MED17

mediator complex subunit 17, the group of Mediator complex

Basic information

Region (hg38): 11:93784227-93814963

Previous symbols: [ "CRSP6" ]

Links

ENSG00000042429

∙ NCBI:9440 ∙ OMIM:603810 ∙ HGNC:2375 ∙ Uniprot:Q9NVC6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (Strong), mode of inheritance: AR
infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (Strong), mode of inheritance: AR
infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Microcephaly, postnatal progressive, with seizures and brain atrophy	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	20950787

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED17 gene.

not_provided (505 variants)
Infantile_cerebral_and_cerebellar_atrophy_with_postnatal_progressive_microcephaly (130 variants)
Inborn_genetic_diseases (77 variants)
not_specified (22 variants)
MED17-related_disorder (11 variants)
Intellectual_disability (2 variants)
Microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED17 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004268.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	6 clinvar	223 clinvar	8 clinvar	238
missense	1 clinvar	3 clinvar	155 clinvar	12 clinvar		171
nonsense	19 clinvar	14 clinvar	1 clinvar			34
start loss						0
frameshift	19 clinvar	6 clinvar				25
splice donor/acceptor (+/-2bp)		19 clinvar				19
Total	39	43	162	235	8

Highest pathogenic variant AF is 0.00005392406

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED17	protein_coding	protein_coding	ENST00000251871	12	30469

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.08e-9	0.996	125700	0	47	125747	0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.878	298	344	0.867	0.0000172	4263
Missense in Polyphen		71	90.435	0.7851		1127
Synonymous	0.598	116	124	0.932	0.00000613	1218
Loss of Function	2.63	20	37.3	0.536	0.00000208	395

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000395	0.000394
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.000285	0.000281
Middle Eastern	0.00	0.00
South Asian	0.000163	0.000163
Other	0.000163	0.000163

dbNSFP

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:16595664}.;
Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Developmental Biology;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;Transcriptional regulation of white adipocyte differentiation (Consensus)

Recessive Scores

pRec: 0.131

Intolerance Scores

loftool: 0.864
rvis_EVS: -0.78
rvis_percentile_EVS: 12.88

Haploinsufficiency Scores

pHI: 0.0872
hipred: Y
hipred_score: 0.715
ghis: 0.619

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.768

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Med17
Phenotype

Gene ontology

Biological process: regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;intracellular steroid hormone receptor signaling pathway;androgen receptor signaling pathway;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
Cellular component: nucleus;nucleoplasm;transcription factor complex;membrane;mediator complex;core mediator complex
Molecular function: transcription coregulator activity;transcription coactivator activity;protein binding;nuclear receptor transcription coactivator activity;signaling receptor activity;vitamin D receptor binding;thyroid hormone receptor binding