MED14

protein-coding

mediator complex subunit 14, the group of Mediator complex

Gene summary

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. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation. [provided by RefSeq, Jul 2008]

Previous symbols:

CXorf4
CRSP2

MANE transcript

NM_004229.4

Inheritance

—

ClinVar variants

U:240B:9

Top phenotype

Intellectual disability

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chrX:40,648,305-40,735,858

External References & Databases

Ensembl (ENSG00000180182)

Transcript & Mutation Effects

hg38 • Region Span ~87.6 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 MED14 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 74

not providedTotal: 13

Intellectual disabilityTotal: 3

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

Neurodevelopmental disorderTotal: 1

MED14-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004229.4. 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			24 clinvar	3 clinvar	3 clinvar	30
missense			166 clinvar	3 clinvar		169
nonsense			22 clinvar			22
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			28 clinvar			28
Total	0	0	240	6	3	249

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004229.4	RefSeq	NP_004220.2	31	MANE Select
ENST00000324817.6	Ensembl	ENSP00000323720.1	31	MANE Select
ENST00000416199.5	Ensembl	ENSP00000392586.1	4	Standard
ENST00000433003.1	Ensembl	ENSP00000411357.1	6	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
med14	Danio rerio	Structure: melanocyte Quality: morphology abnormal

Gene / Model

Organism

Observed Phenotype

med14

Danio rerio

Structure: melanocyte

Quality: morphology

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

regulation of transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
stem cell population maintenance
intracellular steroid hormone receptor signaling pathway
androgen receptor signaling pathway

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
membrane
mediator complex
core mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324817
Coding exons: 31
Length: 87553
Individuals with no LoFs: 125113
Homozygous LoFs: 0
Heterozygous LoFs: 1
Defined: 125114
p: 0.00000400

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	4.13	252	516	0.488	0.0000398	9404
Missense (PolyPhen)		33	139.3	0.2369		2495
Synonymous	1.57	154	181	0.852	0.0000134	2944
Loss of Function	6.54	1	51.7	0.0193	0.00000430	875

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000012	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

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:15340088, ECO:0000269|PubMed:15625066, ECO:0000269|PubMed:16595664}.;

Recessive Scores

pRec: 0.153

Intolerance Scores

RVIS EVS: -0.36
RVIS percentile EVS: 29.31

Essentials

Essential (CRISPR): N
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.783

Gene Damage Prediction

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