MED27

Chr 9

mediator complex subunit 27

Also known as: CRAP34, CRSP34, CRSP8, MED3, NEDSCAC, TRAP37

NCBI Gene: 9442 ENSG00000160563 UniProt: Q6P2C8

MED27 encodes a component of the Mediator complex that functions as a coactivator bridge between gene-specific regulatory proteins and the RNA polymerase II transcription machinery for nearly all RNA polymerase II-dependent genes. Mutations cause autosomal recessive neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia. The gene shows low constraint against loss-of-function variants (pLI 0.00002), suggesting tolerance to heterozygous loss.

ResearchSummary from RefSeq, OMIM, 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. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Dec 2011]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with spasticity, cataracts, and cerebellar atrophy

Clinical highlights

Gene-disease validity (ClinGen)

neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.02

LOEUF

LOF

Mechanism· G2P

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429