MED17

Chr 11AR

mediator complex subunit 17

Also known as: CRSP6, CRSP77, DRIP80, SRB4, TRAP80

NCBI Gene: 9440ENSG00000042429UniProt: Q9NVC6

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. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Microcephaly, postnatal progressive, with seizures and brain atrophyMIM #613668
AR
0
Active trials
32
Pathogenic / LP
290
ClinVar variants
6
Pubs (1 yr)
0.9
Missense Z
0.78
LOEUF
Clinical Summary— MED17
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 123 VUS of 290 total submissions
📖
GeneReview available — MED17
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.78LOEUF
pLI 0.000
Z-score 2.63
OE 0.54 (0.38–0.78)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.88Z-score
OE missense 0.87 (0.79–0.95)
298 obs / 343.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.38–0.78)
0≤0.351.4
Missense OE0.87 (0.79–0.95)
0≤0.61.4
Synonymous OE0.93
0≤1.21.6
LoF obs/exp: 20 / 37.3Missense obs/exp: 298 / 343.8Syn Z: 0.60

ClinVar Variant Classifications

290 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic20
Likely Pathogenic12
VUS123
Likely Benign131
Benign3
Conflicting1
20
Pathogenic
12
Likely Pathogenic
123
VUS
131
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
13
0
20
Likely Pathogenic
8
1
3
0
12
VUS
0
107
11
5
123
Likely Benign
0
2
54
75
131
Benign
0
0
3
0
3
Conflicting
—1
Total151108480290

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

View in ClinVar →

MED17 · protein map & ClinVar variants

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

Gene2Phenotype Curations

MED17-related microcephaly, postnatal progressive, with seizures and brain atrophy

strong
ARUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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