NPM1 (Nucleophosmin) variants and mutations
NPM1 (also known as Nucleophosmin) is a human protein-coding gene encoding a nucleophosmin protein. It coordinates ribosome biogenesis, nucleolar stress responses, centrosome regulation, and nucleocytoplasmic transport. Recurrent frameshift variants that mislocalize the protein to cytoplasm define one of the most common molecular subtypes of acute myeloid leukemia. This analysis covers 526 NPM1 variants and mutations. Of these, 57% have computational variant effect predictions. Disease context includes cancer, non-small cell lung carcinoma, and acute myeloid leukemia. Example NPM1 variants include M1?, E2D, and E2E.
Variant analysis overview
- Gene: NPM1
- Protein: Nucleophosmin
- UniProt accession: P06748
- Organism: Homo sapiens
- Variants analyzed: 526
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 433 unspecified-consequence records; 43 missense variants; 33 synonymous variants; 1 in-frame deletions; 4 splice-region variants; 3 stop-gained variants; 3 frameshift variants; 6 substitution
- Prediction scores: 298 variants have prediction scores (57% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: cancer, non-small cell lung carcinoma, acute myeloid leukemia, neurodegenerative disease, HIV infectious disease, neoplasm, dyskeratosis congenita, anaplastic large cell lymphoma, Hodgkins lymphoma, lymphoid neoplasm, Lymphomatoid Papulosis, peripheral T-cell lymphoma, not otherwise specified.
Protein structure and variant hotspots
- Protein features: 36 post-translational modification sites.
- PTM context: 44 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 NPM1 variants
Examples include M1?, E2D, E2E, D3E, D3H, D3Y, D3D, S4L. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- M1?, cosmic curated COSV10737
- E2D (p.Glu2Asp), gnomAD 5-171387954-A-T, REVEL 0.15, CADD 23.80
- E2E (p.Glu2Glu), rs373962671, gnomAD 5-171387954-A-G, CADD 14.80
- D3E (p.Asp3Glu), Ensembl rs1770334829, REVEL 0.21, CADD 23.70
- D3H (p.Asp3His), NCI-TCGA Cosmic COSV5156, cosmic curated COSV51561, Variant assessed as somatic; moderate impact.
- D3Y (p.Asp3Tyr), NCI-TCGA Cosmic COSV5156, Variant assessed as somatic; moderate impact.
- D3D (p.Asp3Asp), gnomAD 5-171387957-T-C, CADD 15.40
- S4L (p.Ser4Leu), rs1363897984, NCI-TCGA Cosmic COSV9974, cosmic curated COSV99742, gnomAD rs1363897984, AlphaMissense 0.28, MetaLR 0.10, Variant assessed as somatic; moderate impact.
- S4S (p.Ser4Ser), gnomAD 5-171387960-G-T, CADD 15.40
- M5V (p.Met5Val), TOPMed rs1299020514, gnomAD rs1299020514, REVEL 0.20, CADD 22.70
- M5T (p.Met5Thr), gnomAD 5-171387962-T-C, REVEL 0.23, CADD 24.10
- M5I (p.Met5Ile), gnomAD 5-171387963-G-A, REVEL 0.19, CADD 24.40
- M7V (p.Met7Val), ExAC rs772365842, TOPMed rs772365842, gnomAD rs772365842, REVEL 0.25, CADD 22.70
- M7L (p.Met7Leu), gnomAD 5-171387967-A-T, REVEL 0.20, CADD 23.00
- D8N (p.Asp8Asn), gnomAD rs1389753903, REVEL 0.12, CADD 24.10
- M9I (p.Met9Ile), TOPMed rs1349680677, cosmic curated COSV10882
- M9V (p.Met9Val), gnomAD rs925409148, REVEL 0.20, CADD 22.90
- M9T (p.Met9Thr), gnomAD 5-171387974-T-C, REVEL 0.15, CADD 22.90
- S10G (p.Ser10Gly), TOPMed rs1235542368, gnomAD rs1235542368, REVEL 0.11, CADD 22.80
- S10R (p.Ser10Arg), ExAC rs775657228, TOPMed rs775657228, gnomAD rs775657228
- S10T (p.Ser10Thr), gnomAD rs1384214810, REVEL 0.15, CADD 23.00
- p.Ser10 Leu12del, gnomAD 5-171387973-ATGAG, CADD 22.40
- S10S (p.Ser10Ser), rs775657228, gnomAD 5-171387978-C-T, CADD 15.20
- P11L (p.Pro11Leu), cosmic curated COSV10511, REVEL 0.12, CADD 23.30
- P11S (p.Pro11Ser), cosmic curated COSV10964, TOPMed rs1278111812, REVEL 0.12, CADD 22.70
- P11T (p.Pro11Thr), gnomAD 5-171387979-C-A, REVEL 0.18, CADD 22.80
- P11A (p.Pro11Ala), gnomAD 5-171387979-C-G, REVEL 0.18, CADD 23.80
- P11P (p.Pro11Pro), gnomAD 5-171387981-C-A, CADD 14.20
- L12M (p.Leu12Met), NCI-TCGA Cosmic COSV9974, cosmic curated COSV99744, Variant assessed as somatic; moderate impact.
- L12L (p.Leu12Leu), rs935491400, gnomAD 5-171387982-C-T, CADD 14.20
- R13G (p.Arg13Gly), Ensembl rs2113141324
- R13K (p.Arg13Lys), ExAC rs768919750, gnomAD rs768919750
- R13S (p.Arg13Ser), cosmic curated COSV51577
- R13R (p.Arg13Arg), rs142254256, gnomAD 5-171387987-G-A, CADD 15.80
- P14L (p.Pro14Leu), cosmic curated COSV51575
- P14A (p.Pro14Ala), gnomAD 5-171387988-C-G, REVEL 0.14, CADD 23.10
- P14P (p.Pro14Pro), rs1479333062, gnomAD 5-171387990-C-T, CADD 12.00
- Q15* (p.Gln15Ter), cosmic curated COSV10737
- Q15E (p.Gln15Glu), Ensembl rs2113141395
- Q15K (p.Gln15Lys), Ensembl rs2113141395
- Q15L (p.Gln15Leu), cosmic curated COSV10643
- N16N (p.Asn16Asn), rs976072123, gnomAD 5-171387996-C-T, CADD 14.00
- Y17Y (p.Tyr17Tyr), rs762428128, gnomAD 5-171387999-T-C, CADD 12.60
- L18F (p.Leu18Phe), gnomAD rs1446401368, REVEL 0.21, CADD 27.60
- L18V (p.Leu18Val), gnomAD 5-171388000-C-G, REVEL 0.26, CADD 26.20
- L18L (p.Leu18Leu), rs765486682, gnomAD 5-171388002-T-C, CADD 15.30
- F19L (p.Phe19Leu), Ensembl rs2113141479, REVEL 0.27, CADD 29.30
- F19F (p.Phe19Phe), gnomAD 5-171388005-C-T, CADD 22.20
- G20C (p.Gly20Cys), cosmic curated COSV99741
- G20G (p.Gly20Gly), gnomAD 5-171390052-T-G, CADD 18.80
- C21F (p.Cys21Phe), gnomAD 5-171390054-G-T, REVEL 0.55, CADD 32.00
- E22V (p.Glu22Val), gnomAD rs1770493441, REVEL 0.35, CADD 29.40
- E22* (p.Glu22Ter), gnomAD 5-171390056-G-T, CADD 40.00
- E22G (p.Glu22Gly), gnomAD 5-171390057-A-G, REVEL 0.37, CADD 33.00
- E22E (p.Glu22Glu), gnomAD 5-171390058-A-G, CADD 17.70
- L23I (p.Leu23Ile), gnomAD 5-171390059-C-A, REVEL 0.51, CADD 27.10
- L23Q (p.Leu23Gln), gnomAD 5-171390060-T-A, REVEL 0.70, CADD 33.00
- L23L (p.Leu23Leu), rs2113158539, gnomAD 5-171390061-A-G, CADD 15.90
- K24R (p.Lys24Arg), gnomAD 5-171390060-TA-T, CADD 31.00
- K24T (p.Lys24Thr), gnomAD 5-171390063-A-C, REVEL 0.35, CADD 32.00
- K24K (p.Lys24Lys), gnomAD 5-171390064-G-A, CADD 13.40
- K24N (p.Lys24Asn), gnomAD 5-171390064-G-T, REVEL 0.25, CADD 25.20
- A25D (p.Ala25Asp), cosmic curated COSV51548, REVEL 0.31, CADD 29.90
- A25V (p.Ala25Val), gnomAD 5-171390066-C-T, REVEL 0.21, CADD 25.30
- D26N (p.Asp26Asn), gnomAD rs1162204606, REVEL 0.14, CADD 25.10
- D26V (p.Asp26Val), Ensembl rs2113158596
- D26Y (p.Asp26Tyr), gnomAD 5-171390068-G-T, REVEL 0.38, CADD 32.00
- D26E (p.Asp26Glu), gnomAD 5-171390070-C-A, REVEL 0.15, CADD 23.50
- K27N (p.Lys27Asn), NCI-TCGA Cosmic COSV5155, cosmic curated COSV51559, Variant assessed as somatic; moderate impact.
- D28N (p.Asp28Asn), Ensembl rs995892226
- D28V (p.Asp28Val), cosmic curated COSV51564
- Y29D (p.Tyr29Asp), cosmic curated COSV51551
- H30N (p.His30Asn), Ensembl rs1770494180, REVEL 0.20, CADD 23.50
- H30R (p.His30Arg), gnomAD 5-171390081-A-G, REVEL 0.26, CADD 25.00
- H30H (p.His30His), rs773970096, gnomAD 5-171390082-C-T, CADD 14.90
- H30Q (p.His30Gln), gnomAD 5-171390082-C-A, REVEL 0.18, CADD 22.30
- F31L (p.Phe31Leu), gnomAD 5-171390083-T-C, REVEL 0.43, CADD 26.40
- F31F (p.Phe31Phe), rs1054208939, gnomAD 5-171390085-T-C, CADD 14.30
- K32E (p.Lys32Glu), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- K32* (p.Lys32Ter), gnomAD 5-171390082-C-CT, CADD 33.00
- K32N (p.Lys32Asn), gnomAD 5-171390088-G-T, REVEL 0.14, CADD 19.90
- V33M (p.Val33Met), ExAC rs759228926, gnomAD rs759228926, REVEL 0.21, CADD 25.60
- V33L (p.Val33Leu), gnomAD 5-171390089-G-T, REVEL 0.18, CADD 23.80
- V33V (p.Val33Val), gnomAD 5-171390091-G-T, CADD 16.20
- D34E (p.Asp34Glu), Ensembl rs2113158716
- D34H (p.Asp34His), NCI-TCGA TCGA novel, REVEL 0.30, CADD 32.00, Variant assessed as somatic; moderate impact.
- D34N (p.Asp34Asn), Ensembl rs2113158701
- D34Y (p.Asp34Tyr), gnomAD 5-171390092-G-T, REVEL 0.30, CADD 26.60
- D34D (p.Asp34Asp), gnomAD 5-171390094-T-C, CADD 15.30
- N35S (p.Asn35Ser), ExAC rs766975341, TOPMed rs766975341, gnomAD rs766975341, REVEL 0.16, CADD 27.30
- N35D (p.Asn35Asp), gnomAD 5-171390095-A-G, REVEL 0.07, CADD 23.10
- N35I (p.Asn35Ile), gnomAD 5-171390096-A-T, REVEL 0.30, CADD 29.30
- N35N (p.Asn35Asn), gnomAD 5-171390097-T-C, CADD 14.80
- D36E (p.Asp36Glu), Ensembl rs1770494859
- D36Y (p.Asp36Tyr), gnomAD 5-171390098-G-T, REVEL 0.46, CADD 33.00
- D36N (p.Asp36Asn), gnomAD 5-171390098-G-A, REVEL 0.31, CADD 32.00
- D36G (p.Asp36Gly), gnomAD 5-171390099-A-G, REVEL 0.40, CADD 32.00
- E37G (p.Glu37Gly), cosmic curated COSV99744, REVEL 0.27, CADD 32.00
- E37K (p.Glu37Lys), gnomAD 5-171390101-G-A, REVEL 0.26, CADD 34.00
- E37* (p.Glu37Ter), gnomAD 5-171390101-G-T, CADD 45.00
- E37E (p.Glu37Glu), gnomAD 5-171390103-A-G, CADD 15.30
- N38K (p.Asn38Lys), TOPMed rs1324989400, gnomAD rs1324989400, REVEL 0.12, CADD 25.00
- N38M (p.Asn38Met), gnomAD 5-171390101-GA-G, CADD 32.00
- N38N (p.Asn38Asn), gnomAD 5-171390106-T-C, CADD 15.00
- E39* (p.Glu39Ter), gnomAD 5-171390107-G-T, CADD 43.00
- E39K (p.Glu39Lys), gnomAD 5-171390107-G-A, REVEL 0.38, CADD 33.00
- E39G (p.Glu39Gly), gnomAD 5-171390108-A-G, REVEL 0.38, CADD 27.70
- E39E (p.Glu39Glu), rs1266262705, gnomAD 5-171390109-G-A, CADD 13.60
- E39D (p.Glu39Asp), gnomAD 5-171390109-G-T, REVEL 0.19, CADD 20.60
- H40Y (p.His40Tyr), Ensembl rs1770495249, REVEL 0.49, CADD 29.80
- H40N (p.His40Asn), gnomAD 5-171390110-C-A, REVEL 0.35, CADD 27.00
- H40Q (p.His40Gln), gnomAD 5-171390112-C-A, REVEL 0.36, CADD 24.70
- H40H (p.His40His), gnomAD 5-171390112-C-T, CADD 15.80
- Q41* (p.Gln41Ter), cosmic curated COSV10737
- Q41K (p.Gln41Lys), gnomAD 5-171390113-C-A, REVEL 0.25, CADD 26.20
- Q41Q (p.Gln41Gln), rs1230515549, gnomAD 5-171390115-G-A, CADD 14.70
- Q41H (p.Gln41His), gnomAD 5-171390115-G-C, REVEL 0.44, CADD 26.40
- L42S (p.Leu42Ser), cosmic curated COSV51545, REVEL 0.69, CADD 32.00
- L42L (p.Leu42Leu), rs1351633054, gnomAD 5-171390118-A-G, CADD 13.60
- S43Y (p.Ser43Tyr), cosmic curated COSV99744, REVEL 0.38, CADD 32.00
- S43P (p.Ser43Pro), gnomAD 5-171390119-T-C, REVEL 0.40, CADD 31.00
- S43S (p.Ser43Ser), gnomAD 5-171390121-T-C, CADD 14.90
- L44L (p.Leu44Leu), gnomAD 5-171390122-T-C, CADD 15.40
- R45K (p.Arg45Lys), cosmic curated COSV10964, TOPMed rs1770495635, gnomAD rs1770495635, REVEL 0.16, CADD 26.10
- R45I (p.Arg45Ile), gnomAD 5-171390126-G-T, REVEL 0.41, CADD 33.00
- T46M (p.Thr46Met), Ensembl rs1283447658, REVEL 0.23, CADD 25.60
- T46S (p.Thr46Ser), gnomAD 5-171390128-A-T, REVEL 0.22, CADD 32.00
- T46A (p.Thr46Ala), gnomAD 5-171390128-A-G, REVEL 0.23, CADD 29.20
- T46K (p.Thr46Lys), gnomAD 5-171390129-C-A, REVEL 0.43, CADD 25.30
- T46T (p.Thr46Thr), gnomAD 5-171390130-G-T, CADD 32.00
- V47A (p.Val47Ala), Ensembl rs2113167847
- V47D (p.Val47Asp), Ensembl rs2113167847
- V47F (p.Val47Phe), cosmic curated COSV99744, Ensembl rs2113167808, REVEL 0.42, CADD 34.00
- V47G (p.Val47Gly), Ensembl rs2113167847
- V47I (p.Val47Ile), Ensembl rs2113167808
- V47L (p.Val47Leu), Ensembl rs2113167808
- V47V (p.Val47Val), rs771256760, gnomAD 5-171391307-C-A, CADD 17.10
- S48C (p.Ser48Cys), Ensembl rs2113167925
- S48R (p.Ser48Arg), Ensembl rs2113167942
- S48T (p.Ser48Thr), cosmic curated COSV51568
- L49* (p.Leu49Ter), Ensembl rs2113167954
- G50A (p.Gly50Ala), Ensembl rs2113168022
- G50E (p.Gly50Glu), Ensembl rs2113168022
- G50R (p.Gly50Arg), Ensembl rs2113167984
- G50V (p.Gly50Val), Ensembl rs2113168022
- G50W (p.Gly50Trp), Ensembl rs2113167984
- G50G (p.Gly50Gly), rs2113168043, gnomAD 5-171391316-G-A, CADD 7.48
- A51D (p.Ala51Asp), Ensembl rs2113168088
- A51G (p.Ala51Gly), Ensembl rs2113168088
- A51P (p.Ala51Pro), Ensembl rs2113168060
- A51S (p.Ala51Ser), Ensembl rs2113168060
- A51T (p.Ala51Thr), Ensembl rs2113168060
- A51V (p.Ala51Val), Ensembl rs2113168088
- G52A (p.Gly52Ala), ESP rs372208958, TOPMed rs372208958, gnomAD rs372208958, REVEL 0.25, CADD 25.10
- G52C (p.Gly52Cys), Ensembl rs2113168142
- G52D (p.Gly52Asp), ESP rs372208958, TOPMed rs372208958, gnomAD rs372208958, REVEL 0.22, CADD 23.90
- G52R (p.Gly52Arg), Ensembl rs2113168142
- G52S (p.Gly52Ser), Ensembl rs2113168142
- G52V (p.Gly52Val), ESP rs372208958, TOPMed rs372208958, gnomAD rs372208958
- A53E (p.Ala53Glu), ExAC rs774730997, TOPMed rs774730997, gnomAD rs774730997
- A53G (p.Ala53Gly), ExAC rs774730997, TOPMed rs774730997, gnomAD rs774730997
- A53P (p.Ala53Pro), Ensembl rs2113168233
- A53S (p.Ala53Ser), NCI-TCGA Cosmic COSV5157, cosmic curated COSV51577, Variant assessed as somatic; moderate impact.
- A53T (p.Ala53Thr), Ensembl rs2113168233
- A53V (p.Ala53Val), ExAC rs774730997, TOPMed rs774730997, gnomAD rs774730997, REVEL 0.40, CADD 24.90
- K54* (p.Lys54Ter), Ensembl rs2113168313
- K54M (p.Lys54Met), Ensembl rs2113168326
- K54N (p.Lys54Asn), cosmic curated COSV51550, Ensembl rs1288532134
- K54R (p.Lys54Arg), cosmic curated COSV51572, REVEL 0.33, CADD 32.00
- D55E (p.Asp55Glu), Ensembl rs2113168416
- D55G (p.Asp55Gly), Ensembl rs2113168392, NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- D55H (p.Asp55His), Ensembl rs2113168361
- D55N (p.Asp55Asn), NCI-TCGA Cosmic COSV9974, cosmic curated COSV99743, Ensembl rs2113168361, Variant assessed as somatic; moderate impact.
- D55V (p.Asp55Val), Ensembl rs2113168392
- E56A (p.Glu56Ala), Ensembl rs2113168446
- E56D (p.Glu56Asp), TOPMed rs1422337215, gnomAD rs1422337215
- E56G (p.Glu56Gly), Ensembl rs2113168446
- E56K (p.Glu56Lys), cosmic curated COSV51564, Ensembl rs2113168429
- E56Q (p.Glu56Gln), Ensembl rs2113168429
- E56V (p.Glu56Val), Ensembl rs2113168446
Public NPM1 analysis runs
- NPM1 analysis run — NPM1 (526 variants) — completed 2026-08-18