SYN1

Chr XX-linked

synapsin I

Also known as: EPILX, EPILX1, MRX50, SYN1a, SYN1b, SYNI

Synapsin I is a neuronal phosphoprotein that coats synaptic vesicles and regulates neurotransmitter release at presynaptic terminals, while also controlling axon outgrowth and synaptogenesis. Mutations cause X-linked epilepsy with variable learning disabilities and behavior disorders, as well as X-linked intellectual developmental disorder. Disease predominantly results from loss-of-function mutations, consistent with the gene's high intolerance to such variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismX-linkedLOEUF 0.252 OMIM phenotypes
Clinical SummarySYN1
🧬
Gene-Disease Validity (ClinGen)
X-linked complex neurodevelopmental disorder · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.25LOEUF
pLI 0.992
Z-score 3.82
OE 0.05 (0.020.25)
Highly constrained

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

Missense Constraint
2.97Z-score
OE missense 0.47 (0.400.55)
116 obs / 247.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.05 (0.020.25)
00.351.4
Missense OE0.47 (0.400.55)
00.61.4
Synonymous OE0.83
01.21.6
LoF obs/exp: 1 / 18.9Missense obs/exp: 116 / 247.3Syn Z: 1.44
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongSYN1-related epilepsy with variable learning disabilities and behaviour disordersLOFXLR
DN
0.3693th %ile
GOF
0.3888th %ile
LOF
0.74top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.25

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SYN1 · 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 →