MED13L

Summary

MED13L (mediator complex subunit 13L, HGNC:22962) is a protein-coding gene on chromosome 12q24.21, encoding Mediator of RNA polymerase II transcription subunit 13-like (Q71F56). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. It is haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).

Source: NCBI Gene 23389 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 43
• Clinical variants (ClinVar): 1,779 total — 209 pathogenic, 106 likely-pathogenic
• Phenotypes (HPO): 78
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_015335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22962
Approved symbol	MED13L
Name	mediator complex subunit 13L
Location	12q24.21
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1025, TRAP240L
Ensembl gene	ENSG00000123066
Ensembl biotype	protein_coding
OMIM	608771
Entrez	23389

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 18 retained_intron, 7 protein_coding, 6 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000281928, ENST00000548694, ENST00000548743, ENST00000548784, ENST00000549755, ENST00000549786, ENST00000551197, ENST00000552023, ENST00000552340, ENST00000647567, ENST00000647927, ENST00000648067, ENST00000648173, ENST00000648379, ENST00000648593, ENST00000648737, ENST00000648762, ENST00000648825, ENST00000648916, ENST00000649146, ENST00000649378, ENST00000649607, ENST00000649627, ENST00000649655, ENST00000649762, ENST00000649775, ENST00000649937, ENST00000650091, ENST00000650226, ENST00000650375, ENST00000650443, ENST00000650496

RefSeq mRNA: 1 — MANE Select: NM_015335 NM_015335

CCDS: CCDS9177

Canonical transcript exons

ENST00000281928 — 31 exons

Exon	Start	End
ENSE00000835019	115963407	115963519
ENSE00000835022	115970594	115970770
ENSE00000835023	115975171	115975313
ENSE00000835024	115975515	115975738
ENSE00000835026	115982384	115982603
ENSE00000835027	115983117	115983540
ENSE00000835030	115987109	115987288
ENSE00000918038	115986266	115986489
ENSE00000918039	115984180	115984372
ENSE00000918042	115980750	115980938
ENSE00000918047	115968940	115969097
ENSE00001003522	115996476	115996681
ENSE00001092209	115997010	115997230
ENSE00001092211	116008401	116009132
ENSE00001092215	115958576	115961398
ENSE00001092217	116012797	116012901
ENSE00001176289	115966082	115966243
ENSE00001176356	115991020	115991957
ENSE00001209946	116003003	116003102
ENSE00001209951	116005869	116005993
ENSE00001209955	116006306	116006411
ENSE00001209959	116007411	116007636
ENSE00001209971	116015109	116015274
ENSE00001261031	116019224	116019412
ENSE00001406609	116096669	116096752
ENSE00001415556	116277060	116277693
ENSE00001421461	116019778	116019972
ENSE00001424699	116022456	116022601
ENSE00003580741	115972078	115972236
ENSE00003617003	116111428	116111512
ENSE00003786961	116237468	116237705

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 98.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1201 / max 803.2397, expressed in 1800 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133459	6.3989	1683
133456	6.2233	1500
133457	1.8702	815
133458	1.2158	696
133436	0.8270	371
133453	0.2631	63
133454	0.1553	70
133439	0.1123	21
133455	0.0543	15

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.86	gold quality
colonic epithelium	UBERON:0000397	97.88	gold quality
tendon	UBERON:0000043	97.18	gold quality
cortical plate	UBERON:0005343	96.86	gold quality
saphenous vein	UBERON:0007318	96.09	gold quality
adrenal tissue	UBERON:0018303	95.98	gold quality
bone marrow cell	CL:0002092	95.84	gold quality
tendon of biceps brachii	UBERON:0008188	95.79	gold quality
synovial joint	UBERON:0002217	95.33	gold quality
nipple	UBERON:0002030	95.12	gold quality
skin of leg	UBERON:0001511	94.76	gold quality
bone marrow	UBERON:0002371	94.76	gold quality
skin of abdomen	UBERON:0001416	94.71	gold quality
right lung	UBERON:0002167	94.40	gold quality
zone of skin	UBERON:0000014	94.30	gold quality
superior surface of tongue	UBERON:0007371	94.19	gold quality
body of uterus	UBERON:0009853	94.19	gold quality
popliteal artery	UBERON:0002250	94.18	gold quality
tibial artery	UBERON:0007610	94.17	gold quality
corpus callosum	UBERON:0002336	94.16	gold quality
skin of hip	UBERON:0001554	94.06	gold quality
buccal mucosa cell	CL:0002336	93.82	gold quality
artery	UBERON:0001637	93.81	gold quality
bone element	UBERON:0001474	93.80	gold quality
cerebellar hemisphere	UBERON:0002245	93.80	gold quality
cerebellar cortex	UBERON:0002129	93.76	gold quality
cartilage tissue	UBERON:0002418	93.73	gold quality
cerebellum	UBERON:0002037	93.72	gold quality
cervix squamous epithelium	UBERON:0006922	93.72	gold quality
pericardium	UBERON:0002407	93.52	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	32.29
E-HCAD-35	yes	31.97
E-ANND-3	yes	10.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

300 targeting MED13L, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-5696	99.98	72.36	4487
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 16)

• PROSIT240 shows significant homology to the nuclear receptor coactivator TRAP240, suggesting it to be a new component of the thyroid hormone receptor-associated protein (TRAP) complex. PROSIT240 is involved in early heart and brain development. (PMID:14638541)
• Transcripts were most abundant in skeletal muscle. (PMID:15145061)
• We show that the Mediator complex subunit MED13L is required for Rb/E2F control of cell growth, the complete repression of cell cycle target genes, and cell cycle inhibition. (PMID:22249253)
• Description of three patients with copy number changes affecting MED13L and delineation of a recognizable MED13L haploinsufficiency syndrome. (PMID:23403903)
• Impaired development of neural-crest cell-derived organs and intellectual disability caused by MED13L haploinsufficiency. (PMID:25137640)
• A meta-analysis of genome-wide association studies of blood pressure and hypertension in Chinese identified three new loci (CACNA1D, CYP21A2, and MED13L) and a newly discovered variant near SLC4A7. (PMID:25249183)
• Analysis of genomic data in connection with deep clinical evaluation of patients could elucidate genetic heterogeneity of the MED13L haploinsufficiency phenotype (PMID:25712080)
• Heterozygous MED13L variants cause transposition of the great arterie. (PMID:25758992)
• A new syndrome caused by MED13L deleterious variants has been described, which shows similar clinical manifestations including intellectual disability, hypotonia, and other congenital anomalies. In two new cases, one missense variant and one nonsense mutation were found in the MED13L gene. (PMID:27500536)
• Two siblings exhibited an intragenic deletion involving exons 3-14, which led to an in-frame deletion in MED13L. The deletion was inherited from their carrier mother who possessed low frequency mosaicism. The older sister of the siblings showed craniosynostosis; this condition has never been reported in patients with MED13L haploinsufficiency syndrome (PMID:28371282)
• MED13L truncating mutation and missense mutation were identified in two patients with facial resemblance to Kleefstra syndrome as a novel differential diagnosis. (PMID:28645799)
• Our findings suggest that MED13L-related disorders are a possible differential diagnosis for syndromic PRS. (PMID:29159987)
• Study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition. (PMID:29511999)
• MED13L integrates Mediator-regulated epigenetic control into lung cancer radiosensitivity. (PMID:32802198)
• Molecular and Functional Characterisation of a Novel Intragenic 12q24.21 Deletion Resulting in MED13L Haploinsufficiency Syndrome. (PMID:37512036)
• Splice site variants in the canonical donor site of MED13L exon 7 lead to intron retention in patients with MED13L syndrome. (PMID:39181712)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Med13l	ENSMUSG00000018076
rattus_norvegicus	Med13l	ENSRNOG00000001120
drosophila_melanogaster	skd	FBGN0003415
caenorhabditis_elegans		WBGENE00002295

Paralogs (1): MED13 (ENSG00000108510)

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 13-like — Q71F56 (reviewed: Q71F56)

Alternative names: Mediator complex subunit 13-like, Thyroid hormone receptor-associated protein 2, Thyroid hormone receptor-associated protein complex 240 kDa component-like

All UniProt accessions (8): A0A3B3IRS4, A0A3B3IRX3, A0A3B3IS36, A0A3B3IS46, A0A3B3IS48, Q71F56, F8VRB8, H0YHC1

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in brain (cerebellum), heart (aorta), skeletal muscle, kidney, placenta and peripheral blood leukocytes. Highly expressed in fetal brain.

Disease relevance. A chromosomal aberration involving MED13L is found in a patient with transposition of the great arteries, dextro-looped and intellectual disability. Translocation t(12;17)(q24.1;q21). Impaired intellectual development and distinctive facial features with or without cardiac defects (MRFACD) [MIM:616789] An autosomal dominant syndrome characterized by intellectual disability, 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. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Mediator complex subunit 13 family.

RefSeq proteins (1): NP_056150* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009401	Med13_C	Domain
IPR021643	Mediator_Med13_N	Domain
IPR041285	MID_MedPIWI	Domain
IPR051139	Mediator_complx_sub13	Family

Pfam: PF06333, PF11597, PF18296

UniProt features (40 total): compositionally biased region 11, region of interest 8, sequence conflict 8, modified residue 6, sequence variant 4, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q71F56-F1	56.79	0.17

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (6): 553, 560, 817, 826, 923, 2083

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9833110	RSV-host interactions
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5663205	Infectious disease
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways
R-HSA-9843745	Adipogenesis

MSigDB gene sets: 449 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, CHUNG_BLISTER_CYTOTOXICITY_DN, ATACCTC_MIR202, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, FOSTER_TOLERANT_MACROPHAGE_UP, DOANE_RESPONSE_TO_ANDROGEN_DN, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, AAAGGGA_MIR204_MIR211, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, HOEBEKE_LYMPHOID_STEM_CELL_UP, DOUGLAS_BMI1_TARGETS_UP, KIM_WT1_TARGETS_12HR_UP, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (2): positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (2): transcription coactivator activity (GO:0003713), transcription coregulator activity (GO:0003712)

GO Cellular Component (3): nucleoplasm (GO:0005654), mediator complex (GO:0016592), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Regulation of lipid metabolism by PPARalpha	1
Adipogenesis	1
Respiratory Syncytial Virus Infection Pathway	1
Metabolism of lipids	1
Metabolism	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
regulation of DNA-templated transcription	1
transcription coregulator activity	1
transcription regulator activity	1
nuclear lumen	1
cellular anatomical structure	1
core mediator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1284 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED13L	MED12L	Q86YW9	992
MED13L	CCNC	P24863	987
MED13L	MED12	Q93074	977
MED13L	CDK19	Q9BWU1	922
MED13L	CDK8	P49336	897
MED13L	CFC1	P0CG37	847
MED13L	MED14	O60244	745
MED13L	GDF1	P27539	739
MED13L	MED15	Q96RN5	707
MED13L	MED10	Q9BTT4	630
MED13L	DYRK1A	Q13627	595
MED13L	MED6	O75586	580
MED13L	KMT5B	Q4FZB7	574
MED13L	MED26	O95402	571
MED13L	TRIP12	Q14669	543

IntAct

112 interactions, top by confidence:

A	B	Type	Score
HIF1A	EP300	psi-mi:“MI:0914”(association)	0.960
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
CDK8	MED14	psi-mi:“MI:0914”(association)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
MED21	MED19	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
MED31	MED19	psi-mi:“MI:0914”(association)	0.840
MED7	MED19	psi-mi:“MI:0914”(association)	0.840
MED11	MED19	psi-mi:“MI:0914”(association)	0.840

BioGRID (210): MED13L (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED13L (Affinity Capture-MS), MED13L (Affinity Capture-Western), MED13L (Affinity Capture-MS), MED10 (Co-fractionation), MED13L (Co-fractionation), MED16 (Co-fractionation), MED27 (Co-fractionation), MED6 (Co-fractionation), MED13L (Proximity Label-MS), MED13L (Proximity Label-MS), MED13L (Affinity Capture-MS)

ESM2 similar proteins: A0A0A6YY25, A6NGG8, A6X8Z5, B2RQL2, B2RXH4, D3ZMK9, D3ZUE1, E9Q7F2, O08696, O14513, P59598, P97691, Q05860, Q05AH6, Q08050, Q0GGX2, Q0VET5, Q13029, Q2M1Z3, Q3U0P1, Q571I4, Q5PSV9, Q5SSG4, Q5U2M8, Q5VV67, Q63755, Q66H04, Q68DA7, Q69ZL1, Q6DIA7, Q6JPI3, Q6P1D7, Q6PAC4, Q6PG16, Q71F56, Q76N32, Q811R2, Q86YN6, Q86YV5, Q8BJS7

Diamond homologs: A2VCZ5, F4I096, P0C657, Q54S20, Q5SWW4, Q6JPI3, Q71F56, Q93442, Q9UHV7, Q7KTX8

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FBXW7	“down-regulates quantity by destabilization”	MED13L	ubiquitination
SCF-FBW7	“down-regulates quantity by destabilization”	MED13L	ubiquitination
MED13L	“form complex”	“CKM complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Respiratory Syncytial Virus Infection Pathway	26	124.9×	7e-50
RSV-host interactions	26	99.2×	3e-47
Adipogenesis	26	99.2×	3e-47
Regulation of lipid metabolism by PPARalpha	26	89.4×	7e-46
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	17	89.3×	8e-29
Transcriptional regulation of white adipocyte differentiation	27	85.5×	3e-47
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	17	81.6×	4e-28
Epigenetic regulation by WDR5-containing histone modifying complexes	17	64.0×	4e-26

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	22	127.3×	1e-40
positive regulation of transcription initiation by RNA polymerase II	23	120.2×	1e-41
RNA polymerase II preinitiation complex assembly	22	115.0×	1e-39
somatic stem cell population maintenance	11	52.4×	1e-14
transcription initiation at RNA polymerase II promoter	6	43.2×	4e-07
protein ubiquitination	11	8.8×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

1779 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	209
Likely pathogenic	106
Uncertain significance	597
Likely benign	528
Benign	145

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1033770	NM_015335.5(MED13L):c.4271_4276delinsTTCCC (p.Cys1424fs)	Pathogenic
1033771	NM_015335.5(MED13L):c.4975_4976insC (p.Ile1659fs)	Pathogenic
1047900	GRCh37/hg19 12q24.21(chr12:116484240-116564043)	Pathogenic
1064782	NM_015335.5(MED13L):c.2071C>T (p.Gln691Ter)	Pathogenic
1071342	NM_015335.5(MED13L):c.1405dup (p.Thr469fs)	Pathogenic
1164009	NM_015335.5(MED13L):c.541_556delinsA (p.Val181_His186delinsAsn)	Pathogenic
1164010	NM_015335.5(MED13L):c.2320del (p.Ile774fs)	Pathogenic
1199185	NM_015335.5(MED13L):c.1516C>T (p.Gln506Ter)	Pathogenic
1254719	NM_015335.5(MED13L):c.553C>T (p.Gln185Ter)	Pathogenic
1275791	NM_015335.5(MED13L):c.1108_1111dup (p.Lys371fs)	Pathogenic
1300394	NM_015335.5(MED13L):c.1684C>T (p.Gln562Ter)	Pathogenic
1319952	NM_015335.5(MED13L):c.6195dup (p.Gly2066fs)	Pathogenic
1320085	NM_015335.5(MED13L):c.5244_5248dup (p.Met1750fs)	Pathogenic
1321994	NM_015335.5(MED13L):c.2950C>T (p.Gln984Ter)	Pathogenic
1330286	NM_015335.5(MED13L):c.4213G>T (p.Glu1405Ter)	Pathogenic
1340224	GRCh37/hg19 12q24.21(chr12:116456529-116488520)x1	Pathogenic
1527738	GRCh37/hg19 12q24.21(chr12:116523800-116581474)	Pathogenic
1678862	NM_015335.5(MED13L):c.1318C>T (p.Arg440Ter)	Pathogenic
1679237	NM_015335.5(MED13L):c.3309del (p.Glu1105fs)	Pathogenic
1685943	NM_015335.5(MED13L):c.4041G>A (p.Trp1347Ter)	Pathogenic
1699209	NM_015335.5(MED13L):c.5364+1dup	Pathogenic
1699335	NM_015335.5(MED13L):c.3205C>T (p.Gln1069Ter)	Pathogenic
1700209	NM_015335.5(MED13L):c.5941C>T (p.Gln1981Ter)	Pathogenic
1700210	NM_015335.5(MED13L):c.329G>A (p.Trp110Ter)	Pathogenic
1701743	NM_015335.5(MED13L):c.319dup (p.Glu107fs)	Pathogenic
1701855	NM_015335.5(MED13L):c.3760_3761del (p.Leu1254fs)	Pathogenic
1706430	NM_015335.5(MED13L):c.1280+1G>A	Pathogenic
1722316	NM_015335.5(MED13L):c.4011_4024del (p.Ile1338fs)	Pathogenic
1723046	NM_015335.5(MED13L):c.5471del (p.Asn1824fs)	Pathogenic
1805294	NM_015335.5(MED13L):c.6017_6035del (p.Gln2006fs)	Pathogenic

SpliceAI

7206 predictions. Top by Δscore:

Variant	Effect	Δscore
12:115963402:TCTA:T	donor_loss	1.0000
12:115963403:CTACC:C	donor_loss	1.0000
12:115963404:TACCT:T	donor_loss	1.0000
12:115963405:A:C	donor_loss	1.0000
12:115963406:C:CG	donor_loss	1.0000
12:115964758:T:TA	donor_gain	1.0000
12:115966077:CCAA:C	donor_loss	1.0000
12:115966078:CAAC:C	donor_loss	1.0000
12:115966079:AAC:A	donor_loss	1.0000
12:115966080:ACC:A	donor_loss	1.0000
12:115966244:C:CC	acceptor_gain	1.0000
12:115968935:CTT:C	donor_loss	1.0000
12:115968937:TA:T	donor_loss	1.0000
12:115968938:A:AT	donor_loss	1.0000
12:115968939:CCCGA:C	donor_gain	1.0000
12:115969093:ATCAT:A	acceptor_gain	1.0000
12:115969094:TCAT:T	acceptor_gain	1.0000
12:115969095:CAT:C	acceptor_gain	1.0000
12:115969095:CATC:C	acceptor_gain	1.0000
12:115969096:AT:A	acceptor_gain	1.0000
12:115969097:TCTAG:T	acceptor_loss	1.0000
12:115969098:C:CA	acceptor_loss	1.0000
12:115969098:C:CC	acceptor_gain	1.0000
12:115969099:T:C	acceptor_loss	1.0000
12:115970589:CTCA:C	donor_loss	1.0000
12:115970590:TCACC:T	donor_loss	1.0000
12:115970591:CA:C	donor_loss	1.0000
12:115970592:A:AC	donor_gain	1.0000
12:115970592:A:C	donor_loss	1.0000
12:115970592:AC:A	donor_gain	1.0000

AlphaMissense

14552 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:115961367:A:G	W2178R	1.000
12:115961367:A:T	W2178R	1.000
12:115966135:A:G	W2112R	1.000
12:115966135:A:T	W2112R	1.000
12:115966177:C:A	G2098W	1.000
12:115972234:A:G	W1912R	1.000
12:115972234:A:T	W1912R	1.000
12:115984323:C:T	G1463E	1.000
12:115984324:C:A	G1463W	1.000
12:115987138:A:G	F1362S	1.000
12:115987146:C:A	W1359C	1.000
12:115987146:C:G	W1359C	1.000
12:115987148:A:G	W1359R	1.000
12:115987148:A:T	W1359R	1.000
12:115987222:A:G	L1334P	1.000
12:115991468:A:C	C1162W	1.000
12:115991470:A:G	C1162R	1.000
12:115991474:A:C	C1160W	1.000
12:115991476:A:G	C1160R	1.000
12:115991546:G:C	C1136W	1.000
12:115991548:A:G	C1136R	1.000
12:115991552:A:C	C1134W	1.000
12:115991554:A:G	C1134R	1.000
12:116019883:A:G	W239R	1.000
12:116019883:A:T	W239R	1.000
12:116111437:A:G	L129P	1.000
12:116111467:C:A	R119M	1.000
12:116237601:A:C	S59R	1.000
12:116237601:A:T	S59R	1.000
12:116237603:T:G	S59R	1.000

dbSNP variants (sampled 300 via entrez): RS1000019005 (12:116147300 T>C), RS1000043397 (12:115961587 T>A,C,G), RS1000045442 (12:116055119 T>C), RS1000050238 (12:116085315 T>A), RS1000053103 (12:116195917 G>A), RS1000072438 (12:116065263 C>T), RS1000079324 (12:116189535 G>A), RS1000079666 (12:116262953 T>C), RS1000082451 (12:115979588 T>C), RS1000086077 (12:116023199 G>A), RS1000088775 (12:116147607 C>T), RS1000093678 (12:115961945 A>C), RS1000098740 (12:116134104 T>G), RS1000108010 (12:116050633 T>C), RS1000110473 (12:116175952 A>G,T)

Disease associations

OMIM: gene MIM:608771 | disease phenotypes: MIM:608808, MIM:616789, MIM:308350, MIM:261800, MIM:123100, MIM:309800

GenCC curated gene-disease

Disease	Classification	Inheritance
cardiac anomalies - developmental delay - facial dysmorphism syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD
congenital heart disease	Limited	AD

Mondo (13): dextro-looped transposition of the great arteries (MONDO:0019443), cardiac anomalies - developmental delay - facial dysmorphism syndrome (MONDO:0014773), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), genetic developmental and epileptic encephalopathy (MONDO:0100062), strabismus (MONDO:0003432), scoliosis (MONDO:0005392), isolated Pierre-Robin syndrome (MONDO:0009869), breast ductal adenocarcinoma (MONDO:0005590), craniosynostosis (MONDO:0015469), syndromic microphthalmia (MONDO:0016073), vesicoureteral reflux (MONDO:0006007), autism spectrum disorder (MONDO:0005258)

Orphanet (8): Congenitally uncorrected transposition of the great arteries (Orphanet:860), Developmental delay-facial dysmorphism syndrome due to MED13L deficiency (Orphanet:369891), Isolated Pierre Robin sequence (Orphanet:718), Craniosynostosis (Orphanet:1531), Rare genetic intellectual disability (Orphanet:183757), Syndromic microphthalmia-anophthalmia-coloboma (Orphanet:202948), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

78 total (30 of 78 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000194	Open mouth
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000303	Mandibular prognathia
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000325	Triangular face
HP:0000337	Broad forehead
HP:0000341	Narrow forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000508	Ptosis
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000589	Coloboma
HP:0000687	Widely spaced teeth

GWAS associations

43 associations (top):

Study	Trait	p-value
GCST001161_1	Colorectal cancer	6.000000e-06
GCST002627_3	Hypertension	1.000000e-07
GCST002630_3	Systolic blood pressure	6.000000e-16
GCST002631_7	Diastolic blood pressure	2.000000e-18
GCST002829_18	Urate levels in overweight individuals	2.000000e-06
GCST003075_143	Cognitive decline rate in late mild cognitive impairment	2.000000e-07
GCST003075_33	Cognitive decline rate in late mild cognitive impairment	3.000000e-06
GCST003098_26	Diabetic kidney disease	2.000000e-06
GCST003630_1	Left ventricular QRS voltage	8.000000e-08
GCST004184_4	Lung function (FVC)	1.000000e-09
GCST005348_207	Total body bone mineral density	3.000000e-08
GCST005788_20	Heart rate response to recovery post exercise	3.000000e-11
GCST005846_14	Heart rate response to recovery post exercise (10 sec)	5.000000e-11
GCST005847_15	Heart rate response to recovery post exercise (20 sec)	7.000000e-12
GCST005848_3	Heart rate response to recovery post exercise (50 sec)	5.000000e-14
GCST005849_6	Heart rate response to recovery post exercise (40 sec)	4.000000e-15
GCST005850_12	Heart rate response to recovery post exercise (30 sec)	2.000000e-11
GCST005978_16	Diastolic blood pressure	4.000000e-13
GCST005979_21	Systolic blood pressure	5.000000e-15
GCST006010_16	Mean arterial pressure	1.000000e-16
GCST006110_26	Nose morphology	5.000000e-08
GCST006190_1	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	5.000000e-18
GCST006190_52	Diastolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-07
GCST006192_72	Systolic blood pressure x smoking status (ever vs never) interaction (2df test)	1.000000e-14
GCST006193_34	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	7.000000e-18
GCST006193_73	Diastolic blood pressure x smoking status (current vs non-current) interaction (2df test)	6.000000e-08
GCST006195_16	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	7.000000e-06
GCST006195_65	Systolic blood pressure x smoking status (current vs non-current) interaction (2df test)	1.000000e-14
GCST006629_39	Pulse pressure	9.000000e-11
GCST006979_1083	Heel bone mineral density	8.000000e-17

EFO canonical traits (18, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0004531	urate measurement
EFO:0007710	cognitive decline measurement
EFO:0007741	R wave amplitude
EFO:0007742	QRS amplitude
EFO:0004312	vital capacity
EFO:0009185	heart rate response to recovery post exercise
EFO:0006340	mean arterial pressure
EFO:0006527	smoking status measurement
EFO:0005763	pulse pressure measurement
EFO:0009270	heel bone mineral density
EFO:0003924	hair color
EFO:0005035	hippocampal volume
EFO:0004462	PR interval
EFO:1002040	Corneal astigmatism
EFO:0004314	forced expiratory volume
EFO:0009819	comparative body size at age 10, self-reported

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D003398	Craniosynostoses	C05.116.099.370.894.232; C05.660.207.240; C05.660.906.364; C16.131.621.207.240; C16.131.621.906.364
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D010855	Pierre Robin Syndrome	C05.500.460.606; C05.660.207.540.460.606; C07.320.440.606; C07.650.500.460.606; C16.131.621.207.540.460.606; C16.131.850.500.460.606
D012600	Scoliosis	C05.116.900.800.875
D013285	Strabismus	C10.292.562.887; C11.590.810
D014718	Vesico-Ureteral Reflux	C12.050.351.968.829.920; C12.200.777.829.920; C12.950.829.920

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

64 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation, affects cotreatment, increases expression	6
trichostatin A	affects cotreatment, increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Arsenic	decreases methylation, increases abundance, affects cotreatment, decreases expression	2
Hydrogen Peroxide	affects expression, affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
butyraldehyde	decreases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
PCI 5002	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Vorinostat	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SX73	HAP1 MED13L (-) 1	Cancer cell line	Male
CVCL_SX74	HAP1 MED13L (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

299 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays