MED13

Summary

MED13 (mediator complex subunit 13, HGNC:22474) is a protein-coding gene on chromosome 17q23.2, encoding Mediator of RNA polymerase II transcription subunit 13 (Q9UHV7). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.

This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator.

Source: NCBI Gene 9969 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 4
• Clinical variants (ClinVar): 696 total — 33 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 20
• MANE Select transcript: NM_005121

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22474
Approved symbol	MED13
Name	mediator complex subunit 13
Location	17q23.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0593, TRAP240
Ensembl gene	ENSG00000108510
Ensembl biotype	protein_coding
OMIM	603808
Entrez	9969

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 3 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000397786, ENST00000578132, ENST00000580896, ENST00000581994, ENST00000582786, ENST00000583958, ENST00000934727

RefSeq mRNA: 1 — MANE Select: NM_005121 NM_005121

CCDS: CCDS42366

Canonical transcript exons

ENST00000397786 — 30 exons

Exon	Start	End
ENSE00000925264	61984171	61984367
ENSE00000925266	61985000	61985090
ENSE00000925268	61992540	61992621
ENSE00001113094	61965006	61965468
ENSE00001113096	61955382	61955567
ENSE00001113097	61955680	61955838
ENSE00001113098	61956339	61956481
ENSE00001113104	61968035	61968258
ENSE00001113105	61972727	61972888
ENSE00001113106	61952965	61953113
ENSE00001113114	61960867	61961090
ENSE00001113115	61961588	61961779
ENSE00001113122	61962752	61962971
ENSE00001132333	61946917	61947017
ENSE00001132341	61950825	61950998
ENSE00001132677	61982198	61983114
ENSE00001132685	61984651	61984865
ENSE00001132694	61987007	61987128
ENSE00001132708	61995152	61995365
ENSE00001132715	62010550	62011233
ENSE00001132720	62029541	62029651
ENSE00001132738	62033787	62033984
ENSE00001132743	62035463	62035608
ENSE00001226079	61966462	61966651
ENSE00001226185	61942605	61946600
ENSE00001428504	62065140	62065278
ENSE00001530180	62052537	62052705
ENSE00001530182	62063067	62063301
ENSE00003460463	62029851	62030013
ENSE00003599872	62031444	62031638

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.72.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.9953 / max 125.9296, expressed in 1191 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167419	2.3850	1040
167410	0.6103	233

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	98.72	gold quality
visceral pleura	UBERON:0002401	98.35	gold quality
germinal epithelium of ovary	UBERON:0001304	98.18	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.16	gold quality
secondary oocyte	CL:0000655	98.02	gold quality
pleura	UBERON:0000977	97.99	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.99	gold quality
parietal pleura	UBERON:0002400	97.97	gold quality
buccal mucosa cell	CL:0002336	97.93	gold quality
tibia	UBERON:0000979	97.92	gold quality
pylorus	UBERON:0001166	97.86	gold quality
renal medulla	UBERON:0000362	97.76	gold quality
jejunal mucosa	UBERON:0000399	97.76	gold quality
cardia of stomach	UBERON:0001162	97.73	gold quality
mammary duct	UBERON:0001765	97.64	gold quality
pigmented layer of retina	UBERON:0001782	97.63	gold quality
CA1 field of hippocampus	UBERON:0003881	97.63	gold quality
jejunum	UBERON:0002115	97.54	gold quality
pericardium	UBERON:0002407	97.53	gold quality
superior surface of tongue	UBERON:0007371	97.51	gold quality
epithelium of mammary gland	UBERON:0003244	97.46	gold quality
body of tongue	UBERON:0011876	97.41	gold quality
superficial temporal artery	UBERON:0001614	97.39	gold quality
palpebral conjunctiva	UBERON:0001812	97.38	gold quality
tongue	UBERON:0001723	97.36	gold quality
vena cava	UBERON:0004087	97.34	gold quality
choroid plexus epithelium	UBERON:0003911	97.32	gold quality
inferior olivary complex	UBERON:0002127	97.27	gold quality
hair follicle	UBERON:0002073	97.24	gold quality
trigeminal ganglion	UBERON:0001675	97.23	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

328 targeting MED13, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6740-5P	100.00	65.64	932
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-12118	100.00	65.88	1270
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955

Literature-anchored findings (GeneRIF, showing 8)

• Med12 and Med13 are critical for human CDK8 subcomplex -dependent repression, whereas CDK8 kinase activity is not (PMID:19240132)
• Cardiac overexpression of MED13 in transgenic mice confers a lean phenotype that is associated with increased lipid uptake, beta-oxidation and mitochondrial content in white adipose tissue and liver (PMID:25422356)
• Data suggest that MED13, MED12, CDK8 and cyclin C (CycC) comprise a four-subunit “kinase” module of the Mediator complex that functions as a major ingress of oncogenic and developmental signaling/gene expression in humans. [REVIEW] (PMID:26182352)
• Each of HSPA4 and MED13 mutations were detected in GC. (PMID:27129500)
• De novo mutations in MED13, a component of the Mediator complex, are associated with a novel neurodevelopmental disorder. (PMID:29740699)
• Could the MED13 mutations manifest as a Kabuki-like syndrome? (PMID:33258286)
• Potential roles of mediator Complex Subunit 13 in Cardiac Diseases. (PMID:33390853)
• MED13 and glycolysis are conserved modifiers of alpha-synuclein-associated neurodegeneration. (PMID:36543134)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	med13b	ENSDARG00000003910
danio_rerio	med13a	ENSDARG00000053884
mus_musculus	Med13	ENSMUSG00000034297
rattus_norvegicus	Med13	ENSRNOG00000003679
drosophila_melanogaster	skd	FBGN0003415
caenorhabditis_elegans		WBGENE00002295

Paralogs (1): MED13L (ENSG00000123066)

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 13 — Q9UHV7 (reviewed: Q9UHV7)

Alternative names: Activator-recruited cofactor 250 kDa component, Mediator complex subunit 13, Thyroid hormone receptor-associated protein 1, Thyroid hormone receptor-associated protein complex 240 kDa component, Vitamin D3 receptor-interacting protein complex component DRIP250

All UniProt accessions (2): Q9UHV7, J3QRB7

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.

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. Ubiquitous.

Disease relevance. Intellectual developmental disorder, autosomal dominant 61 (MRD61) [MIM:618009] An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD61 is characterized by global developmental delay apparent in infancy with mildly impaired intellectual development, expressive speech delay, and behavioral abnormalities, including autism spectrum disorder and attention deficit-hyperactivity disorder. Additional features are highly variable and may include non-specific dysmorphic features, obstipation, ocular anomalies, and poor overall growth. 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_005112* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF06333, PF18296

UniProt features (48 total): sequence variant 12, compositionally biased region 9, region of interest 8, modified residue 8, sequence conflict 8, short sequence motif 2, chain 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
8TRH	ELECTRON MICROSCOPY	3.7
8TQ2	ELECTRON MICROSCOPY	3.8
8TQC	ELECTRON MICROSCOPY	3.8
8T9D	ELECTRON MICROSCOPY	4.66
8TQW	ELECTRON MICROSCOPY	8.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHV7-F1	57.89	0.19

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 (8): 395, 500, 504, 530, 537, 826, 890, 1029

Function

Pathways and Gene Ontology

Reactome pathways

20 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-9833110	RSV-host interactions
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-1643685	Disease
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-556833	Metabolism of lipids
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes
R-HSA-9820952	Respiratory Syncytial Virus Infection Pathway
R-HSA-9824446	Viral Infection Pathways
R-HSA-9843745	Adipogenesis
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 370 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, GOBP_ACYLGLYCEROL_HOMEOSTASIS, CREL_01, AAGCAAT_MIR137, GOBP_STEROL_HOMEOSTASIS, LFA1_Q6, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, TATTATA_MIR374, TGACCTY_ERR1_Q2, TAL1ALPHAE47_01, CAGCTG_AP4_Q5, ATGTTAA_MIR302C, COUP_01, SRF_Q5_01, GOBP_LIPID_HOMEOSTASIS

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), cholesterol homeostasis (GO:0042632), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), triglyceride homeostasis (GO:0070328), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), nuclear vitamin D receptor binding (GO:0042809), nuclear thyroid hormone receptor binding (GO:0046966), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), mediator complex (GO:0016592), CKM complex (GO:1990508)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Gene expression (Transcription)	2
Regulation of lipid metabolism by PPARalpha	1
RNA Polymerase II Transcription	1
Adipogenesis	1
Respiratory Syncytial Virus Infection Pathway	1
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	1
Metabolism of lipids	1
Metabolism	1
Disease	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Viral Infection Pathways	1
Infectious disease	1
Developmental Biology	1
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
nuclear receptor binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
sterol homeostasis	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
transcription initiation at RNA polymerase II promoter	1
positive regulation of transcription by RNA polymerase II	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
acylglycerol homeostasis	1
transcription regulator activity	1
transcription coregulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
core mediator complex	1
nuclear protein-containing complex	1
nuclear cyclin-dependent protein kinase holoenzyme complex	1

Protein interactions and networks

STRING

1538 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED13	MED12	Q93074	998
MED13	CCNC	P24863	998
MED13	CDK8	P49336	997
MED13	CDK19	Q9BWU1	995
MED13	MED12L	Q86YW9	974
MED13	MED14	O60244	952
MED13	MED15	Q96RN5	894
MED13	MED23	Q9ULK4	888
MED13	MED19	A0JLT2	871
MED13	MYH7B	A7E2Y1	829
MED13	MED26	O95402	823
MED13	MED17	Q9NVC6	819
MED13	MED10	Q9BTT4	772
MED13	MED6	O75586	766
MED13	MED29	Q9NX70	757

IntAct

142 interactions, top by confidence:

A	B	Type	Score
CDK8	CCNC	psi-mi:“MI:0914”(association)	0.980
CCNC	CDK8	psi-mi:“MI:0915”(physical association)	0.980
HIF1A	EP300	psi-mi:“MI:0914”(association)	0.960
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
CDK8	MED14	psi-mi:“MI:0914”(association)	0.900
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	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

BioGRID (276): MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-MS), MED13 (Affinity Capture-Western), MED13 (Affinity Capture-Western), MED13 (Affinity Capture-MS), EFTUD2 (Co-fractionation), MED1 (Co-fractionation), MED10 (Co-fractionation), MED13 (Co-fractionation), MED13 (Co-fractionation)

ESM2 similar proteins: A0A140LFM6, A0A1B0GUA6, A0JMD2, A2VCZ5, A5WUT8, A6H5Y1, A6NKB5, B8JKP6, D3ZJ47, F1M5M3, F1MJR8, M0R5D6, O14513, O60284, P0CAX8, Q0P4S0, Q15468, Q1LV19, Q1RMQ5, Q4V7H1, Q5DU28, Q5DW34, Q5REU9, Q5SW75, Q5SWW4, Q5U4U4, Q5ZM13, Q60664, Q60988, Q6P9N1, Q6ZPK7, Q76I76, Q76I79, Q80TA9, Q80TY4, Q8BLN6, Q8BYM7, Q8IWB6, Q8JGS1, Q8K2J4

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

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MED13	“form complex”	“CKM complex”	binding
FBXW7	“down-regulates quantity by destabilization”	MED13	ubiquitination
SCF-FBW7	“down-regulates quantity by destabilization”	MED13	ubiquitination
CDK8	“down-regulates quantity by destabilization”	MED13	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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	94.8×	2e-45
RSV-host interactions	26	75.3×	1e-42
Adipogenesis	26	75.3×	1e-42
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	18	71.8×	2e-28
Regulation of lipid metabolism by PPARalpha	26	67.9×	2e-41
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	18	65.6×	1e-27
Transcriptional regulation of white adipocyte differentiation	27	64.9×	2e-42
Epigenetic regulation by WDR5-containing histone modifying complexes	19	54.3×	1e-27

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	25	115.7×	6e-45
RNA polymerase II preinitiation complex assembly	23	96.2×	3e-39
positive regulation of transcription initiation by RNA polymerase II	23	96.2×	3e-39
somatic stem cell population maintenance	11	41.9×	2e-13
transcription initiation at RNA polymerase II promoter	7	40.3×	3e-08
protein ubiquitination	12	7.6×	3e-06
transcription by RNA polymerase II	6	6.5×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	33
Uncertain significance	430
Likely benign	113
Benign	21

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1189232	NM_005121.3(MED13):c.6160dup (p.Glu2054fs)	Pathogenic
1198348	NM_005121.3(MED13):c.3465_3466del (p.Cys1155fs)	Pathogenic
1698767	NM_005121.3(MED13):c.2524C>T (p.Gln842Ter)	Pathogenic
1699136	NM_005121.3(MED13):c.712C>T (p.Gln238Ter)	Pathogenic
1700230	NM_005121.3(MED13):c.4191+1G>A	Pathogenic
1708262	NM_005121.3(MED13):c.2593_2594del (p.Gly865fs)	Pathogenic
2287183	NM_005121.3(MED13):c.5002C>T (p.Arg1668Ter)	Pathogenic
235901	NM_005121.3(MED13):c.4198C>T (p.Arg1400Ter)	Pathogenic
2500279	NM_005121.3(MED13):c.4417_4418del (p.Leu1473fs)	Pathogenic
2572179	NM_005121.3(MED13):c.1513C>T (p.Gln505Ter)	Pathogenic
2671898	NM_005121.3(MED13):c.1968-867_2181+479del	Pathogenic
2672057	NM_005121.3(MED13):c.1968-866_2181+621del	Pathogenic
2672058	NM_005121.3(MED13):c.1968-501_2181+590del	Pathogenic
3381432	NM_005121.3(MED13):c.1034G>A (p.Trp345Ter)	Pathogenic
3391180	NM_005121.3(MED13):c.2489T>G (p.Leu830Arg)	Pathogenic
3394551	NM_005121.3(MED13):c.4057_4060del (p.Pro1353fs)	Pathogenic
3602571	NM_005121.3(MED13):c.5405G>A (p.Trp1802Ter)	Pathogenic
3629476	NM_005121.3(MED13):c.1987_1999del (p.Lys663fs)	Pathogenic
3893341	NM_005121.3(MED13):c.2263+2T>C	Pathogenic
4526888	NM_005121.3(MED13):c.1856dup (p.Phe620fs)	Pathogenic
4624794	NM_005121.3(MED13):c.2175dup (p.His726fs)	Pathogenic
620176	NM_005121.3(MED13):c.1745T>A (p.Leu582Ter)	Pathogenic
620177	NM_005121.3(MED13):c.1864A>T (p.Lys622Ter)	Pathogenic
620178	NM_005121.3(MED13):c.5627G>A (p.Trp1876Ter)	Pathogenic
620179	NM_005121.3(MED13):c.5161C>T (p.Gln1721Ter)	Pathogenic
810684	NM_005121.3(MED13):c.4487del (p.Thr1496fs)	Pathogenic
817068	NM_005121.3(MED13):c.125del (p.Pro42fs)	Pathogenic
817070	NM_005121.3(MED13):c.5149del (p.Ser1717fs)	Pathogenic
817075	NM_005121.3(MED13):c.3005_3008del (p.Pro1002fs)	Pathogenic
817887	NM_005121.3(MED13):c.3889del (p.Arg1297fs)	Pathogenic

SpliceAI

4841 predictions. Top by Δscore:

Variant	Effect	Δscore
17:61946405:AAT:A	donor_gain	1.0000
17:61950955:T:TA	donor_gain	1.0000
17:61950997:CC:C	acceptor_gain	1.0000
17:61950998:CC:C	acceptor_gain	1.0000
17:61950999:C:T	acceptor_gain	1.0000
17:61951000:T:C	acceptor_gain	1.0000
17:61953112:ATCTA:A	acceptor_loss	1.0000
17:61953114:C:CC	acceptor_gain	1.0000
17:61955563:AGAAT:A	acceptor_gain	1.0000
17:61955564:GAAT:G	acceptor_gain	1.0000
17:61955565:AAT:A	acceptor_gain	1.0000
17:61955566:AT:A	acceptor_gain	1.0000
17:61955567:TCTGA:T	acceptor_loss	1.0000
17:61955568:C:CC	acceptor_gain	1.0000
17:61955574:A:AC	acceptor_gain	1.0000
17:61955574:A:C	acceptor_gain	1.0000
17:61955852:CAG:C	acceptor_gain	1.0000
17:61955853:A:T	acceptor_gain	1.0000
17:61960869:A:AC	donor_gain	1.0000
17:61960870:T:C	donor_gain	1.0000
17:61961089:CT:C	acceptor_gain	1.0000
17:61961090:TCTAT:T	acceptor_loss	1.0000
17:61961091:C:CC	acceptor_gain	1.0000
17:61961091:CT:C	acceptor_loss	1.0000
17:61961092:T:C	acceptor_loss	1.0000
17:61961583:CTTA:C	donor_loss	1.0000
17:61961584:TTA:T	donor_loss	1.0000
17:61961585:TACAT:T	donor_loss	1.0000
17:61961586:A:AC	donor_gain	1.0000
17:61961587:C:CC	donor_gain	1.0000

AlphaMissense

14247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:61955729:A:C	S1911R	1.000
17:61955729:A:T	S1911R	1.000
17:61955731:T:G	S1911R	1.000
17:61955836:A:G	W1876R	1.000
17:61955836:A:T	W1876R	1.000
17:61982288:C:A	G1239W	1.000
17:61982711:A:G	C1098R	1.000
17:61982715:A:C	C1096W	1.000
17:61982717:A:G	C1096R	1.000
17:62033895:A:G	W236R	1.000
17:62033895:A:T	W236R	1.000
17:62063163:A:G	W69R	1.000
17:62063163:A:T	W69R	1.000
17:62063200:A:C	S56R	1.000
17:62063200:A:T	S56R	1.000
17:62063202:T:G	S56R	1.000
17:61946569:A:G	W2142R	0.999
17:61946569:A:T	W2142R	0.999
17:61946595:A:T	V2133D	0.999
17:61946920:A:G	L2130P	0.999
17:61946947:A:G	L2121P	0.999
17:61946947:A:T	L2121H	0.999
17:61950874:A:G	F2081S	0.999
17:61950878:A:G	W2080R	0.999
17:61950878:A:T	W2080R	0.999
17:61955468:A:G	L1961P	0.999
17:61955471:A:C	I1960R	0.999
17:61955471:A:T	I1960K	0.999
17:61955723:G:C	C1913W	0.999
17:61955725:A:G	C1913R	0.999

dbSNP variants (sampled 300 via entrez): RS1000033417 (17:62066319 T>C,G), RS1000035834 (17:62017237 A>G), RS1000067333 (17:61981089 C>A), RS1000081897 (17:62019966 G>A,C,T), RS1000105491 (17:62026645 G>A), RS1000108887 (17:61967368 A>G), RS1000149986 (17:62043979 T>TA), RS1000179801 (17:61968810 G>A), RS1000180951 (17:61947073 T>C,G), RS1000182332 (17:61975847 T>A,C), RS1000186912 (17:62059994 T>C), RS1000193269 (17:61984425 TAAAC>T), RS1000201370 (17:62008966 T>C), RS1000222040 (17:62051858 G>C), RS1000282067 (17:62016658 A>G,T)

Disease associations

OMIM: gene MIM:603808 | disease phenotypes: MIM:618009, MIM:173100, MIM:614563, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder 61	Definitive	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (9): intellectual developmental disorder 61 (MONDO:0032485), neurodevelopmental disorder (MONDO:0700092), autism spectrum disorder (MONDO:0005258), isolated growth hormone deficiency type II (MONDO:0008250), intellectual disability, autosomal dominant 13 (MONDO:0013805), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), intellectual disability (MONDO:0001071), syndromic intellectual disability (MONDO:0000508)

Orphanet (5): Isolated growth hormone deficiency type II (Orphanet:231679), Non-acquired isolated growth hormone deficiency (Orphanet:631), Renal or urinary tract malformation (Orphanet:93545), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000154	Wide mouth
HP:0000219	Thin upper lip vermilion
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000629	Periorbital fullness
HP:0000664	Synophrys
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0002194	Delayed gross motor development
HP:0007018	Attention deficit hyperactivity disorder
HP:0009921	Duane anomaly
HP:0011098	Speech apraxia
HP:0011170	Generalized myoclonic-atonic seizure
HP:0012450	Chronic constipation
HP:0045025	Narrow palpebral fissure

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002456_6	PR segment duration	8.000000e-13
GCST003159_4	Objective response to lithium treatment	4.000000e-07
GCST005023_40	Initial pursuit acceleration	6.000000e-07
GCST008526_46	Coffee consumption	2.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005095	PR segment
EFO:0008434	initial pursuit acceleration
EFO:0006781	coffee consumption measurement

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)
C562704	Isolated Growth Hormone Deficiency, Type II (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
cobaltous chloride	increases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
benzo(e)pyrene	decreases methylation	1
coumarin	decreases phosphorylation	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	decreases expression	1
cylindrospermopsin	increases expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	decreases expression	1
Irinotecan	decreases expression	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Lead	decreases expression	1

Clinical trials (associated diseases)

202 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,
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
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
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
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
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice