TIAM2

Chr 6

TIAM Rac1 associated GEF 2

Also known as: STEF, TIAM-2

NCBI Gene: 26230 ENSG00000146426 UniProt: Q8IVF5 OMIM: 604709

TIAM2 encodes a guanine nucleotide exchange factor that activates RAC1 GTPase, mediating extracellular laminin signals essential for neurite growth, neuronal migration in the cerebral cortex, and growth cone advancement in developing neurons. Mutations cause autosomal recessive intellectual disability with seizures and cortical malformations, reflecting the protein's critical role in neuronal development and migration. The gene is highly constrained against loss-of-function variants (LOEUF 0.433), indicating that complete loss of protein function is likely pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a guanine nucleotide exchange factor. A highly similar mouse protein specifically activates ras-related C3 botulinum substrate 1, converting this Rho-like guanosine triphosphatase (GTPase) from a guanosine diphosphate-bound inactive state to a guanosine triphosphate-bound active state. The encoded protein may play a role in neural cell development. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.43

LOEUF

Multiple*

Mechanism· predicted