MED1

Chr 17

mediator complex subunit 1

Also known as: CRSP1, CRSP200, DRIP205, DRIP230, PBP, PPARBP, PPARGBP, RB18A

NCBI Gene: 5469UniProt: Q15648

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]

0
Active trials
180
ClinVar variants
8
Pathogenic / LP
2.1
Missense Z
0.12
LOEUF· LoF intolerant
10
Pubs (2 yr)
Clinical Summary— MED1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 160 VUS of 180 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.12LOEUF
pLI 1.000
Z-score 6.53
OE 0.04 (0.01–0.12)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.14Z-score
OE missense 0.79 (0.74–0.84)
661 obs / 834.9 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.04 (0.01–0.12)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.74–0.84)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.87
0≤1.21.6
LoF obs/exp: 2 / 53.6Missense obs/exp: 661 / 834.9Syn Z: 1.83

ClinVar Variant Classifications

180 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
VUS160
Likely Benign10
Benign2
8
Pathogenic
160
VUS
10
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
0
0
0
VUS
1
154
5
0
160
Likely Benign
0
6
2
2
10
Benign
0
0
1
1
2
Total1160163180

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MED1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
MED1 Regulates BMP/TGF-β in Endothelium: Implication for Pulmonary Hypertension.
Wang C et al.·Circ Res
2022
KLF7 regulates super-enhancer-driven IGF2BP2 overexpression to promote the progression of head and neck squamous cell carcinoma.
Cai H et al.·J Exp Clin Cancer Res
2024
MED1 may explain the interaction between receptor tyrosine kinases and ERα66 in the complicated network of Tamoxifen resistance.
Mansouri S et al.·Eur J Pharmacol
2017Review
Synthetic ZFTA fusions pinpoint disordered protein domain acquisition as a mechanism of brain tumorigenesis.
Arabzade A et al.·Nat Cell Biol
2025Functional
MED1 Downregulation Contributes to TGFβ-Induced Metastasis by Inhibiting SMAD2 Ubiquitination Degradation in Cutaneous Melanoma.
Li Y et al.·J Invest Dermatol
2022
DNA hypermethylation of MED1 and MED23 as early diagnostic biomarkers for unsolved issues in atrial fibrillation.
Schiano C et al.·Int J Cardiol
2025
Involvement of Mediator complex in malignancy.
Schiano C et al.·Biochim Biophys Acta
2014Review
Targeting CDK12 disrupts estrogen-receptor chromatin recruitment and ER-MED1 transcription in advanced ER+ breast cancer.
Ottaviani D et al.·J Natl Cancer Inst
2026
Genomic Landscapes of Endometrioid and Mucinous Ovarian Cancers and Morphologically Similar Tumor Types.
Hallberg D et al.·Cancer Res Commun
2025
Mediator subunit MED1 differentially modulates mutant thyroid hormone receptor intracellular dynamics in Resistance to Thyroid Hormone syndrome.
Wang M et al.·Mol Cell Endocrinol
2023
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Characterization of Fusarium verticillioides Med1 LxxLL Motif Involved in Fumonisin Biosynthesis
Zhou Z et al.·Toxins (Basel)
2023
MED1 Deficiency in Macrophages Accelerates Intimal Hyperplasia via ROS Generation and Inflammation
Zhang Y et al.·Oxid Med Cell Longev
2021
Preparation of MED1(transcription mediator subunit) gene nanocarrier and its mechanism of action on liver cell regeneration in chronic acute liver failure
Guo J et al.·Bioengineered
2021Functional
MED1 Ablation Promotes Oral Mucosal Wound Healing via JNK Signaling Pathway
Meng Z et al.·Int J Mol Sci
2022
Mediator complex subunit 1 promotes oral squamous cell carcinoma progression by activating MMP9 transcription and suppressing CD8+ T cell antitumor immunity
Li Z et al.·J Exp Clin Cancer Res
2024
MED1 is a lipogenesis coactivator required for postnatal adipose expansion
Jang Y et al.·Genes Dev
2021
Phosphorylated MED1 links transcription recycling and cancer growth
Chen Z et al.·Nucleic Acids Res
2022
Mir-483-5p-mediated activating of IGF2/H19 enhancer up-regulates IGF2/H19 expression via chromatin loops to promote the malignant progression of hepatocellular carcinoma
Chen W et al.·Mol Cancer
2025
Retrospective analysis of dissemination of the 2.MED1 phylogenetic branch of Yersinia pestis in the Caucasus
Eroshenko GA et al.·PLoS One
2023
Top 9 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients