MED16

protein-coding

mediator complex subunit 16, the group of Mediator complex|WD repeat domain containing

Gene summary

Enables nuclear thyroid hormone receptor binding activity and transcription coactivator activity. Involved in positive regulation of transcription initiation by RNA polymerase II. Located in nucleus. Part of mediator complex. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

THRAP5

MANE transcript

NM_005481.3

Inheritance

ClinVar variants

P:13U:237B:26

Top phenotype

complex neurodevelopmental disorder

gnomAD constraint

pLI —, LoF o/e 0.74

Max pathogenic AF

—

Genomic locus

chr19:867,630-893,218

External References & Databases

Ensembl (ENSG00000175221)

Transcript & Mutation Effects

hg38 • Region Span ~25.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

complex neurodevelopmental disorderSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: PanelApp Australia

complex neurodevelopmental disorder with or without congenital anomaliesMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0100465

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to MED16 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 222

not providedTotal: 36

Guillouet-Gordon syndromeTotal: 21

Syndromic intellectual disabilityTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005481.3. 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			2 clinvar	11 clinvar	5 clinvar	18
missense	7 clinvar	1 clinvar	223 clinvar	10 clinvar		241
nonsense	1 clinvar		2 clinvar			3
start loss						0
frameshift	2 clinvar		3 clinvar			5
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	7 clinvar			9
Total	11	2	237	21	5	276

Highest pathogenic variant AF is 0.00025286298

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 40 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005481.3	RefSeq	NP_005472.2	15	MANE Select
ENST00000325464.6	Ensembl	ENSP00000325612.1	15	MANE Select
ENST00000312090.10	Ensembl	ENSP00000308528.4	15	Standard
ENST00000312090.11	Ensembl	ENSP00000308528.4	15	Standard

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 by RNA polymerase II
transcription initiation from RNA polymerase II promoter
intracellular steroid hormone receptor signaling pathway
androgen receptor signaling pathway

Molecular Function

transcription coregulator activity
transcription coactivator activity
catalytic activity
protein binding
thyroid hormone receptor coactivator activity

Cellular Component

nucleus
nucleoplasm
membrane
mediator complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000325464
Coding exons: 15
Length: 25257
Individuals with no LoFs: 125531
Homozygous LoFs: 1
Heterozygous LoFs: 186
Defined: 125718
p: 0.000744

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.67	703	589	1.19	0.0000422	5574
Missense (PolyPhen)		74	82.567	0.89624		753
Synonymous	-9.45	478	278	1.72	0.0000223	1803
Loss of Function	1.41	26	35.0	0.743	0.00000159	383

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00061	0.00055	rare
Latino/Admixed American	0.00092	0.00087	rare
Ashkenazi Jewish	0.00033	0.00030	rare
East Asian	0.00039	0.00038	rare
Finnish	0.00035	0.00032	rare
European (Non-Finnish)	0.0011	0.0010	notable
South Asian	0.00027	0.00026	rare
Other	0.0015	0.0015	notable

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:10198638, ECO:0000269|PubMed:10235266}.;

Recessive Scores

pRec: 0.125

Intolerance Scores

LoFtool: 0.477
RVIS EVS: -2.73
RVIS percentile EVS: 0.7

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.957

Gene Damage Prediction

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