SYP

Chr XXLR

synaptophysin

Also known as: MRX96, MRXSYP, XLID96

NCBI Gene: 6855ENSG00000102003UniProt: P08247OMIM: 313475

This gene encodes synaptophysin, an integral membrane protein of synaptic vesicles that regulates synaptic plasticity and directs targeting of synaptobrevin to intracellular compartments. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is highly constrained against loss-of-function variants (pLI 0.92, LOEUF 0.39), indicating that complete loss of function is likely not tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLRLOEUF 0.391 OMIM phenotype
Clinical Summary— SYP
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Gene-Disease Validity (ClinGen)
non-syndromic X-linked intellectual disability · XLModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.92). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
78 unique Pathogenic / Likely Pathogenic· 74 VUS of 200 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.39LOEUF
pLI 0.915
Z-score 2.99
OE 0.08 (0.03–0.39)
Highly constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.33Z-score
OE missense 0.67 (0.56–0.80)
87 obs / 129.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.08 (0.03–0.39)
0≤0.351.4
Missense OE0.67 (0.56–0.80)
0≤0.61.4
Synonymous OE1.18
0≤1.21.6
LoF obs/exp: 1 / 12.3Missense obs/exp: 87 / 129.8Syn Z: -1.09
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSYP-related intellectual developmental disorder, X-linkedLOFXLR
DN
0.5082th %ile
GOF
0.6736th %ile
LOF
0.53top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and loss-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median
LOFLOEUF 0.39

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

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

200 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic68
Likely Pathogenic10
VUS74
Likely Benign16
Benign2
Conflicting2
68
Pathogenic
10
Likely Pathogenic
74
VUS
16
Likely Benign
2
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
67
0
68
Likely Pathogenic
7
1
2
0
10
VUS
4
58
11
1
74
Likely Benign
0
6
2
8
16
Benign
0
0
0
2
2
Conflicting
—2
Total12658211172

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

View in ClinVar →

Protein Context — Lollipop Plot

SYP · 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
Renal Protective Mechanisms of Shenyuan Particle in Db/Db Mice: A Study Based on Network Pharmacology
Zhu G et al.·Evid Based Complement Alternat Med
2022Functional
Efficacy and Safety of Ginseng Berry Extract (SIRTBERRY ) in Treating Andropause Symptoms: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Park SY et al.·World J Mens Health
2025
SYP-5 regulates meiotic thermotolerance in Caenorhabditis elegans
Liu Y et al.·J Mol Cell Biol
2021
Gender differences in the associations among adolescent problem behaviors: a secondary data analysis of the 2023 Korea Youth Risk Behavior Survey
Lee J et al.·Child Health Nurs Res
2025
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: its updated diagnostic criteria, preoperative cytologic diagnoses and impact on the risk of malignancy
Na HY et al.·J Pathol Transl Med
2022
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
Discovery of New Angucyclin(on)e Derivatives and Their Genetic Architecture from Streptomyces sp. SYP-A7185 in the Rhizosphere Soil of Panax notoginseng.
Xue JY et al.·ACS Omega
2025Open Access
Fungicide Resistance to SYP-34773 Mediated by Overexpression of the MFS Gene PoDHA1 in Pyricularia oryzae.
Xiao W et al.·J Agric Food Chem
2025
A single point mutation is sufficient to drive syp-dependent biofilm formation and promote colonization by Vibrio fischeri.
Fung BL et al.·J Bacteriol
2025Open Access
Imp/IGF2BP and Syp/SYNCRIP temporal RNA interactomes uncover combinatorial networks of regulators of Drosophila brain development.
Lee JY et al.·Sci Adv
2025Open Access
The role of Imp and Syp RNA-binding proteins in precise neuronal elimination by apoptosis through the regulation of transcription factors.
Guan W et al.·Elife
2024Open Access
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