MED9

Summary

MED9 (mediator complex subunit 9, HGNC:25487) is a protein-coding gene on chromosome 17p11.2, encoding Mediator of RNA polymerase II transcription subunit 9 (Q9NWA0). Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. It is a selective cancer dependency (DepMap: 83.4% of cell lines).

The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. The protein encoded by this gene is thought to be a subunit of the Mediator complex. This gene is located within the Smith-Magenis syndrome region on chromosome 17.

Source: NCBI Gene 55090 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 856 total — 2 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 87
• Cancer dependency (DepMap): dependent in 83.4% of screened cell lines
• MANE Select transcript: NM_018019

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25487
Approved symbol	MED9
Name	mediator complex subunit 9
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10193, MED25
Ensembl gene	ENSG00000141026
Ensembl biotype	protein_coding
OMIM	609878
Entrez	55090

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 TEC

ENST00000268711, ENST00000580462, ENST00000581315, ENST00000585041, ENST00000624097

RefSeq mRNA: 1 — MANE Select: NM_018019 NM_018019

CCDS: CCDS11184

Canonical transcript exons

ENST00000268711 — 2 exons

Exon	Start	End
ENSE00000946197	17477000	17477265
ENSE00001298787	17491279	17493221

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 90.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.3210 / max 161.1649, expressed in 1811 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
159744	20.0289	1811
159745	0.2921	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	90.39	gold quality
heart left ventricle	UBERON:0002084	89.20	gold quality
cardiac ventricle	UBERON:0002082	88.66	gold quality
right atrium auricular region	UBERON:0006631	88.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	88.47	gold quality
right frontal lobe	UBERON:0002810	88.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.98	gold quality
gastrocnemius	UBERON:0001388	87.80	gold quality
anterior cingulate cortex	UBERON:0009835	87.48	gold quality
muscle of leg	UBERON:0001383	87.46	gold quality
cingulate cortex	UBERON:0003027	87.42	gold quality
nucleus accumbens	UBERON:0001882	87.38	gold quality
cardiac atrium	UBERON:0002081	86.99	gold quality
caudate nucleus	UBERON:0001873	86.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.42	gold quality
prefrontal cortex	UBERON:0000451	86.34	gold quality
heart	UBERON:0000948	86.34	gold quality
putamen	UBERON:0001874	86.00	gold quality
adrenal tissue	UBERON:0018303	85.95	gold quality
right adrenal gland cortex	UBERON:0035827	85.54	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.94	gold quality
neocortex	UBERON:0001950	84.68	gold quality
cerebellar hemisphere	UBERON:0002245	84.60	gold quality
cerebellar cortex	UBERON:0002129	84.51	gold quality
frontal cortex	UBERON:0001870	84.40	gold quality
amygdala	UBERON:0001876	84.33	gold quality
right lobe of liver	UBERON:0001114	84.27	gold quality
right adrenal gland	UBERON:0001233	84.18	gold quality
mucosa of transverse colon	UBERON:0004991	84.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting MED9, 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-5193	100.00	67.26	1744
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-3660	99.68	67.33	1149
HSA-MIR-4526	99.68	67.07	1136
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-1207-5P	99.49	69.11	2983

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 2)

• the FLJ10193 protein, which we designate Med25, is a bona fide subunit of the mammalian Mediator complex (PMID:14638676)
• Familial Dilated Cardiomyopathy: A Novel MED9 Short Isoform Identification. (PMID:38474301)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	med9	ENSDARG00000096631
mus_musculus	Med9	ENSMUSG00000061650
rattus_norvegicus	Med9	ENSRNOG00000053961
drosophila_melanogaster	MED9	FBGN0260401

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 9 — Q9NWA0 (reviewed: Q9NWA0)

Alternative names: Mediator complex subunit 9

All UniProt accessions (2): Q9NWA0, J3KTK5

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.

Similarity. Belongs to the Mediator complex subunit 9 family.

RefSeq proteins (1): NP_060489* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011425	Med9	Family
IPR037212	Med7/Med21-like	Homologous_superfamily
IPR039242	MED9_metazoa	Family

Pfam: PF07544

UniProt features (10 total): helix 3, modified residue 2, initiator methionine 1, chain 1, region of interest 1, coiled-coil region 1, compositionally biased region 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-Q9NWA0-F1	76.52	0.49

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 (2): 2, 110

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: 452 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, MODULE_255, GOBP_POSITIVE_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, MODULE_317, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_NEGATIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, EFC_Q6, BILD_HRAS_ONCOGENIC_SIGNATURE, GOBP_POSITIVE_REGULATION_OF_BINDING, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_POSITIVE_REGULATION_OF_MOLECULAR_FUNCTION, GOBP_REGULATION_OF_DNA_TEMPLATED_TRANSCRIPTION_INITIATION, MODULE_301, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_DN

GO Biological Process (4): positive regulation of transcription elongation by RNA polymerase II (GO:0032968), RNA polymerase II preinitiation complex assembly (GO:0051123), positive regulation of transcription initiation by RNA polymerase II (GO:0060261), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (2): transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), mediator complex (GO:0016592), core mediator complex (GO:0070847)

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
positive regulation of transcription by RNA polymerase II	2
transcription initiation at RNA polymerase II promoter	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
transcription preinitiation complex assembly	1
regulation of transcription initiation by RNA polymerase II	1
positive regulation of DNA-templated transcription initiation	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
core mediator complex	1
nuclear protein-containing complex	1
RNA polymerase II transcription regulator complex	1

Protein interactions and networks

STRING

664 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED9	MED4	Q9NPJ6	987
MED9	MED10	Q9BTT4	977
MED9	MED19	A0JLT2	910
MED9	MED7	O43513	906
MED9	MED31	Q9Y3C7	873
MED9	MED22	Q15528	843
MED9	MED18	Q9BUE0	832
MED9	MED26	O95402	803
MED9	MED21	Q13503	803
MED9	MED15	Q96RN5	797
MED9	MED20	Q9H944	770
MED9	MED6	O75586	768
MED9	MED11	Q9P086	736
MED9	MED30	Q96HR3	735
MED9	MED14	O60244	733

IntAct

116 interactions, top by confidence:

A	B	Type	Score
MED4	MED9	psi-mi:“MI:0915”(physical association)	0.920
MED9	MED4	psi-mi:“MI:0915”(physical association)	0.920
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
MED10	MED19	psi-mi:“MI:0915”(physical association)	0.910
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MED21	MED9	psi-mi:“MI:0915”(physical 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

BioGRID (289): MED9 (Affinity Capture-MS), MED9 (Affinity Capture-MS), MED9 (Affinity Capture-MS), MED9 (Affinity Capture-MS), MED29 (Affinity Capture-Western), MED17 (Affinity Capture-Western), MED1 (Affinity Capture-Western), MED19 (Affinity Capture-Western), MED4 (Affinity Capture-Western), MED8 (Affinity Capture-Western), MED18 (Affinity Capture-Western), MED22 (Affinity Capture-Western), MED11 (Affinity Capture-Western), MED9 (Affinity Capture-Western), MED4 (Reconstituted Complex)

ESM2 similar proteins: A1A4Q8, A4IIZ9, A5WUL3, A8E4X8, A8E5U3, B5DF93, D3ZXK7, F4HPA7, O57595, O75934, P68943, P97578, Q08BU1, Q08D01, Q0IHI6, Q2KHX9, Q2TBN4, Q3TC46, Q5HZZ6, Q5PPY2, Q5R8Q4, Q5RAX7, Q5RBZ4, Q5RKN3, Q5XIX8, Q5XPI3, Q62415, Q66KX4, Q6DD30, Q6GQ95, Q6P4S8, Q6PC45, Q6TYB5, Q86TB9, Q86UW7, Q8BYR5, Q8JHI6, Q8N201, Q8VCS6, Q920D3

Diamond homologs: A1ZB42, Q290F0, Q2KHX9, Q4V7L5, Q8VCS6, Q9NWA0

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MED9	“form complex”	“Core mediator complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 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	146.3×	6e-53
RSV-host interactions	26	116.2×	4e-50
Adipogenesis	26	116.2×	4e-50
Regulation of lipid metabolism by PPARalpha	26	104.7×	8e-49
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	16	98.5×	4e-28
Transcriptional regulation of white adipocyte differentiation	26	96.4×	8e-48
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	16	90.0×	2e-27
Epigenetic regulation by WDR5-containing histone modifying complexes	16	70.5×	1e-25

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	22	161.5×	5e-44
positive regulation of transcription initiation by RNA polymerase II	23	152.5×	3e-45
RNA polymerase II preinitiation complex assembly	22	145.8×	5e-43
somatic stem cell population maintenance	11	66.5×	2e-16
transcription initiation at RNA polymerase II promoter	7	63.9×	4e-10
protein ubiquitination	12	12.1×	4e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	4
Uncertain significance	361
Likely benign	402
Benign	26

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
203445	NM_030973.4(MED25):c.116A>G (p.Tyr39Cys)	Pathogenic
2285740	NM_030973.4(MED25):c.781_791del (p.Pro261fs)	Pathogenic
1064794	NM_030973.4(MED25):c.820-1G>A	Likely pathogenic
3063666	NM_030973.4(MED25):c.2T>G (p.Met1Arg)	Likely pathogenic
421748	NM_030973.4(MED25):c.1165del (p.Leu389fs)	Likely pathogenic
504289	NM_030973.4(MED25):c.1939C>T (p.Arg647Ter)	Likely pathogenic

SpliceAI

2523 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17491276:C:G	acceptor_gain	1.0000
17:17491277:A:AG	acceptor_gain	1.0000
17:17491277:A:T	acceptor_loss	1.0000
17:17491277:AGCAT:A	acceptor_gain	1.0000
17:17491278:G:GA	acceptor_gain	1.0000
17:17491278:GC:G	acceptor_gain	1.0000
17:17491278:GCA:G	acceptor_gain	1.0000
17:17491278:GCAT:G	acceptor_gain	1.0000
17:17491278:GCATG:G	acceptor_gain	1.0000
19:49818472:TCGA:T	donor_gain	1.0000
19:49818474:GA:G	donor_gain	1.0000
19:49818476:G:GG	donor_gain	1.0000
19:49818614:GAC:G	donor_gain	1.0000
19:49818617:G:GG	donor_gain	1.0000
19:49819170:A:AG	acceptor_gain	1.0000
19:49819171:G:GG	acceptor_gain	1.0000
19:49819289:GGCAT:G	donor_gain	1.0000
19:49819290:GCAT:G	donor_gain	1.0000
19:49819293:T:G	donor_gain	1.0000
19:49819293:T:TG	donor_gain	1.0000
19:49819297:G:GG	donor_gain	1.0000
19:49828444:TGCA:T	acceptor_loss	1.0000
19:49828447:A:AT	acceptor_loss	1.0000
19:49828545:GAT:G	donor_gain	1.0000
19:49828548:G:GG	donor_gain	1.0000
19:49828964:T:TA	acceptor_gain	1.0000
19:49828965:G:A	acceptor_gain	1.0000
19:49828968:A:AG	acceptor_gain	1.0000
19:49828968:AGT:A	acceptor_gain	1.0000
19:49828969:G:GA	acceptor_gain	1.0000

AlphaMissense

959 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17491446:T:C	L131P	1.000
17:17477247:T:A	V69D	0.999
17:17491323:T:C	L90P	0.999
17:17491438:G:C	K128N	0.999
17:17491438:G:T	K128N	0.999
17:17491449:T:C	L132P	0.999
17:17491437:A:T	K128M	0.998
17:17491446:T:A	L131H	0.998
17:17491457:T:C	Y135H	0.998
17:17491457:T:G	Y135D	0.998
17:17477259:T:A	I73N	0.997
17:17491407:T:C	L118P	0.997
17:17491416:T:C	L121P	0.997
17:17491458:A:C	Y135S	0.997
17:17477238:T:C	L66S	0.996
17:17491314:T:C	L87P	0.996
17:17491323:T:A	L90H	0.996
17:17491436:A:G	K128E	0.996
17:17491458:A:G	Y135C	0.996
17:17491462:G:C	K136N	0.995
17:17491462:G:T	K136N	0.995
17:17491323:T:G	L90R	0.994
17:17491335:T:C	F94S	0.994
17:17491347:G:C	R98P	0.994
17:17491395:A:C	Q114P	0.994
17:17477235:T:C	F65S	0.993
17:17477259:T:C	I73T	0.993
17:17477259:T:G	I73S	0.993
17:17491437:A:C	K128T	0.993
17:17491457:T:A	Y135N	0.993

dbSNP variants (sampled 300 via entrez): RS1000166224 (17:17487229 C>G,T), RS1000411298 (17:17478634 C>T), RS1000479786 (17:17492360 G>T), RS1000527883 (17:17489767 T>C), RS1000633677 (17:17486543 C>A,T), RS1000701736 (17:17487367 T>C), RS1000795558 (17:17485105 C>G,T), RS1000820978 (17:17491490 G>A), RS1001291467 (17:17486994 A>G), RS1001299740 (17:17481739 A>G), RS1001517776 (17:17491874 T>C), RS1001646388 (17:17481466 C>T), RS1001871415 (17:17485592 G>A,C), RS1001988960 (17:17490947 T>C), RS1002071974 (17:17490186 A>G)

Disease associations

OMIM: gene MIM:609878 | disease phenotypes: MIM:616449, MIM:605589, MIM:118220, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome	Definitive	Autosomal recessive
Charcot-Marie-Tooth disease type 2B2	Supportive	Autosomal recessive
autosomal recessive non-syndromic intellectual disability	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease type 2B2	Disputed	AR

Mondo (8): Charcot-Marie-Tooth disease type 2 (MONDO:0018993), congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome (MONDO:0014643), neurodevelopmental disorder (MONDO:0700092), Charcot-Marie-Tooth disease type 2B2 (MONDO:0011570), Charcot-Marie-Tooth disease (MONDO:0015626), polyneuropathy (MONDO:0001824), autism (MONDO:0005260), autosomal recessive non-syndromic intellectual disability (MONDO:0019502)

Orphanet (4): Autosomal dominant Charcot-Marie-Tooth disease type 2 (Orphanet:64746), Basel-Vanagaite-Smirin-Yosef syndrome (Orphanet:464738), Charcot-Marie-Tooth disease type 2B2 (Orphanet:101101), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166)

HPO phenotypes

87 total (30 of 87 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000221	Furrowed tongue
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000303	Mandibular prognathia
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000463	Anteverted nares
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000519	Developmental cataract
HP:0000568	Microphthalmia
HP:0000646	Amblyopia
HP:0000718	Aggressive behavior
HP:0000768	Pectus carinatum
HP:0000954	Single transverse palmar crease
HP:0001081	Cholelithiasis
HP:0001181	Adducted thumb

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002039_7	Blood trace element (Se levels)	1.000000e-07
GCST008059_144	Estimated glomerular filtration rate	9.000000e-12
GCST008362_63	Birth weight	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
D065886	Neurodevelopmental Disorders	F03.625
D011115	Polyneuropathies	C10.668.829.800
C537991	Charcot-Marie-Tooth disease, Type 2B2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases methylation, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
FR900359	increases phosphorylation	1
methylmercuric chloride	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, increases expression	1
K 7174	increases expression	1
ICG 001	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	affects methylation	1
Cytarabine	decreases expression	1
Manganese	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	increases expression	1
Copper Sulfate	increases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

203 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
NCT05902351	Not specified	RECRUITING	Natural History Study for Charcot Marie Tooth Disease
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