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 (40 variants)
• Inborn genetic diseases (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				213	10	223
missense		3	75	7	1	86
nonsense	23	4	1			28
start loss						0
frameshift	17	1				18
inframe indel						0
splice donor/acceptor (+/-2bp)		15				15
splice region			3	42	1	46
non coding				93	35	128
Total	40	23	76	313	46

Highest pathogenic variant AF is 0.0000197

Variants in MED17

This is a list of pathogenic ClinVar variants found in the MED17 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-93784261-C-T			Likely benign (Mar 21, 2019)
11-93784298-A-C			Benign (Jul 26, 2018)
11-93784345-C-T			Likely benign (Aug 30, 2018)
11-93784489-C-T			Likely benign (Jul 07, 2018)
11-93784504-C-T		Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly • MED17-related disorder	Conflicting classifications of pathogenicity (Apr 17, 2020)
11-93784511-A-G		Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly	Uncertain significance (Apr 17, 2020)
11-93784518-C-G			Uncertain significance (Oct 03, 2023)
11-93784519-C-T			Likely benign (Jun 13, 2021)
11-93784521-G-T		Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly • Inborn genetic diseases	Uncertain significance (Nov 23, 2022)
11-93784522-G-C			Likely benign (Oct 06, 2023)
11-93784525-G-A			Likely benign (Nov 23, 2020)
11-93784528-C-G			Likely benign (Jun 30, 2022)
11-93784534-G-T			Likely benign (Oct 14, 2023)
11-93784537-G-A			Likely benign (Dec 16, 2023)
11-93784537-G-C			Likely benign (Oct 03, 2021)
11-93784537-G-T			Likely benign (Sep 05, 2023)
11-93784540-C-T			Likely benign (Feb 04, 2022)
11-93784558-C-T			Likely benign (Dec 26, 2023)
11-93784559-G-T			Pathogenic (Feb 21, 2023)
11-93784567-G-A			Likely benign (Aug 22, 2023)
11-93784570-C-T			Likely benign (Oct 22, 2022)
11-93784573-T-C			Likely benign (Apr 03, 2021)
11-93784582-C-A			Likely benign (Aug 14, 2021)
11-93784583-C-T			Likely benign (Feb 11, 2022)
11-93784600-G-T			Likely benign (Jul 07, 2020)

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

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