MED24

protein-coding

mediator complex subunit 24, the group of Mediator complex|MicroRNA protein coding host genes|Small nucleolar RNA protein coding host genes

Gene summary

This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Previous symbols:

THRAP4
CRSP4

MANE transcript

NM_014815.4

Inheritance

—

ClinVar variants

P:2U:124B:5

Top phenotype

Short stature

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr17:40,019,097-40,061,215

External References & Databases

Ensembl (ENSG00000008838)

Transcript & Mutation Effects

hg38 • Region Span ~42.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MED24 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 115

not providedTotal: 3

Short statureTotal: 2

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014815.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				1 clinvar		1
missense		2 clinvar	119 clinvar	3 clinvar	1 clinvar	125
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	2	124	4	1	131

Highest pathogenic variant AF is 0.00002169106

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 86 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014815.4	RefSeq	NP_055630.2	25	MANE Select
ENST00000394128.7	Ensembl	ENSP00000377686.2	25	MANE Select
NM_001079518.2	RefSeq	NP_001072986.1	24	Standard
NM_001267797.2	RefSeq	NP_001254726.1	24	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
med24	Danio rerio	Structure: mid intestine Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

med24

Danio rerio

Structure: mid intestine

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Thyroid hormone signaling pathway - Homo sapiens (human)
Developmental Biology
Gene expression (Transcription)
Generic Transcription Pathway
RNA Polymerase II Transcription

Biological Process

transcription initiation from RNA polymerase II promoter
intracellular steroid hormone receptor signaling pathway
androgen receptor signaling pathway
positive regulation of transcription, DNA-templated

Molecular Function

transcription coregulator activity
protein binding
nuclear receptor transcription coactivator activity
signaling receptor activity
vitamin D receptor binding

Cellular Component

nucleus
nucleoplasm
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394128
Coding exons: 25
Length: 42119
Individuals with no LoFs: 125637
Homozygous LoFs: 0
Heterozygous LoFs: 111
Defined: 125748
p: 0.000441

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.63	414	594	0.697	0.0000356	6425
Missense (PolyPhen)		106	172.13	0.61582		1995
Synonymous	0.715	235	249	0.942	0.0000157	1964
Loss of Function	3.31	26	51.7	0.503	0.00000255	576

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00044	0.00043	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00076	0.00076	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00051	0.00049	rare
South Asian	0.00034	0.00033	rare
Other	0.0010	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. {ECO:0000269|PubMed:12218053, ECO:0000269|PubMed:16595664}.;

Recessive Scores

pRec: 0.132

Intolerance Scores

LoFtool: 0.902
RVIS EVS: -1.41
RVIS percentile EVS: 4.13

Essentials

Essential (CRISPR): E
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.747

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium