MED14

Chr X

mediator complex subunit 14

Also known as: CRSP150, CRSP2, CSRP, CXorf4, DRIP150, EXLM1, RGR1, TRAP170

The protein is a component of the Mediator complex that functions as a coactivator for RNA polymerase II-dependent gene transcription, serving as a bridge between gene-specific regulatory proteins and the basal transcription machinery. Mutations cause X-linked intellectual disability with variable additional features including seizures, behavioral problems, and dysmorphic features. This gene is extremely intolerant to loss-of-function variants and escapes X-inactivation, which may contribute to phenotypic expression in carrier females.

Summary from RefSeq, UniProt
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0
Active trials
8
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.09
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryMED14
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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.09LOEUF
pLI 1.000
Z-score 6.54
OE 0.02 (0.010.09)
Highly constrained

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

Missense Constraint
4.13Z-score
OE missense 0.49 (0.440.54)
252 obs / 516.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.02 (0.010.09)
00.351.4
Missense OE0.49 (0.440.54)
00.61.4
Synonymous OE0.85
01.21.6
LoF obs/exp: 1 / 51.7Missense obs/exp: 252 / 516.3Syn Z: 1.57
DN
0.2598th %ile
GOF
0.2099th %ile
LOF
0.84top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.09

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

MED14 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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