LEMD3

Chr 12AD

LEM domain containing 3

Also known as: MAN1

NCBI Gene: 23592 ENSG00000174106 UniProt: Q9Y2U8 OMIM: 607844

The protein functions as a specific repressor of TGF-beta, activin, and BMP signaling pathways at the inner nuclear membrane through interaction with R-SMAD proteins. Mutations cause Buschke-Ollendorff syndrome and osteopoikilosis with or without melorheostosis, which are skeletal disorders affecting bone development and connective tissue. The gene follows autosomal dominant inheritance and is highly constrained against loss-of-function variants.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This locus encodes a LEM domain-containing protein. The encoded protein functions to antagonize transforming growth factor-beta signaling at the inner nuclear membrane. Two transcript variants encoding different isoforms have been found for this gene. Mutations in this gene have been associated with osteopoikilosis, Buschke-Ollendorff syndrome and melorheostosis.[provided by RefSeq, Nov 2009]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Buschke-Ollendorff syndromeMIM #166700

Osteopoikilosis with or without melorheostosisMIM #166700

Clinical highlights

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

0.25

LOEUF· LoF intol.

LOF

Mechanism· G2P