protein
Triple functional domain protein
Gene
TRIO
Organism
Homo sapiens(9606)
Length
3097 aa
Mass
346,900 Da
TRIO (triple functional domain protein) is a guanine nucleotide exchange factor (GEF) for the RHOA and RAC1 GTPases (UniProt: O75962). It coordinates actin remodeling necessary for cell migration and growth, and plays a key role in regulating neurite outgrowth and lamellipodia formation. In developing hippocampal neurons, TRIO limits dendrite formation and regulates synaptic function by controlling endocytosis of AMPA-selective glutamate receptors at CA1 excitatory synapses.
TRIO is implicated in two forms of autosomal dominant intellectual developmental disorder: MRD44 (with microcephaly, developmental delay, and distinctive facial features) and MRD63 (with macrocephaly, moderate to severe intellectual impairment, poor speech, and global developmental delay). Both conditions feature variable dysmorphic features.
TRIO is classified as SFARI Category 1 for autism spectrum disorder risk with syndromic presentation (SFARI Cat 1), indicating strong evidence for causative involvement in ASD, particularly in syndromic forms associated with intellectual disability and neurodevelopmental phenotypes.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
Function
Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases (PubMed:22155786, PubMed:27418539, PubMed:8643598). Involved in coordinating actin remodeling, which is necessary for cell migration and growth (PubMed:10341202, PubMed:22155786). Plays a key role in the regulation of neurite outgrowth and lamellipodia formation (PubMed:32109419). In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses (By similarity). May act as a regulator of adipogenesis (By similarity)
Disease associations
Intellectual developmental disorder, autosomal dominant 44, with microcephalyMRD44
A disorder characterized by developmental delay, variable intellectual disability, distinctive facial features, and abnormalities of the fingers. Most patients also have microcephaly.
Intellectual developmental disorder, autosomal dominant 63, with macrocephalyMRD63
An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD63 is characterized by moderate to severe impaired intellectual development with poor or absent speech, global developmental delay, and variable behavioral abnormalities. Variable dysmorphic features are preset in half of the patients.
Sources
Last updated 5/6/2026, 5:25:10 AM