SYNJ1

Chr 21AR

synaptojanin 1

NCBI Gene: 8867ENSG00000159082UniProt: O43426

Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:23804563, PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity)

Primary Disease Associations & Inheritance

Developmental and epileptic encephalopathy 53MIM #617389
AR
Parkinson disease 20, early-onsetMIM #615530
AR
682
ClinVar variants
40
Pathogenic / LP
0.43
pLI score
1
Active trials
Clinical Summary— SYNJ1
🧬
Gene-Disease Validity (ClinGen)
developmental and epileptic encephalopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
40 Pathogenic / Likely Pathogenic· 220 VUS of 682 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.427
Z-score 6.61
OE 0.22 (0.16–0.33)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.25Z-score
OE missense 0.78 (0.73–0.83)
667 obs / 851.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.22 (0.16–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.78 (0.73–0.83)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.97
0≤1.21.6
LoF obs/exp: 19 / 84.5Missense obs/exp: 667 / 851.7Syn Z: 0.41

ClinVar Variant Classifications

682 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic10
VUS220
Likely Benign404
Benign12
Conflicting6
30
Pathogenic
10
Likely Pathogenic
220
VUS
404
Likely Benign
12
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
23
0
30
Likely Pathogenic
5
1
4
0
10
VUS
5
189
26
0
220
Likely Benign
1
3
174
226
404
Benign
0
0
11
1
12
Conflicting
—6
Total18193238227682

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SYNJ1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
SYNAPTOJANIN 1; SYNJ1
MIM #604297 · *

Developmental and epileptic encephalopathy 53

MIM #617389

Molecular basis of disorder known

Autosomal recessive

Parkinson disease 20, early-onset

MIM #615530

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SYNJ1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Monogenic Parkinson's Disease: Genotype, Phenotype, Pathophysiology, and Genetic Testing.
Jia F et al.·Genes (Basel)
2022Review
Genotype-Phenotype Relations for the Atypical Parkinsonism Genes: MDSGene Systematic Review.
Wittke C et al.·Mov Disord
2021Review
A novel SYNJ1 homozygous variant causing developmental and epileptic encephalopathy in an Afro-Caribbean individual.
Maj M et al.·Mol Genet Genomic Med
2023
'Atypical' Parkinson's disease - genetic.
Weissbach A et al.·Int Rev Neurobiol
2019Review
Mini-review: Synaptojanin 1 and its implications in membrane trafficking.
Choudhry H et al.·Neurosci Lett
2021Review
Clonazepam improves the symptoms of two siblings with novel variants in the SYNJ1 gene.
Hong D et al.·Parkinsonism Relat Disord
2019Review
The genetic landscape of Parkinson's disease.
Lunati A et al.·Rev Neurol (Paris)
2018Review
Co-occurrence of PRKN and SYNJ1 variants in Early-Onset Parkinson's disease.
Cotrin JC et al.·Metab Brain Dis
2024Case report
New Genes Causing Hereditary Parkinson's Disease or Parkinsonism.
Puschmann A·Curr Neurol Neurosci Rep
2017Review
The genetics of autosomal recessive early-onset Parkinson's disease.
Cogan G et al.·Curr Opin Neurobiol
2025Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Parkinson Disease

Aquaporin-4 Single Nucleotide Polymorphisms in Patients With Idiopathic and Familial Parkinson's Disease

ACTIVE NOT RECRUITING
NCT04553185University of ExeterStarted 2018-11-28
Study procedure

External Resources

Links to major genomics databases and tools