20.80
- C39T (p.Cys39Thr), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact., in TCS2
- C39L (p.Cys39Leu), gnomAD 13-27622959-A-ACA, CADD 28.60
- C39R (p.Cys39Arg), gnomAD 13-27622963-T-C, REVEL 0.73, CADD 31.00
- C39S (p.Cys39Ser), gnomAD 13-27622963-T-A, REVEL 0.71, CADD 25.00
- C39* (p.Cys39Ter), gnomAD 13-27650042-C-A, CADD 1.17
- C39C (p.Cys39Cys), rs901340034, gnomAD 13-27650042-C-T, CADD 3.31
- V40A (p.Val40Ala), gnomAD rs1275701517, REVEL 0.52, CADD 24.00
- V40K (p.Val40Lys), gnomAD 13-27622009-G-GAA, CADD 32.00
- V40M (p.Val40Met), gnomAD 13-27622966-G-A, REVEL 0.56, CADD 23.40
- T41T (p.Thr41Thr), gnomAD 13-27622971-A-G, CADD 11.10
- T41A (p.Thr41Ala), gnomAD 13-27650061-A-G, CADD 7.69
- T41R (p.Thr41Arg), rs747115559, gnomAD 13-27650062-C-G, CADD 9.35
- F42L (p.Phe42Leu), Ensembl rs886050108, MetaLR 0.80, MetaSVM 0.62
- F42V (p.Phe42Val), gnomAD 13-27622972-T-G, REVEL 0.78, CADD 25.20
- F42Y (p.Phe42Tyr), gnomAD 13-27622973-T-A, REVEL 0.68, CADD 24.90
- L44F (p.Leu44Phe), rs2500474648, ClinGen CA387635062, ClinVar RCV002716159, REVEL 0.46, CADD 22.30, Uncertain significance, not provided
- H45R (p.His45Arg), gnomAD rs1484150438, REVEL 0.59, CADD 22.80
- H45H (p.His45His), rs1179947533, gnomAD 13-27622983-C-T, CADD 11.70
- H45Q (p.His45Gln), gnomAD 13-27622983-C-A, REVEL 0.56, CADD 20.70
- E46K (p.Glu46Lys), rs1255169536, NCI-TCGA Cosmic COSV1002, cosmic curated COSV10026, gnomAD rs1255169536, REVEL 0.47, CADD 23.40, Uncertain significance, not provided
- E47K (p.Glu47Lys), rs767196650, ClinGen CA6927259, ClinVar RCV000024044, ClinVar RCV002513218, REVEL 0.93, CADD 32.00, Likely pathogenic, not provided
- D48E (p.Asp48Glu), rs750965300, ClinGen CA387635106, ClinVar RCV003291128, REVEL 0.90, CADD 24.40, Uncertain significance, Inborn genetic diseases
- D48Y (p.Asp48Tyr), rs1189463043, NCI-TCGA Cosmic COSV5725, cosmic curated COSV57256, gnomAD rs1189463043, REVEL 0.91, CADD 31.00, Variant assessed as somatic; moderate impact.
- D48D (p.Asp48Asp), rs750965300, gnomAD 13-27622992-C-T, CADD 11.80
- H49N (p.His49Asn), gnomAD 13-27622993-C-A, REVEL 0.83, CADD 25.70
- T50A (p.Thr50Ala), TOPMed rs1955965440, CADD 25.90
- T50I (p.Thr50Ile), rs2500474755, ClinGen CA387635129, ClinVar RCV003416960, UniProt VAR 064893, REVEL 0.94, CADD 26.20, Uncertain significance, POLR1D-related disorder
- T50T (p.Thr50Thr), rs756626537, gnomAD 13-27622998-C-G, CADD 11.20
- L51R (p.Leu51Arg), rs1593275448, ClinGen CA387635144, ClinVar RCV000024045, UniProt VAR 064894, AlphaMissense 0.96, MetaLR 0.94, Pathogenic, Treacher Collins syndrome 2
- L51L (p.Leu51Leu), rs895912704, gnomAD 13-27622999-C-T, CADD 12.00
- G52E (p.Gly52Glu), UniProt VAR 064895, MetaLR 0.94, MetaSVM 1.04, Pathogenic, in TCS2
- G52R (p.Gly52Arg), gnomAD 13-27623002-G-A, REVEL 0.86, CADD 29.70
- G52G (p.Gly52Gly), rs1955965597, gnomAD 13-27623004-A-G, CADD 13.50
- N53N (p.Asn53Asn), rs1457040804, gnomAD 13-27650066-C-T, CADD 6.68
- N53K (p.Asn53Lys), gnomAD 13-27650066-C-G, CADD 5.60
- S54A (p.Ser54Ala), ESP rs142365486, ExAC rs142365486, TOPMed rs142365486, gnomAD rs142365486, REVEL 0.27, CADD 17.20, Uncertain significance, not provided
- S54C (p.Ser54Cys), ExAC rs749563986, gnomAD rs749563986, REVEL 0.47, CADD 23.40
- L55V (p.Leu55Val), rs587777841, ClinGen CA270801, ClinVar RCV000144520, ClinVar RCV003319179, REVEL 0.89, CADD 25.20, Pathogenic, Treacher Collins syndrome 2
- L55R (p.Leu55Arg), gnomAD 13-27623012-T-G, REVEL 0.95, CADD 29.30
- L55L (p.Leu55Leu), rs755398859, gnomAD 13-27623013-A-G, CADD 4.36
- R56C (p.Arg56Cys), rs1014369151, ClinGen CA247287196, NCI-TCGA Cosmic COSV5725, cosmic curated COSV57256, REVEL 0.83, CADD 29.40, Uncertain significance, not specified
- R56H (p.Arg56His), TOPMed rs1181354265, gnomAD rs1181354265, REVEL 0.78, CADD 31.00
Public POLR1D analysis runs
- POLR1D analysis run — POLR1D (346 variants) — completed 2026-09-13