MED10

Chr 5

mediator complex subunit 10

Also known as: L6, NUT2, TRG20

NCBI Gene: 84246 ENSG00000133398 UniProt: Q9BTT4 OMIM: 612382

MED10 encodes a component of the Mediator complex, which functions as a coactivator that bridges gene-specific regulatory proteins to the RNA polymerase II transcription machinery for regulated transcription of nearly all RNA polymerase II-dependent genes. Mutations in MED10 cause autosomal recessive infantile-onset epileptic encephalopathy with developmental delay and intellectual disability. The gene shows relatively low constraint to loss-of-function variation.

OMIM ResearchSummary from RefSeq, UniProt

MED10 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.09

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.09LOEUF

pLI 0.049

Z-score 1.42

OE 0.42 (0.19–1.09)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.69Z-score

OE missense 0.78 (0.63–0.97)

58 obs / 74.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.42 (0.19–1.09)

0≤0.351.4

Missense OE?0.78 (0.63–0.97)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 7.1Missense obs/exp: 58 / 74.7Syn Z: 0.09

Background carrier burden — how many people carry a rare variant somewhere in MED10?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 730

140 rare PASS variants

Rare truncating (LoF)

1 in 3,600

23 rare PASS variants

Rare synonymous (reference)

1 in 670

67 rare PASS variants

Rare missense and truncating variants are carried at similar rates in MED10; this gene does not show strong loss-of-function constraint by this measure. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 770	1 in 4,200
South Asian	~43k	1 in 380	1 in 3,600
Remaining (unassigned)	~30k	1 in 890	1 in 6,000
European (Finnish)	~27k	1 in 3,800	1 in 1,200
Admixed American	~22k	1 in 1,100	none seen
African / African American	~21k	1 in 630	≈ 1 in 4,900
East Asian	~20k	1 in 580	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 1,100	none seen
Middle Eastern	~2,884	1 in 360	none seen

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓