SYNGAP1

Chr 6AD

synaptic Ras GTPase activating protein 1

Also known as: MRD5, RASA5, SYNGAP

NCBI Gene: 8831 ENSG00000197283 UniProt: Q96PV0 OMIM: 603384

The protein negatively regulates Ras, Rap, and AMPA receptor trafficking to the postsynaptic membrane, controlling synaptic plasticity and neuronal homeostasis as part of the NMDA receptor complex. Mutations cause autosomal dominant intellectual developmental disorder with autism spectrum features, predominantly through loss-of-function mechanisms. The gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the primary disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, Mechanism

This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Allelic variants of this gene are associated with intellectual disability and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, autosomal dominant 5MIM #612621

Clinical highlights

Management implications

SYNGAP1 has therapies in development

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

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LOEUF

LOF

Mechanism· G2P

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GeneReview available — SYNGAP1

Authoritative clinical overview · Recommended first read

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Some data sources returned errors (1)

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SYNGAP1-upregulation programs
ASOPreclinical
Increase SYNGAP1 to counter haploinsufficiency.
Delivery: Intrathecal

Therapeutic landscape as of 2026-07. Educational only. Investigational ≠ available; not medical advice or eligibility. Approved entries are precise; investigational program names/phases are conservative and move fast. Curated from FDA/EMA approvals and the clinical-trial literature; verify against current labeling + ClinicalTrials.gov.

ClinicalTrials.gov