DMAP1

Summary

DMAP1 (DNA methyltransferase 1 associated protein 1, HGNC:18291) is a protein-coding gene on chromosome 1p34.1, encoding DNA methyltransferase 1-associated protein 1 (Q9NPF5). Involved in transcription repression and activation. It is a common-essential gene (DepMap: required in 99.4% of cancer cell lines).

This gene encodes a subunit of several, distinct complexes involved in the repression or activation of transcription. The encoded protein can independently repress transcription and is targeted to replication foci throughout S phase by interacting directly with the N-terminus of DNA methyltransferase 1. During late S phase, histone deacetylase 2 is added to this complex, providing a means to deacetylate histones in transcriptionally inactive heterochromatin following replication. The encoded protein is also a component of the nucleosome acetyltransferase of H4 complex and interacts with the transcriptional corepressor tumor susceptibility gene 101 and the pro-apoptotic death-associated protein 6, among others. Alternatively spliced transcript variants encoding the same protein have been described.

Source: NCBI Gene 55929 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 75 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 99.4% of screened cell lines (common-essential)
• MANE Select transcript: NM_019100

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18291
Approved symbol	DMAP1
Name	DNA methyltransferase 1 associated protein 1
Location	1p34.1
Locus type	gene with protein product
Status	Approved
Aliases	DNMAP1, FLJ11543, KIAA1425, DNMTAP1, EAF2, MEAF2, SWC4
Ensembl gene	ENSG00000178028
Ensembl biotype	protein_coding
OMIM	605077
Entrez	55929

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 7 protein_coding_CDS_not_defined

ENST00000315913, ENST00000361745, ENST00000372289, ENST00000372290, ENST00000436069, ENST00000437511, ENST00000440641, ENST00000446292, ENST00000463950, ENST00000471829, ENST00000475794, ENST00000483741, ENST00000487922, ENST00000488433, ENST00000494092, ENST00000891874, ENST00000891875, ENST00000891876, ENST00000924540, ENST00000942392, ENST00000942393

RefSeq mRNA: 3 — MANE Select: NM_019100 NM_001034023, NM_001034024, NM_019100

CCDS: CCDS509

Canonical transcript exons

ENST00000372289 — 10 exons

Exon	Start	End
ENSE00001235437	44218311	44218469
ENSE00001457447	44213471	44213858
ENSE00003539633	44220017	44220309
ENSE00003583235	44214350	44214441
ENSE00003604123	44219806	44219878
ENSE00003680157	44218588	44218755
ENSE00003683913	44214703	44214898
ENSE00003692513	44219406	44219477
ENSE00003790675	44219056	44219241
ENSE00003849289	44220559	44220673

Expression profiles

Bgee: expression breadth ubiquitous, 224 present calls, max score 95.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.1410 / max 54.2742, expressed in 1780 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2596	7.1959	1752
2597	2.0402	1284
2598	0.9048	479

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland cortex	UBERON:0035827	95.71	gold quality
right adrenal gland	UBERON:0001233	95.64	gold quality
left adrenal gland cortex	UBERON:0035825	95.13	gold quality
left adrenal gland	UBERON:0001234	95.08	gold quality
right uterine tube	UBERON:0001302	94.27	gold quality
adrenal gland	UBERON:0002369	94.18	gold quality
granulocyte	CL:0000094	94.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.98	gold quality
cerebellar hemisphere	UBERON:0002245	93.79	gold quality
adrenal cortex	UBERON:0001235	93.68	gold quality
cerebellar cortex	UBERON:0002129	93.64	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.40	gold quality
right frontal lobe	UBERON:0002810	93.38	gold quality
adenohypophysis	UBERON:0002196	93.35	gold quality
right lobe of thyroid gland	UBERON:0001119	93.28	gold quality
mucosa of transverse colon	UBERON:0004991	93.26	gold quality
body of pancreas	UBERON:0001150	93.19	gold quality
adrenal tissue	UBERON:0018303	93.12	gold quality
left ovary	UBERON:0002119	92.97	gold quality
right ovary	UBERON:0002118	92.96	gold quality
anterior cingulate cortex	UBERON:0009835	92.78	gold quality
embryo	UBERON:0000922	92.63	gold quality
ganglionic eminence	UBERON:0004023	92.63	gold quality
left lobe of thyroid gland	UBERON:0001120	92.59	gold quality
endocervix	UBERON:0000458	92.55	gold quality
prefrontal cortex	UBERON:0000451	92.37	gold quality
cerebellum	UBERON:0002037	92.29	gold quality
sural nerve	UBERON:0015488	92.24	gold quality
apex of heart	UBERON:0002098	92.21	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.52

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
ATM	Unknown
BAX	Unknown
CDH1
CDKN1A	Unknown
DNMT1	Unknown

Upstream regulators (CollecTRI, top): BRD4, JMJD6

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.4% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• RGS6 inhibited the transcriptional repressor activity of DMAP1. (PMID:14734556)
• Knocking down DMAP1 caused hypomethylation of the DNA repair products. (PMID:20864525)
• MMTR is an intrinsic negative cell cycle regulator that modulates the CAK kinase activity via interaction with MAT1. (PMID:20920467)
• positive staining for DNMT1 in clinical cancer specimens was significantly linked to lower rates of response to treatments and shorter survival of patients with pharyngeal cancer. (PMID:21284050)
• These results suggest that DMAP1 is a critical regulator of ATM activity and function (PMID:23318425)
• Targeted knockdown of human DNA methyltransferase 1 expression restores the expression levels of tumor suppressor genes, thus inhibiting the proliferation of cholangiocarcinoma cell line cells. (PMID:24361215)
• A novel tumour suppressor gene, MDGA2, which is frequently inactivated by promoter methylation in Gastric cancer, exerts a tumour suppressive function by cooperating with DMAP1 to activate the p53/p21 signalling cascade. (PMID:26206665)
• Findings reveal a regulatory role of Bub3 in DMAP1-mediated DNA methylation upon mitotic stress. (PMID:30553276)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	dmap1	ENSDARG00000042087
mus_musculus	Dmap1	ENSMUSG00000009640
rattus_norvegicus	Dmap1	ENSRNOG00000019407
drosophila_melanogaster	DMAP1	FBGN0034537
caenorhabditis_elegans	ekl-4	WBGENE00013676

Protein

Protein identifiers

DNA methyltransferase 1-associated protein 1 — Q9NPF5 (reviewed: Q9NPF5)

All UniProt accessions (6): Q9NPF5, Q5TG36, Q5TG37, Q5TG38, Q5TG39, Q5TG40

UniProt curated annotations — full annotation on UniProt →

Function. Involved in transcription repression and activation. Its interaction with HDAC2 may provide a mechanism for histone deacetylation in heterochromatin following replication of DNA at late firing origins. Can also repress transcription independently of histone deacetylase activity. May specifically potentiate DAXX-mediated repression of glucocorticoid receptor-dependent transcription. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Participates in the nuclear localization of URI1 and increases its transcriptional corepressor activity.

Subunit / interactions. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. DMAP1 also forms a complex with DNMT1 and HDAC2. Throughout S phase it interacts directly with the N-terminus of DNMT1, which serves to recruit DMAP1 to replication foci. DMAP1 interacts with ING1, a component of the mSin3A transcription repressor complex, although this interaction is not required for recruitment of ING1 to heterochromatin. Interacts directly with the transcriptional corepressor TSG101. Interacts with the pro-apoptotic protein DAXX. Interacts with URI1.

Subcellular location. Nucleus. Cytoplasm.

RefSeq proteins (3): NP_001029195, NP_001029196, NP_061973* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008468	DMAP1	Domain
IPR027109	Swc4/Dmap1	Family
IPR032563	DAMP1_SANT-like	Domain

Pfam: PF05499, PF16282

UniProt features (36 total): helix 9, strand 7, sequence conflict 4, compositionally biased region 4, region of interest 3, modified residue 2, cross-link 2, turn 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

13 structures.

PDB	Method	Resolution (Å)
4IEJ	X-RAY DIFFRACTION	1.45
3HM5	X-RAY DIFFRACTION	1.8
8QR1	ELECTRON MICROSCOPY	2.4
9C57	ELECTRON MICROSCOPY	2.75
9CAE	ELECTRON MICROSCOPY	3.07
8X15	ELECTRON MICROSCOPY	3.2
8X19	ELECTRON MICROSCOPY	3.2
8X1C	ELECTRON MICROSCOPY	3.2
8XVT	ELECTRON MICROSCOPY	3.2
9C6N	ELECTRON MICROSCOPY	3.29
9CAC	ELECTRON MICROSCOPY	3.43
9C62	ELECTRON MICROSCOPY	5.28
8XVG	ELECTRON MICROSCOPY	9.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPF5-F1	75.46	0.40

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 (4): 445, 448, 27, 214

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones

MSigDB gene sets: 391 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_NEGATIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_RESPONSE_TO_ETHANOL, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, FISCHER_G1_S_CELL_CYCLE, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, MODULE_511, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION_TO_ORGANELLE

GO Biological Process (13): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA repair (GO:0006281), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), positive regulation of protein import into nucleus (GO:0042307), regulation of apoptotic process (GO:0042981), response to ethanol (GO:0045471), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of cell cycle (GO:0051726), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), chromatin organization (GO:0006325)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (9): nucleosome (GO:0000786), Swr1 complex (GO:0000812), nucleus (GO:0005634), nucleoplasm (GO:0005654), replication fork (GO:0005657), cytoplasm (GO:0005737), cytosol (GO:0005829), NuA4 histone acetyltransferase complex (GO:0035267), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Chromatin modifying enzymes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
DNA-templated transcription	3
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
DNA metabolic process	1
DNA damage response	1
chromatin organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
apoptotic process	1
regulation of programmed cell death	1
response to alcohol	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
cell cycle	1
regulation of cellular process	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
regulation of DNA repair	1
double-strand break repair	1
cellular component organization	1
transcription coregulator activity	1
DNA-binding transcription factor binding	1
binding	1
chromatin	1
protein-DNA complex	1
histone deacetylase complex	1
nuclear chromosome	1
INO80-type complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

2258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DMAP1	DNMT1	P26358	996
DMAP1	YEATS4	O95619	994
DMAP1	RUVBL1	P82276	988
DMAP1	DIP2B	Q9P265	984
DMAP1	RUVBL2	Q9Y230	980
DMAP1	BRD8	Q9H0E9	970
DMAP1	TRRAP	Q9Y4A5	961
DMAP1	VPS72	Q15906	950
DMAP1	EP400	Q96L91	935
DMAP1	ACTL6A	O96019	931
DMAP1	MRGBP	Q9NV56	910
DMAP1	HDAC2	Q92769	909
DMAP1	EPC2	Q52LR7	898
DMAP1	MEAF6	Q9HAF1	893
DMAP1	KAT5	Q92993	890

IntAct

258 interactions, top by confidence:

A	B	Type	Score
ACTR6	ZNHIT1	psi-mi:“MI:0914”(association)	0.820
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
MRGBP	KAT5	psi-mi:“MI:0914”(association)	0.790
MRGBP	KAT5	psi-mi:“MI:0915”(physical association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730
MBTD1	MORF4L2	psi-mi:“MI:0914”(association)	0.730
PPP2R2D	YEATS4	psi-mi:“MI:0914”(association)	0.730
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
DMAP1	MORF4L1	psi-mi:“MI:0915”(physical association)	0.670
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
P4HA3	FAM171A2	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
MORF4L2	YEATS4	psi-mi:“MI:0914”(association)	0.640
FOXR1	YEATS4	psi-mi:“MI:0914”(association)	0.640
EPC2	YEATS4	psi-mi:“MI:0914”(association)	0.640
PPP2R2D	ENSA	psi-mi:“MI:0914”(association)	0.570
PPP2R2D	ENSA	psi-mi:“MI:2364”(proximity)	0.570
LRSAM1	DMAP1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (361): DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Affinity Capture-MS), DMAP1 (Two-hybrid), BRD3 (Co-fractionation), DMAP1 (Co-fractionation)

ESM2 similar proteins: A0M8U1, A6H6W9, A6QL63, F1LSG8, O14639, P42229, P42230, P42232, P51692, P52632, P97875, Q12800, Q13330, Q1RLU8, Q2PG42, Q4V860, Q5RAN1, Q5RBB8, Q5ZKV9, Q62599, Q6AYJ2, Q6GQW0, Q6NRB5, Q6NZH6, Q6ZUT9, Q78E65, Q7T2U9, Q7Z6J6, Q8BR65, Q8CI71, Q8K4B0, Q8K4G5, Q8K4Q0, Q8N122, Q8R3S6, Q8WYK2, Q95115, Q9D2N4, Q9ERA0, Q9H7L9

Diamond homologs: O14308, P0CO96, P0CO97, P53201, Q4WNY4, Q5AAJ7, Q5B4T5, Q752S6, Q9JI44, Q9NPF5, Q4PG15, Q7K3D8, Q870Q1, Q8VZL6, Q4HY90, Q6C9M6, Q6FTV1, Q6CSS3

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MDGA2	“up-regulates quantity by stabilization”	DMAP1	binding
DMAP1	“form complex”	“NuA4 complex”	binding
SRC	“down-regulates activity”	DMAP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 139 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
HATs acetylate histones	20	19.1×	6e-18
DNA Damage Recognition in GG-NER	5	17.2×	8e-04
Chromatin organization	14	13.8×	2e-10
Chromatin modifying enzymes	15	13.1×	9e-11
Formation of the beta-catenin:TCF transactivating complex	7	10.1×	6e-04
DNA Damage/Telomere Stress Induced Senescence	5	9.8×	7e-03
Deposition of new CENPA-containing nucleosomes at the centromere	5	9.6×	7e-03
B-WICH complex positively regulates rRNA expression	6	8.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	17	79.7×	7e-27
positive regulation of double-strand break repair via homologous recombination	18	55.6×	4e-25
regulation of DNA replication	7	20.7×	3e-06
regulation of embryonic development	6	16.0×	1e-04
regulation of apoptotic process	22	14.8×	2e-17
positive regulation of DNA repair	5	14.5×	1e-03
regulation of cell cycle	24	14.4×	7e-19
regulation of DNA repair	6	13.4×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	59
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1679375	NM_019100.5(DMAP1):c.1024del (p.Glu342fs)	Likely pathogenic

SpliceAI

2619 predictions. Top by Δscore:

Variant	Effect	Δscore
1:44213854:ACAAG:A	donor_loss	1.0000
1:44213855:CAAG:C	donor_loss	1.0000
1:44213856:AAG:A	donor_loss	1.0000
1:44214701:A:AC	acceptor_loss	1.0000
1:44214701:AG:A	acceptor_gain	1.0000
1:44214701:AGG:A	acceptor_gain	1.0000
1:44214702:G:GT	acceptor_loss	1.0000
1:44214702:GG:G	acceptor_gain	1.0000
1:44214702:GGG:G	acceptor_gain	1.0000
1:44214702:GGGAT:G	acceptor_gain	1.0000
1:44214897:AGG:A	donor_loss	1.0000
1:44214899:G:GG	donor_gain	1.0000
1:44214900:T:A	donor_loss	1.0000
1:44218573:T:A	acceptor_gain	1.0000
1:44218578:T:TA	acceptor_gain	1.0000
1:44218582:CCTCA:C	acceptor_loss	1.0000
1:44218583:CTCA:C	acceptor_loss	1.0000
1:44218584:TCAG:T	acceptor_loss	1.0000
1:44218585:CAG:C	acceptor_loss	1.0000
1:44218586:A:AG	acceptor_gain	1.0000
1:44218587:G:A	acceptor_loss	1.0000
1:44218587:G:GT	acceptor_gain	1.0000
1:44218587:GA:G	acceptor_gain	1.0000
1:44218587:GAA:G	acceptor_gain	1.0000
1:44218587:GAAGC:G	acceptor_gain	1.0000
1:44218751:AGCAG:A	donor_gain	1.0000
1:44218752:GCAG:G	donor_gain	1.0000
1:44218752:GCAGG:G	donor_gain	1.0000
1:44218753:CAG:C	donor_gain	1.0000
1:44218754:AG:A	donor_gain	1.0000

AlphaMissense

3024 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:44214390:G:C	R49T	1.000
1:44214391:G:C	R49S	1.000
1:44214391:G:T	R49S	1.000
1:44214402:T:C	M53T	1.000
1:44214407:C:G	R55G	1.000
1:44214410:G:A	E56K	1.000
1:44214411:A:G	E56G	1.000
1:44214411:A:T	E56V	1.000
1:44214412:A:C	E56D	1.000
1:44214412:A:T	E56D	1.000
1:44214419:G:C	A59P	1.000
1:44214423:T:C	L60S	1.000
1:44214423:T:G	L60W	1.000
1:44214426:T:C	L61P	1.000
1:44214788:T:A	W95R	1.000
1:44214788:T:C	W95R	1.000
1:44214790:G:C	W95C	1.000
1:44214790:G:T	W95C	1.000
1:44214803:T:C	F100L	1.000
1:44214804:T:C	F100S	1.000
1:44214805:C:A	F100L	1.000
1:44214805:C:G	F100L	1.000
1:44214818:C:A	R105S	1.000
1:44214842:C:G	H113D	1.000
1:44214845:T:A	W114R	1.000
1:44214845:T:C	W114R	1.000
1:44214846:G:C	W114S	1.000
1:44214847:G:C	W114C	1.000
1:44214847:G:T	W114C	1.000
1:44214881:T:C	F126L	1.000

dbSNP variants (sampled 300 via entrez): RS1000046346 (1:44220156 A>G), RS1000541562 (1:44221045 G>A), RS1002855111 (1:44216258 C>G), RS1003506469 (1:44216244 CTTT>C), RS1004209386 (1:44214100 T>C), RS1005049828 (1:44213338 A>G), RS1005711145 (1:44216270 G>A), RS1006159472 (1:44215267 C>A,T), RS1006209467 (1:44217036 C>T), RS1006243096 (1:44216519 C>T), RS1006995582 (1:44215816 C>G,T), RS1007026574 (1:44216176 C>T), RS1007996788 (1:44217458 G>A), RS1008027822 (1:44217818 T>A), RS1008476778 (1:44211610 A>T)

Disease associations

OMIM: gene MIM:605077 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive

Mondo (2): intellectual disability (MONDO:0001071), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_1139	Metabolite levels	3.000000e-06
GCST009391_1415	Metabolite levels	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010458	alpha-hydroxybutyric acid measurement
EFO:0010451	aconitate measurement

MeSH disease descriptors (2)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724908 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	increases expression	1
jinfukang	increases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Dexamethasone	affects cotreatment, increases expression	1
Dimethyl Sulfoxide	affects expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697415	Binding	Inhibition of DMAP1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

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