MED17

Chr 11AR

mediator complex subunit 17

Also known as: CRSP6, CRSP77, DRIP80, SRB4, TRAP80

NCBI Gene: 9440 ENSG00000042429 UniProt: Q9NVC6 OMIM: 603810

MED17 encodes a component of the Mediator complex, which functions as a coactivator for RNA polymerase II transcription by bridging gene-specific regulatory proteins to the basal transcription machinery. Mutations cause autosomal recessive microcephaly with postnatal progressive features including seizures and brain atrophy. The gene is highly constrained against loss-of-function variants, indicating its critical importance for normal cellular function.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

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. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

ARLOEUF 0.781 OMIM phenotype

Clinical Summary— MED17

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

95 unique Pathogenic / Likely Pathogenic· 186 VUS of 732 total submissions

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GeneReview available — MED17

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.78LOEUF

pLI 0.000

Z-score 2.63

OE 0.54 (0.38–0.78)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.88Z-score

OE missense 0.87 (0.79–0.95)

298 obs / 343.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.54 (0.38–0.78)

0≤0.351.4

Missense OE?0.87 (0.79–0.95)

0≤0.61.4

Synonymous OE?0.93

0≤1.21.6

LoF obs/exp: 20 / 37.3Missense obs/exp: 298 / 343.8Syn Z: 0.60

ClinVar Variant Classifications

732 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43

Likely Pathogenic52

VUS186

Likely Benign377

Benign51

Conflicting13

Pathogenic

Likely Pathogenic

186

VUS

377

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	33	0	10	0	43
Likely Pathogenic	48	2	2	0	52
VUS	1	165	14	6	186
Likely Benign	0	6	147	224	377
Benign	0	1	40	10	51
Conflicting	—				13
Total	82	174	213	240	722

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

17 pathogenic / likely-pathogenic (of 24) ClinVar copy-number / structural variants overlap MED17 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →