RAI1

Chr 17

retinoic acid induced 1

Also known as: SMCR, SMS

NCBI Gene: 10743 ENSG00000108557 UniProt: Q7Z5J4

RAI1 encodes a protein that contains a polyglutamine tract and is highly expressed in neuronal tissues, where its expression is induced by retinoic acid. Loss-of-function mutations cause Smith-Magenis syndrome through an autosomal dominant inheritance pattern, though most cases are isolated (de novo) occurrences. The protein localizes to the cytoplasm and is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene is located within the Smith-Magenis syndrome region on chromosome 17. It is highly similar to its mouse counterpart and is expressed at high levels mainly in neuronal tissues. The protein encoded by this gene includes a polymorphic polyglutamine tract in the N-terminal domain. Expression of the mouse counterpart in neurons is induced by retinoic acid. This gene is associated with both the severity of the phenotype and the response to medication in schizophrenic patients. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSmith-Magenis syndrome

Clinical highlights

Gene-disease validity (ClinGen)

Smith-Magenis syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.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

0.12

LOEUF· LoF intol.

LOF

Mechanism· G2P

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GeneReview available — RAI1