SYNGAP1

Protein identityUniProt · HPA

UniProt accession

Q96PV0

Gene

SYNGAP1

Ensembl

ENSG00000197283

Chromosome

6

Canonical length

1343 aa

Protein class

Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, RAS pathway related proteins

Subcellular location

Nucleoplasm

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1343 residues, UniProt reviewed canonical sequence.

>Q96PV0|SYNGAP1
     1  MSRSRASIHR GSIPAMSYAP FRDVRGPSMH RTQYVHSPYD RPGWNPRFCI ISGNQLLMLD
    61  EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY HLGRSRRKSV PGGKQYSMEG
   121  APAAPFRPSQ GFLSRRLKSS IKRTKSQPKL DRTSSFRQIL PRFRSADHDR ARLMQSFKES
   181  HSHESLLSPS SAAEALELNL DEDSIIKPVH SSILGQEFCF EVTTSSGTKC FACRSAAERD
   241  KWIENLQRAV KPNKDNSRRV DNVLKLWIIE ARELPPKKRY YCELCLDDML YARTTSKPRS
   301  ASGDTVFWGE HFEFNNLPAV RALRLHLYRD SDKKRKKDKA GYVGLVTVPV ATLAGRHFTE
   361  QWYPVTLPTG SGGSGGMGSG GGGGSGGGSG GKGKGGCPAV RLKARYQTMS ILPMELYKEF
   421  AEYVTNHYRM LCAVLEPALN VKGKEEVASA LVHILQSTGK AKDFLSDMAM SEVDRFMERE
   481  HLIFRENTLA TKAIEEYMRL IGQKYLKDAI GEFIRALYES EENCEVDPIK CTASSLAEHQ
   541  ANLRMCCELA LCKVVNSHCV FPRELKEVFA SWRLRCAERG REDIADRLIS ASLFLRFLCP
   601  AIMSPSLFGL MQEYPDEQTS RTLTLIAKVI QNLANFSKFT SKEDFLGFMN EFLELEWGSM
   661  QQFLYEISNL DTLTNSSSFE GYIDLGRELS TLHALLWEVL PQLSKEALLK LGPLPRLLND
   721  ISTALRNPNI QRQPSRQSER PRPQPVVLRG PSAEMQGYMM RDLNSSIDLQ SFMARGLNSS
   781  MDMARLPSPT KEKPPPPPPG GGKDLFYVSR PPLARSSPAY CTSSSDITEP EQKMLSVNKS
   841  VSMLDLQGDG PGGRLNSSSV SNLAAVGDLL HSSQASLTAA LGLRPAPAGR LSQGSGSSIT
   901  AAGMRLSQMG VTTDGVPAQQ LRIPLSFQNP LFHMAADGPG PPGGHGGGGG HGPPSSHHHH
   961  HHHHHHRGGE PPGDTFAPFH GYSKSEDLSS GVPKPPAASI LHSHSYSDEF GPSGTDFTRR
  1021  QLSLQDNLQH MLSPPQITIG PQRPAPSGPG GGSGGGSGGG GGGQPPPLQR GKSQQLTVSA
  1081  AQKPRPSSGN LLQSPEPSYG PARPRQQSLS KEGSIGGSGG SGGGGGGGLK PSITKQHSQT
  1141  PSTLNPTMPA SERTVAWVSN MPHLSADIES AHIEREEYKL KEYSKSMDES RLDRVKEYEE
  1201  EIHSLKERLH MSNRKLEEYE RRLLSQEEQT SKILMQYQAR LEQSEKRLRQ QQAEKDSQIK
  1261  SIIGRLMLVE EELRRDHPAM AEPLPEPKKR LLDAQERQLP PLGPTNPRVT LAPPWNGLAP
  1321  PAPPPPPRLQ ITENGEFRNT ADH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SYNGAP1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.51

Highest tissue expression

16 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SYNGAP1.

Disease | AllUniProt

Conditions SYNGAP1 is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 5 (MRD5) MIM:612621

Disease | GeneticClinVar

437 pathogenic / likely-pathogenic of 1,901 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability, autosomal dominant 5
• Inborn genetic diseases
• Complex neurodevelopmental disorder
• Intellectual disability
• SYNGAP1-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.05

gnomAD pLI

1

gnomAD missense Z

5.6

DepMap mean gene effect

-0.13

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• axonogenesis
• dendrite development
• maintenance of postsynaptic specialization structure
• negative regulation of axonogenesis
• negative regulation of neuron apoptotic process
• negative regulation of Ras protein signal transduction
• neuron apoptotic process
• pattern specification process
• Ras protein signal transduction
• receptor clustering
• regulation of intracellular signal transduction
• regulation of long-term neuronal synaptic plasticity
• regulation of MAPK cascade
• regulation of synapse structure or activity
• regulation of synaptic plasticity
• visual learning

Molecular functions

• GTPase activator activity
• SH3 domain binding

Cellular components

• cytosol
• dendritic shaft
• glutamatergic synapse
• plasma membrane
• postsynaptic density

Protein domainsUniProt · Pfam · InterPro

• C2 domain
• Pleckstrin homology domain
• Ras GTPase-activating domain
• Rho GTPase activation protein
• PH-like domain superfamily
• Disabled homolog 2-interacting protein, C-terminal domain
• Ras GTPase-activating protein, conserved site
• C2 domain superfamily
• Ras GTPase-activating protein
• Ras/Rap GTPase-activating protein SynGAP-like, PH domain
• C2 domain
• GTPase-activator protein for Ras-like GTPase
• Disabled homolog 2-interacting protein, C-terminal domain
• PH domain-like
• SynGAP, PH domain

KeywordsUniProt

• Autism
• Autism spectrum disorder
• GTPase activation
• Intellectual disability
• Phosphoprotein
• SH3-binding

InteractionsUniProt · HPA

Protein binding partners of SYNGAP1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CAMK2A
• CAMK2B
• FAM81A
• KLHL17
• MPDZ
• DLG4
• ULK2
• ELAVL3
• H1-4
• ISL1
• LDB1
• SMARCC2