MED13L

mediator complex subunit 13L, the group of MicroRNA protein coding host genes|Mediator complex

Basic information

Region (hg38): 12:115957904-116277693

Previous symbols: [ "THRAP2" ]

Links

ENSG00000123066 ∙ NCBI:23389 ∙ OMIM:608771 ∙ HGNC:22962 ∙ Uniprot:Q71F56 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal dominant 40 (Strong), mode of inheritance: AD
• cardiac anomalies - developmental delay - facial dysmorphism syndrome (Definitive), mode of inheritance: AD
• cardiac anomalies - developmental delay - facial dysmorphism syndrome (Supportive), mode of inheritance: AD
• cardiac anomalies - developmental delay - facial dysmorphism syndrome (Strong), mode of inheritance: AD
• syndromic intellectual disability (Definitive), mode of inheritance: AD
• congenital heart disease (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Impaired intellectual development and distinctive facial features with or without cardiac defects	AD/AR	Cardiovascular	Among other features, the condition may involve congenital cardiac anomalies, some of which may be subtle or occult, and which may benefit from surveillance and/or interventions to ameliorate sequelae	Cardiovascular; Craniofacial; Neurologic	14638541; 21937992; 23403903; 24781760; 25137640; 25356899; 25712080; 25758992

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MED13L gene.

• Transposition of the great arteries, dextro-looped (535 variants)
• not provided (405 variants)
• Cardiac anomalies - developmental delay - facial dysmorphism syndrome (182 variants)
• Inborn genetic diseases (84 variants)
• Intellectual disability (17 variants)
• MED13L-related condition (16 variants)
• not specified (15 variants)
• See cases (8 variants)
• Neurodevelopmental disorder (4 variants)
• MED13L-Related Disorder (4 variants)
• Transposition of the great arteries, dextro-looped;Cardiac anomalies - developmental delay - facial dysmorphism syndrome (3 variants)
• MED13L-related neurodevelopmental disorder (3 variants)
• Global developmental delay (2 variants)
• Impaired intellectual development and distinctive facial features with cardiac defects (1 variants)
• Motor delay;Delayed speech and language development;Strabismus;Vesicoureteral reflux (1 variants)
• Autism spectrum disorder (1 variants)
• Cardiac anomalies - developmental delay - facial dysmorphism syndrome;Transposition of the great arteries, dextro-looped (1 variants)
• Rare genetic intellectual disability (1 variants)
• Marfanoid habitus and intellectual disability (1 variants)
• Kabuki-like syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MED13L 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	160	34	197
missense	3	27	311	105	28	474
nonsense	48	7				55
start loss	1	1				2
frameshift	69	18	1			88
inframe indel			4	2		6
splice donor/acceptor (+/-2bp)	9	7	4		1	21
splice region		2	9	22	3	36
non coding		1	5	83	50	139
Total	130	61	328	350	113

Variants in MED13L

This is a list of pathogenic ClinVar variants found in the MED13L region.

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

Position	Type	Phenotype	Significance	ClinVar
12-115960981-A-G			Likely benign (Sep 29, 2019)
12-115961255-T-C			Benign (Mar 03, 2021)
12-115961273-A-G		Cardiac anomalies - developmental delay - facial dysmorphism syndrome	Uncertain significance (Mar 24, 2022)
12-115961283-T-C		Inborn genetic diseases	Likely benign (Mar 11, 2022)
12-115961307-C-G			Uncertain significance (Apr 22, 2022)
12-115961316-G-A		See cases	Likely pathogenic (Apr 26, 2021)
12-115961317-G-A		Transposition of the great arteries, dextro-looped	Likely benign (Aug 01, 2023)
12-115961319-C-T		Intellectual disability • Transposition of the great arteries, dextro-looped	Benign (Aug 17, 2023)
12-115961320-G-A		Transposition of the great arteries, dextro-looped	Benign (Mar 11, 2022)
12-115961322-G-T		Cardiac anomalies - developmental delay - facial dysmorphism syndrome	Uncertain significance (Dec 03, 2020)
12-115961328-A-AG		Transposition of the great arteries, dextro-looped	Uncertain significance (Aug 06, 2018)
12-115961330-G-C		Transposition of the great arteries, dextro-looped	Uncertain significance (Aug 23, 2022)
12-115961337-G-A		Transposition of the great arteries, dextro-looped	Uncertain significance (Jul 07, 2023)
12-115961343-G-A		Cardiac anomalies - developmental delay - facial dysmorphism syndrome	Likely pathogenic (Aug 18, 2017)
12-115961345-G-T			Uncertain significance (Mar 07, 2022)
12-115961350-C-T		Transposition of the great arteries, dextro-looped	Likely benign (Jan 11, 2024)
12-115961351-G-A			Uncertain significance (Feb 01, 2024)
12-115961354-T-C		Transposition of the great arteries, dextro-looped	Benign (Dec 21, 2023)
12-115961359-C-T		Transposition of the great arteries, dextro-looped	Likely benign (Aug 02, 2023)
12-115961360-G-A			Uncertain significance (Oct 28, 2019)
12-115961377-G-A		Transposition of the great arteries, dextro-looped	Likely benign (Nov 27, 2023)
12-115961390-A-C			Likely pathogenic (Sep 12, 2022)
12-115961399-CT-C		Cardiac anomalies - developmental delay - facial dysmorphism syndrome	Likely pathogenic (Mar 22, 2024)
12-115961407-G-C		Transposition of the great arteries, dextro-looped	Likely benign (Nov 20, 2021)
12-115961416-C-G		Transposition of the great arteries, dextro-looped	Likely benign (Dec 08, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MED13L	protein_coding	protein_coding	ENST00000281928	31	319433

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.92e-15	125615	0	13	125628	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.69	839	1.20e+3	0.700	0.0000686	14509
Missense in Polyphen		100	212.31	0.471		2560
Synonymous	-0.196	463	458	1.01	0.0000277	4387
Loss of Function	9.01	2	98.5	0.0203	0.00000509	1150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000327	0.000326
Finnish	0.0000536	0.0000462
European (Non-Finnish)	0.0000284	0.0000264
Middle Eastern	0.000327	0.000326
South Asian	0.0000385	0.0000327
Other	0.00	0.00

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. This subunit may specifically regulate transcription of targets of the Wnt signaling pathway and SHH signaling pathway.
• Disease: DISEASE: Note=A chromosomal aberration involving MED13L is found in a patient with transposition of the great arteries, dextro- looped and mental retardation. Translocation t(12;17)(q24.1;q21). {ECO:0000269|PubMed:14638541}.; DISEASE: Mental retardation and distinctive facial features with or without cardiac defects (MRFACD) [MIM:616789]: An autosomal dominant, syndromic form of mental retardation characterized by delayed psychomotor development, profound language impairment, and facial dysmorphism, including frontal bossing, upslanting palpebral fissures, depressed nasal bridge with bulbous tip, and macrostomia. There is variable penetrance of cardiac malformations, ranging from no malformations to patent foramen ovale to septal defects and/or transposition of the great arteries. Mental retardation is defined by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. {ECO:0000269|PubMed:24781760, ECO:0000269|PubMed:25167861, ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:25712080, ECO:0000269|PubMed:25758992}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Thyroid hormone signaling pathway - Homo sapiens (human);Developmental Biology;Transcriptional regulation of white adipocyte differentiation (Consensus)

Recessive Scores

• pRec: 0.116

Intolerance Scores

• loftool: 0.0362
• rvis_EVS: -2.74
• rvis_percentile_EVS: 0.69

Haploinsufficiency Scores

• pHI: 0.803
• hipred: Y
• hipred_score: 0.783
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.905

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Med13l

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II
• Cellular component: mediator complex
• Molecular function: transcription coregulator activity