MED14

Summary

MED14 (mediator complex subunit 14, HGNC:2370) is a protein-coding gene on chromosome Xp11.4, encoding Mediator of RNA polymerase II transcription subunit 14 (O60244). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. It is a common-essential gene (DepMap: required in 97.7% of cancer cell lines).

The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation.

Source: NCBI Gene 9282 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 261 total
• Cancer dependency (DepMap): dependent in 97.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_004229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2370
Approved symbol	MED14
Name	mediator complex subunit 14
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	EXLM1, CRSP150, TRAP170, RGR1, CSRP
Ensembl gene	ENSG00000180182
Ensembl biotype	protein_coding
OMIM	300182
Entrez	9282

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000324817, ENST00000416199, ENST00000433003, ENST00000463072, ENST00000472736, ENST00000482034, ENST00000492219, ENST00000495865, ENST00000496531, ENST00000883181, ENST00000883182, ENST00000883183, ENST00000883184, ENST00000918215, ENST00000918216, ENST00000918217

RefSeq mRNA: 1 — MANE Select: NM_004229 NM_004229

CCDS: CCDS14254

Canonical transcript exons

ENST00000324817 — 31 exons

Exon	Start	End
ENSE00001227655	40654364	40654556
ENSE00001227662	40654935	40655060
ENSE00001227679	40659428	40659607
ENSE00001227684	40662925	40663160
ENSE00001227689	40664307	40664489
ENSE00001227693	40666720	40666851
ENSE00001227696	40671861	40671972
ENSE00001227705	40679864	40680133
ENSE00001227715	40681852	40681943
ENSE00001227733	40682836	40682996
ENSE00001227741	40688454	40688530
ENSE00001227749	40692183	40692317
ENSE00001227756	40692708	40692902
ENSE00001227763	40697024	40697183
ENSE00001227769	40701165	40701243
ENSE00001227775	40703444	40703569
ENSE00001227786	40709348	40709459
ENSE00001227795	40709979	40710129
ENSE00001227804	40711169	40711301
ENSE00001227814	40712186	40712293
ENSE00001227822	40712914	40713042
ENSE00001227831	40713778	40713907
ENSE00001227875	40648305	40651879
ENSE00001299237	40735198	40735542
ENSE00003469899	40680758	40680910
ENSE00003500797	40682603	40682749
ENSE00003501271	40726746	40726851
ENSE00003529951	40714537	40714710
ENSE00003569120	40659227	40659334
ENSE00003659165	40675221	40675361
ENSE00003659859	40729319	40729345

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 96.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.4502 / max 260.8431, expressed in 1816 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
198956	19.3820	1796
198950	6.5547	1693
198953	3.6837	1301
198955	2.1775	1163
198949	0.6647	275
198954	0.5572	304
198951	0.2723	113
198952	0.1581	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	96.70	gold quality
jejunal mucosa	UBERON:0000399	95.74	gold quality
cartilage tissue	UBERON:0002418	94.92	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.82	gold quality
muscle of leg	UBERON:0001383	93.14	gold quality
gastrocnemius	UBERON:0001388	93.04	gold quality
ventricular zone	UBERON:0003053	92.78	gold quality
muscle organ	UBERON:0001630	92.77	gold quality
vastus lateralis	UBERON:0001379	92.70	gold quality
biceps brachii	UBERON:0001507	91.99	gold quality
quadriceps femoris	UBERON:0001377	91.94	gold quality
oocyte	CL:0000023	91.22	gold quality
skeletal muscle tissue	UBERON:0001134	91.21	gold quality
jejunum	UBERON:0002115	91.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	91.01	gold quality
bone marrow cell	CL:0002092	90.70	gold quality
corpus epididymis	UBERON:0004359	90.42	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.40	gold quality
ganglionic eminence	UBERON:0004023	90.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.38	gold quality
embryo	UBERON:0000922	90.32	gold quality
stromal cell of endometrium	CL:0002255	89.99	gold quality
colonic mucosa	UBERON:0000317	89.82	gold quality
muscle tissue	UBERON:0002385	89.51	gold quality
adrenal tissue	UBERON:0018303	89.00	gold quality
diaphragm	UBERON:0001103	88.91	gold quality
calcaneal tendon	UBERON:0003701	88.76	gold quality
duodenum	UBERON:0002114	88.69	gold quality
cortical plate	UBERON:0005343	88.57	gold quality
skin of leg	UBERON:0001511	88.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

170 targeting MED14, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AA	99.96	70.64	3753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• DRIP150 binds to ISGF3 and regulates transcription (PMID:12509459)
• CRSP2 gene is expressed in the retina and its exact genomic location is on Xp11.4 between DXS1368 and DXS993 (PMID:12825353)
• Coactivation of ERalpha by DRIP150 in ZR-75 cells is NR box-independent and requires a novel sequence with putative alpha-helical structure. (PMID:15625066)
• MED14 and MED1 are used by glucocorticoid receptor in a gene-specific manner, providing a mechanism for promoter selectivity by glucocorticoid receptor (PMID:16239257)
• Coactivator that enhances estrogen receptor alpha- and specificity protein (SP)-1-mediated transactivation in breast cancer cells. (PMID:17306756)
• VitD-mediated stimulation of GC anti-inflammatory affects human monocytes in a process involving GM-CSF and MED14 (PMID:23572530)
• This results from a dramatically enhanced ability of MED14-containing complexes to associate with Pol II. (PMID:25383669)
• Functional analysis implicates TNRC6A, NAT10, MED14, and WDR5 in RNA-mediated transcriptional activation. (PMID:28813667)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	med14	ENSDARG00000009953
mus_musculus	Med14	ENSMUSG00000064127
rattus_norvegicus	Med14	ENSRNOG00000003792
rattus_norvegicus	LOC103694537	ENSRNOG00000060437
drosophila_melanogaster	MED14	FBGN0035145
caenorhabditis_elegans		WBGENE00004343

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 14 — O60244 (reviewed: O60244)

Alternative names: Activator-recruited cofactor 150 kDa component, Cofactor required for Sp1 transcriptional activation subunit 2, Mediator complex subunit 14, RGR1 homolog, Thyroid hormone receptor-associated protein complex 170 kDa component, Transcriptional coactivator CRSP150, Vitamin D3 receptor-interacting protein complex 150 kDa component

All UniProt accessions (3): O60244, H7C017, H7C3E5

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. Interacts with GATA1. 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. Interacts with AR, ESR1, SREBF1 and STAT2.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Similarity. Belongs to the Mediator complex subunit 14 family.

RefSeq proteins (1): NP_004220* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013947	Mediator_Med14	Family
IPR055107	Med14_RM8	Domain
IPR055113	Med14_RM2	Domain
IPR055114	Med14_RM6	Domain
IPR055122	Med14_N	Domain
IPR056877	Med14_C	Domain
IPR056878	RM5_Med14	Domain
IPR056879	RM3_Med14	Domain

Pfam: PF08638, PF22981, PF22983, PF22984, PF25065, PF25067, PF25069

UniProt features (112 total): strand 45, helix 28, turn 15, modified residue 7, compositionally biased region 6, region of interest 4, sequence conflict 3, short sequence motif 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7EMF	ELECTRON MICROSCOPY	3.5
8TRH	ELECTRON MICROSCOPY	3.7
7ENA	ELECTRON MICROSCOPY	4.07
7ENC	ELECTRON MICROSCOPY	4.13
8GXS	ELECTRON MICROSCOPY	4.16
7ENJ	ELECTRON MICROSCOPY	4.4
7NVR	ELECTRON MICROSCOPY	4.5
8T9D	ELECTRON MICROSCOPY	4.66
7LBM	ELECTRON MICROSCOPY	4.8
8GXQ	ELECTRON MICROSCOPY	5.04
8TQW	ELECTRON MICROSCOPY	8.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60244-F1	73.93	0.18

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 (7): 617, 986, 1112, 1119, 1128, 1136, 1144

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: 209 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, MODULE_97, AAGCAAT_MIR137, TGCACTT_MIR519C_MIR519B_MIR519A, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GOZGIT_ESR1_TARGETS_DN, MODULE_182, CATTTCA_MIR203, RUTELLA_RESPONSE_TO_CSF2RB_AND_IL4_UP, WANG_RESPONSE_TO_BEXAROTENE_DN, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, WTGAAAT_UNKNOWN, RUTELLA_RESPONSE_TO_HGF_VS_CSF2RB_AND_IL4_DN, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_DNA_TEMPLATED_TRANSCRIPTION_INITIATION

GO Biological Process (7): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), somatic stem cell population maintenance (GO:0035019), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261)

GO Molecular Function (4): transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), nuclear vitamin D receptor binding (GO:0042809), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), mediator complex (GO:0016592), core mediator complex (GO:0070847)

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
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
positive regulation of transcription by RNA polymerase II	2
positive regulation of DNA-templated transcription	2
transcription initiation at RNA polymerase II promoter	2
cellular anatomical structure	2
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
stem cell population maintenance	1
DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
transcription preinitiation complex assembly	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
transcription regulator activity	1
transcription coregulator activity	1
nuclear receptor binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
core mediator complex	1
nuclear protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

4702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED14	MED6	O75586	995
MED14	MED17	Q9NVC6	988
MED14	MED21	Q13503	988
MED14	MED7	O43513	988
MED14	MED24	O75448	973
MED14	MED10	Q9BTT4	972
MED14	MED15	Q96RN5	964
MED14	MED23	Q9ULK4	964
MED14	MED1	Q15648	961
MED14	MED13	Q9UHV7	952
MED14	MED18	Q9BUE0	931
MED14	MED12	Q93074	927
MED14	CCNC	P24863	919
MED14	MED16	Q9Y2X0	918
MED14	MED22	Q15528	906

IntAct

179 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED10	MED19	psi-mi:“MI:0915”(physical 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
CDK8	MED19	psi-mi:“MI:0914”(association)	0.850
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
MED31	MED19	psi-mi:“MI:0914”(association)	0.840

BioGRID (390): MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-MS), MED14 (Affinity Capture-Western), MED14 (Affinity Capture-RNA), MED14 (Affinity Capture-MS), MED1 (Co-fractionation), MED10 (Co-fractionation), MED11 (Co-fractionation), MED12 (Co-fractionation), MED14 (Co-fractionation)

ESM2 similar proteins: A1C5W6, A1CJ92, A1CLT5, A1CV59, A1D887, A1DG38, A2ABV5, A2QFK0, A4R0J9, F4K0C4, G0S0E7, O60244, P0CT47, Q03570, Q0CBX9, Q0CG59, Q0CL23, Q0V6H6, Q16U49, Q1DHH9, Q1DLD2, Q1DZL3, Q1EAK2, Q29FF7, Q2HA26, Q2HDU8, Q2QNU0, Q2U513, Q2UC64, Q2UJ16, Q2UMJ1, Q4W9B7, Q4WH96, Q4WWL0, Q5AW92, Q5B3Y9, Q5B8A6, Q5BAD4, Q61IR6, Q6C022

Diamond homologs: A2ABV5, O60244, P0CB66, Q16U49, Q29FF7, Q4P0P3, Q7Q6S8, Q9P7Y4, Q9W0P8, Q61IR6, Q6BPK1, Q03570, Q5AW92, Q0CL23

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MED14	“form complex”	“Core mediator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 113 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	29	73.2×	7e-47
RSV-host interactions	29	58.2×	1e-43
Adipogenesis	29	58.2×	1e-43
Regulation of lipid metabolism by PPARalpha	29	52.4×	4e-42
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	18	49.7×	5e-25
FGFR2 mutant receptor activation	5	48.8×	7e-07
Transcriptional regulation of white adipocyte differentiation	29	48.2×	6e-41
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	18	45.4×	2e-24

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	25	78.4×	1e-39
RNA polymerase II preinitiation complex assembly	25	70.8×	8e-39
positive regulation of transcription initiation by RNA polymerase II	25	70.8×	8e-39
transcription initiation at RNA polymerase II promoter	8	31.2×	2e-08
somatic stem cell population maintenance	12	31.0×	6e-13
mitotic cell cycle	6	8.4×	5e-03
transcription by RNA polymerase II	10	7.3×	1e-04
protein ubiquitination	12	5.2×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	76
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

4614 predictions. Top by Δscore:

Variant	Effect	Δscore
X:40659221:ACTT:A	donor_loss	1.0000
X:40659222:CTTA:C	donor_loss	1.0000
X:40659223:TTACC:T	donor_loss	1.0000
X:40659224:TAC:T	donor_loss	1.0000
X:40659225:A:AC	donor_gain	1.0000
X:40659225:ACC:A	donor_loss	1.0000
X:40659226:C:CC	donor_gain	1.0000
X:40659226:CCAG:C	donor_gain	1.0000
X:40659335:C:CA	acceptor_loss	1.0000
X:40659336:T:G	acceptor_loss	1.0000
X:40659424:ATAC:A	donor_loss	1.0000
X:40659425:TACTC:T	donor_loss	1.0000
X:40659426:A:AC	donor_gain	1.0000
X:40659426:ACT:A	donor_gain	1.0000
X:40659427:C:CG	donor_gain	1.0000
X:40659427:CT:C	donor_gain	1.0000
X:40659427:CTC:C	donor_gain	1.0000
X:40659427:CTCT:C	donor_gain	1.0000
X:40659427:CTCTT:C	donor_gain	1.0000
X:40659603:TGCAG:T	acceptor_gain	1.0000
X:40659605:CAG:C	acceptor_gain	1.0000
X:40659608:C:CC	acceptor_gain	1.0000
X:40662596:A:AC	donor_gain	1.0000
X:40662597:C:CC	donor_gain	1.0000
X:40664302:CTTA:C	donor_gain	1.0000
X:40664303:TTA:T	donor_loss	1.0000
X:40664304:TA:T	donor_loss	1.0000
X:40664305:A:AC	donor_gain	1.0000
X:40664305:ACT:A	donor_loss	1.0000
X:40664306:C:CG	donor_gain	1.0000

AlphaMissense

9463 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:40651855:A:T	V1439D	1.000
X:40651867:A:T	I1435K	1.000
X:40654399:A:G	L1419P	1.000
X:40654411:A:T	V1415D	1.000
X:40654459:G:T	A1399E	1.000
X:40654498:G:C	P1386R	1.000
X:40654498:G:T	P1386Q	1.000
X:40654501:A:T	V1385D	1.000
X:40654549:A:G	L1369P	1.000
X:40654555:A:G	L1367P	1.000
X:40654935:A:C	F1366L	1.000
X:40654935:A:T	F1366L	1.000
X:40654937:A:G	F1366L	1.000
X:40654942:A:G	L1364P	1.000
X:40654942:A:T	L1364Q	1.000
X:40654949:T:C	K1362E	1.000
X:40654966:G:T	A1356D	1.000
X:40654975:C:T	G1353E	1.000
X:40654984:G:T	A1350E	1.000
X:40654987:A:T	I1349N	1.000
X:40655020:A:G	F1338S	1.000
X:40655026:A:T	V1336D	1.000
X:40655033:A:G	W1334R	1.000
X:40655033:A:T	W1334R	1.000
X:40659253:A:G	C1316R	1.000
X:40659255:T:A	D1315V	1.000
X:40659285:A:G	L1305P	1.000
X:40659333:A:T	V1289D	1.000
X:40659475:A:G	W1273R	1.000
X:40659475:A:T	W1273R	1.000

dbSNP variants (sampled 300 via entrez): RS1000022126 (X:40688189 C>A), RS1000115760 (X:40705372 A>T), RS1000127737 (X:40727270 T>A), RS1000304532 (X:40688788 G>A), RS1000328570 (X:40688214 A>G), RS1000417907 (X:40700609 AAG>A), RS1000488477 (X:40678310 A>C), RS1000498964 (X:40698166 C>G,T), RS1000533341 (X:40666384 G>A), RS1000567265 (X:40677925 A>G), RS1000592965 (X:40652380 T>TA), RS1000625917 (X:40670775 A>T), RS1000645008 (X:40690885 T>G), RS1000679267 (X:40737656 G>T), RS1000691375 (X:40725904 AGAT>A)

Disease associations

OMIM: gene MIM:300182 | disease phenotypes: MIM:300423

GenCC curated gene-disease

Mondo (3): neurodevelopmental disorder (MONDO:0700092), syndromic X-linked intellectual disability Hedera type (MONDO:0010319), intellectual disability (MONDO:0001071)

Orphanet (2): X-linked intellectual disability, Hedera type (Orphanet:93952), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003720_6	Migraine	2.000000e-08

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
C564516	Mental Retardation, X-Linked, with Epilepsy (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation, affects cotreatment	6
entinostat	affects cotreatment, increases expression	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
kojic acid	increases expression	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	decreases expression	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	decreases expression, affects cotreatment, increases expression	1
jinfukang	decreases expression	1
Temozolomide	decreases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Carbamazepine	affects expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Diclofenac	affects expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Hydrogen Peroxide	increases expression	1

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