MED15

Chr 22

mediator complex subunit 15

Also known as: ARC105, CAG7A, CTG7A, PCQAP, TIG-1, TIG1, TNRC7

NCBI Gene: 51586ENSG00000099917UniProt: Q96RN5

The protein encoded by this gene is a subunit of the multiprotein complexes PC2 and ARC/DRIP and may function as a transcriptional coactivator in RNA polymerase II transcription. This gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

482
ClinVar variants
345
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— MED15
⚡
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
345 Pathogenic / Likely Pathogenic· 119 VUS of 482 total submissions

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.
0.24LOEUF
pLI 1.000
Z-score 5.96
OE 0.13 (0.07–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.53Z-score
OE missense 0.67 (0.61–0.74)
319 obs / 474.3 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.0.13 (0.07–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.61–0.74)
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.1.06
0≤1.21.6
LoF obs/exp: 7 / 54.5Missense obs/exp: 319 / 474.3Syn Z: -0.68

ClinVar Variant Classifications

482 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic324
Likely Pathogenic21
VUS119
Likely Benign10
Benign6
Conflicting2
324
Pathogenic
21
Likely Pathogenic
119
VUS
10
Likely Benign
6
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
324
0
324
Likely Pathogenic
0
0
21
0
21
VUS
0
81
38
0
119
Likely Benign
0
4
3
3
10
Benign
0
0
6
0
6
Conflicting
—2
Total0853923482

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

View in ClinVar →

Protein Context — Lollipop Plot

MED15 · 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
Clinical and molecular implications of MED15 in head and neck squamous cell carcinoma.
Adler D et al.·Am J Pathol
2015
GRPR-induced FAM135A expression promote perineural invasion in prostate cancer.
Zhang N et al.·Mol Cancer
2025
Renal Neoplasia: Rare Subtypes and Uncommon Clinical Presentations.
Gupta S et al.·Surg Pathol Clin
2025Review
MED15 prion-like domain forms a coiled-coil responsible for its amyloid conversion and propagation.
Batlle C et al.·Commun Biol
2021
MED15 overexpression in prostate cancer arises during androgen deprivation therapy via PI3K/mTOR signaling.
Offermann A et al.·Oncotarget
2017
MED15, encoding a subunit of the mediator complex, is overexpressed at high frequency in castration-resistant prostate cancer.
Adler D et al.·Int J Cancer
2014
Increasing evidence of pathogenic role of the Mediator (MED) complex in the development of cardiovascular diseases.
Napoli C et al.·Biochimie
2019Review
Cystic Features in Renal Epithelial Neoplasms and Their Increasing Clinical and Pathologic Significance.
Tretiakova M et al.·Adv Anat Pathol
2024Review
Novel MED15::ATF1 fusion in a pediatric melanoma with spitzoid features and aggressive presentation.
Furtado LV et al.·Genes Chromosomes Cancer
2024
Fusion-Associated Cutaneous Tumors with Melanocytic Differentiation.
Ko JS·Surg Pathol Clin
2026Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Role of MED15 in Enhancing EMT and Metastasis in Bladder Cancer Through YAP1 Stabilization.
Liu ZX et al.·FASEB J
2026
MED15-TFE3 rearranged renal cell carcinoma: a subtype of TFE3-rearranged renal cell carcinoma with unique clinicopathologic features and better prognosis.
Deng Z et al.·World J Surg Oncol
2025🔓 Open Access
A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline.
Li H et al.·Cell Discov
2025🔓 Open Access
Clinicopathologic Features, Management, and Outcomes Of Pediatric CRTC1::TRIM11 and MED15::ATF1 Tumors With Spitzoid Morphology: A Case Series.
Sargen MR et al.·Pediatr Blood Cancer
2025Cohort
The mediator subunit complex protein MED15 promotes lipid deposition and cancer progression during hypoxia.
Zhang B et al.·J Biol Chem
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

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