SYNJ1 (O43426) variants and mutations
SYNJ1 (also known as O43426) is a human protein-coding gene encoding a polyphosphatidylinositol phosphatase protein. It remodels phosphoinositides during clathrin-mediated synaptic-vesicle recycling and helps nerve terminals rapidly regenerate release-ready vesicles. Biallelic pathogenic variants can cause early-onset parkinsonism or severe developmental and epileptic encephalopathy. This analysis covers 50 SYNJ1 variants and mutations. Of these, 92% have computational variant effect predictions. Disease context includes atypical juvenile parkinsonism, genetic developmental and epileptic encephalopathy, and hereditary disease. Example SYNJ1 variants include S19A, R219Q, and K295R.
Variant analysis overview
- Gene: SYNJ1
- Protein: O43426
- UniProt accession: O43426
- Organism: Homo sapiens
- Variants analyzed: 50
- Variant scope: all variants
- Completed: 2026-08-18
Variant and mutation evidence
- Variant composition: 11 unspecified-consequence records; 26 missense variants; 7 synonymous variants; 3 frameshift variants; 3 substitution
- Prediction scores: 46 variants have prediction scores (92% of the analyzed set).
Clinical, disease, and population context
- Disease context: 25 disease associations are represented. Top associations: atypical juvenile parkinsonism, genetic developmental and epileptic encephalopathy, hereditary disease, young-onset Parkinson disease, undetermined early-onset epileptic encephalopathy, Young adult-onset Parkinsonism, Spasticity - intellectual disability - X-linked epilepsy, developmental and epileptic encephalopathy, 1, Alzheimer disease, Dravet syndrome, Parkinson disease, autosomal dominant severe congenital neutropenia.
Protein structure and variant hotspots
- Protein features: 3 domains; 9 binding sites; 13 post-translational modification sites.
- Structural context: 6 variants have structural context.
- PTM context: 4 variants overlap post-translational modification sites.
Data sources
Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, MaveDB, LitVar.
Notable SYNJ1 variants
Examples include S19A, R219Q, K295R, Q287PfsX27, R420P, Y793C, R800C, Y849C. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.
- S19A (p.Ser19Ala), rs907760868, Uncertain significance
- R219Q (p.Arg219Gln), rs398122403, ClinGen CA145358, cosmic curated COSV59155, ClinVar RCV000074432, MetaLR 0.74, MetaSVM 0.79, Conflicting interpretations, Young-onset Parkinson disease; Early-onset Parkinson disease 20; Developmental a
- K295R (p.Lys295Arg), rs2254562, ClinGen CA10004008, cosmic curated COSV59145, ClinVar RCV000713723, MetaLR 0.00, MetaSVM -1.10, Benign, Developmental and epileptic encephalopathy, 53; Early-onset Parkinson disease 20
- Q287PfsX27, rs886039732, Pathogenic
- R420P (p.Arg420Pro), rs1060499619, ClinGen CA410090187, cosmic curated COSV10815, ClinVar RCV001977051, AlphaMissense 1.00, MetaLR 0.16, Uncertain significance, Developmental and epileptic encephalopathy, 53; not provided
- Y793C (p.Tyr793Cys), rs1283151166, ClinGen CA410075420, ClinVar RCV000703018, UniProt VAR 091259, MetaLR 0.95, MetaSVM 1.10, Uncertain significance, Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53
- R800C (p.Arg800Cys), rs1286247510, ClinGen CA410075311, cosmic curated COSV59153, ClinVar RCV003323271, MetaLR 0.98, MetaSVM 1.05, Likely pathogenic, Early-onset Parkinson disease 20
- Y849C (p.Tyr849Cys), rs1057524877, ClinGen CA16609236, ClinVar RCV000445434, ClinVar RCV002522729, MetaLR 0.95, MetaSVM 1.10, Uncertain significance, Developmental and epileptic encephalopathy, 53; Early-onset Parkinson disease 20
- M981I (p.Met981Ile), rs115683257, ClinGen CA10003539, ClinVar RCV000655774, ClinVar RCV001662715, MetaLR 0.46, MetaSVM -0.48, Benign/Likely benign, Early-onset Parkinson disease 20; Developmental and epileptic encephalopathy, 53
- Y1018S (p.Tyr1018Ser), UniProt VAR 078806, Benign, in DEE53
- A1194T (p.Ala1194Thr), rs977170996, []
- V1366A (p.Val1366Ala), rs9980589, cosmic curated COSV59148, UniProt VAR 047309, ExAC rs9980589, AlphaMissense 0.11, MetaLR 0.44
- S1383R (p.Ser1383Arg), rs769099271, ClinGen CA10003148, ClinVar RCV001067626, UniProt VAR 070906, AlphaMissense 0.56, MetaLR 0.61, Uncertain significance, in PARK20
- P1547L (p.Pro1547Leu), rs2230767, ClinGen CA10003055, ClinVar RCV000713734, ClinVar RCV001084764, CADD 16.10, SIFT 0.10, Benign/Likely benign, not provided; not specified; Developmental and epileptic encephalopathy, 53
- G1549G (p.Gly1549Gly), gnomAD 21-32631070-G-A, CADD 2.66
- G1549S (p.Gly1549Ser), rs758953009, gnomAD 21-32631072-C-T, CADD 0.71, SIFT 0.34
- V1554V (p.Val1554Val), rs767006933, gnomAD 21-32631055-T-C, CADD 1.77
- V1554L (p.Val1554Leu), gnomAD 21-32631057-C-G, CADD 14.80, SIFT 0.03
- K1563* (p.Lys1563Ter), rs745526137, gnomAD 21-32631030-T-TA, CADD 33.00
- A1564V (p.Ala1564Val), rs1569013261, gnomAD 21-32631026-G-A, CADD 10.90, SIFT 0.22
- A1564T (p.Ala1564Thr), rs762039918, gnomAD 21-32631036-C-T, CADD 13.50, SIFT 0.06
- S1565S (p.Ser1565Ser), rs1222519292, gnomAD 21-32631022-T-C, CADD 2.28
- S1565L (p.Ser1565Leu), rs1256155308, gnomAD 21-32631023-G-A, CADD 18.40, SIFT 0.03
- S1565C (p.Ser1565Cys), gnomAD 21-32631032-G-C, CADD 23.10, SIFT 0.00
- S1565N (p.Ser1565Asn), rs752303366, gnomAD 21-32631065-C-T, CADD 10.20, SIFT 0.07
- P1566S (p.Pro1566Ser), rs776747094, gnomAD 21-32631021-G-A, CADD 17.20, SIFT 0.05
- P1566T (p.Pro1566Thr), rs776747094, gnomAD 21-32631021-G-T, CADD 21.60, SIFT 0.00
- P1566L (p.Pro1566Leu), rs769381981, gnomAD 21-32631049-AG-A, CADD 33.00
- P1566P (p.Pro1566Pro), rs1601193795, gnomAD 21-32631058-T-C, CADD 0.66
- P1566R (p.Pro1566Arg), gnomAD 21-32631059-G-C, CADD 19.10, SIFT 0.00
- L1568V (p.Leu1568Val), gnomAD 21-32631015-G-C, CADD 14.20, SIFT 0.02
- L1568F (p.Leu1568Phe), gnomAD 21-32631037-C-G, CADD 12.10, SIFT 0.02
- L1568S (p.Leu1568Ser), rs764949465, gnomAD 21-32631038-A-G, CADD 14.70, SIFT 0.07
- L1568W (p.Leu1568Trp), rs764949465, gnomAD 21-32631038-A-C, CADD 19.20, SIFT 0.04
- D1569Y (p.Asp1569Tyr), rs536572904, gnomAD 21-32631012-C-A, CADD 24.70, SIFT 0.00
- D1569D (p.Asp1569Asp), rs2145654435, gnomAD 21-32631052-A-G, CADD 1.63
- F1570L (p.Phe1570Leu), rs1007414965, gnomAD 21-32631007-A-C, CADD 2.21, SIFT 0.17
- F1570F (p.Phe1570Phe), rs1007414965, gnomAD 21-32631007-A-G, CADD 0.41
- T1571T (p.Thr1571Thr), rs747065956, gnomAD 21-32631004-T-C, CADD 1.74
- T1571P (p.Thr1571Pro), rs1326305824, gnomAD 21-32631006-T-G, CADD 25.30, SIFT 0.00
- T1571A (p.Thr1571Ala), rs1266763591, gnomAD 21-32631018-T-C, CADD 16.40, SIFT 0.02
- T1571I (p.Thr1571Ile), gnomAD 21-32631041-G-A, CADD 15.80, SIFT 0.00
- T1571K (p.Thr1571Lys), gnomAD 21-32631044-G-T, CADD 18.70, SIFT 0.00
- T1571M (p.Thr1571Met), rs111516740, gnomAD 21-32631044-G-A, CADD 19.50, SIFT 0.00
- T1571S (p.Thr1571Ser), rs746226206, gnomAD 21-32631068-G-C, CADD 15.50, SIFT 0.03
- T1571H (p.Thr1571His), gnomAD 21-32631069-T-TG, CADD 24.20
- R1573S (p.Arg1573Ser), gnomAD 21-32630998-T-A, CADD 24.20, SIFT 0.00
- R1573T (p.Arg1573Thr), rs772562248, gnomAD 21-32630999-C-G, CADD 24.40, SIFT 0.00
- R1573K (p.Arg1573Lys), rs772562248, gnomAD 21-32630999-C-T, CADD 24.40, SIFT 0.00
- R1573G (p.Arg1573Gly), gnomAD 21-32631000-T-C, CADD 24.80, SIFT 0.00
Public SYNJ1 analysis runs
- SYNJ1 analysis run — SYNJ1 (50 variants) — completed 2026-08-18