MED14

Chr X

mediator complex subunit 14

Also known as: CRSP150, CRSP2, CSRP, CXorf4, DRIP150, EXLM1, RGR1, TRAP170

NCBI Gene: 9282 ENSG00000180182 UniProt: O60244

The protein is a component of the Mediator complex that functions as a coactivator for RNA polymerase II-dependent gene transcription, serving as a bridge between gene-specific regulatory proteins and the basal transcription machinery. Mutations cause X-linked intellectual disability with variable additional features including seizures, behavioral problems, and dysmorphic features. This gene is extremely intolerant to loss-of-function variants and escapes X-inactivation, which may contribute to phenotypic expression in carrier females.

ResearchSummary from RefSeq, UniProt

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation. [provided by RefSeq, Jul 2008]

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)

—

P/LP submissions

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P/LP missense

0.09

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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