GeneBe

MED1

protein-coding

mediator complex subunit 1, the group of Mediator complex

Gene summary

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. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize. [provided by RefSeq, Jul 2008]

Previous symbols:
  • TRIP2
  • PPARGBP
  • PPARBP

MANE transcript

NM_004774.4

Inheritance

—

ClinVar variants

U:167B:10

Top phenotype

Intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.04

Max pathogenic AF

—

Genomic locus

chr17:39,404,285-39,451,272

External References & Databases

Ensembl (ENSG00000125686)NCBI Gene (5469)OMIM (604311)HGNC:9234GenCCUniProt (Q15648)AlphaFoldClinVar (MED1)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~47.0 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MED1 variants in ClinVar

5 Conditions Cataloged
not specifiedTotal: 156
Intellectual disabilityTotal: 6
not providedTotal: 5
MED1-related conditionTotal: 5
Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004774.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
2
clinvar
2
clinvar
1
clinvar
 5
missense
157
clinvar
7
clinvar
 164
nonsense
2
clinvar
 2
start loss
0
frameshift
2
clinvar
 2
splice donor/acceptor (+/-2bp)
4
clinvar
 4
Total0016791177
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_004774.4RefSeqNP_004765.217MANE Select
ENST00000300651.11EnsemblENSP00000300651.617MANE Select
ENST00000394287.7EnsemblENSP00000377828.318Standard
ENST00000394287.8EnsemblENSP00000377828.318Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Thyroid hormone signaling pathway - Homo sapiens (human)
  • Energy Metabolism
  • H19 action Rb-E2F1 signaling and CDK-β-catenin activity
  • role of ppar-gamma coactivators in obesity and thermogenesis
  • Developmental Biology

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • cell morphogenesis
  • angiogenesis
  • liver development
  • embryonic placenta development

Molecular Function

  • RNA polymerase II proximal promoter sequence-specific DNA binding
  • RNA polymerase II core promoter sequence-specific DNA binding
  • core promoter binding
  • chromatin binding
  • transcription coregulator activity

Cellular Component

  • ubiquitin ligase complex
  • chromatin
  • nucleus
  • nucleoplasm
  • nucleolus

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000300651
Coding exons
17
Length
47002
Individuals with no LoFs
125741
Homozygous LoFs
0
Heterozygous LoFs
7
Defined
125748
p
0.0000278
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense2.146618350.7920.000042010435
Missense (PolyPhen)160247.260.64713164
Synonymous1.832713120.8680.00001673159
Loss of Function6.53253.60.03730.00000287724

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian00.0absent
Finnish00.0absent
European (Non-Finnish)0.0000440.000044rare
South Asian0.0000330.000033rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
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 preinitiation complex with RNA polymerase II and the general transcription factors (PubMed:10406464, PubMed:11867769, PubMed:12037571, PubMed:12218053, PubMed:12556447, PubMed:14636573, PubMed:15340084, PubMed:15471764, PubMed:15989967, PubMed:16574658, PubMed:9653119). Acts as a coactivator for GATA1-mediated transcriptional activation during erythroid differentiation of K562 erythroleukemia cells (PubMed:24245781). {ECO:0000269|PubMed:10406464, ECO:0000269|PubMed:11867769, ECO:0000269|PubMed:12037571, ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:12556447, ECO:0000269|PubMed:14636573, ECO:0000269|PubMed:15340084, ECO:0000269|PubMed:15471764, ECO:0000269|PubMed:15989967, ECO:0000269|PubMed:16574658, ECO:0000269|PubMed:24245781, ECO:0000269|PubMed:9653119}.;

Recessive Scores

pRec
0.304

Intolerance Scores

LoFtool
0.0189
RVIS EVS
-1.55
RVIS percentile EVS
3.28

Essentials

Essential (CRISPR)
E
Essential (CRISPR2)
E
Essential (gene trap)
E
Indispensability pred.
E
Indispensability score
0.963

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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