SYNJ1

Chr 21AR

synaptojanin 1

Also known as: DEE53, EIEE53, INPP5G, PARK20

NCBI Gene: 8867ENSG00000159082UniProt: O43426OMIM: 604297

The protein is a phosphoinositide phosphatase that regulates membrane phosphatidylinositol-4,5-bisphosphate levels, affecting synaptic transmission and membrane trafficking. Autosomal recessive mutations cause developmental and epileptic encephalopathy 53 and early-onset Parkinson disease 20. The pathogenic mechanism involves disruption of synaptic function and cellular membrane trafficking processes.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.332 OMIM phenotypes
Clinical Summary— SYNJ1
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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
31 unique Pathogenic / Likely Pathogenic· 123 VUS of 400 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — SYNJ1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
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
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
LoF OE0.22 (0.16–0.33)
0≤0.351.4
Missense OE0.78 (0.73–0.83)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 19 / 84.5Missense obs/exp: 667 / 851.7Syn Z: 0.41

ClinVar Variant Classifications

400 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic6
VUS123
Likely Benign216
Benign6
Conflicting6
25
Pathogenic
6
Likely Pathogenic
123
VUS
216
Likely Benign
6
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
14
0
11
0
25
Likely Pathogenic
6
0
0
0
6
VUS
3
115
5
0
123
Likely Benign
0
7
65
144
216
Benign
0
2
3
1
6
Conflicting
—6
Total2312484145382

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients