MED23

Chr 6AR

mediator complex subunit 23

Also known as: ARC130, CRSP130, CRSP133, CRSP3, DRIP130, MRT18, SUR-2, SUR2

NCBI Gene: 9439ENSG00000112282UniProt: Q9ULK4OMIM: 605042

The MED23 protein is a subunit of the CRSP cofactor complex required for SP1-mediated gene transcription activation and also functions as a component of thyroid hormone receptor-associated protein complexes that facilitate transcription initiation by RNA polymerase II. Biallelic mutations cause autosomal recessive intellectual developmental disorder-18, with or without epilepsy. The pathogenic mechanism involves disrupted transcriptional regulation due to loss of cofactor function in gene activation processes.

OMIMResearchSummary from RefSeq, OMIM, UniProt
ARLOEUF 0.501 OMIM phenotype
Clinical Summary— MED23
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
75 unique Pathogenic / Likely Pathogenic· 203 VUS of 500 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint
0.50LOEUF
pLI 0.000
Z-score 5.09
OE 0.36 (0.27–0.50)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
4.73Z-score
OE missense 0.51 (0.47–0.55)
369 obs / 728.1 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.36 (0.27–0.50)
0≤0.351.4
Missense OE0.51 (0.47–0.55)
0≤0.61.4
Synonymous OE0.90
0≤1.21.6
LoF obs/exp: 27 / 74.4Missense obs/exp: 369 / 728.1Syn Z: 1.21

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic41
VUS203
Likely Benign176
Benign4
Conflicting3
34
Pathogenic
41
Likely Pathogenic
203
VUS
176
Likely Benign
4
Benign
3
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
20
6
8
0
34
Likely Pathogenic
35
3
3
0
41
VUS
5
179
18
1
203
Likely Benign
1
3
68
104
176
Benign
0
0
4
0
4
Conflicting
—3
Total61191101105461

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

View in ClinVar →

Protein Context — Lollipop Plot

MED23 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
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