MED27

mediator complex subunit 27, the group of Mediator complex

Basic information

Region (hg38): 9:131852928-132079867

Previous symbols: [ "CRSP8" ]

Links

ENSG00000160563 ∙ NCBI:9442 ∙ OMIM:605044 ∙ HGNC:2377 ∙ Uniprot:Q6P2C8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia (Strong), mode of inheritance: AR
• neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia (Strong), mode of inheritance: AR
• neurodevelopmental disorder (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	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	Craniofacial; Neurologic; Ophthalmologic	33443317

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED27 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED27 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				3		3
missense			18			18
nonsense			4			4
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	24	4	0

Variants in MED27

This is a list of pathogenic ClinVar variants found in the MED27 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-131860568-G-C			Likely benign (Sep 01, 2024)
9-131860576-G-A		not specified	Uncertain significance (May 09, 2024)
9-131860596-G-A		Intellectual disability	Uncertain significance (-)
9-131860603-C-T		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Uncertain significance (Jun 17, 2023)
9-131860608-T-C		Inborn genetic diseases	Uncertain significance (Sep 27, 2022)
9-131860624-A-G		Inborn genetic diseases	Uncertain significance (Dec 09, 2023)
9-131860635-G-A		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Uncertain significance (Apr 28, 2021)
9-131860655-G-GT		Inborn genetic diseases	Uncertain significance (Sep 13, 2021)
9-131863088-G-A		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Pathogenic (Apr 23, 2021)
9-131884070-T-A		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
9-131884101-T-C		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Pathogenic (Apr 23, 2021)
9-131887958-A-G			Likely benign (Apr 01, 2023)
9-131893988-G-C		Inborn genetic diseases	Uncertain significance (Dec 21, 2022)
9-131939387-C-G		See cases	Uncertain significance (Nov 25, 2022)
9-131939387-CAT-C		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Uncertain significance (Apr 28, 2021)
9-131939427-A-T			Uncertain significance (Jun 17, 2022)
9-131939431-C-T			Uncertain significance (Jun 17, 2022)
9-131939471-A-T			Uncertain significance (May 02, 2024)
9-132014365-G-A			Uncertain significance (May 12, 2024)
9-132014368-C-T		Inborn genetic diseases	Uncertain significance (Jul 08, 2021)
9-132014374-G-T		Inborn genetic diseases	Uncertain significance (Oct 20, 2023)
9-132014396-C-T		Inborn genetic diseases	Uncertain significance (Jul 14, 2024)
9-132014407-C-A		Inborn genetic diseases	Uncertain significance (May 28, 2024)
9-132014422-ACT-A		Neurodevelopmental disorder with spasticity, cataracts, and cerebellar hypoplasia	Pathogenic (Apr 23, 2021)
9-132077471-G-C		Inborn genetic diseases	Uncertain significance (Nov 15, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED27	protein_coding	protein_coding	ENST00000292035	8	219802

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000177	0.890	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.26	131	179	0.734	0.00000971	2029
Missense in Polyphen		21	44.504	0.47187		466
Synonymous	0.0300	70	70.3	0.995	0.00000381	599
Loss of Function	1.52	10	16.7	0.599	8.60e-7	190

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000172	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000177	0.000176
Middle Eastern	0.000172	0.000163
South Asian	0.0000980	0.0000980
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:10882111, ECO:0000269|PubMed:9989412}.
• 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: 0.109

Intolerance Scores

• loftool: 0.371
• rvis_EVS: -0.47
• rvis_percentile_EVS: 23.04

Haploinsufficiency Scores

• pHI: 0.175
• hipred: Y
• hipred_score: 0.661
• ghis: 0.616

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med27

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;transcription initiation from RNA polymerase II promoter;protein ubiquitination;stem cell population maintenance;positive regulation of nucleic acid-templated transcription
• Cellular component: ubiquitin ligase complex;nucleus;nucleoplasm;transcription factor complex;nucleolus;cytosol;mediator complex
• Molecular function: transcription coactivator activity;protein binding;ubiquitin protein ligase activity