HNRNPA1 (P09651) variants and mutations
HNRNPA1 (also known as P09651) is a human protein-coding gene encoding a heterogeneous nuclear ribonucleoprotein A1 protein. It regulates pre-mRNA splicing, RNA transport, translation, and stress-granule dynamics through RNA binding and reversible self-assembly. Rare pathogenic variants can cause multisystem proteinopathy, amyotrophic lateral sclerosis, or related neuromuscular degeneration through altered RNA and protein homeostasis. This analysis covers 469 HNRNPA1 variants and mutations. Of these, 74% have computational variant effect predictions. Disease context includes amyotrophic lateral sclerosis, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, and chronic progressive multiple sclerosis. Example HNRNPA1 variants include S2T, S4L, and S4S.
Variant analysis overview
- Gene: HNRNPA1
- Protein: P09651
- UniProt accession: P09651
- Organism: Homo sapiens
- Variants analyzed: 469
- Variant scope: all variants
- Completed: 2026-08-21
Variant and mutation evidence
- Variant composition: 315 unspecified-consequence records; 84 missense variants; 49 synonymous variants; 4 splice-region variants; 4 stop-gained variants; 7 frameshift variants; 2 in-frame deletions; 2 in-frame insertions; 2 substitution
- Prediction scores: 346 variants have prediction scores (74% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: amyotrophic lateral sclerosis, inclusion body myopathy with Paget disease of bone and frontotemporal dementia, chronic progressive multiple sclerosis, Finnish upper limb-onset distal myopathy, amyotrophic lateral sclerosis type 20, inclusion body myopathy with early-onset Paget disease with or without frontotem, severe acute respiratory syndrome, dengue disease, relapsing-remitting multiple sclerosis, distal myopathy, neurodegenerative disease, hereditary disease.
Protein structure and variant hotspots
- Protein features: 2 domains; 33 post-translational modification sites.
- Structural context: 214 variants have structural context.
- PTM context: 33 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 HNRNPA1 variants
Examples include S2T, S4L, S4S, S4A, S4T, S4*, E5Q, E5E. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S2T (p.Ser2Thr), gnomAD 12-54280811-T-A, REVEL 0.49, CADD 22.60
- S4L (p.Ser4Leu), rs1256552845, ClinGen CA385118243, ClinVar RCV003482070, gnomAD rs1256552845, REVEL 0.49, CADD 25.30, Uncertain significance, not provided
- S4S (p.Ser4Ser), rs1476156887, gnomAD 12-54280819-A-T, CADD 4.99
- S4A (p.Ser4Ala), gnomAD 12-54281032-T-G, CADD 8.49
- S4T (p.Ser4Thr), rs1257601954, gnomAD 12-54281032-T-A, CADD 8.33
- S4* (p.Ser4Ter), gnomAD 12-54281033-C-A, CADD 0.03
- E5Q (p.Glu5Gln), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52936, Variant assessed as somatic; moderate impact.
- E5E (p.Glu5Glu), rs1311990822, gnomAD 12-54280822-G-A, CADD 23.50
- S6C (p.Ser6Cys), TOPMed rs1944167400, gnomAD rs1944167400, REVEL 0.41, CADD 25.80
- S6F (p.Ser6Phe), NCI-TCGA Cosmic COSV5293, NCI-TCGA Cosmic COSV9926, cosmic curated COSV99267, REVEL 0.36, CADD 24.80, Variant assessed as somatic; moderate impact.
- S6P (p.Ser6Pro), gnomAD 12-54281386-T-C, REVEL 0.46, CADD 32.00
- S6Y (p.Ser6Tyr), gnomAD 12-54281387-C-A, REVEL 0.45, CADD 32.00
- S6S (p.Ser6Ser), rs755898648, gnomAD 12-54281388-T-G, CADD 12.90
- P7L (p.Pro7Leu), ExAC rs766224014, gnomAD rs766224014, REVEL 0.46, CADD 24.80
- P7R (p.Pro7Arg), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52935, Variant assessed as somatic; moderate impact.
- P7T (p.Pro7Thr), gnomAD 12-54281389-C-A, REVEL 0.59, CADD 25.10
- P7P (p.Pro7Pro), gnomAD 12-54281391-T-C, CADD 12.70
- K8E (p.Lys8Glu), TOPMed rs1944167576
- K8T (p.Lys8Thr), gnomAD 12-54281047-A-ACG, CADD 6.08
- K8N (p.Lys8Asn), rs555887521, gnomAD 12-54281049-A-C, CADD 10.10
- K8K (p.Lys8Lys), rs1348081641, gnomAD 12-54281394-A-G, CADD 12.20
- E9R (p.Glu9Arg), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- E9S (p.Glu9Ser), gnomAD 12-54281391-TA-T, CADD 29.80
- E9A (p.Glu9Ala), gnomAD 12-54281396-A-C, REVEL 0.89, CADD 31.00
- E9E (p.Glu9Glu), rs1236962738, gnomAD 12-54281397-G-A, CADD 12.30
- E9D (p.Glu9Asp), gnomAD 12-54281397-G-T, REVEL 0.27, CADD 23.20
- P10S (p.Pro10Ser), NCI-TCGA Cosmic COSV9926, cosmic curated COSV99267, gnomAD rs1944167744, REVEL 0.59, CADD 24.70, Variant assessed as somatic; moderate impact.
- P10T (p.Pro10Thr), gnomAD 12-54281398-C-A, REVEL 0.70, CADD 25.90
- P10H (p.Pro10His), gnomAD 12-54281399-C-A, REVEL 0.67, CADD 28.10
- P10P (p.Pro10Pro), rs753643060, gnomAD 12-54281400-C-G, CADD 5.88
- E11K (p.Glu11Lys), gnomAD rs1944167845, REVEL 0.69, CADD 29.30
- Q12* (p.Gln12Ter), rs1466874538, gnomAD 12-54281062-C-T, CADD 0.10
- Q12K (p.Gln12Lys), gnomAD 12-54281062-C-A, CADD 0.08
- Q12R (p.Gln12Arg), rs1944152931, gnomAD 12-54281063-A-G, CADD 8.25
- Q12Q (p.Gln12Gln), rs748862330, gnomAD 12-54281064-G-A, CADD 0.07
- Q12H (p.Gln12His), rs748862330, gnomAD 12-54281064-G-T, CADD 0.06
- L13P (p.Leu13Pro), NCI-TCGA Cosmic COSV9926, cosmic curated COSV99267, Variant assessed as somatic; moderate impact.
- L13L (p.Leu13Leu), gnomAD 12-54281035-T-C, CADD 0.04
- L13* (p.Leu13Ter), gnomAD 12-54281036-T-A, CADD 1.76
- L13T (p.Leu13Thr), rs1295308839, gnomAD 12-54281036-T-TA, CADD 1.04
- L13V (p.Leu13Val), gnomAD 12-54281038-C-G, CADD 0.46
- L13F (p.Leu13Phe), rs1944152154, gnomAD 12-54281038-C-T, CADD 0.56
- L13M (p.Leu13Met), gnomAD 12-54281407-C-A, REVEL 0.47, CADD 26.30
- R14W (p.Arg14Trp), rs573025229, gnomAD 12-54281026-C-T, CADD 3.07
- R14G (p.Arg14Gly), rs573025229, gnomAD 12-54281026-C-G, CADD 2.61
- R14R (p.Arg14Arg), gnomAD 12-54281026-C-A, CADD 2.43
- R14Q (p.Arg14Gln), rs963350310, gnomAD 12-54281027-G-A, CADD 1.26
- R14P (p.Arg14Pro), rs963350310, gnomAD 12-54281027-G-C, CADD 1.06
- K15R (p.Lys15Arg), gnomAD 12-54281414-A-G, REVEL 0.80, CADD 32.00
- K15K (p.Lys15Lys), gnomAD 12-54281415-G-A, CADD 13.20
- L16V (p.Leu16Val), ExAC rs754983468, gnomAD rs754983468, CADD 0.03
- L16F (p.Leu16Phe), rs992712963, gnomAD 12-54281068-C-T, CADD 0.04
- L16H (p.Leu16His), rs544572492, gnomAD 12-54281069-T-A, CADD 3.77
- L16I (p.Leu16Ile), rs73304506, gnomAD 12-54281074-C-A, CADD 2.09
- L16P (p.Leu16Pro), rs1944153574, gnomAD 12-54281075-T-C, CADD 3.08
- L16L (p.Leu16Leu), rs1175839222, gnomAD 12-54281076-T-A, CADD 4.34
- F17N (p.Phe17Asn), gnomAD 12-54281045-C-CAA, CADD 8.84
- F17L (p.Phe17Leu), rs780033895, gnomAD 12-54281052-C-A, CADD 2.13
- F17F (p.Phe17Phe), rs780033895, gnomAD 12-54281052-C-T, CADD 2.72
- F17S (p.Phe17Ser), rs1424839032, gnomAD 12-54281078-T-C, CADD 6.32
- I18V (p.Ile18Val), gnomAD 12-54281422-A-G, REVEL 0.20, CADD 24.80
- I18I (p.Ile18Ile), gnomAD 12-54281424-T-A, CADD 12.90
- G19S (p.Gly19Ser), rs769513044, gnomAD 12-54281056-G-A, CADD 7.17
- G19R (p.Gly19Arg), rs769513044, gnomAD 12-54281056-G-C, CADD 6.79
- G19D (p.Gly19Asp), gnomAD 12-54281057-G-A, CADD 5.86
- G19G (p.Gly19Gly), gnomAD 12-54281058-C-A, CADD 8.04
- G20G (p.Gly20Gly), gnomAD 12-54281430-G-A, CADD 7.49
- L21* (p.Leu21Ter), gnomAD 12-54281074-CT-C, CADD 0.99
- L21F (p.Leu21Phe), rs766831350, gnomAD 12-54281074-C-CT, CADD 2.40
- L21L (p.Leu21Leu), gnomAD 12-54281080-T-C, CADD 0.12
- p.Leu20 Asn21insGlu, gnomAD 12-54281081-T-TAG, CADD 5.23
- L21V (p.Leu21Val), gnomAD 12-54281086-C-G, CADD 0.68
- L21I (p.Leu21Ile), gnomAD 12-54281086-C-A, CADD 0.64
- L21P (p.Leu21Pro), rs1332373919, gnomAD 12-54281087-T-C, CADD 7.76
- L21H (p.Leu21His), gnomAD 12-54281087-T-A, CADD 7.33
- L21M (p.Leu21Met), gnomAD 12-54281092-T-A, CADD 2.56
- L21S (p.Leu21Ser), gnomAD 12-54281093-T-C, CADD 2.06
- L21W (p.Leu21Trp), gnomAD 12-54281432-T-G, REVEL 0.62, CADD 32.00
- S22S (p.Ser22Ser), gnomAD 12-54281436-C-T, CADD 15.60
- p.Thr13 Phe19del, gnomAD 12-54281057-GCACA, CADD 7.08
- T25A (p.Thr25Ala), rs942786333, gnomAD 12-54281059-A-G, CADD 7.76
- T25P (p.Thr25Pro), rs942786333, gnomAD 12-54281059-A-C, CADD 7.47
- T25K (p.Thr25Lys), gnomAD 12-54281060-C-A, CADD 7.12
- T25I (p.Thr25Ile), rs2137039920, gnomAD 12-54281060-C-T, CADD 7.70
- T25T (p.Thr25Thr), gnomAD 12-54281061-A-T, CADD 5.83
- T26T (p.Thr26Thr), gnomAD 12-54281448-T-A, CADD 8.48
- D27G (p.Asp27Gly), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52939, Variant assessed as somatic; moderate impact.
- D27N (p.Asp27Asn), gnomAD 12-54281029-G-A, CADD 3.90
- D27D (p.Asp27Asp), rs759484713, gnomAD 12-54281031-C-T, CADD 1.58
- D27E (p.Asp27Glu), gnomAD 12-54281031-C-A, CADD 1.20
- D27H (p.Asp27His), gnomAD 12-54281065-G-C, CADD 0.83
- D27Y (p.Asp27Tyr), rs1238371534, gnomAD 12-54281065-G-T, CADD 0.79
- D27A (p.Asp27Ala), gnomAD 12-54281066-A-C, CADD 0.06
- D27del (p.Asp27del), gnomAD 12-54281447-CTGA-, CADD 22.60
- E28* (p.Glu28Ter), Ensembl rs1944168205
- E28K (p.Glu28Lys), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52937, Variant assessed as somatic; moderate impact.
- S29G (p.Ser29Gly), gnomAD 12-54281455-A-G, REVEL 0.59, CADD 29.20
- S29T (p.Ser29Thr), gnomAD 12-54281456-G-C, REVEL 0.55, CADD 29.30
- L30P (p.Leu30Pro), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52938, CADD 20.60, Variant assessed as somatic; moderate impact.
- L30L (p.Leu30Leu), rs1192540679, gnomAD 12-54281458-C-T, CADD 14.10
- R31M (p.Arg31Met), NCI-TCGA Cosmic COSV9926, cosmic curated COSV99267, Variant assessed as somatic; moderate impact.
- R31R (p.Arg31Arg), rs757914524, gnomAD 12-54281463-G-A, CADD 11.30
- S32I (p.Ser32Ile), TOPMed rs1466891120, gnomAD rs1466891120
- S32R (p.Ser32Arg), Ensembl rs1944168534, REVEL 0.49, CADD 23.90
- S32T (p.Ser32Thr), TOPMed rs1466891120, gnomAD rs1466891120, REVEL 0.28, CADD 23.60
- H33Y (p.His33Tyr), TOPMed rs1944168575
- H33H (p.His33His), rs1195302766, gnomAD 12-54281469-T-C, CADD 14.40
- F34C (p.Phe34Cys), TOPMed rs1205561899
- E35E (p.Glu35Glu), gnomAD 12-54281475-G-A, CADD 13.90
- Q36Q (p.Gln36Gln), rs28758594, gnomAD 12-54281478-A-G, CADD 14.40
- W37S (p.Trp37Ser), gnomAD 12-54281480-G-C, REVEL 0.49, CADD 33.00
- W37C (p.Trp37Cys), gnomAD 12-54281481-G-T, REVEL 0.48, CADD 33.00
- G38E (p.Gly38Glu), gnomAD 12-54281483-G-A, REVEL 0.56, CADD 32.00
- T39M (p.Thr39Met), TOPMed rs1592170668, REVEL 0.42, CADD 24.10
- T39S (p.Thr39Ser), gnomAD 12-54281485-AC-A, CADD 32.00
- T39A (p.Thr39Ala), gnomAD 12-54281485-A-G, REVEL 0.28, CADD 23.20
- T39T (p.Thr39Thr), gnomAD 12-54281487-G-A, CADD 8.98
- L40P (p.Leu40Pro), gnomAD 12-54281489-T-C, REVEL 0.97, CADD 32.00
- L40L (p.Leu40Leu), rs777342318, gnomAD 12-54281490-C-T, CADD 10.90
- T41P (p.Thr41Pro), gnomAD 12-54281491-A-C, REVEL 0.87, CADD 24.00
- T41K (p.Thr41Lys), gnomAD 12-54281492-C-A, REVEL 0.83, CADD 27.80
- T41M (p.Thr41Met), gnomAD 12-54281492-C-T, REVEL 0.78, CADD 25.10
- T41T (p.Thr41Thr), gnomAD 12-54281493-G-T, CADD 7.41
- D42H (p.Asp42His), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52937, Variant assessed as somatic; moderate impact.
- D42N (p.Asp42Asn), rs61910737, NCI-TCGA Cosmic COSV5293, cosmic curated COSV52938, AlphaMissense 0.98, MetaLR 0.73, Variant assessed as somatic; moderate impact.
- D42V (p.Asp42Val), gnomAD rs1433844425, REVEL 0.90, CADD 32.00
- D42E (p.Asp42Glu), gnomAD 12-54281496-C-A, REVEL 0.60, CADD 23.30
- D42D (p.Asp42Asp), rs1011227682, gnomAD 12-54281496-C-T, CADD 11.40
- C43S (p.Cys43Ser), gnomAD 12-54281070-TTG-T, CADD 4.54
- C43R (p.Cys43Arg), gnomAD 12-54281071-T-C, CADD 7.32
- C43F (p.Cys43Phe), rs1592170079, gnomAD 12-54281072-G-T, CADD 1.19
- C43W (p.Cys43Trp), rs1944153335, gnomAD 12-54281073-T-G, CADD 1.14
- V44L (p.Val44Leu), rs1440396946, gnomAD 12-54281041-G-T, CADD 0.04
- V44I (p.Val44Ile), rs1440396946, gnomAD 12-54281041-G-A, CADD 0.05
- V44A (p.Val44Ala), rs1302443104, gnomAD 12-54281042-T-C, CADD 2.93
- V44G (p.Val44Gly), gnomAD 12-54281042-T-G, CADD 2.59
- V44V (p.Val44Val), gnomAD 12-54281502-G-A, CADD 24.80
- V45I (p.Val45Ile), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- V45V (p.Val45Val), gnomAD 12-54281797-A-G, CADD 10.00
- M46T (p.Met46Thr), NCI-TCGA Cosmic COSV9926, cosmic curated COSV99267, TOPMed rs1944177420, Variant assessed as somatic; moderate impact.
- D48A (p.Asp48Ala), gnomAD 12-54281805-A-C, REVEL 0.85, CADD 32.00
- D48D (p.Asp48Asp), gnomAD 12-54281806-T-C, CADD 13.50
- P49A (p.Pro49Ala), 1000Genomes rs566750529, REVEL 0.62, CADD 25.80
- P49S (p.Pro49Ser), gnomAD 12-54281807-C-T, REVEL 0.74, CADD 27.40
- P49Q (p.Pro49Gln), gnomAD 12-54281808-C-A, REVEL 0.80, CADD 28.30
- P49P (p.Pro49Pro), gnomAD 12-54281809-A-G, CADD 11.60
- N50S (p.Asn50Ser), rs545336320, gnomAD 12-54281084-A-G, CADD 6.03
- N50N (p.Asn50Asn), gnomAD 12-54281085-C-T, CADD 1.21
- N50K (p.Asn50Lys), gnomAD 12-54281085-C-A, CADD 0.92
- T51S (p.Thr51Ser), gnomAD 12-54281814-C-G, REVEL 0.09, CADD 22.80
- T51T (p.Thr51Thr), rs1016482750, gnomAD 12-54281815-C-G, CADD 14.40
- K52R (p.Lys52Arg), gnomAD rs1162097034, REVEL 0.61, CADD 28.70
- R53R (p.Arg53Arg), gnomAD 12-54281821-C-A, CADD 10.30
- S54C (p.Ser54Cys), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52939, Variant assessed as somatic; moderate impact.
- S54S (p.Ser54Ser), gnomAD 12-54281824-C-G, CADD 15.00
- R55M (p.Arg55Met), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- V60L (p.Val60Leu), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52935, Variant assessed as somatic; moderate impact.
- V60V (p.Val60Val), rs1944177708, gnomAD 12-54281842-C-T, CADD 13.20
- T61T (p.Thr61Thr), gnomAD 12-54281845-A-G, CADD 4.48
- Y62Y (p.Tyr62Tyr), rs762971933, gnomAD 12-54281848-T-C, CADD 1.48
- A63V (p.Ala63Val), ExAC rs763870366, gnomAD rs763870366, REVEL 0.58, CADD 24.20
- A63S (p.Ala63Ser), rs759290053, gnomAD 12-54281089-G-T, CADD 0.28
- A63T (p.Ala63Thr), rs759290053, gnomAD 12-54281089-G-A, CADD 0.35
- A63P (p.Ala63Pro), rs759290053, gnomAD 12-54281089-G-C, CADD 0.30
- A63G (p.Ala63Gly), rs933958597, gnomAD 12-54281090-C-G, CADD 0.58
- A63A (p.Ala63Ala), gnomAD 12-54281091-C-G, CADD 1.90
- T64A (p.Thr64Ala), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52937, REVEL 0.31, CADD 21.10, Variant assessed as somatic; moderate impact.
- T64T (p.Thr64Thr), rs1394850876, gnomAD 12-54281854-T-C, CADD 6.00
- V65L (p.Val65Leu), gnomAD 12-54281855-G-T, REVEL 0.49, CADD 24.10
- E66V (p.Glu66Val), gnomAD 12-54281859-A-T, REVEL 0.54, CADD 29.50
- D69D (p.Asp69Asp), gnomAD 12-54281869-T-C, CADD 13.80
- A70T (p.Ala70Thr), ExAC rs751147157, gnomAD rs751147157, REVEL 0.18, CADD 31.00
- A70V (p.Ala70Val), Ensembl rs1225931732, REVEL 0.15, CADD 29.80
- A70A (p.Ala70Ala), rs1314098630, gnomAD 12-54281872-A-G, CADD 11.80
- A71V (p.Ala71Val), gnomAD rs1357903521, REVEL 0.29, CADD 25.70
- A71T (p.Ala71Thr), gnomAD 12-54281873-G-A, REVEL 0.37, CADD 26.50
- M72I (p.Met72Ile), NCI-TCGA Cosmic COSV5293, cosmic curated COSV52937, Variant assessed as somatic; moderate impact.
- N73S (p.Asn73Ser), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- N73T (p.Asn73Thr), TOPMed rs1347946127, REVEL 0.02, CADD 23.50
- N73D (p.Asn73Asp), gnomAD 12-54281879-A-G, REVEL 0.04, CADD 22.90
Public HNRNPA1 analysis runs
- HNRNPA1 analysis run — HNRNPA1 (469 variants) — completed 2026-08-21