KIRREL3

Chr 11

kirre like nephrin family adhesion molecule 3

Also known as: KIRRE, MRD4, NEPH2, PRO4502

NCBI Gene: 84623 ENSG00000149571 UniProt: Q8IZU9

KIRREL3 encodes a synaptic cell adhesion molecule that is required for formation of target-specific synapses, particularly hippocampal mossy fiber synapses connecting dentate granule and GABA neurons. Mutations cause autosomal dominant intellectual disability, autism spectrum disorder, and other neurodevelopmental disorders. This gene is highly constrained against loss-of-function variants, indicating that haploinsufficiency is likely not tolerated in the general population.

ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is a member of the nephrin-like protein family. These proteins are expressed in fetal and adult brain, and also in podocytes of kidney glomeruli. The cytoplasmic domains of these proteins interact with the C-terminus of podocin, also expressed in the podocytes, cells involved in ensuring size- and charge-selective ultrafiltration. The protein encoded by this gene is a synaptic cell adhesion molecule with multiple extracellular immunoglobulin-like domains and a cytoplasmic PDZ domain-binding motif. Mutations in this gene are associated with several neurological and cognitive disorders. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2017]

ResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDisputedevidence questions this relationship

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.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

0.32

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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