EZH1 (Q92800) variants and mutations
EZH1 (also known as Q92800) is a human protein-coding gene encoding a histone-lysine N-methyltransferase protein. It provides H3K27 methyltransferase activity in Polycomb repressive complex 2 and helps maintain transcriptional repression, particularly in differentiated and quiescent cells. Dysregulation can influence stem-cell function and cancer biology, but strong monogenic human disease associations remain limited. This analysis covers 760 EZH1 variants and mutations. Of these, 62% have computational variant effect predictions. Disease context includes Weaver syndrome, diffuse large B-cell lymphoma, and neurodegenerative disease. Example EZH1 variants include M1?, I3M, and P4A.
Variant analysis overview
- Gene: EZH1
- Protein: Q92800
- UniProt accession: Q92800
- Organism: Homo sapiens
- Variants analyzed: 760
- Variant scope: all variants
- Completed: 2026-08-20
Variant and mutation evidence
- Variant composition: 604 unspecified-consequence records; 2 stop lost; 5 frameshift variants; 55 synonymous variants; 81 missense variants; 2 in-frame deletions; 4 stop-gained variants; 4 splice-region variants; 3 substitution
- Prediction scores: 470 variants have prediction scores (62% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: Weaver syndrome, diffuse large B-cell lymphoma, neurodegenerative disease, follicular lymphoma, viral infectious disease, melanoma, breast carcinoma, lymphoma, acute myeloid leukemia, neoplasm, non-Hodgkin lymphoma, cancer.
Protein structure and variant hotspots
- Protein features: 2 domains.
- Structural context: 238 variants have structural context.
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 EZH1 variants
Examples include M1?, I3M, P4A, P4S, N5I, P6H, P6S, P7A. 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.
- I3M (p.Ile3Met), ExAC rs746093812, TOPMed rs746093812, gnomAD rs746093812, REVEL 0.34, CADD 16.30
- P4A (p.Pro4Ala), Ensembl rs2053881433
- P4S (p.Pro4Ser), cosmic curated COSV70549, REVEL 0.11, CADD 10.20
- N5I (p.Asn5Ile), Ensembl rs1597855392
- P6H (p.Pro6His), TOPMed rs1413076086, gnomAD rs1413076086, REVEL 0.42, CADD 23.60
- P6S (p.Pro6Ser), cosmic curated COSV70549
- P7A (p.Pro7Ala), ESP rs376554057, ExAC rs376554057, TOPMed rs376554057, gnomAD rs376554057
- T8I (p.Thr8Ile), cosmic curated COSV10751
- T8N (p.Thr8Asn), cosmic curated COSV70549, REVEL 0.23, CADD 20.40
- S9F (p.Ser9Phe), rs867508196, ClinGen CA290780985, ClinVar RCV004119906, TOPMed rs867508196, REVEL 0.66, CADD 25.20, Uncertain significance, not specified
- I12M (p.Ile12Met), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I12V (p.Ile12Val), gnomAD rs1389999641, REVEL 0.26, CADD 18.00
- Y14G (p.Tyr14Gly), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V19G (p.Val19Gly), cosmic curated COSV70550
- S21Y (p.Ser21Tyr), NCI-TCGA Cosmic COSV7055, cosmic curated COSV70550, Variant assessed as somatic; moderate impact.
- Y23H (p.Tyr23His), ExAC rs778710525, gnomAD rs778710525, REVEL 0.84, CADD 27.30
- Y23S (p.Tyr23Ser), cosmic curated COSV10133
- M24T (p.Met24Thr), Ensembl rs2053880202, REVEL 0.78, CADD 22.60
- R25* (p.Arg25Ter), cosmic curated COSV70550, CADD 34.00
- R25Q (p.Arg25Gln), NCI-TCGA Cosmic COSV7054, cosmic curated COSV70548, REVEL 0.55, CADD 26.70, Variant assessed as somatic; moderate impact.
- R27* (p.Arg27Ter), NCI-TCGA Cosmic COSV7054, cosmic curated COSV70549, TOPMed rs1693554854, CADD 36.00, Variant assessed as somatic; high impact.
- R27Q (p.Arg27Gln), cosmic curated COSV70550, ExAC rs754966338, REVEL 0.52, CADD 23.90
- Q28H (p.Gln28His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L29I (p.Leu29Ile), ExAC rs753285574, TOPMed rs753285574, gnomAD rs753285574, REVEL 0.39, CADD 22.40
- L29H (p.Leu29His), rs780531216, []
- R31Q (p.Arg31Gln), ExAC rs760277636, gnomAD rs760277636, REVEL 0.64, CADD 24.40
- R31W (p.Arg31Trp), ExAC rs765876793, TOPMed rs765876793, gnomAD rs765876793, REVEL 0.69, CADD 25.30, Uncertain significance, not specified
- Q33* (p.Gln33Ter), ExAC rs767244181, gnomAD rs767244181
- Q33K (p.Gln33Lys), NCI-TCGA Cosmic COSV7054, cosmic curated COSV70548, Variant assessed as somatic; moderate impact.
- A34T (p.Ala34Thr), cosmic curated COSV10893
- N35D (p.Asn35Asp), Ensembl rs2053879425, REVEL 0.25, CADD 22.10
- M36I (p.Met36Ile), gnomAD rs1194330891, REVEL 0.38, CADD 22.90
- M36V (p.Met36Val), TOPMed rs2053879320, REVEL 0.40, CADD 20.70
- A40T (p.Ala40Thr), TOPMed rs969050561, gnomAD rs969050561, REVEL 0.25, CADD 22.80
- L41V (p.Leu41Val), rs1209219306, ClinGen CA399651387, ClinVar RCV004385744, TOPMed rs1209219306, REVEL 0.29, CADD 8.49, Uncertain significance, not specified
- Y42H (p.Tyr42His), ExAC rs755595172, gnomAD rs755595172, REVEL 0.57, CADD 25.50
- V43L (p.Val43Leu), TOPMed rs2053850227, gnomAD rs2053850227, REVEL 0.25, CADD 20.20
- A44V (p.Ala44Val), TOPMed rs2053850171
- N45K (p.Asn45Lys), cosmic curated COSV70549
- K48E (p.Lys48Glu), gnomAD rs1267102173, REVEL 0.60, CADD 23.20
- V49F (p.Val49Phe), ExAC rs749985288, gnomAD rs749985288, REVEL 0.46, CADD 24.50
- V49I (p.Val49Ile), ExAC rs749985288, gnomAD rs749985288, REVEL 0.40, CADD 16.00
- Q50R (p.Gln50Arg), gnomAD rs1349278047, REVEL 0.28, CADD 19.70
- E51* (p.Glu51Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E51K (p.Glu51Lys), ESP rs138789077, ExAC rs138789077, TOPMed rs138789077, gnomAD rs138789077, REVEL 0.46, CADD 23.30
- E51Q (p.Glu51Gln), ESP rs138789077, ExAC rs138789077, TOPMed rs138789077, gnomAD rs138789077, REVEL 0.33, CADD 22.40
- K52E (p.Lys52Glu), Ensembl rs1597853439
- K52R (p.Lys52Arg), ExAC rs761588489, TOPMed rs761588489, gnomAD rs761588489, REVEL 0.28, CADD 18.10
- T53N (p.Thr53Asn), TOPMed rs2053849579, NCI-TCGA TCGA novel, REVEL 0.43, CADD 23.00, Uncertain significance, not provided
- Q54* (p.Gln54Ter), Ensembl rs267604889
- Q54K (p.Gln54Lys), cosmic curated COSV70551
- L56F (p.Leu56Phe), cosmic curated COSV70548
- N57H (p.Asn57His), TOPMed rs1386478282, gnomAD rs1386478282, REVEL 0.47, CADD 23.20
- N57S (p.Asn57Ser), ESP rs145586889, ExAC rs145586889, TOPMed rs145586889, gnomAD rs145586889, REVEL 0.38, CADD 22.30
- E58K (p.Glu58Lys), rs867021719, NCI-TCGA Cosmic COSV7055, cosmic curated COSV70550, Ensembl rs867021719, AlphaMissense 0.14, MetaLR 0.46, Variant assessed as somatic; moderate impact.
- W60* (p.Trp60Ter), Ensembl rs1439142197, CADD 36.00
- L63F (p.Leu63Phe), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- L63I (p.Leu63Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- R64C (p.Arg64Cys), cosmic curated COSV10133, TOPMed rs917590262, gnomAD rs917590262, REVEL 0.64, CADD 28.70
- R64H (p.Arg64His), ExAC rs770961875, TOPMed rs770961875, gnomAD rs770961875, REVEL 0.47, CADD 22.90
- Q66* (p.Gln66Ter), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; high impact.
- P67T (p.Pro67Thr), cosmic curated COSV70550
- V68I (p.Val68Ile), 1000Genomes rs199830078, ExAC rs199830078, TOPMed rs199830078, gnomAD rs199830078, REVEL 0.27, CADD 17.80, Uncertain significance, not specified
- V68L (p.Val68Leu), 1000Genomes rs199830078, ExAC rs199830078, TOPMed rs199830078, gnomAD rs199830078, REVEL 0.27, CADD 19.40
- Q69R (p.Gln69Arg), TOPMed rs1284876132, gnomAD rs1284876132, REVEL 0.28, CADD 20.60
- S70A (p.Ser70Ala), gnomAD rs1197942975, REVEL 0.12, CADD 12.30
- S70P (p.Ser70Pro), gnomAD rs1197942975, REVEL 0.08, CADD 15.90
- M71I (p.Met71Ile), Ensembl rs2053847916
- M71L (p.Met71Leu), rs140377472, ClinGen CA399650737, ClinVar RCV004385745, AlphaMissense 0.07, MetaLR 0.70, Uncertain significance, not specified
- M71R (p.Met71Arg), gnomAD rs1291958592
- M71V (p.Met71Val), rs140377472, ClinGen CA8583045, ClinVar RCV004213546, ESP rs140377472, AlphaMissense 0.07, MetaLR 0.70, Uncertain significance, not specified
- P73T (p.Pro73Thr), 1000Genomes rs199753838, gnomAD rs199753838, REVEL 0.29, CADD 18.90
- V74A (p.Val74Ala), cosmic curated COSV70550
- V74L (p.Val74Leu), cosmic curated COSV70549
- V74M (p.Val74Met), cosmic curated COSV10534, ExAC rs773976800, TOPMed rs773976800, gnomAD rs773976800
- S75G (p.Ser75Gly), ExAC rs768459667, TOPMed rs768459667, gnomAD rs768459667, REVEL 0.23, CADD 22.40, Uncertain significance, not specified
- S75N (p.Ser75Asn), 1000Genomes rs530196145, ExAC rs530196145, TOPMed rs530196145, gnomAD rs530196145, REVEL 0.28, CADD 22.30
- S75R (p.Ser75Arg), 1000Genomes rs200504064, ExAC rs200504064, TOPMed rs200504064, gnomAD rs200504064, REVEL 0.39, CADD 19.50
- S75T (p.Ser75Thr), 1000Genomes rs530196145, ExAC rs530196145, TOPMed rs530196145, gnomAD rs530196145, REVEL 0.27, CADD 21.70
- G76R (p.Gly76Arg), Ensembl rs2053847380
- P78L (p.Pro78Leu), ExAC rs745361319, TOPMed rs745361319, gnomAD rs745361319, REVEL 0.43, CADD 22.60
- P78R (p.Pro78Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P78T (p.Pro78Thr), 1000Genomes rs146736585, ESP rs146736585, ExAC rs146736585, TOPMed rs146736585, REVEL 0.30, CADD 20.40, Likely benign, not provided
- F79C (p.Phe79Cys), gnomAD rs1319202364, REVEL 0.45, CADD 22.50
- L80P (p.Leu80Pro), ExAC rs780768939, gnomAD rs780768939, REVEL 0.68, CADD 19.90, Uncertain significance, not specified
- K81T (p.Lys81Thr), ExAC rs756796549, gnomAD rs756796549
- C83R (p.Cys83Arg), ExAC rs769663372, gnomAD rs769663372, REVEL 0.84, CADD 26.40
- T84A (p.Thr84Ala), cosmic curated COSV10133
- I85T (p.Ile85Thr), Ensembl rs1567998201, REVEL 0.51, CADD 23.80
- I85V (p.Ile85Val), gnomAD rs1335187211, REVEL 0.35, CADD 15.30
- E86D (p.Glu86Asp), cosmic curated COSV70550
- S87I (p.Ser87Ile), cosmic curated COSV70550
- I88F (p.Ile88Phe), ExAC rs780531216, gnomAD rs780531216, REVEL 0.20, CADD 21.80
- F89C (p.Phe89Cys), Ensembl rs868175843
- P90L (p.Pro90Leu), rs1396708479, ClinGen CA399649682, ClinVar RCV004299426, TOPMed rs1396708479, REVEL 0.53, CADD 22.60, Uncertain significance, not specified
- P90S (p.Pro90Ser), cosmic curated COSV10582, TOPMed rs1451105979
- G91E (p.Gly91Glu), Ensembl rs1015659917
- F92S (p.Phe92Ser), ESP rs372139294, ExAC rs372139294, TOPMed rs372139294, gnomAD rs372139294, REVEL 0.50, CADD 23.00, Uncertain significance, not specified
- Q95H (p.Gln95His), ExAC rs777539005, gnomAD rs777539005, REVEL 0.60, CADD 22.10
- H96N (p.His96Asn), gnomAD rs1482022257, REVEL 0.35, CADD 17.60
- H96R (p.His96Arg), 1000Genomes rs534076480, ExAC rs534076480, TOPMed rs534076480, gnomAD rs534076480, REVEL 0.45, CADD 19.00
- M97I (p.Met97Ile), ExAC rs765698931, TOPMed rs765698931, gnomAD rs765698931, REVEL 0.20, CADD 16.00
- M97K (p.Met97Lys), gnomAD rs768571484
- M97L (p.Met97Leu), ExAC rs753051260, TOPMed rs753051260, gnomAD rs753051260, REVEL 0.31, CADD 18.80
- M97T (p.Met97Thr), gnomAD rs768571484, REVEL 0.36, CADD 20.90
- R100G (p.Arg100Gly), ESP rs369111500, ExAC rs369111500, TOPMed rs369111500, gnomAD rs369111500, REVEL 0.59, CADD 22.60
- R100M (p.Arg100Met), cosmic curated COSV10133
- S101L (p.Ser101Leu), ESP rs150134802, TOPMed rs150134802, gnomAD rs150134802, REVEL 0.42, CADD 23.30
- N103K (p.Asn103Lys), ExAC rs754390812, gnomAD rs754390812, REVEL 0.46, CADD 22.90
- T104I (p.Thr104Ile), Ensembl rs2053775416
- A106E (p.Ala106Glu), gnomAD rs1300525501, REVEL 0.66, CADD 24.50
- L107* (p.Leu107Ter), cosmic curated COSV10534
- P109H (p.Pro109His), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- P109S (p.Pro109Ser), TOPMed rs1000322448, gnomAD rs1000322448, REVEL 0.91, CADD 26.30
- M111R (p.Met111Arg), TOPMed rs1158866506
- M111V (p.Met111Val), ExAC rs766839992, gnomAD rs766839992, REVEL 0.75, CADD 23.00
- S113F (p.Ser113Phe), cosmic curated COSV10534
- W114L (p.Trp114Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- P116S (p.Pro116Ser), gnomAD rs2053774861, REVEL 0.83, CADD 24.20
- L117P (p.Leu117Pro), Ensembl rs2143812737
- Q119* (p.Gln119Ter), gnomAD rs1284834316, CADD 38.00
- N120I (p.Asn120Ile), ExAC rs773344466, gnomAD rs773344466, REVEL 0.79, CADD 28.20
- M122I (p.Met122Ile), cosmic curated COSV70550, gnomAD rs1470814709, REVEL 0.70, CADD 34.00
- V123I (p.Val123Ile), ExAC rs780604960, gnomAD rs780604960, REVEL 0.48, CADD 30.00
- T127M (p.Thr127Met), rs756635466, ClinGen CA8582992, ClinVar RCV004138587, ExAC rs756635466, REVEL 0.78, CADD 28.50, Uncertain significance, not specified
- L129C (p.Leu129Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- L129V (p.Leu129Val), cosmic curated COSV10825, Ensembl rs2053743404, REVEL 0.59, CADD 24.10
- L129W (p.Leu129Trp), Ensembl rs2053743331, REVEL 0.85, CADD 29.40
- C130* (p.Cys130Ter), cosmic curated COSV70550
- C130Y (p.Cys130Tyr), cosmic curated COSV70549
- P133L (p.Pro133Leu), NCI-TCGA Cosmic COSV7054, cosmic curated COSV70548, Variant assessed as somatic; moderate impact.
- P133S (p.Pro133Ser), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; moderate impact.
- G136E (p.Gly136Glu), cosmic curated COSV70549
- E138* (p.Glu138Ter), cosmic curated COSV10593
- V139A (p.Val139Ala), TOPMed rs2053743058
- V139L (p.Val139Leu), cosmic curated COSV10825
- V139M (p.Val139Met), Ensembl rs2053743124
- K140E (p.Lys140Glu), cosmic curated COSV70548
- E142D (p.Glu142Asp), NCI-TCGA Cosmic COSV7054, cosmic curated COSV70549, Variant assessed as somatic; moderate impact.
- T145N (p.Thr145Asn), gnomAD rs1252172630, REVEL 0.44, CADD 24.00
- F146V (p.Phe146Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- I147V (p.Ile147Val), ExAC rs761988205
- E148K (p.Glu148Lys), cosmic curated COSV10471
- L150V (p.Leu150Val), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; moderate impact.
- I151F (p.Ile151Phe), cosmic curated COSV70548
- N152S (p.Asn152Ser), rs748670427, ClinGen CA290777248, ClinVar RCV004385746, TOPMed rs748670427, REVEL 0.33, CADD 22.10, Uncertain significance, not specified
- V158D (p.Val158Asp), cosmic curated COSV70548
- V158I (p.Val158Ile), Ensembl rs944543032
- H159Y (p.His159Tyr), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; moderate impact.
- E162* (p.Glu162Ter), rs759344526, NCI-TCGA Cosmic COSV7054, cosmic curated COSV70548, ExAC rs759344526, CADD 54.00, Variant assessed as somatic; high impact.
- M164I (p.Met164Ile), rs763144680, ClinGen CA399647424, ClinVar RCV004385747, ExAC rs763144680, REVEL 0.39, CADD 24.10, Uncertain significance, not specified
- P166S (p.Pro166Ser), Ensembl rs2053683338, REVEL 0.20, CADD 20.30
- S168F (p.Ser168Phe), cosmic curated COSV10534
- V169I (p.Val169Ile), ExAC rs766116813, TOPMed rs766116813, gnomAD rs766116813, REVEL 0.42, CADD 21.30
- S172N (p.Ser172Asn), gnomAD rs1472973980, REVEL 0.32, CADD 16.50
- A174T (p.Ala174Thr), TOPMed rs906561674, gnomAD rs906561674, REVEL 0.39, CADD 23.00
- A174V (p.Ala174Val), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- E178Q (p.Glu178Gln), NCI-TCGA Cosmic COSV7055, cosmic curated COSV70550, Variant assessed as somatic; moderate impact.
- V180I (p.Val180Ile), TOPMed rs1015592884, gnomAD rs1015592884, REVEL 0.39, CADD 21.90
- D181G (p.Asp181Gly), Ensembl rs1597843195
- D181N (p.Asp181Asn), rs541410310, ClinGen CA8582964, cosmic curated COSV10133, ClinVar RCV004302585, REVEL 0.26, CADD 18.50, Uncertain significance, not specified
- Q185* (p.Gln185Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- Q185L (p.Gln185Leu), rs1369771439, NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, TOPMed rs1369771439, REVEL 0.51, CADD 22.60, Variant assessed as somatic; moderate impact.
- Y186S (p.Tyr186Ser), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; moderate impact.
- S187L (p.Ser187Leu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- D188N (p.Asp188Asn), cosmic curated COSV10133
- D188Y (p.Asp188Tyr), NCI-TCGA Cosmic COSV1013, Variant assessed as somatic; moderate impact.
- E191D (p.Glu191Asp), cosmic curated COSV70550
- E192K (p.Glu192Lys), Ensembl rs2053682254, REVEL 0.21, CADD 22.50
- G193W (p.Gly193Trp), cosmic curated COSV10893
- H194D (p.His194Asp), ExAC rs773788984, gnomAD rs773788984, REVEL 0.41, CADD 21.50
- H194Y (p.His194Tyr), ExAC rs773788984, gnomAD rs773788984, REVEL 0.44, CADD 22.10
- N195S (p.Asn195Ser), rs150955298, ClinGen CA290776411, ClinVar RCV004239083, ESP rs150955298, REVEL 0.25, CADD 18.40, Uncertain significance, not specified
- D196G (p.Asp196Gly), gnomAD rs1465203821, REVEL 0.34, CADD 22.80
- D196N (p.Asp196Asn), NCI-TCGA Cosmic COSV1013, cosmic curated COSV10133, Variant assessed as somatic; moderate impact.
- T197A (p.Thr197Ala), Ensembl rs933531876
- T197I (p.Thr197Ile), TOPMed rs1378626218, gnomAD rs1378626218, REVEL 0.46, CADD 14.70
- S198A (p.Ser198Ala), ExAC rs768293257, TOPMed rs768293257, gnomAD rs768293257, REVEL 0.30, CADD 13.10
- D199G (p.Asp199Gly), TOPMed rs1380880034, gnomAD rs1380880034, REVEL 0.33, CADD 22.90
Public EZH1 analysis runs
- EZH1 analysis run — EZH1 (760 variants) — completed 2026-08-20