• 0
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
MED12 (HGNC:11957) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
mediator complex subunit 12
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
TNRC11, FGS1
Alias symbols
CAGH45, HOPA, OPA1, TRAP230, KIAA0192, OKS, ARC240, Kto
%HI
6.34(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.07(Read more about gnomAD LOEUF score)
Cytoband
Xq13.1
Genomic Coordinates
GRCh37/hg19: chrX:70338446-70362300 NCBI Ensembl UCSC
GRCh38/hg38: chrX:71118596-71142450 NCBI Ensembl UCSC
MANE Select Transcript
NM_005120.3 ENST00000374080.8 (Read more about MANE Select)
Function
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene- specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcript... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-511
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
No Evidence for Haploinsufficiency (0)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
08/22/2018

Haploinsufficiency (HI) Score Details

HI Score:
0
HI Evidence Strength:
No Evidence for Haploinsufficiency (Disclaimer)
HI Evidence:
  • PUBMED: 24039113
    Lesca et al. 2013 identified a c.5898dupC mutation causing p.Ser1967GlnfsX84 segregating in one family with non-syndromic intellectual disability (ID) in 9 affected males. There were 10 carrier females, seven with variable cognitive impairment including 1 with significant ID. Expression studies performed produced two abnormal mRNAs (one with the frameshift and the other one with an in-frame 75-bp deletion due to the activation of two cryptic splice sites in exon 41), and therefore escaped non-sense-mediated RNA decay. It is unclear if this mutation would be consistent with haploinsufficiency.
HI Evidence Comments:
No clear loss of function mutations have been described in MED12. Missense mutations have been associated with three different established XLR disorders: Opitz-Kaveggia syndrome, Lujan-Fryns syndrome and Ohdo syndrome. In addition, missense mutations have also been observed in individuals with non-syndromic X-linked Intellectual disability (p.R521H) (Fieremans 2016), (p.R621Q) (Prescott 2016), (p.I771T) (Prontera 2016), (p.R815Q) (Tzschach 2015), (p.I1023V) (Yamamoto 2015) (p.A1383T) (Langley 2015) and (p.E1974H) (Bouazzi 2015). The disease mechanism of some missense mutations do not appear to be loss of function. Donnio 2017: PMID: 28369444.
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)
NOTE:

The loss-of-function and triplosensitivity ratings for genes on the X chromosome are made in the context of a male genome to account for the effects of hemizygous duplications or nullizygous deletions. In contrast, disruption of some genes on the X chromosome causes male lethality and the ratings of dosage sensitivity instead take into account the phenotype in female individuals. Factors that may affect the severity of phenotypes associated with X-linked disorders include the presence of variable copies of the X chromosome (i.e. 47,XXY or 45,X) and skewed X-inactivation in females.

Genomic View

Select assembly: (NC_000023.10) (NC_000023.11)