MED15

protein-coding

mediator complex subunit 15, the group of Mediator complex

Gene summary

The protein encoded by this gene is a subunit of the multiprotein complexes PC2 and ARC/DRIP and may function as a transcriptional coactivator in RNA polymerase II transcription. This gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

Previous symbols:

TNRC7
PCQAP

MANE transcript

NM_001003891.3

Inheritance

—

ClinVar variants

U:96B:9

Top phenotype

Aganglionic megacolon

gnomAD constraint

pLI —, LoF o/e 0.13

Max pathogenic AF

—

Genomic locus

chr22:20,495,913-20,587,632

External References & Databases

Ensembl (ENSG00000099917)

Transcript & Mutation Effects

hg38 • Region Span ~91.7 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 MED15 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 87

not providedTotal: 8

Aganglionic megacolonTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001003891.3. 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				5 clinvar		5
missense			87 clinvar	4 clinvar		91
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	96	9	0	105

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 109 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001003891.3	RefSeq	NP_001003891.1	18	MANE Select
ENST00000263205.11	Ensembl	ENSP00000263205.7	18	MANE Select
NM_001293234.2	RefSeq	NP_001280163.1	17	Standard
NM_001293235.2	RefSeq	NP_001280164.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
med15	Danio rerio	Structure: mesendoderm development Quality: disrupted abnormal

Gene / Model

Organism

Observed Phenotype

med15

Danio rerio

Structure: mesendoderm development

Quality: disrupted

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Sterol Regulatory Element-Binding Proteins (SREBP) signalling
SREBF and miR33 in cholesterol and lipid homeostasis
Developmental Biology
Gene expression (Transcription)
Generic Transcription Pathway

Biological Process

regulation of transcription by RNA polymerase II
transcription initiation from RNA polymerase II promoter
stem cell population maintenance

Molecular Function

transcription coregulator activity
protein binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
membrane
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000263205
Coding exons: 18
Length: 91720
Individuals with no LoFs: 125736
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 125748
p: 0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.53	319	474	0.673	0.0000284	5141
Missense (PolyPhen)		46	95.771	0.48031		1064
Synonymous	-0.678	214	202	1.06	0.0000136	1532
Loss of Function	5.96	7	54.5	0.128	0.00000281	480

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	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. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway. {ECO:0000269|PubMed:12167862, ECO:0000269|PubMed:16630888, ECO:0000269|PubMed:16799563}.;

Recessive Scores

pRec: 0.166

Intolerance Scores

LoFtool: 0.0513
RVIS EVS: -1.46
RVIS percentile EVS: 3.78

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 1.00

Gene Damage Prediction

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