EMC3

Chr 3

ER membrane protein complex subunit 3

Also known as: POB, TMEM111

NCBI Gene: 55831 ENSG00000125037 UniProt: Q9P0I2 OMIM: 620273

EMC3 encodes a component of the endoplasmic reticulum membrane protein complex (EMC) that facilitates the insertion of newly synthesized membrane proteins into ER membranes, particularly those with weakly hydrophobic transmembrane domains or destabilizing features. Mutations cause a neurodevelopmental disorder with global developmental delay, intellectual disability, and seizures, inherited in an autosomal recessive pattern. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.547), consistent with its essential role in cellular protein trafficking.

OMIM ResearchSummary from RefSeq, UniProt

Contributes to membrane insertase activity. Involved in protein insertion into ER membrane by stop-transfer membrane-anchor sequence and tail-anchored membrane protein insertion into ER membrane. Located in endoplasmic reticulum membrane. Part of EMC complex. [provided by Alliance of Genome Resources, Jul 2025]

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

0.55

LOEUF

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Mechanism