MED22

protein-coding

mediator complex subunit 22, the group of Mediator complex

Gene summary

This gene encodes a protein component of the mediator complex, which functions in the regulation of transcription by bridging interactions between gene-specific regulatory factors, RNA polymerase II, and general transcription factors. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

Previous symbols:

SURF5

MANE transcript

NM_133640.5

Inheritance

ClinVar variants

U:33B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.65

Max pathogenic AF

—

Genomic locus

chr9:133,338,312-133,348,131

External References & Databases

Ensembl (ENSG00000148297)

Transcript & Mutation Effects

hg38 • Region Span ~9.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MED22 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 34

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_133640.5. 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			33 clinvar	1 clinvar		34
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	33	2	0	35

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 27 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_133640.5	RefSeq	NP_598395.1	4	MANE Select
ENST00000343730.10	Ensembl	ENSP00000342343.5	4	MANE Select
NM_181491.3	RefSeq	NP_852468.1	3	Standard
ENST00000371999.5	Ensembl	ENSP00000361067.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Developmental Biology
Transcriptional regulation of white adipocyte differentiation

Biological Process

regulation of transcription by RNA polymerase II

Molecular Function

transcription coregulator activity
protein binding

Cellular Component

cytoplasm
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000491289
Coding exons: 4
Length: 9827
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.370	112	124	0.906	0.00000817	1286
Missense (PolyPhen)		31	37.85	0.81902		417
Synonymous	-0.277	64	61.2	1.05	0.00000482	407
Loss of Function	1.13	8	12.3	0.651	8.82e-7	96

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00016	0.00016	rare
South Asian	0.00013	0.00013	rare
Other	0.00016	0.00016	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.;

Recessive Scores

pRec: 0.111

Intolerance Scores

LoFtool: 0.349
RVIS EVS: -0.07
RVIS percentile EVS: 48.35

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.919

Gene Damage Prediction

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