MED12L

Summary

MED12L (mediator complex subunit 12L, HGNC:16050) is a protein-coding gene on chromosome 3q25.1, encoding Mediator of RNA polymerase II transcription subunit 12-like protein (Q86YW9). May be a component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes.

The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery.

Source: NCBI Gene 116931 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Nizon-Isidor syndrome (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 757 total — 11 pathogenic, 20 likely-pathogenic
• Phenotypes (HPO): 45
• MANE Select transcript: NM_001393769

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16050
Approved symbol	MED12L
Name	mediator complex subunit 12L
Location	3q25.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1635, TNRC11L, TRALPUSH, TRALP
Ensembl gene	ENSG00000144893
Ensembl biotype	protein_coding
OMIM	611318
Entrez	116931

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 4 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000273432, ENST00000309237, ENST00000422248, ENST00000468305, ENST00000469768, ENST00000474524, ENST00000480026, ENST00000488092, ENST00000491549, ENST00000685357, ENST00000686666, ENST00000687756, ENST00000688234, ENST00000693531, ENST00000934758, ENST00000934759

RefSeq mRNA: 2 — MANE Select: NM_001393769 NM_001393769, NM_053002

CCDS: CCDS33876, CCDS93408

Canonical transcript exons

ENST00000687756 — 45 exons

Exon	Start	End
ENSE00000967747	151357213	151357376
ENSE00000967748	151360474	151360605
ENSE00000967749	151364979	151365206
ENSE00000967750	151365850	151365991
ENSE00000967751	151367646	151367766
ENSE00000967752	151368150	151368251
ENSE00000967753	151369436	151369549
ENSE00000967754	151372567	151372766
ENSE00000967755	151376026	151376214
ENSE00000967756	151376800	151376874
ENSE00000967757	151376991	151377178
ENSE00000967758	151378012	151378173
ENSE00000967759	151380113	151380224
ENSE00000967761	151384083	151384218
ENSE00000967763	151387810	151388172
ENSE00000967766	151394656	151394867
ENSE00000967767	151409243	151409332
ENSE00000967768	151411278	151411507
ENSE00000967769	151430299	151430380
ENSE00001006020	151413139	151413295
ENSE00001076914	151192550	151192654
ENSE00001076918	151163893	151164042
ENSE00001076921	151165846	151165982
ENSE00001076964	151382656	151382745
ENSE00001076965	151389979	151390135
ENSE00001076966	151383779	151383888
ENSE00001209002	151188354	151188480
ENSE00001209007	151185330	151185461
ENSE00001209017	151165420	151165519
ENSE00001209022	151159832	151160101
ENSE00001209024	151158689	151158799
ENSE00001209026	151156161	151156330
ENSE00001209030	151127825	151127984
ENSE00001209038	151122783	151122974
ENSE00001209044	151190717	151190931
ENSE00001311525	151193490	151193666
ENSE00001507343	151385030	151385191
ENSE00003510622	151116338	151116442
ENSE00003610250	151416312	151416422
ENSE00003648607	151355896	151356039
ENSE00003675695	151355121	151355239
ENSE00003678202	151350059	151350206
ENSE00003922964	151086798	151087025
ENSE00003930427	151432752	151436653
ENSE00003931587	151085664	151085936

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 89.22.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8779 / max 504.1870, expressed in 777 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39217	4.1063	737
39219	0.4762	198
39220	0.3820	173
39221	0.2899	118
202980	0.1891	88
39218	0.1620	84
39234	0.1485	76
39232	0.0864	3
39231	0.0279	2
202981	0.0096	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	89.22	gold quality
leukocyte	CL:0000738	87.52	gold quality
adrenal tissue	UBERON:0018303	84.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.61	gold quality
secondary oocyte	CL:0000655	79.17	gold quality
bone marrow cell	CL:0002092	78.29	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.54	gold quality
ventricular zone	UBERON:0003053	76.06	gold quality
ganglionic eminence	UBERON:0004023	73.55	gold quality
sural nerve	UBERON:0015488	73.37	gold quality
prefrontal cortex	UBERON:0000451	72.88	gold quality
calcaneal tendon	UBERON:0003701	71.20	gold quality
Brodmann (1909) area 9	UBERON:0013540	71.03	gold quality
anterior cingulate cortex	UBERON:0009835	68.19	gold quality
cerebellar cortex	UBERON:0002129	67.62	gold quality
right frontal lobe	UBERON:0002810	67.57	gold quality
cerebellar hemisphere	UBERON:0002245	67.51	gold quality
corpus callosum	UBERON:0002336	67.43	gold quality
right hemisphere of cerebellum	UBERON:0014890	66.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.60	gold quality
caudate nucleus	UBERON:0001873	66.12	gold quality
cerebellum	UBERON:0002037	65.84	gold quality
neocortex	UBERON:0001950	65.76	gold quality
frontal cortex	UBERON:0001870	65.67	gold quality
islet of Langerhans	UBERON:0000006	65.57	gold quality
granulocyte	CL:0000094	65.36	gold quality
nucleus accumbens	UBERON:0001882	65.07	gold quality
adrenal gland	UBERON:0002369	64.62	gold quality
adenohypophysis	UBERON:0002196	64.53	gold quality
right adrenal gland	UBERON:0001233	64.21	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3683.57
E-GEOD-76312	yes	1323.63
E-MTAB-9067	yes	221.65
E-HCAD-6	yes	22.35
E-ANND-3	yes	6.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

256 targeting MED12L, 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-3646	100.00	73.56	5283
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
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-4650-5P	99.98	64.69	999

Literature-anchored findings (GeneRIF, showing 1)

• Rare MED12L Variants Are Associated with Susceptibility to Guttate Psoriasis in the Han Chinese Population. (PMID:38735287)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Med12l	ENSMUSG00000056476
rattus_norvegicus	Med12l	ENSRNOG00000010680
drosophila_melanogaster	kto	FBGN0001324
caenorhabditis_elegans		WBGENE00001081

Paralogs (1): MED12 (ENSG00000184634)

Protein

Protein identifiers

Mediator of RNA polymerase II transcription subunit 12-like protein — Q86YW9 (reviewed: Q86YW9)

Alternative names: Mediator complex subunit 12-like protein, Thyroid hormone receptor-associated-like protein, Trinucleotide repeat-containing gene 11 protein-like

All UniProt accessions (6): Q86YW9, A0A8I5KW22, A0A8I5KX78, A0A8I5KY35, F8WAE6, H7C4I9

UniProt curated annotations — full annotation on UniProt →

Function. May be a 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. May be a component of the Mediator complex, which is known to be 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.

Disease relevance. Nizon-Isidor syndrome (NIZIDS) [MIM:618872] An autosomal dominant neurodevelopmental disorder characterized by intellectual disability, global developmental delay, speech impairment, and behavioral abnormalities including autism spectrum disorder and aggressive behavior. Other features include a thin corpus callosum, and mild facial dysmorphism. Disease onset is in infancy or early childhood. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Mediator complex subunit 12 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q86YW9-1	1	yes
Q86YW9-2	2, NOPAR
Q86YW9-3	3, NOPAR2
Q86YW9-4	4

RefSeq proteins (2): NP_001380698, NP_443728 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019035	Mediator_Med12	Domain
IPR021989	Mediator_Med12_catenin-bd	Domain
IPR021990	Mediator_Med12_LCEWAV	Domain
IPR051647	Mediator_comp_sub12	Family

Pfam: PF09497, PF12144, PF12145

UniProt features (25 total): compositionally biased region 7, sequence variant 7, region of interest 4, splice variant 4, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YW9-F1	66.04	0.24

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 (1): 462

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 333 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, MODULE_255, MODULE_317, TATTATA_MIR374, HNF1_Q6, LHX3_01, NKX62_Q2, MODULE_301, AACTTT_UNKNOWN, TCCAGAG_MIR518C, ACTTTAT_MIR1425P, CUI_TCF21_TARGETS_2_DN, CREBP1_01, MODULE_188, YYCATTCAWW_UNKNOWN

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 (4): transcription coactivator activity (GO:0003713), beta-catenin binding (GO:0008013), transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (2): mediator complex (GO:0016592), nucleus (GO:0005634)

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
protein binding	1
transcription regulator activity	1
binding	1
core mediator complex	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1040 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MED12L	CCNC	P24863	993
MED12L	MED13L	Q71F56	992
MED12L	MED13	Q9UHV7	974
MED12L	CDK19	Q9BWU1	953
MED12L	CDK8	P49336	932
MED12L	MED19	A0JLT2	694
MED12L	MED9	Q9NWA0	624
MED12L	MED26	O95402	606
MED12L	MED15	Q96RN5	572
MED12L	MED14	O60244	514
MED12L	GPR87	Q9BY21	485
MED12L	MED18	Q9BUE0	476
MED12L	SOX10	P56693	462
MED12L	MED10	Q9BTT4	439
MED12L	MED29	Q9NX70	437

IntAct

69 interactions, top by confidence:

A	B	Type	Score
MED10	MED19	psi-mi:“MI:0914”(association)	0.910
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
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
MED18	MED19	psi-mi:“MI:0914”(association)	0.840
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
MED1	MED19	psi-mi:“MI:0914”(association)	0.840
MED19	MED7	psi-mi:“MI:0914”(association)	0.840
MED10	MED14	psi-mi:“MI:0914”(association)	0.830
CDK19	MED14	psi-mi:“MI:0914”(association)	0.800
MED14	MED19	psi-mi:“MI:0914”(association)	0.790
MED9	MED19	psi-mi:“MI:0914”(association)	0.790
MED19	MED14	psi-mi:“MI:0914”(association)	0.790
MED22	MED19	psi-mi:“MI:0914”(association)	0.790
CDK19	MED19	psi-mi:“MI:0914”(association)	0.770

BioGRID (90): MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), NCAPD2 (Co-fractionation), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS), MED12L (Affinity Capture-MS)

ESM2 similar proteins: A0JP85, A1A5H6, A2AGH6, A2RRV3, A5GFY4, A5YKK6, B1AY13, E9Q8I9, O55007, O75448, O94915, O95155, Q0KK59, Q15648, Q24134, Q2PW47, Q2QCI8, Q4V8B3, Q5F3M0, Q5RCU2, Q5RES4, Q5RFA0, Q5TBA9, Q642P2, Q6GLR7, Q6GYP7, Q6GYQ0, Q6P4S8, Q6PI53, Q6ZQ08, Q7YQK8, Q80TJ1, Q80X82, Q80YV3, Q86YW9, Q8BL99, Q8BQM9, Q8IXH7, Q8N201, Q922L6

Diamond homologs: A2AGH6, Q2QCI8, Q5RCU2, Q7YQK8, Q86YW9, Q8BQM9, Q93074, Q9VW47

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 38 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	21	125.3×	9e-40
RSV-host interactions	21	99.5×	9e-38
Adipogenesis	21	99.5×	9e-38
Regulation of lipid metabolism by PPARalpha	21	89.7×	9e-37
Transcriptional regulation of white adipocyte differentiation	21	82.6×	5e-36
Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	12	78.3×	2e-19
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	12	71.6×	5e-19
PPARA activates gene expression	21	60.1×	7e-33

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of transcription elongation by RNA polymerase II	18	150.5×	1e-34
positive regulation of transcription initiation by RNA polymerase II	19	143.4×	5e-36
RNA polymerase II preinitiation complex assembly	18	135.9×	7e-34
somatic stem cell population maintenance	7	48.2×	6e-09
protein ubiquitination	7	8.1×	8e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	11
Likely pathogenic	20
Uncertain significance	569
Likely benign	101
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
2576787	NM_001393769.1(MED12L):c.3385C>T (p.Arg1129Ter)	Pathogenic
3378093	NM_001393769.1(MED12L):c.2895_2896del (p.Tyr966fs)	Pathogenic
4833027	NM_001393769.1(MED12L):c.744del (p.Lys248fs)	Pathogenic
4839079	NM_001393769.1(MED12L):c.5944C>T (p.Gln1982Ter)	Pathogenic
4839141	NM_001393769.1(MED12L):c.1296_1300del (p.Gln433fs)	Pathogenic
592153	NM_001393769.1(MED12L):c.5476C>T (p.Arg1826Ter)	Pathogenic
598930	NM_001393769.1(MED12L):c.4482G>A (p.Met1494Ile)	Pathogenic
599023	NM_001393769.1(MED12L):c.1746dup (p.Ser583fs)	Pathogenic
870507	NM_001393769.1(MED12L):c.1747dup (p.Ser583fs)	Pathogenic
870508	NM_001393769.1(MED12L):c.4479-1G>A	Pathogenic
9081	NM_022788.5(P2RY12):c.717_718del (p.Ile240fs)	Pathogenic
1180497	NM_001393769.1(MED12L):c.4009G>T (p.Glu1337Ter)	Likely pathogenic
1698751	NM_001393769.1(MED12L):c.2221C>T (p.Gln741Ter)	Likely pathogenic
1705475	NM_001393769.1(MED12L):c.2746_2747dup (p.Cys917fs)	Likely pathogenic
1804112	NM_001393769.1(MED12L):c.5329_5330delinsTG (p.Pro1777Ter)	Likely pathogenic
2441646	NM_001393769.1(MED12L):c.3664+2T>G	Likely pathogenic
2584459	NM_001393769.1(MED12L):c.6287_6288del (p.Arg2096fs)	Likely pathogenic
2626925	NM_001393769.1(MED12L):c.3664+1G>A	Likely pathogenic
2663853	NM_001393769.1(MED12L):c.348G>A (p.Trp116Ter)	Likely pathogenic
2687885	NM_001393769.1(MED12L):c.565C>T (p.Gln189Ter)	Likely pathogenic
3054015	NM_022788.5(P2RY12):c.561T>A (p.His187Gln)	Likely pathogenic
3337280	NM_001393769.1(MED12L):c.4927-1G>T	Likely pathogenic
3338560	NM_001393769.1(MED12L):c.1946del (p.Lys649fs)	Likely pathogenic
3340877	NM_001393769.1(MED12L):c.6298-2A>C	Likely pathogenic
3361598	NM_001393769.1(MED12L):c.4354_4355insG (p.Leu1452fs)	Likely pathogenic
3896327	NM_001393769.1(MED12L):c.205-2A>T	Likely pathogenic
3897937	NM_001393769.1(MED12L):c.4590+1G>A	Likely pathogenic
4056608	NM_001393769.1(MED12L):c.3493C>T (p.Arg1165Ter)	Likely pathogenic
446247	NM_001393769.1(MED12L):c.6097C>T (p.Gln2033Ter)	Likely pathogenic
4526892	NM_001393769.1(MED12L):c.5782C>T (p.Arg1928Ter)	Likely pathogenic

SpliceAI

9714 predictions. Top by Δscore:

Variant	Effect	Δscore
3:151087022:GGAG:G	donor_gain	1.0000
3:151087023:GAGG:G	donor_gain	1.0000
3:151087023:GAGGT:G	donor_loss	1.0000
3:151087026:G:GA	donor_loss	1.0000
3:151087027:T:G	donor_loss	1.0000
3:151116429:T:G	donor_gain	1.0000
3:151116438:CAAAG:C	donor_loss	1.0000
3:151116439:AAAG:A	donor_loss	1.0000
3:151116440:AAGGT:A	donor_loss	1.0000
3:151116441:AGG:A	donor_loss	1.0000
3:151116442:GG:G	donor_loss	1.0000
3:151116444:T:A	donor_loss	1.0000
3:151122777:CCACA:C	acceptor_loss	1.0000
3:151122779:ACAG:A	acceptor_loss	1.0000
3:151122780:C:G	acceptor_gain	1.0000
3:151122780:CAG:C	acceptor_loss	1.0000
3:151122781:A:AG	acceptor_gain	1.0000
3:151122781:A:AT	acceptor_loss	1.0000
3:151122781:AGATT:A	acceptor_gain	1.0000
3:151122782:G:GA	acceptor_gain	1.0000
3:151122782:GA:G	acceptor_gain	1.0000
3:151122782:GATT:G	acceptor_gain	1.0000
3:151122782:GATTG:G	acceptor_gain	1.0000
3:151122865:T:G	donor_gain	1.0000
3:151122877:A:G	donor_gain	1.0000
3:151122943:G:GT	donor_gain	1.0000
3:151127981:TTGGG:T	donor_loss	1.0000
3:151127983:GG:G	donor_gain	1.0000
3:151127983:GGGTA:G	donor_loss	1.0000
3:151127984:GG:G	donor_gain	1.0000

AlphaMissense

14332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:151116345:T:C	L36P	1.000
3:151122924:T:A	W116R	1.000
3:151122924:T:C	W116R	1.000
3:151127828:C:T	P134S	1.000
3:151127829:C:A	P134H	1.000
3:151127829:C:G	P134R	1.000
3:151127900:T:A	W158R	1.000
3:151127900:T:C	W158R	1.000
3:151127904:T:C	L159P	1.000
3:151127924:T:G	Y166D	1.000
3:151156163:T:A	W187R	1.000
3:151156163:T:C	W187R	1.000
3:151163926:T:A	W381R	1.000
3:151163926:T:C	W381R	1.000
3:151165486:T:A	W442R	1.000
3:151165486:T:C	W442R	1.000
3:151165488:G:C	W442C	1.000
3:151165488:G:T	W442C	1.000
3:151185372:T:A	W513R	1.000
3:151185372:T:C	W513R	1.000
3:151185374:G:C	W513C	1.000
3:151185374:G:T	W513C	1.000
3:151185427:T:C	L531P	1.000
3:151185430:T:C	L532P	1.000
3:151190759:T:C	L599P	1.000
3:151190798:T:C	F612S	1.000
3:151190825:T:C	L621P	1.000
3:151190828:T:A	I622K	1.000
3:151190834:G:C	R624P	1.000
3:151350089:C:A	R726S	1.000

dbSNP variants (sampled 300 via entrez): RS1000012027 (3:151098619 C>G), RS1000024182 (3:151329251 A>G), RS1000041894 (3:151170633 G>C), RS1000049511 (3:151276390 A>G), RS1000055540 (3:151179900 A>G,T), RS1000063047 (3:151403110 T>C), RS1000063757 (3:151237579 G>A), RS1000069760 (3:151359348 CTT>C), RS1000084983 (3:151107565 T>A), RS1000085399 (3:151323347 C>G,T), RS1000091648 (3:151270171 T>C), RS1000093594 (3:151171065 G>A), RS1000095363 (3:151184231 T>C), RS1000097247 (3:151353863 C>A,T), RS1000101041 (3:151422121 C>T)

Disease associations

OMIM: gene MIM:611318 | disease phenotypes: MIM:618872, MIM:609821

GenCC curated gene-disease

Disease	Classification	Inheritance
Nizon-Isidor syndrome	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant
autosomal dominant non-syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Nizon-Isidor syndrome	Definitive	AD

Mondo (6): Nizon-Isidor syndrome (MONDO:0030030), platelet-type bleeding disorder 8 (MONDO:0012354), intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092), thrombocytopenia (MONDO:0002049), autosomal dominant non-syndromic intellectual disability (MONDO:0015802)

Orphanet (2): Bleeding disorder due to P2Y12 defect (Orphanet:36355), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

45 total (30 of 45 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000160	Narrow mouth
HP:0000194	Open mouth
HP:0000219	Thin upper lip vermilion
HP:0000232	Everted lower lip vermilion
HP:0000307	Pointed chin
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000325	Triangular face
HP:0000348	High forehead
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000540	Hypermetropia
HP:0000545	Myopia
HP:0000612	Iris coloboma
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001212	Prominent fingertip pads
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001270	Motor delay
HP:0001274	Agenesis of corpus callosum
HP:0001290	Generalized hypotonia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002579_6	Heschl’s gyrus morphology	5.000000e-06
GCST007576_190	Chronotype	6.000000e-09
GCST008154_35	Trunk fat mass	8.000000e-06
GCST009325_94	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	1.000000e-10
GCST010991_35	Parkinson’s disease	2.000000e-07
GCST90002381_192	Eosinophil count	1.000000e-09
GCST90002388_473	Lymphocyte count	3.000000e-22
GCST90002407_414	White blood cell count	2.000000e-15
GCST90006899_1	Epstein-Barr virus EBNA-1 antibody levels	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004842	eosinophil count
EFO:0004587	lymphocyte count

MeSH disease descriptors (4)

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
D013921	Thrombocytopenia	C15.378.140.855; C15.378.243.937
C565220	Bleeding Disorder Due To P2RY12 Defect (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

25 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2046934	MED12L, P2RY12	3	1.75	2	clopidogrel
rs5853517	MED12L, P2RY12		0.00	0
rs6785930	MED12L, P2RY12	4	-2.25	1	clopidogrel
rs6787801	MED12L, P2RY12	3	2.50	2	cangrelor;clopidogrel
rs6798347	MED12L		0.00	0
rs6801273	MED12L, P2RY12		0.00	0
rs6809699	MED12L, P2RY12	3	2.25	1	clopidogrel
rs9859552	MED12L, P2RY12	3	0.50	1	cangrelor
rs10935838	MED12L, P2RY12		0.00	0
rs16846673	MED12L, P2RY12		0.00	0
rs1907637	MED12L		0.00	0
rs16863356	MED12L		0.00	0
rs6798637	MED12L		0.00	0
rs10935842	MED12L, P2RY12		0.00	0
rs4603933	MED12L, P2RY12		0.00	0
rs1491974	MED12L, P2RY12		0.00	0
rs9859538	MED12L, P2RY12		0.00	0
rs7634096	MED12L, P2RY12		0.00	0
rs12487835	MED12L, P2RY12		0.00	0
rs16863336	MED12L, P2RY12		0.00	0
rs12497330	MED12L, P2RY12		0.00	0
rs12637988	MED12L, P2RY12		0.00	0
rs16863323	MED12L, P2RY12		0.00	0
rs7428575	MED12L, P2RY12		0.00	0
rs3732759	MED12L, P2RY12	3	2.00	1	clopidogrel

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects methylation	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Estradiol	affects binding, increases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects cotreatment, decreases expression, increases abundance	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
perfluoro-n-nonanoic acid	increases expression	1
perfluorohexanesulfonic acid	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Phthalic Acids	decreases methylation	1
Urethane	increases expression	1
Vanadates	decreases expression	1
Aflatoxin B1	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

390 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