RELN

Chr 7ADAR

reelin

Also known as: ETL7, LIS2, PRO1598, RL

NCBI Gene: 5649 ENSG00000189056 UniProt: P78509 OMIM: 600514

The protein is a large secreted extracellular matrix protein that controls cell positioning and neuronal migration during brain development. Mutations cause autosomal recessive lissencephaly type 2 (Norman-Roberts type) with cerebellar hypoplasia and autosomal dominant familial temporal lobe epilepsy type 7. The pathogenic mechanism involves loss of function, disrupting normal neuronal migration patterns.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a large secreted extracellular matrix protein thought to control cell-cell interactions critical for cell positioning and neuronal migration during brain development. This protein may be involved in schizophrenia, autism, bipolar disorder, major depression and in migration defects associated with temporal lobe epilepsy. Mutations of this gene are associated with autosomal recessive lissencephaly with cerebellar hypoplasia. Two transcript variants encoding distinct isoforms have been identified for this gene. Other transcript variants have been described but their full length nature has not been determined. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Epilepsy, familial temporal lobe, 7}MIM #616436

Lissencephaly 2 (Norman-Roberts type)MIM #257320

Clinical highlights

Gene-disease validity (ClinGen)

lissencephaly with cerebellar hypoplasia · ARDefinitivesufficient evidence for diagnostic panels2 gene-disease associations curated in total

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)

—

P/LP submissions

—

P/LP missense

0.18

LOEUF· LoF intol.

LOF

Mechanism· G2P