ZRSR2 (Q15696) variants and mutations
ZRSR2 (also known as Q15696) is a human protein-coding gene encoding an u2 small nuclear ribonucleoprotein auxiliary factor 35 kDa subunit-related protein 2 protein. It is particularly important for recognition and removal of U12-type minor introns during RNA splicing. Somatic loss-of-function mutations are recurrent in myelodysplastic syndromes and other myeloid neoplasms and produce characteristic minor-intron retention. This analysis covers 567 ZRSR2 variants and mutations. Of these, 93% have computational variant effect predictions. Disease context includes neurodegenerative disease, orofaciodigital syndrome 21, and myelodysplastic syndrome. Example ZRSR2 variants include A2D, A2G, and A2T.
Variant analysis overview
- Gene: ZRSR2
- Protein: Q15696
- UniProt accession: Q15696
- Organism: Homo sapiens
- Variants analyzed: 567
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 367 unspecified-consequence records; 126 missense variants; 47 synonymous variants; 3 in-frame deletions; 7 stop-gained variants; 7 splice-region variants; 7 frameshift variants; 2 substitution
- Prediction scores: 525 variants have prediction scores (93% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: neurodegenerative disease, orofaciodigital syndrome 21, myelodysplastic syndrome, CD4+/CD56+ hematodermic neoplasm, chronic myelomonocytic leukemia, myelofibrosis, colorectal adenocarcinoma, acute myeloid leukemia, lysosomal storage disease, myeloproliferative disorder, diffuse large B-cell lymphoma, chronic myelogenous leukemia, BCR-ABL1 positive.
Protein structure and variant hotspots
- Protein features: 1 domains; 2 post-translational modification sites.
- Structural context: 59 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, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable ZRSR2 variants
Examples include A2D, A2G, A2T, A2S, A2V, A3E, A3S, A3T. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- A2D (p.Ala2Asp), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.06, MetaSVM -1.04, Variant assessed as somatic; moderate impact.
- A2G (p.Ala2Gly), gnomAD rs1478814299, REVEL 0.08, MetaLR 0.06
- A2T (p.Ala2Thr), gnomAD X-15790499-G-A, REVEL 0.08, MetaLR 0.07
- A2S (p.Ala2Ser), gnomAD X-15790499-G-T, REVEL 0.06, MetaLR 0.07
- A2V (p.Ala2Val), gnomAD X-15790500-C-T, REVEL 0.04, MetaLR 0.06
- A3E (p.Ala3Glu), gnomAD rs1171488245, REVEL 0.05, MetaLR 0.06
- A3S (p.Ala3Ser), gnomAD X-15790502-G-T, REVEL 0.04, MetaLR 0.06
- A3T (p.Ala3Thr), gnomAD X-15790502-G-A, REVEL 0.04, MetaLR 0.05
- A3V (p.Ala3Val), gnomAD X-15790503-C-T, REVEL 0.02, MetaLR 0.04
- A3A (p.Ala3Ala), gnomAD X-15790504-G-A, CADD 8.04
- P4L (p.Pro4Leu), gnomAD rs1420055483, REVEL 0.09, MetaLR 0.05
- P4S (p.Pro4Ser), Ensembl rs1036634845, MetaLR 0.05, MetaSVM -1.05
- P4H (p.Pro4His), gnomAD X-15790506-C-A, REVEL 0.13, MetaLR 0.09
- P4P (p.Pro4Pro), gnomAD X-15790507-C-G, CADD 5.68
- E5G (p.Glu5Gly), gnomAD rs1404694257, REVEL 0.01, MetaLR 0.03
- E5K (p.Glu5Lys), gnomAD X-15790508-G-A, REVEL 0.07, MetaLR 0.04
- E5* (p.Glu5Ter), gnomAD X-15790508-G-T, CADD 32.00
- E5V (p.Glu5Val), gnomAD X-15790509-A-T, REVEL 0.04, MetaLR 0.03
- E5D (p.Glu5Asp), gnomAD X-15790510-G-T, REVEL 0.01, MetaLR 0.03
- E5E (p.Glu5Glu), rs1162672398, gnomAD X-15790510-G-A, CADD 7.65
- K6N (p.Lys6Asn), NCI-TCGA TCGA novel, Ensembl rs906223771, REVEL 0.01, MetaLR 0.02, Variant assessed as somatic; moderate impact.
- K6T (p.Lys6Thr), TOPMed rs1198313061, gnomAD rs1198313061, REVEL 0.03, MetaLR 0.02, Uncertain significance, not specified
- K6Q (p.Lys6Gln), gnomAD X-15790511-A-C, REVEL 0.02, MetaLR 0.02
- K6R (p.Lys6Arg), gnomAD X-15790512-A-G, REVEL 0.04, MetaLR 0.02
- K6K (p.Lys6Lys), gnomAD X-15790513-G-A, CADD 7.28
- M7L (p.Met7Leu), Ensembl rs1932235690
- M7V (p.Met7Val), NCI-TCGA Cosmic COSV5706, cosmic curated COSV57067, MetaLR 0.03, MetaSVM -1.06, Variant assessed as somatic; moderate impact.
- p.Met7 Lys12del, gnomAD X-15790504-GCCCGA, CADD 13.80
- M7I (p.Met7Ile), gnomAD X-15790516-G-A, REVEL 0.01, MetaLR 0.04
- T8A (p.Thr8Ala), Ensembl rs2147275075, REVEL 0.01, MetaLR 0.01
- T8M (p.Thr8Met), ExAC rs747435591, gnomAD rs747435591, REVEL 0.02, MetaLR 0.02
- T8S (p.Thr8Ser), gnomAD X-15790517-A-T, REVEL 0.02, MetaLR 0.02
- T8K (p.Thr8Lys), gnomAD X-15790518-C-A, REVEL 0.01, MetaLR 0.02
- T8R (p.Thr8Arg), gnomAD X-15790518-C-G, REVEL 0.01, MetaLR 0.02
- T8T (p.Thr8Thr), gnomAD X-15790519-G-A, CADD 9.47
- F9I (p.Phe9Ile), gnomAD X-15790520-T-A, REVEL 0.03, MetaLR 0.02
- F9L (p.Phe9Leu), gnomAD X-15790522-T-G, REVEL 0.04, MetaLR 0.02
- F9F (p.Phe9Phe), gnomAD X-15790522-T-C, CADD 8.80
- F9S (p.Phe9Ser), rs1932453306, gnomAD X-15796204-T-C, CADD 4.70
- P10T (p.Pro10Thr), gnomAD X-15790523-C-A, REVEL 0.01, MetaLR 0.05
- P10L (p.Pro10Leu), gnomAD X-15790524-C-T, REVEL 0.03, MetaLR 0.06
- P10H (p.Pro10His), gnomAD X-15790524-C-A, REVEL 0.06, MetaLR 0.07
- P10P (p.Pro10Pro), rs1405377723, gnomAD X-15790525-C-T, CADD 2.05
- E11A (p.Glu11Ala), Ensembl rs1932235920, MetaLR 0.04, MetaSVM -1.01
- E11K (p.Glu11Lys), gnomAD X-15790526-G-A, REVEL 0.03, MetaLR 0.06
- E11* (p.Glu11Ter), gnomAD X-15790526-G-T, CADD 34.00
- E11E (p.Glu11Glu), gnomAD X-15790528-G-A, CADD 7.83
- E11D (p.Glu11Asp), gnomAD X-15790528-G-T, REVEL 0.04, MetaLR 0.06
- K12K (p.Lys12Lys), gnomAD X-15790531-A-G, CADD 8.13
- P13T (p.Pro13Thr), gnomAD X-15790532-C-A, REVEL 0.09, MetaLR 0.06
- P13Q (p.Pro13Gln), gnomAD X-15790533-C-A, REVEL 0.03, MetaLR 0.03
- P13R (p.Pro13Arg), gnomAD X-15790533-C-G, REVEL 0.02, MetaLR 0.03
- P13P (p.Pro13Pro), gnomAD X-15790534-A-G, CADD 1.89
- S14G (p.Ser14Gly), gnomAD X-15790535-A-G, REVEL 0.09, MetaLR 0.05
- S14C (p.Ser14Cys), gnomAD X-15790535-A-T, REVEL 0.10, MetaLR 0.07
- S14I (p.Ser14Ile), gnomAD X-15790536-G-T, REVEL 0.12, MetaLR 0.06
- S14L (p.Ser14Leu), rs745330542, gnomAD X-15796234-C-T, CADD 0.58, SIFT 0.07
- S14S (p.Ser14Ser), rs1366458733, gnomAD X-15796235-G-A, CADD 0.46
- H15N (p.His15Asn), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.01, MetaSVM -1.01, Variant assessed as somatic; moderate impact.
- H15R (p.His15Arg), ExAC rs746007790, gnomAD rs746007790, REVEL 0.21, MetaLR 0.00
- H15H (p.His15His), gnomAD X-15790937-C-T, CADD 12.90
- K16R (p.Lys16Arg), gnomAD X-15790939-A-G, REVEL 0.19, MetaLR 0.01
- K17R (p.Lys17Arg), TOPMed rs1932255174, REVEL 0.11, MetaLR 0.01
- K17K (p.Lys17Lys), gnomAD X-15799885-G-A, CADD 6.58, SIFT 0.01
- Y18C (p.Tyr18Cys), NCI-TCGA TCGA novel, Variant assessed as somatic; moderate impact.
- Y18V (p.Tyr18Val), NCI-TCGA TCGA novel, MetaLR 0.01, MetaSVM -1.04, Variant assessed as somatic; high impact.
- Y18Y (p.Tyr18Tyr), gnomAD X-15790946-C-T, CADD 12.60
- R19K (p.Arg19Lys), NCI-TCGA Cosmic COSV1003, Variant assessed as somatic; moderate impact.
- R19W (p.Arg19Trp), ExAC rs758956631, gnomAD rs758956631, MetaLR 0.08, MetaSVM -0.98
- A20V (p.Ala20Val), gnomAD rs1384197720, REVEL 0.12, MetaLR 0.07
- A20A (p.Ala20Ala), rs780755210, gnomAD X-15790952-C-G, CADD 8.67
- A20S (p.Ala20Ser), rs769526864, gnomAD X-15796242-G-T, CADD 1.01, SIFT 0.21
- A20T (p.Ala20Thr), rs769526864, gnomAD X-15796242-G-A, CADD 1.27, SIFT 0.09
- A21T (p.Ala21Thr), Ensembl rs1569061838, REVEL 0.04, MetaLR 0.05
- A21S (p.Ala21Ser), gnomAD X-15790953-G-T, REVEL 0.03, MetaLR 0.06
- A21A (p.Ala21Ala), gnomAD X-15790955-C-T, CADD 9.17
- L22L (p.Leu22Leu), gnomAD X-15790958-G-T, CADD 12.60
- L22P (p.Leu22Pro), rs1205105872, gnomAD X-15796237-T-C, CADD 3.83, SIFT 0.16
- K23K (p.Lys23Lys), gnomAD X-15790961-G-A, CADD 13.30
- K24R (p.Lys24Arg), gnomAD X-15790963-A-G, REVEL 0.09, MetaLR 0.12
- E25* (p.Glu25Ter), Ensembl rs1932256028
- E25D (p.Glu25Asp), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, Variant assessed as somatic; moderate impact.
- E25G (p.Glu25Gly), ExAC rs769172943, TOPMed rs769172943, gnomAD rs769172943, MetaLR 0.07, MetaSVM -1.07
- R27* (p.Arg27Ter), NCI-TCGA TCGA novel, Variant assessed as somatic; high impact.
- R27Q (p.Arg27Gln), NCI-TCGA Cosmic COSV1003, NCI-TCGA Cosmic COSV5706, cosmic curated COSV57063, MetaLR 0.09, MetaSVM -0.96, Variant assessed as somatic; moderate impact.
- R27R (p.Arg27Arg), rs1356367704, gnomAD X-15790973-A-T, CADD 8.94
- K28R (p.Lys28Arg), Ensembl rs2147275406, REVEL 0.05, MetaLR 0.46
- K28K (p.Lys28Lys), rs776097997, gnomAD X-15790976-G-A, CADD 14.10
- R30P (p.Arg30Pro), TOPMed rs913798919, MetaLR 0.67, MetaSVM 0.65
- R30C (p.Arg30Cys), gnomAD X-15790980-C-T, REVEL 0.18, MetaLR 0.55
- Q32H (p.Gln32His), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, MetaLR 0.74, MetaSVM 0.53, Variant assessed as somatic; moderate impact.
- Q32L (p.Gln32Leu), gnomAD rs1278239441, REVEL 0.21, MetaLR 0.70
- E33D (p.Glu33Asp), TOPMed rs1439175665
- E33G (p.Glu33Gly), ExAC rs747852506, gnomAD rs747852506, MetaLR 0.06, MetaSVM -1.03
- E33E (p.Glu33Glu), rs1439175665, gnomAD X-15790991-A-G, CADD 12.60
- L34P (p.Leu34Pro), gnomAD X-15790993-T-C, REVEL 0.14, MetaLR 0.13
- R36L (p.Arg36Leu), TOPMed rs1395906760, REVEL 0.12, MetaLR 0.17
- R36R (p.Arg36Arg), gnomAD X-15790998-C-A, CADD 15.20
- R36P (p.Arg36Pro), gnomAD X-15790999-G-C, REVEL 0.12, MetaLR 0.15
- D39E (p.Asp39Glu), gnomAD X-15791009-C-A, REVEL 0.07, MetaLR 0.04
- S40S (p.Ser40Ser), gnomAD X-15791012-A-G, CADD 22.10
- G41V (p.Gly41Val), gnomAD X-15799872-G-T, REVEL 0.08, MetaLR 0.07
- G41E (p.Gly41Glu), gnomAD X-15799872-G-A, REVEL 0.03, MetaLR 0.03
- G41G (p.Gly41Gly), gnomAD X-15799873-A-G, CADD 16.40
- G41C (p.Gly41Cys), gnomAD X-15801287-G-T, CADD 2.21, SIFT 0.00
- G41D (p.Gly41Asp), gnomAD X-15801288-G-A, CADD 1.16, SIFT 0.09
- L42I (p.Leu42Ile), NCI-TCGA TCGA novel, REVEL 0.10, MetaLR 0.54, Variant assessed as somatic; moderate impact.
- L42F (p.Leu42Phe), gnomAD X-15799874-C-T, REVEL 0.06, MetaLR 0.43
- L42P (p.Leu42Pro), gnomAD X-15799875-T-C, REVEL 0.09, MetaLR 0.52
- S43P (p.Ser43Pro), ExAC rs769474729, TOPMed rs769474729, gnomAD rs769474729, REVEL 0.10, MetaLR 0.07
- S43* (p.Ser43Ter), gnomAD X-15799878-C-A, CADD 33.00
- S43N (p.Ser43Asn), gnomAD X-15801285-G-A, CADD 1.97, SIFT 0.40
- S43S (p.Ser43Ser), gnomAD X-15801286-T-C, CADD 6.61, SIFT 0.07
- S43Y (p.Ser43Tyr), gnomAD X-15801297-C-A, CADD 0.63, SIFT 0.01
- S43L (p.Ser43Leu), gnomAD X-15801327-C-T, CADD 0.59, SIFT 0.02
- S43T (p.Ser43Thr), gnomAD X-15801335-T-A, CADD 2.72, SIFT 0.00
- S43F (p.Ser43Phe), rs1327157948, gnomAD X-15801336-C-T, CADD 1.14, SIFT 0.01
- Q44K (p.Gln44Lys), gnomAD X-15799880-C-A, REVEL 0.02, MetaLR 0.45
- K45E (p.Lys45Glu), gnomAD rs1476833485, REVEL 0.06, MetaLR 0.28
- K45R (p.Lys45Arg), gnomAD X-15799884-A-G, REVEL 0.04, MetaLR 0.38
- K45N (p.Lys45Asn), gnomAD X-15799885-G-T, REVEL 0.05, MetaLR 0.38
- E46G (p.Glu46Gly), gnomAD X-15799887-A-G, REVEL 0.07, MetaLR 0.52
- E47K (p.Glu47Lys), NCI-TCGA TCGA novel, gnomAD rs1932608014, REVEL 0.07, MetaLR 0.01, Variant assessed as somatic; moderate impact.
- E47G (p.Glu47Gly), gnomAD X-15799890-A-G, REVEL 0.08, MetaLR 0.02
- E47E (p.Glu47Glu), gnomAD X-15799891-A-G, CADD 7.21, SIFT 0.02
- E48D (p.Glu48Asp), cosmic curated COSV57064, ExAC rs748769419, TOPMed rs748769419, gnomAD rs748769419, MetaLR 0.65, MetaSVM -0.13
- E48K (p.Glu48Lys), rs777454064, NCI-TCGA Cosmic COSV5706, cosmic curated COSV57063, ExAC rs777454064, REVEL 0.20, MetaLR 0.74, Variant assessed as somatic; moderate impact.
- E48E (p.Glu48Glu), rs748769419, gnomAD X-15799894-G-A, CADD 3.07
- E49* (p.Glu49Ter), NCI-TCGA Cosmic COSV5706, Variant assessed as somatic; high impact.
- E49Q (p.Glu49Gln), gnomAD X-15799895-G-C, REVEL 0.12, MetaLR 0.06
- D50D (p.Asp50Asp), gnomAD X-15799900-C-T, CADD 0.96
- D50H (p.Asp50His), gnomAD X-15801332-G-C, CADD 0.81, SIFT 0.35
- D50Y (p.Asp50Tyr), gnomAD X-15801332-G-T, CADD 0.89, SIFT 0.02
- D50N (p.Asp50Asn), rs1280161466, gnomAD X-15801332-G-A, CADD 1.09, SIFT 0.47
- T51A (p.Thr51Ala), rs770461833, ClinGen CA412452186, ClinVar RCV004145419, ExAC rs770461833, AlphaMissense 0.07, MetaLR 0.15, Likely benign, not specified
- T51P (p.Thr51Pro), ExAC rs770461833, TOPMed rs770461833, gnomAD rs770461833, REVEL 0.08, AlphaMissense 0.07, Likely benign
- T51S (p.Thr51Ser), gnomAD X-15799901-A-T, REVEL 0.04, MetaLR 0.16
- T51I (p.Thr51Ile), gnomAD X-15799902-C-T, REVEL 0.11, MetaLR 0.33
- T51T (p.Thr51Thr), gnomAD X-15799903-T-A, CADD 5.95
- T51K (p.Thr51Lys), gnomAD X-15801369-C-A, CADD 1.22, SIFT 0.01
- F52C (p.Phe52Cys), ESP rs201893706, ExAC rs201893706, TOPMed rs201893706, gnomAD rs201893706, REVEL 0.10, MetaLR 0.39
- F52S (p.Phe52Ser), cosmic curated COSV57068, ESP rs201893706, ExAC rs201893706, TOPMed rs201893706, REVEL 0.10, MetaLR 0.31
- F52Y (p.Phe52Tyr), ESP rs201893706, ExAC rs201893706, TOPMed rs201893706, gnomAD rs201893706, REVEL 0.12, MetaLR 0.36
- F52L (p.Phe52Leu), gnomAD X-15799902-CT-C, CADD 16.10
- I53T (p.Ile53Thr), TOPMed rs1332738431, REVEL 0.03, MetaLR 0.34
- I53L (p.Ile53Leu), gnomAD X-15799907-A-C, REVEL 0.02, MetaLR 0.42
- E54K (p.Glu54Lys), ExAC rs771966906, gnomAD rs771966906, REVEL 0.08, MetaLR 0.06
- E54G (p.Glu54Gly), gnomAD X-15799911-A-G, REVEL 0.05, MetaLR 0.06
- E54E (p.Glu54Glu), gnomAD X-15799912-A-G, CADD 11.00
- E55K (p.Glu55Lys), Ensembl rs1555899273, REVEL 0.09, MetaLR 0.05
- E55* (p.Glu55Ter), gnomAD X-15799913-G-T, CADD 35.00
- E55E (p.Glu55Glu), rs775337499, gnomAD X-15799915-A-G, CADD 10.10
- Q56Q (p.Gln56Gln), rs1425197107, gnomAD X-15799918-A-G, CADD 6.25
- Q57del (p.Gln57del), rs757369196, gnomAD X-15799913-GAAC-G, CADD 15.20
- Q57K (p.Gln57Lys), gnomAD X-15799919-C-A, REVEL 0.04, MetaLR 0.04
- Q57Q (p.Gln57Gln), gnomAD X-15799921-A-G, CADD 6.01
- L58P (p.Leu58Pro), Ensembl rs1569065513, REVEL 0.12, MetaLR 0.04
- E59* (p.Glu59Ter), NCI-TCGA Cosmic COSV1003, cosmic curated COSV10031, NCI-TCGA Cosmic COSV5706, Variant assessed as somatic; high impact.
- E59Q (p.Glu59Gln), gnomAD X-15799925-G-C, REVEL 0.16, MetaLR 0.75
- E60K (p.Glu60Lys), gnomAD X-15799928-G-A, REVEL 0.18, MetaLR 0.71
- E60D (p.Glu60Asp), gnomAD X-15799930-A-C, REVEL 0.20, MetaLR 0.66
- E61del (p.Glu61del), rs781227781, gnomAD X-15799923-TAGA-T, CADD 16.20
- E61G (p.Glu61Gly), gnomAD X-15799932-A-G, REVEL 0.11, MetaLR 0.16
- K62E (p.Lys62Glu), Ensembl rs112463846, REVEL 0.11, MetaLR 0.42
- K62N (p.Lys62Asn), cosmic curated COSV57065, gnomAD rs1932610535, REVEL 0.05, MetaLR 0.43
- K62R (p.Lys62Arg), gnomAD X-15799935-A-G, REVEL 0.10, MetaLR 0.26
- K62K (p.Lys62Lys), gnomAD X-15799936-G-A, CADD 7.62
- L63I (p.Leu63Ile), gnomAD X-15799937-C-A, REVEL 0.06, MetaLR 0.51
- L63L (p.Leu63Leu), rs760432507, gnomAD X-15799939-A-G, CADD 8.52
- L64L (p.Leu64Leu), rs1157687587, gnomAD X-15799940-T-C, CADD 6.23
- E65K (p.Glu65Lys), gnomAD X-15799941-TG-T, CADD 24.30
- E65Q (p.Glu65Gln), gnomAD X-15799943-G-C, REVEL 0.16, MetaLR 0.14
- E67D (p.Glu67Asp), TOPMed rs1329781895, gnomAD rs1329781895, REVEL 0.19, MetaLR 0.71
- E67G (p.Glu67Gly), gnomAD X-15799950-A-G, REVEL 0.28, MetaLR 0.75
- E67E (p.Glu67Glu), rs1329781895, gnomAD X-15799951-G-A, CADD 13.40
- R68G (p.Arg68Gly), gnomAD X-15799952-A-G, REVEL 0.40, MetaLR 0.77
- R68R (p.Arg68Arg), gnomAD X-15799952-A-C, CADD 22.30, SIFT 1.00
- R68K (p.Arg68Lys), gnomAD X-15799953-G-A, REVEL 0.19, MetaLR 0.73
- Q69E (p.Gln69Glu), NCI-TCGA TCGA novel, MetaLR 0.53, MetaSVM -0.10, Variant assessed as somatic; moderate impact.
- L71M (p.Leu71Met), gnomAD X-15801275-C-A, CADD 1.50, SIFT 0.00
Public ZRSR2 analysis runs
- ZRSR2 analysis run — ZRSR2 (567 variants) — completed 2026-08-18