MSI1 (O43347) variants and mutations
MSI1 (also known as O43347) is a human protein-coding gene encoding a RNA-binding protein Musashi homolog 1 protein. It regulates translation and stability of selected messenger RNAs in neural and epithelial stem or progenitor cells. Abnormal expression can reinforce stem-like programs in cancers, although definitive Mendelian disease associations are limited. This analysis covers 633 MSI1 variants and mutations. Of these, 85% have computational variant effect predictions. Disease context includes neurodegenerative disease, glioblastoma, and lumbar disc herniation. Example MSI1 variants include T3A, D4E, and A5E.
Variant analysis overview
- Gene: MSI1
- Protein: O43347
- UniProt accession: O43347
- Organism: Homo sapiens
- Variants analyzed: 633
- Variant scope: all variants
- Completed: 2026-08-22
Variant and mutation evidence
- Variant composition: 344 unspecified-consequence records; 84 synonymous variants; 170 missense variants; 4 splice-region variants; 16 frameshift variants; 5 stop-gained variants; 3 in-frame insertions; 3 in-frame deletions; 4 substitution
- Prediction scores: 538 variants have prediction scores (85% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, glioblastoma, lumbar disc herniation, palmar fibromatosis, neoplasm, cancer, fibroblastic disorder, retinitis pigmentosa, lung carcinoma, lung cancer, cervical carcinoma, cervical cancer.
Protein structure and variant hotspots
- Protein features: 2 domains; 2 post-translational modification sites.
- Structural context: 149 variants have structural context.
- PTM context: 1 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable MSI1 variants
Examples include T3A, D4E, A5E, A5S, A5V, P6L, P8L, G9S. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- T3A (p.Thr3Ala), Ensembl rs1213368645, REVEL 0.03, CADD 15.20
- D4E (p.Asp4Glu), TOPMed rs1876225459, gnomAD rs1876225459, REVEL 0.02, CADD 14.30
- A5E (p.Ala5Glu), rs1277433654, ClinGen CA386573384, ClinVar RCV004095093, REVEL 0.06, CADD 18.30, Uncertain significance, not specified
- A5S (p.Ala5Ser), TOPMed rs1876225285, REVEL 0.04, CADD 15.50, Uncertain significance, not specified
- A5V (p.Ala5Val), rs1277433654, ClinGen CA386573382, ClinVar RCV004498410, TOPMed rs1277433654, REVEL 0.06, CADD 22.20, Uncertain significance, not specified
- P6L (p.Pro6Leu), gnomAD rs1876224805, REVEL 0.02, CADD 19.00
- P8L (p.Pro8Leu), TOPMed rs945870488, REVEL 0.03, CADD 18.60
- G9S (p.Gly9Ser), TOPMed rs914408580, gnomAD rs914408580, REVEL 0.06, CADD 14.60
- A11S (p.Ala11Ser), TOPMed rs1188321039, gnomAD rs1188321039, REVEL 0.05, CADD 13.80, Uncertain significance, not specified
- A11T (p.Ala11Thr), TOPMed rs1188321039, gnomAD rs1188321039, REVEL 0.07, CADD 16.60
- S12F (p.Ser12Phe), Ensembl rs1241648802, REVEL 0.09, CADD 22.60
- P13L (p.Pro13Leu), TOPMed rs1876223690, gnomAD rs1876223690, REVEL 0.06, CADD 19.10
- D14E (p.Asp14Glu), 1000Genomes rs1475027871, TOPMed rs1475027871, gnomAD rs1475027871, REVEL 0.04, CADD 17.80
- D14H (p.Asp14His), TOPMed rs1876223515, gnomAD rs1876223515, REVEL 0.07, CADD 22.90
- P16S (p.Pro16Ser), TOPMed rs1876222984, gnomAD rs1876222984, REVEL 0.24, CADD 18.40
- H17Q (p.His17Gln), Ensembl rs1876222624, REVEL 0.18, CADD 19.10
- H17Y (p.His17Tyr), TOPMed rs1876222806, REVEL 0.38, CADD 22.80
- D18A (p.Asp18Ala), Ensembl rs892094273, REVEL 0.24, CADD 23.10
- D18H (p.Asp18His), TOPMed rs1876222447
- K21N (p.Lys21Asn), NCI-TCGA TCGA novel, REVEL 0.45, CADD 28.60, Variant assessed as somatic; moderate impact.
- M22I (p.Met22Ile), TOPMed rs1876206771, REVEL 0.23, CADD 23.00
- M22V (p.Met22Val), gnomAD rs1410602534, REVEL 0.24, CADD 23.80
- F23L (p.Phe23Leu), gnomAD rs1159575895, REVEL 0.37, CADD 33.00
- G25W (p.Gly25Trp), TOPMed rs1489462649, gnomAD rs1489462649, REVEL 0.63, CADD 28.60
- G26E (p.Gly26Glu), TOPMed rs1201892838, gnomAD rs1201892838, REVEL 0.81, CADD 26.40
- G26R (p.Gly26Arg), gnomAD rs1409958906, REVEL 0.79, CADD 26.50
- E34G (p.Glu34Gly), gnomAD rs1271247387
- E34Q (p.Glu34Gln), TOPMed rs1876204913, gnomAD rs1876204913, REVEL 0.53, CADD 35.00
- G35R (p.Gly35Arg), Ensembl rs1565895821, REVEL 0.65, CADD 25.30
- L36R (p.Leu36Arg), rs866298359, []
- R37C (p.Arg37Cys), NCI-TCGA TCGA novel, REVEL 0.85, CADD 32.00, Variant assessed as somatic; moderate impact.
- R37H (p.Arg37His), gnomAD rs866298359, REVEL 0.81, CADD 28.90, Uncertain significance, not specified
- R37L (p.Arg37Leu), gnomAD rs866298359, REVEL 0.83, CADD 29.20
- E38K (p.Glu38Lys), gnomAD rs1339175713, REVEL 0.57, CADD 23.80
- F40L (p.Phe40Leu), Ensembl rs2136995757, REVEL 0.56, CADD 34.00
- F40V (p.Phe40Val), Ensembl rs2136995763
- G41D (p.Gly41Asp), Ensembl rs2136995747, REVEL 0.32, CADD 22.80
- Q42* (p.Gln42Ter), Ensembl rs2136995726, CADD 38.00
- Q42H (p.Gln42His), gnomAD rs998335180, REVEL 0.13, CADD 23.30, Uncertain significance, not specified
- Q42P (p.Gln42Pro), Ensembl rs2136995719
- E45* (p.Glu45Ter), TOPMed rs867317880, CADD 39.00
- E45Q (p.Glu45Gln), TOPMed rs867317880
- V46G (p.Val46Gly), Ensembl rs1592952900
- K47N (p.Lys47Asn), ESP rs376421673, ExAC rs376421673, TOPMed rs376421673, gnomAD rs376421673, REVEL 0.28, CADD 22.90
- L50V (p.Leu50Val), gnomAD rs1187821952, REVEL 0.28, CADD 22.40
- V51G (p.Val51Gly), Ensembl rs1592952881, REVEL 0.94, CADD 32.00
- V51M (p.Val51Met), ExAC rs746523102, gnomAD rs746523102, REVEL 0.84, CADD 27.60
- M52I (p.Met52Ile), gnomAD rs1244738754, REVEL 0.76, CADD 26.00
- R53W (p.Arg53Trp), gnomAD rs1350244081, REVEL 0.89, CADD 32.00
- D54H (p.Asp54His), TOPMed rs1876140491
- D54V (p.Asp54Val), Ensembl rs1876140300
- P55S (p.Pro55Ser), gnomAD rs1482812721, REVEL 0.80, CADD 25.70
- L56* (p.Leu56Ter), NCI-TCGA TCGA novel, CADD 32.00, Variant assessed as somatic; high impact.
- R59K (p.Arg59Lys), rs1206220387, gnomAD rs1206220387, REVEL 0.31, CADD 27.90, Variant assessed as somatic; moderate impact.
- F65S (p.Phe65Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V66F (p.Val66Phe), NCI-TCGA Cosmic COSV9998, Variant assessed as somatic; moderate impact.
- T67I (p.Thr67Ile), TOPMed rs1876129319
- F68V (p.Phe68Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- M69L (p.Met69Leu), gnomAD rs1367563284
- M69T (p.Met69Thr), 1000Genomes rs542793076, gnomAD rs542793076, REVEL 0.24, CADD 21.60
- D70H (p.Asp70His), TOPMed rs1038401875, gnomAD rs1038401875, REVEL 0.78, CADD 29.30
- D70N (p.Asp70Asn), TOPMed rs1038401875, gnomAD rs1038401875, REVEL 0.55, CADD 32.00
- Q71H (p.Gln71His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Q71R (p.Gln71Arg), NCI-TCGA TCGA novel, REVEL 0.56, CADD 25.90, Variant assessed as somatic; moderate impact.
- A72E (p.Ala72Glu), gnomAD rs1366486687
- A72S (p.Ala72Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A72T (p.Ala72Thr), gnomAD rs1228479601, REVEL 0.47, CADD 24.50
- G73R (p.Gly73Arg), NCI-TCGA Cosmic COSV5745, REVEL 0.73, CADD 24.80, Variant assessed as somatic; moderate impact.
- V74G (p.Val74Gly), ExAC rs756156286, gnomAD rs756156286, REVEL 0.48, CADD 33.00
- V74M (p.Val74Met), rs777720670, ClinGen CA6827863, ClinVar RCV004293901, ExAC rs777720670, REVEL 0.38, CADD 28.20, Uncertain significance, not specified
- D75G (p.Asp75Gly), Ensembl rs1592952649
- D75H (p.Asp75His), Ensembl rs1876126363
- V77E (p.Val77Glu), Ensembl rs1592952644
- L78M (p.Leu78Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- A79V (p.Ala79Val), NCI-TCGA Cosmic COSV9998, REVEL 0.18, CADD 23.60, Variant assessed as somatic; moderate impact.
- Q80L (p.Gln80Leu), ExAC rs752795681, gnomAD rs752795681, REVEL 0.26, CADD 26.00
- Q80R (p.Gln80Arg), ExAC rs752795681, gnomAD rs752795681, REVEL 0.22, CADD 23.50
- S81L (p.Ser81Leu), gnomAD rs1488476791
- S81P (p.Ser81Pro), TOPMed rs1876125120, REVEL 0.14, CADD 22.50
- R82P (p.Arg82Pro), TOPMed rs1876124672
- R82Q (p.Arg82Gln), TOPMed rs1876124672
- E84K (p.Glu84Lys), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; moderate impact.
- L85F (p.Leu85Phe), ExAC rs755234912, gnomAD rs755234912, REVEL 0.65, CADD 24.90
- L85I (p.Leu85Ile), ExAC rs755234912, gnomAD rs755234912
- D86N (p.Asp86Asn), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K88E (p.Lys88Glu), ExAC rs751873020, gnomAD rs751873020, REVEL 0.52, CADD 32.00
- T89I (p.Thr89Ile), ExAC rs766509915, TOPMed rs766509915, gnomAD rs766509915, REVEL 0.28, CADD 24.40
- I90V (p.Ile90Val), ExAC rs754277796
- D91N (p.Asp91Asn), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; moderate impact.
- A95T (p.Ala95Thr), gnomAD rs1402399207, REVEL 0.87, CADD 27.20
- A95V (p.Ala95Val), NCI-TCGA Cosmic COSV9998, Variant assessed as somatic; moderate impact.
- P97L (p.Pro97Leu), gnomAD rs1159725235, REVEL 0.75, CADD 29.90
- R98Q (p.Arg98Gln), rs1033191114, NCI-TCGA Cosmic COSV5745, TOPMed rs1033191114, gnomAD rs1033191114, REVEL 0.72, CADD 32.00, Variant assessed as somatic; moderate impact.
- R98W (p.Arg98Trp), rs769131701, ClinGen CA244420025, ClinVar RCV004176943, Ensembl rs769131701, REVEL 0.82, CADD 33.00, Uncertain significance, not specified
- R99Q (p.Arg99Gln), TOPMed rs1464070599, gnomAD rs1464070599, REVEL 0.58, CADD 29.90
- A100T (p.Ala100Thr), NCI-TCGA Cosmic COSV5745, REVEL 0.46, CADD 22.90, Variant assessed as somatic; moderate impact.
- A100V (p.Ala100Val), 1000Genomes rs201913745, ExAC rs201913745, TOPMed rs201913745, gnomAD rs201913745, REVEL 0.47, CADD 25.50
- M104V (p.Met104Val), TOPMed rs1875784780, Uncertain significance, not specified
- V105L (p.Val105Leu), ExAC rs764990217, gnomAD rs764990217
- R107* (p.Arg107Ter), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; high impact.
- R107Q (p.Arg107Gln), TOPMed rs1337094477, gnomAD rs1337094477, REVEL 0.59, CADD 24.70, Uncertain significance, not specified
- T108M (p.Thr108Met), gnomAD rs1308278218, REVEL 0.79, CADD 28.20
- K109R (p.Lys109Arg), TOPMed rs1875783456
- K110M (p.Lys110Met), NCI-TCGA Cosmic COSV9998, Variant assessed as somatic; moderate impact.
- I111V (p.Ile111Val), gnomAD rs1306687185
- V113A (p.Val113Ala), Ensembl rs1875781881, REVEL 0.54, CADD 26.40, Uncertain significance, not specified
- V113L (p.Val113Leu), ExAC rs768605844, gnomAD rs768605844, REVEL 0.50, CADD 24.90
- G115E (p.Gly115Glu), NCI-TCGA Cosmic COSV9998, TOPMed rs1592947803, Variant assessed as somatic; moderate impact.
- G115V (p.Gly115Val), NCI-TCGA Cosmic COSV9998, Variant assessed as somatic; moderate impact.
- S117L (p.Ser117Leu), NCI-TCGA TCGA novel, TOPMed rs1875780206, Variant assessed as somatic; moderate impact.
- V118L (p.Val118Leu), gnomAD rs1249650405, REVEL 0.55, CADD 23.30
- T121A (p.Thr121Ala), NCI-TCGA TCGA novel, REVEL 0.79, CADD 25.30, Variant assessed as somatic; moderate impact.
- T121M (p.Thr121Met), rs149956156, ESP rs149956156, ExAC rs149956156, TOPMed rs149956156, REVEL 0.88, CADD 27.70, Uncertain significance, not specified
- T121P (p.Thr121Pro), ExAC rs749624371, gnomAD rs749624371
- V122L (p.Val122Leu), TOPMed rs917973761, gnomAD rs917973761, REVEL 0.36, CADD 18.80
- V122M (p.Val122Met), TOPMed rs917973761, gnomAD rs917973761, REVEL 0.54, CADD 24.80
- D124G (p.Asp124Gly), ExAC rs753215074, REVEL 0.80, CADD 29.50
- V125M (p.Val125Met), NCI-TCGA TCGA novel, Ensembl rs1875777436, Variant assessed as somatic; moderate impact.
- Q127E (p.Gln127Glu), gnomAD rs1227350893, REVEL 0.33, CADD 21.60
- Y128C (p.Tyr128Cys), Ensembl rs1875776688
- F129C (p.Phe129Cys), Ensembl rs866648227
- Q131* (p.Gln131Ter), Ensembl rs2136979343
- F132L (p.Phe132Leu), TOPMed rs1255945115
- V135M (p.Val135Met), TOPMed rs1875404132
- D136E (p.Asp136Glu), ExAC rs755538859, TOPMed rs755538859, gnomAD rs755538859, REVEL 0.45, CADD 0.03
- D136N (p.Asp136Asn), rs1181920771, TOPMed rs1181920771, gnomAD rs1181920771, REVEL 0.35, CADD 24.30, Variant assessed as somatic; moderate impact.
- D137N (p.Asp137Asn), gnomAD rs1424495218, REVEL 0.37, CADD 23.00
- A138T (p.Ala138Thr), rs769968859, NCI-TCGA Cosmic COSV9998, gnomAD rs769968859, REVEL 0.23, CADD 23.00, Variant assessed as somatic; moderate impact.
- M139R (p.Met139Arg), TOPMed rs1159858509, gnomAD rs1159858509, REVEL 0.64, CADD 27.40
- M141I (p.Met141Ile), ExAC rs778613474, TOPMed rs778613474, gnomAD rs778613474, REVEL 0.73, CADD 23.90, Uncertain significance, not specified
- F142Y (p.Phe142Tyr), ESP rs375673859, ExAC rs375673859, TOPMed rs375673859, gnomAD rs375673859, REVEL 0.47, CADD 23.00, Uncertain significance, not specified
- T145P (p.Thr145Pro), Ensembl rs1592941956
- T145S (p.Thr145Ser), ExAC rs753612372, gnomAD rs753612372, REVEL 0.25, CADD 22.80
- N147S (p.Asn147Ser), rs1197064821, Ensembl rs1197064821, REVEL 0.34, CADD 22.80, Variant assessed as somatic; moderate impact.
- R148G (p.Arg148Gly), 1000Genomes rs1210336675, TOPMed rs1210336675, gnomAD rs1210336675, REVEL 0.75, CADD 26.10
- R148Q (p.Arg148Gln), TOPMed rs1311127832, gnomAD rs1311127832, REVEL 0.72, CADD 29.50
- R148W (p.Arg148Trp), 1000Genomes rs1210336675, TOPMed rs1210336675, gnomAD rs1210336675, REVEL 0.73, CADD 28.60
- R150* (p.Arg150Ter), 1000Genomes rs2136961673, CADD 37.00
- R150L (p.Arg150Leu), Ensembl rs868119585, REVEL 0.81, CADD 33.00
- G153E (p.Gly153Glu), TOPMed rs1034947159, gnomAD rs1034947159, REVEL 0.89, CADD 24.00
- V155L (p.Val155Leu), Ensembl rs758809527, REVEL 0.83, CADD 23.70
- T156M (p.Thr156Met), ExAC rs767407412, TOPMed rs767407412, gnomAD rs767407412, REVEL 0.86, CADD 25.50, Uncertain significance, not specified
- F157L (p.Phe157Leu), ExAC rs751436633, gnomAD rs751436633, REVEL 0.69, CADD 16.90
- E158D (p.Glu158Asp), ExAC rs766320746, gnomAD rs766320746, REVEL 0.42, CADD 14.30
- E158Q (p.Glu158Gln), TOPMed rs1875273448, REVEL 0.67, CADD 22.70, Uncertain significance, not specified
- S159N (p.Ser159Asn), Ensembl rs1875272764, REVEL 0.30, CADD 16.30
- E160Q (p.Glu160Gln), UniProt VAR 035485, Uncertain significance, in a breast cancer sample
- D161H (p.Asp161His), Ensembl rs1875272452
- V163L (p.Val163Leu), TOPMed rs1270520592, gnomAD rs1270520592, REVEL 0.61, CADD 23.40
- V163M (p.Val163Met), rs1270520592, TOPMed rs1270520592, gnomAD rs1270520592, REVEL 0.67, CADD 25.80, Variant assessed as somatic; moderate impact.
- E164D (p.Glu164Asp), rs2500233382, ClinGen CA386567678, ClinVar RCV004498417, REVEL 0.38, CADD 16.30, Uncertain significance, not specified
- V166A (p.Val166Ala), TOPMed rs1282815934, REVEL 0.36, CADD 24.10
- E168A (p.Glu168Ala), Ensembl rs1321714586
- I169N (p.Ile169Asn), NCI-TCGA Cosmic COSV9998, Variant assessed as somatic; moderate impact.
- H170R (p.His170Arg), ESP rs376073182, ExAC rs376073182, TOPMed rs376073182, gnomAD rs376073182, REVEL 0.66, CADD 25.20
- F171C (p.Phe171Cys), TOPMed rs796665575
- I174V (p.Ile174Val), 1000Genomes rs200535151
- N175S (p.Asn175Ser), rs1287732568, NCI-TCGA Cosmic COSV5745, gnomAD rs1287732568, REVEL 0.61, CADD 23.90, Variant assessed as somatic; moderate impact.
- N176S (p.Asn176Ser), 1000Genomes rs201777721
- K177R (p.Lys177Arg), 1000Genomes rs199511098, ExAC rs199511098, gnomAD rs199511098, Uncertain significance
- K177T (p.Lys177Thr), rs199511098, ClinGen CA6827740, ClinVar RCV004159643, 1000Genomes rs199511098, AlphaMissense 0.81, MetaLR 0.32, Uncertain significance, not specified
- M178I (p.Met178Ile), ExAC rs769208022, TOPMed rs769208022, gnomAD rs769208022, REVEL 0.68, CADD 30.00
- V179G (p.Val179Gly), gnomAD rs1190971675, REVEL 0.90, CADD 32.00
- C181S (p.Cys181Ser), ExAC rs776037606, gnomAD rs776037606, REVEL 0.78, CADD 24.60
- K183N (p.Lys183Asn), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; moderate impact.
- A184S (p.Ala184Ser), ExAC rs746446964, gnomAD rs746446964, REVEL 0.77, CADD 24.30
- A184V (p.Ala184Val), rs770133777, []
- P186A (p.Pro186Ala), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P186R (p.Pro186Arg), Ensembl rs908466021
- P186S (p.Pro186Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K187N (p.Lys187Asn), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; moderate impact.
- V189G (p.Val189Gly), TOPMed rs1875189384
- V189L (p.Val189Leu), TOPMed rs1166807366
- V189M (p.Val189Met), NCI-TCGA Cosmic COSV9998, TOPMed rs1166807366, REVEL 0.60, CADD 26.70, Variant assessed as somatic; moderate impact.
- M190I (p.Met190Ile), ExAC rs772595393, gnomAD rs772595393, REVEL 0.47, CADD 23.70
- M190T (p.Met190Thr), gnomAD rs1232444067, REVEL 0.51, CADD 24.00
- S191L (p.Ser191Leu), ESP rs375135447, ExAC rs375135447, TOPMed rs375135447, gnomAD rs375135447, REVEL 0.35, CADD 23.30
- P192S (p.Pro192Ser), NCI-TCGA Cosmic COSV5745, Variant assessed as somatic; moderate impact.
- T193A (p.Thr193Ala), ExAC rs780777611, gnomAD rs780777611, REVEL 0.20, CADD 20.20
- T193M (p.Thr193Met), rs768324684, ClinGen CA6827713, ClinVar RCV004299722, ExAC rs768324684, REVEL 0.38, CADD 25.00, Uncertain significance, not specified
Public MSI1 analysis runs
- MSI1 analysis run — MSI1 (633 variants) — completed 2026-08-22