SETD1A

Summary

SETD1A (SET domain containing 1A, histone lysine methyltransferase, HGNC:29010) is a protein-coding gene on chromosome 16p11.2, encoding Histone-lysine N-methyltransferase SETD1A (O15047). Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism. It is a common-essential gene (DepMap: required in 94.7% of cancer cell lines) and haploinsufficient (ClinGen: sufficient evidence).

The protein encoded by this gene is a component of a histone methyltransferase (HMT) complex that produces mono-, di-, and trimethylated histone H3 at Lys4. Trimethylation of histone H3 at lysine 4 (H3K4me3) is a chromatin modification known to generally mark the transcription start sites of active genes. The protein contains SET domains, a RNA recognition motif domain and is a member of the class V-like SAM-binding methyltransferase superfamily.

Source: NCBI Gene 9739 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with speech impairment and dysmorphic facies (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 10
• Clinical variants (ClinVar): 810 total — 33 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 43
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 94.7% of screened cell lines (common-essential)
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014712

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29010
Approved symbol	SETD1A
Name	SET domain containing 1A, histone lysine methyltransferase
Location	16p11.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0339, Set1, KMT2F, SET1A
Ensembl gene	ENSG00000099381
Ensembl biotype	protein_coding
OMIM	611052
Entrez	9739

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000262519, ENST00000452917, ENST00000640410, ENST00000682768, ENST00000684162, ENST00000710314

RefSeq mRNA: 1 — MANE Select: NM_014712 NM_014712

CCDS: CCDS32435

Canonical transcript exons

ENST00000262519 — 19 exons

Exon	Start	End
ENSE00000648519	30967501	30967588
ENSE00000648520	30966884	30967060
ENSE00000869456	30969305	30969462
ENSE00000869458	30971378	30971719
ENSE00000869478	30981061	30981180
ENSE00000994328	30969602	30969689
ENSE00001238418	30980739	30980849
ENSE00001238475	30965601	30966386
ENSE00001238486	30964612	30965461
ENSE00001238494	30964094	30964323
ENSE00001345614	30983635	30983772
ENSE00001345859	30983850	30984664
ENSE00001505117	30980485	30980657
ENSE00001505118	30979145	30980194
ENSE00001671296	30961267	30961537
ENSE00001764972	30963433	30963554
ENSE00002198157	30959091	30959186
ENSE00003916250	30958717	30958881
ENSE00004011398	30957754	30957964

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 89.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9497 / max 137.5056, expressed in 1771 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153749	6.8083	1718
153747	1.1054	683
153750	0.9154	599
153748	0.7253	400
153746	0.3954	210

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	89.87	silver quality
sural nerve	UBERON:0015488	89.47	gold quality
parotid gland	UBERON:0001831	89.18	silver quality
middle frontal gyrus	UBERON:0002702	87.86	silver quality
Brodmann (1909) area 10	UBERON:0013541	86.72	silver quality
right testis	UBERON:0004534	85.71	gold quality
left testis	UBERON:0004533	85.59	gold quality
endometrium epithelium	UBERON:0004811	85.56	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	85.08	gold quality
granulocyte	CL:0000094	85.06	gold quality
gastrocnemius	UBERON:0001388	84.89	gold quality
cerebellar vermis	UBERON:0004720	84.85	silver quality
testis	UBERON:0000473	84.52	gold quality
inferior olivary complex	UBERON:0002127	84.49	gold quality
right hemisphere of cerebellum	UBERON:0014890	84.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.11	gold quality
mucosa of stomach	UBERON:0001199	84.07	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.96	gold quality
muscle of leg	UBERON:0001383	83.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	83.59	gold quality
cerebellar hemisphere	UBERON:0002245	83.46	gold quality
cerebellar cortex	UBERON:0002129	83.43	gold quality
monocyte	CL:0000576	83.42	gold quality
heart right ventricle	UBERON:0002080	83.41	silver quality
mononuclear cell	CL:0000842	83.27	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.23	gold quality
leukocyte	CL:0000738	83.18	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.18	gold quality
lower esophagus	UBERON:0013473	83.15	gold quality
body of uterus	UBERON:0009853	83.09	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

Upstream regulators (CollecTRI, top): TCF3

miRNA regulators (miRDB)

33 targeting SETD1A, 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-6798-5P	100.00	65.77	699
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-LET-7C-3P	99.95	73.42	2862
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-6794-5P	99.76	66.38	1048
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-4716-3P	99.69	66.73	1022
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-4296	96.35	63.55	1233
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280
HSA-MIR-3943	95.87	64.57	523

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 94.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• HCF-1 was required for recruitment of the histone methyltransferases Set1 and MLL1, leading to histone H3K4 trimethylation and transcriptional activation. (PMID:17578910)
• suggest a model for how the mammalian RNA polymerase II machinery is linked with histone H3-Lys4 histone methyltransferase complexes at transcriptionally active genes (PMID:17998332)
• CGBP interacts with MLL1, MLL2 as well as Set1 H3-Lysine 4 (H3K4) specific methyl-transferases and plays critical roles in regulations of MLL target genes. (PMID:18082152)
• BORIS acts as a platform upon which BAT3 and SET1A assemble and exert effects upon chromatin structure and gene expression. (PMID:18765639)
• Data show that Wdr82, which associates with chromatin in a histone H2B ubiquitination-dependent manner, is a specific component of Set1 complexes but not that of MLL1-4 complexes. (PMID:18838538)
• A synergistic role of hSET1 and NURF in regulating the USF-bound barrier insulator to prevent erythroid genes from encroachment of heterochromatin. (PMID:21653943)
• These results demonstrate that the increase of H3K4me3 by human Set1 complex is involved in activation of lytic genes during the lytic infection of KSHV. (PMID:23306522)
• our findings reveal that the guided-recruitment of the hSET1A histone methyltransferase complex and its H3K4 methyltransferase activity by transcription regulator USF1 safeguards hematopoietic transcription programs (PMID:23754954)
• hSETD1A regulates Wnt target genes and controls tumor growth of colorectal cancer cells. (PMID:24247718)
• This study demonistrated that Loss-of-function variants of loss of function variants of SETD1A is a canadate susceptibility of Schizophrenia. (PMID:24853937)
• Co-immunoprecipitation demonstrated LANA association with endogenous hSET1 complexes in both lymphoid and endothelial cells suggesting that LANA may contribute to the epigenetic profile of KSHV episomes (PMID:25033463)
• Study reveals that SETD1A controls tumor metastasis by activating matrix metalloproteinases (MMP) expression and provides an epigenetic link among SETD1A, MMPs, and metastasis of breast cancer. (PMID:25373480)
• Based on our structural data and cross-linking results, we suggest that Dpy30 may regulate H3K4 methylation according to its copy number in COMPASS (PMID:25542209)
• these results form the basis for understanding how WRAD(DRY-30) differentially regulates SET1 family complexes in vivo. (PMID:25561738)
• results demonstrate a novel function of BAF as an epigenetic regulator of HSV lytic infection; hypothesize that BAF facilitates Herpes Simplex Virus IE and E gene expression by recruiting the SETD1A methyltransferase to viral IE and E gene promoters (PMID:26015494)
• suppresses BTG2 expression through its induction of several BTG2-targeting miRNAs (PMID:26394836)
• Set1/MLL complex is indispensable for the transcriptional ability of HSF2. (PMID:26478434)
• Set1 role in cellular reprogramming and its interactions with Dpy30,Myc,Sox2 and Ash2l reprogramming factors (PMID:26691508)
• Given the critical tumor suppressor role of p53, SETD1A-mediated suppression of this pathway (even in the absence of p53 mutations), would be predicted to have profound consequences on tumorigenesis. (PMID:26865005)
• This study demonstrated that SETD1A mutation showing the highest statistical significance in Autism and Schizophrenia. (PMID:26938441)
• Loss-of-function variants in SETD1A cause a range of neurodevelopmental disorders in a Finnish population. (PMID:26974950)
• data indicate that Setd1a and NURF complexes are specifically targeted to and coordinately regulate erythroid promoter chromatin dynamics during erythroid lineage differentiation (PMID:27141965)
• Study showed that repressed HBV cccDNA chromatin state is activated by Set1A which mediates its activation by methylating H3K4. Also, Set1A was showed to be recruited to viral promoters in an HBx dependent manner. (PMID:27174370)
• Targeted Disruption of the Interaction between WD-40 Repeat Protein 5 (WDR5) and Mixed Lineage Leukemia (MLL)/SET1 Family Proteins Specifically Inhibits MLL1 and SETd1A Methyltransferase Complexes. (PMID:27563068)
• the expression of hSETD1A occurs at a high rate in hepatocellular carcinoma patients. The expression state of hSETD1A may be a prognostic factor in hepatocellular carcinoma. (PMID:27656834)
• Study provides evidence that increased Set1 binding at the promoter induces aberrant epigenetic alterations and up-regulates CREMA in systemic lupus erythematosus. (PMID:27904655)
• Collectively called the WRAD complex, these proteins are pivotal to the HMT activity of the SET1 complexes. Recent reports highlight the novel non-canonical functions of WRAD in cellular processes other than its well-studied role in histone methylation and gene expression. (PMID:28229975)
• Rare loss-of-function variants in SETD1A are associated with Schizophrenia and Developmental disorders. SETD1A is the only gene implicated to date by whole-exome sequencing studies. (PMID:28969442)
• SETD1A and cyclin K complexes may represent a therapeutic opportunity for acute myeloid leukemia and, potentially, for other cancers. (PMID:29474905)
• The ability of SETD1A to prevent degradation of these structures is mediated by its ability to catalyze methylation on Lys4 of histone H3 (H3K4) at replication forks, which enhances FANCD2-dependent histone chaperone activity. (PMID:29937342)
• SETD1A contributes to retinoic acid -induced thrombomodulin expression in vascular endothelial cells by modulating the activity and expression of KLF4. (PMID:29940355)
• Study report that Uhrf1 forms a complex with the active trithorax group, the Setd1a/COMPASS complex, to maintain bivalent histone marks, particularly those associated with neuroectoderm and mesoderm specification. (PMID:29968706)
• SET1A-mediated mono-methylation at K342 is an essential regulatory mechanism for regulating YAP activity and tumorigenesis. (PMID:30008322)
• SETD1A may serve as a molecular target and prognostic indicator in ERalpha-positive breast cancer. (PMID:30191958)
• H3K4me3 levels positively correlate with WHO grade malignancy in pediatric EPNs and are associated with progression free survival in patients with posterior fossa group A EPNs (PF-EPN-A). Reduction of H3K4me3 by silencing its methyltransferase SETD1A, in primary cultured EPN cells increased cell response to chemotherapy (PMID:31005631)
• SETD1A, but not RBBP5 or ASH2L, was found to interact with the DNA damage repair protein RAD18. (PMID:31076518)
• SETD1A is essential to maintain mitosis and proliferation and its suppression unleashes the tumor suppressive effects of senescence. (PMID:31253781)
• Results found that SETD1A is highly regulated in the poor outcome triple negative breast cancer (TNBC) cell line and may epigenetically regulate miR205 in TNBCs. (PMID:31552595)
• Histone methyltransferase SETD1A interacts with HIF1alpha to enhance glycolysis and promote cancer progression in gastric cancer. (PMID:32291851)
• Characterization of SETD1A haploinsufficiency in humans and Drosophila defines a novel neurodevelopmental syndrome. (PMID:32346159)

Cross-species orthologs

14 orthologs

Organism	Symbol	Gene ID
rattus_norvegicus	Setd1a	ENSRNOG00000055028
drosophila_melanogaster	Set2	FBGN0030486
drosophila_melanogaster	CG4565	FBGN0037841
drosophila_melanogaster	G9a	FBGN0040372
caenorhabditis_elegans	set-32	WBGENE00008062
caenorhabditis_elegans		WBGENE00008206
caenorhabditis_elegans		WBGENE00008527
caenorhabditis_elegans	met-1	WBGENE00016603
caenorhabditis_elegans		WBGENE00018023
caenorhabditis_elegans		WBGENE00019584
caenorhabditis_elegans		WBGENE00019690
caenorhabditis_elegans		WBGENE00020006
caenorhabditis_elegans		WBGENE00020919
caenorhabditis_elegans		WBGENE00021282

Paralogs (19): KMT2C (ENSG00000055609), SUV39H1 (ENSG00000101945), EZH2 (ENSG00000106462), EZH1 (ENSG00000108799), NSD2 (ENSG00000109685), ASH1L (ENSG00000116539), KMT2A (ENSG00000118058), SETDB2 (ENSG00000136169), SETD1B (ENSG00000139718), SETDB1 (ENSG00000143379), NSD3 (ENSG00000147548), SETBP1 (ENSG00000152217), SUV39H2 (ENSG00000152455), NSD1 (ENSG00000165671), KMT2D (ENSG00000167548), EHMT1 (ENSG00000181090), SETD2 (ENSG00000181555), EHMT2 (ENSG00000204371), KMT2B (ENSG00000272333)

Protein

Protein identifiers

Histone-lysine N-methyltransferase SETD1A — O15047 (reviewed: O15047)

Alternative names: Lysine N-methyltransferase 2F, SET domain-containing protein 1A, Set1/Ash2 histone methyltransferase complex subunit SET1

All UniProt accessions (3): O15047, A0AAA9YGD9, C9J2Z9

UniProt curated annotations — full annotation on UniProt →

Function. Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of ‘Lys-4’ of histone H3 (H3K4) via a non-processive mechanism. Part of chromatin remodeling machinery, forms H3K4me1, H3K4me2 and H3K4me3 methylation marks at active chromatin sites where transcription and DNA repair take place. Responsible for H3K4me3 enriched promoters and transcriptional programming of inner mass stem cells and neuron progenitors during embryogenesis. Required for H3K4me1 mark at stalled replication forks. Mediates FANCD2-dependent nucleosome remodeling and RAD51 nucleofilaments stabilization at reversed forks, protecting them from nucleolytic degradation. Does not methylate ‘Lys-4’ of histone H3 if the neighboring ‘Lys-9’ residue is already methylated. Binds RNAs involved in RNA processing and the DNA damage response.

Subunit / interactions. Component of the SET1A/COMPASS complex composed of the catalytic subunit SETD1A, WDR5, WDR82, RBBP5, ASH2L/ASH2, CXXC1/CFP1, HCFC1 and DPY30 homotrimer. Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity. Interacts with BOD1L1 (via COMPASS-Shg1 domain) at replication forks. Interacts with HCFC1. Interacts with ASH2/ASH2L. Interacts with CXXC1/CFP1. Interacts with RBBP5. Interacts (via N-terminal region) with WDR82; the interaction is direct. Interacts (via the RRM domain) with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A) only in the presence of WDR82. Binds specifically to CTD heptad repeats phosphorylated on ‘Ser-5’ of each heptad. Interacts with ZNF335. Interacts with SUPT6H. Interacts with NAP1L1. Interacts (via WIN motif) with WDR5.

Subcellular location. Nucleus speckle. Chromosome. Cytoplasm.

Disease relevance. Epilepsy, early-onset, 2, with or without developmental delay (EPEO2) [MIM:618832] An autosomal dominant neurologic disorder characterized by early onset of generalized tonic-clonic seizures associated with sharp wave and sharp slow wave discharges on EEG. Some EPEO2 patients have normal psychomotor development and normal brain imaging, whereas others may show developmental delay associated with abnormalities on brain imaging. The disease is caused by variants affecting the gene represented in this entry. Neurodevelopmental disorder with speech impairment and dysmorphic facies (NEDSID) [MIM:619056] An autosomal dominant disorder characterized by global developmental delay, intellectual disability, speech delay, subtle facial dysmorphism, and behavioral and psychiatric problems. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The RRM domain confers RNA binding activity.

Similarity. Belongs to the class V-like SAM-binding methyltransferase superfamily.

RefSeq proteins (1): NP_055527* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR001214	SET_dom	Domain
IPR003616	Post-SET_dom	Domain
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR024657	COMPASS_Set1_N-SET	Domain
IPR034467	Set1A_RRM	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR037841	SET_SETD1A/B	Domain
IPR044570	Set1-like	Family
IPR046341	SET_dom_sf	Homologous_superfamily

Pfam: PF00076, PF00856, PF11764

Enzyme classification (BRENDA):

• EC 2.1.1.354 — [histone H3]-lysine4 N-trimethyltransferase (BRENDA: 18 organisms, 22 substrates, 3 inhibitors, 20 Km, 20 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ART(KME1)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.002	5
ART(KME2)QTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0003–0.004	5
ARTKQTARKSTGGKAPRKQLATKAA-GK-BIOTIN	0.0002–0.0017	5
S-ADENOSYL-L-METHIONINE	0.014–0.9	5

Catalyzed reactions (Rhea), 3 shown:

• L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60264)
• N(6)-methyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60268)
• N(6),N(6)-dimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl(4)-[histone H3] + S-adenosyl-L-homocysteine + H(+) (RHEA:60272)

UniProt features (74 total): compositionally biased region 22, region of interest 12, sequence variant 11, modified residue 6, strand 5, helix 4, domain 3, short sequence motif 3, turn 3, sequence conflict 2, chain 1, binding site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3S8S	X-RAY DIFFRACTION	1.3
4EWR	X-RAY DIFFRACTION	1.5
8ILY	X-RAY DIFFRACTION	1.7
3UVN	X-RAY DIFFRACTION	1.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15047-F1	49.20	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 1684

Post-translational modifications (6): 459, 464, 508, 565, 915, 1103

Mutagenesis-validated functional residues (1):

Position	Phenotype
1646	abolishes interaction with s-adenosyl-l-methionine.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 214 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GCM_GSPT1, TTTGTAG_MIR520D, GOBP_HEMATOPOIETIC_STEM_CELL_DIFFERENTIATION, chr16p11, GOBP_DNA_DAMAGE_RESPONSE, KEGG_LYSINE_DEGRADATION, GOBP_HEAD_DEVELOPMENT, GOBP_REGULATION_OF_HEMATOPOIETIC_PROGENITOR_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, AFFAR_YY1_TARGETS_DN, ACTTTAT_MIR1425P, GCM_NF2, GOBP_STEM_CELL_DIFFERENTIATION

GO Biological Process (7): DNA damage response (GO:0006974), brain development (GO:0007420), methylation (GO:0032259), regulation of hematopoietic stem cell differentiation (GO:1902036), regulation of chromatin organization (GO:1902275), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338)

GO Molecular Function (11): RNA binding (GO:0003723), beta-catenin binding (GO:0008013), histone H3K4 methyltransferase activity (GO:0042800), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), histone H3K4 monomethyltransferase activity (GO:0140945), nucleic acid binding (GO:0003676), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740), histone H3 methyltransferase activity (GO:0140938), histone H3K4 trimethyltransferase activity (GO:0140999)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), histone methyltransferase complex (GO:0035097), Set1C/COMPASS complex (GO:0048188), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Gene expression (Transcription)	2
Chromatin modifying enzymes	1
Transcriptional regulation by RUNX1	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
RNA Polymerase II Transcription	1
Chromatin organization	1
Generic Transcription Pathway	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
chromatin organization	2
histone H3K4 methyltransferase activity	2
binding	2
cellular response to stress	1
central nervous system development	1
animal organ development	1
head development	1
metabolic process	1
hematopoietic stem cell differentiation	1
regulation of hematopoietic progenitor cell differentiation	1
regulation of stem cell differentiation	1
regulation of cellular component organization	1
cellular component organization	1
nucleic acid binding	1
protein binding	1
protein-lysine N-methyltransferase activity	1
histone H3 methyltransferase activity	1
DNA-binding transcription factor binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
histone methyltransferase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
methyltransferase complex	1
nuclear protein-containing complex	1
histone methyltransferase complex	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3390 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SETD1A	RBBP5	Q15291	999
SETD1A	WDR82	Q6UXN9	999
SETD1A	ASH2L	Q9UBL3	998
SETD1A	WDR5	P61964	997
SETD1A	CXXC1	Q9P0U4	995
SETD1A	HCFC1	P51610	990
SETD1A	DPY30	Q9C005	983
SETD1A	KMT2C	Q8NEZ4	971
SETD1A	SETD1B	Q9UPS6	956
SETD1A	CTNNB1	P35222	946
SETD1A	KDM1A	O60341	933
SETD1A	H3-3A	P06351	892
SETD1A	H3C1	P02295	892
SETD1A	H3-4	Q16695	885
SETD1A	H3-7	Q5TEC6	885
SETD1A	H3-5	Q6NXT2	885
SETD1A	H3C14	Q71DI3	885

IntAct

133 interactions, top by confidence:

A	B	Type	Score
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
ASH2L	KMT2D	psi-mi:“MI:0914”(association)	0.890
WDR5	SETD1A	psi-mi:“MI:0914”(association)	0.880
SETD1A	WDR5	psi-mi:“MI:0914”(association)	0.880
RBBP5	KMT2D	psi-mi:“MI:0914”(association)	0.840
NUP50	KPNA4	psi-mi:“MI:0914”(association)	0.830
CXXC1	SETD1A	psi-mi:“MI:0914”(association)	0.760
ASH2L	SETD1A	psi-mi:“MI:0914”(association)	0.760
SETD1A	RBBP5	psi-mi:“MI:0915”(physical association)	0.740
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
Ctnnb1	SETD1A	psi-mi:“MI:0407”(direct interaction)	0.540
Ctnnb1	SETD1A	psi-mi:“MI:0915”(physical association)	0.540
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
RSBN1	SETD1A	psi-mi:“MI:0914”(association)	0.530
HCFC2	SETD1A	psi-mi:“MI:0914”(association)	0.530
WDR82	SETD1A	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L3	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (339): HIST1H3A (Biochemical Activity), SETD1A (Affinity Capture-Western), HIST1H3A (Biochemical Activity), RBBP5 (Reconstituted Complex), CXXC1 (Reconstituted Complex), ASH2L (Reconstituted Complex), WDR5 (Reconstituted Complex), DPY30 (Reconstituted Complex), CXXC1 (Affinity Capture-Western), ASH2L (Affinity Capture-Western), RBBP5 (Affinity Capture-Western), WDR5 (Affinity Capture-Western), WDR82 (Affinity Capture-Western), DPY30 (Affinity Capture-Western), SETD1A (Affinity Capture-Western)

ESM2 similar proteins: A2A6A1, B0BN49, B0QZF7, D2H526, E1BB50, E9PYH6, E9Q4F7, E9Q6J5, F1Q8W0, O15047, O88453, P30414, P30415, Q01538, Q14AX6, Q17QQ9, Q27450, Q3KPW4, Q3UMU9, Q4V8I5, Q505I5, Q5BKY9, Q5SW79, Q5VZP5, Q62417, Q66648, Q66PJ3, Q6A065, Q6P9P0, Q6UB99, Q7TQC7, Q7Z4V5, Q80U49, Q86VM9, Q8BYK8, Q8C5W0, Q8CFC2, Q8NEY8, Q8R0F5, Q8R2M2

Diamond homologs: A7E2Z2, A8XI75, C6KTD2, E9PYH6, E9Q5F9, F4K1J4, G0SDW4, O08550, O14686, O15047, O17514, O43463, O54864, O65312, O96028, P0CB22, P0CO26, P0CO27, P20659, P38827, P42124, P55200, P70351, P93831, Q03164, Q08BS4, Q08D57, Q10MI4, Q15910, Q18221, Q1DR06, Q1DU03, Q1LY77, Q24742, Q28CQ7, Q28D84, Q2GWF3, Q2H988, Q2NL30, Q2UMH3

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SETD1A	“form complex”	“Set1-Ash2 HMT 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
Formation of WDR5-containing histone-modifying complexes	14	47.7×	5e-18
Deactivation of the beta-catenin transactivating complex	6	17.9×	1e-04
Neurexins and neuroligins	6	15.2×	2e-04
Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	6	15.2×	2e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	13.1×	1e-04
Formation of the beta-catenin:TCF transactivating complex	8	12.3×	4e-05
PKMTs methylate histone lysines	5	10.3×	5e-03
Epigenetic regulation by WDR5-containing histone modifying complexes	5	9.9×	6e-03

GO biological processes:

GO term	Partners	Fold	FDR
actomyosin structure organization	5	27.0×	2e-04
transcription initiation-coupled chromatin remodeling	7	25.8×	4e-06
chromatin remodeling	9	6.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	33
Likely pathogenic	33
Uncertain significance	494
Likely benign	185
Benign	10

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1072463	NM_014712.3(SETD1A):c.1228_1229dup (p.Ser411fs)	Pathogenic
1076067	NM_014712.3(SETD1A):c.442dup (p.Ala148fs)	Pathogenic
1275794	NM_014712.3(SETD1A):c.1304del (p.Pro435fs)	Pathogenic
1330308	NM_014712.3(SETD1A):c.757C>T (p.Arg253Ter)	Pathogenic
1699408	NM_014712.3(SETD1A):c.1256_1259dup (p.Thr421fs)	Pathogenic
1804046	NM_014712.3(SETD1A):c.4618C>T (p.Gln1540Ter)	Pathogenic
1878499	NM_014712.3(SETD1A):c.526C>T (p.Arg176Ter)	Pathogenic
224650	NM_014712.3(SETD1A):c.518-2A>G	Pathogenic
224651	NM_014712.3(SETD1A):c.1272del (p.Tyr425fs)	Pathogenic
224652	NM_014712.3(SETD1A):c.2209C>T (p.Gln737Ter)	Pathogenic
224653	NM_014712.3(SETD1A):c.2171dup (p.Ala725fs)	Pathogenic
224654	NM_014712.3(SETD1A):c.1938C>G (p.Tyr646Ter)	Pathogenic
2430127	NM_014712.3(SETD1A):c.2825del (p.Pro942fs)	Pathogenic
2580113	NM_014712.3(SETD1A):c.3706C>T (p.Arg1236Ter)	Pathogenic
2609891	NM_014712.3(SETD1A):c.2002C>T (p.Arg668Ter)	Pathogenic
3160576	NM_014712.3(SETD1A):c.154_155del (p.Ser52fs)	Pathogenic
3317700	NM_014712.3(SETD1A):c.3171del (p.Ser1058fs)	Pathogenic
3336414	NM_014712.3(SETD1A):c.4209_4236del (p.Pro1404fs)	Pathogenic
3378411	NM_014712.3(SETD1A):c.336del (p.Asp112fs)	Pathogenic
3440151	NM_014712.3(SETD1A):c.1381dup (p.Arg461fs)	Pathogenic
3764629	NM_014712.3(SETD1A):c.4358dup (p.Thr1454fs)	Pathogenic
3952793	NM_014712.3(SETD1A):c.3953dup (p.Glu1319fs)	Pathogenic
3952794	NM_014712.3(SETD1A):c.3831dup (p.Glu1278fs)	Pathogenic
4163127	NM_014712.3(SETD1A):c.3422dup (p.Ala1142fs)	Pathogenic
4279552	NM_014712.3(SETD1A):c.2944G>T (p.Glu982Ter)	Pathogenic
4538460	NM_014712.3(SETD1A):c.273del (p.Pro92fs)	Pathogenic
521559	NM_014712.3(SETD1A):c.214del (p.Arg72fs)	Pathogenic
834091	NM_014712.3(SETD1A):c.806A>G (p.Gln269Arg)	Pathogenic
834092	NM_014712.3(SETD1A):c.4105G>A (p.Gly1369Arg)	Pathogenic
976774	NM_014712.3(SETD1A):c.1287dup (p.Ser430fs)	Pathogenic

SpliceAI

2664 predictions. Top by Δscore:

Variant	Effect	Δscore
16:30958715:A:AG	acceptor_gain	1.0000
16:30958716:G:GA	acceptor_gain	1.0000
16:30958716:GT:G	acceptor_gain	1.0000
16:30958716:GTGT:G	acceptor_gain	1.0000
16:30958716:GTGTA:G	acceptor_gain	1.0000
16:30958880:AC:A	donor_gain	1.0000
16:30958881:CGT:C	donor_loss	1.0000
16:30958882:G:GG	donor_gain	1.0000
16:30958883:T:A	donor_loss	1.0000
16:30958884:GAGT:G	donor_loss	1.0000
16:30961262:CCCA:C	acceptor_loss	1.0000
16:30961263:CCA:C	acceptor_loss	1.0000
16:30961264:CA:C	acceptor_loss	1.0000
16:30961265:A:AC	acceptor_loss	1.0000
16:30961265:A:AG	acceptor_gain	1.0000
16:30961265:AGCT:A	acceptor_gain	1.0000
16:30961265:AGCTG:A	acceptor_gain	1.0000
16:30961266:G:GT	acceptor_gain	1.0000
16:30961266:GC:G	acceptor_gain	1.0000
16:30961266:GCT:G	acceptor_gain	1.0000
16:30961266:GCTG:G	acceptor_gain	1.0000
16:30961266:GCTGG:G	acceptor_gain	1.0000
16:30961534:AAAGG:A	donor_loss	1.0000
16:30961536:AGG:A	donor_loss	1.0000
16:30961537:GGTGA:G	donor_loss	1.0000
16:30961539:T:G	donor_loss	1.0000
16:30963427:CTCCA:C	acceptor_loss	1.0000
16:30963428:TCCAG:T	acceptor_loss	1.0000
16:30963429:CCA:C	acceptor_loss	1.0000
16:30963430:CA:C	acceptor_loss	1.0000

AlphaMissense

10981 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:30958796:T:C	L22P	1.000
16:30958855:T:G	Y42D	1.000
16:30961307:T:A	V96E	1.000
16:30961313:T:C	F98S	1.000
16:30961322:T:A	L101Q	1.000
16:30961322:T:C	L101P	1.000
16:30961325:A:T	N102I	1.000
16:30961326:T:A	N102K	1.000
16:30961326:T:G	N102K	1.000
16:30961327:G:C	D103H	1.000
16:30961328:A:C	D103A	1.000
16:30961328:A:T	D103V	1.000
16:30961345:T:C	F109L	1.000
16:30961346:T:C	F109S	1.000
16:30961346:T:G	F109C	1.000
16:30961347:C:A	F109L	1.000
16:30961347:C:G	F109L	1.000
16:30961349:T:A	L110Q	1.000
16:30961349:T:C	L110P	1.000
16:30961360:T:C	C114R	1.000
16:30961361:G:A	C114Y	1.000
16:30961362:C:G	C114W	1.000
16:30961424:T:C	L135P	1.000
16:30961426:G:C	G136R	1.000
16:30961427:G:A	G136D	1.000
16:30961427:G:T	G136V	1.000
16:30961430:T:C	L137P	1.000
16:30961432:G:C	A138P	1.000
16:30961433:C:A	A138D	1.000
16:30961444:T:A	F142I	1.000

dbSNP variants (sampled 300 via entrez): RS1000087854 (16:30974955 G>T), RS1000116656 (16:30964073 T>C), RS1000127637 (16:30969695 C>T), RS1000222502 (16:30960690 G>A,C), RS1000288536 (16:30975359 T>C), RS1000367816 (16:30957929 C>T), RS1000423385 (16:30964554 A>C,G), RS1000525494 (16:30970615 T>G), RS1000543011 (16:30975284 T>G), RS1000754418 (16:30965933 C>G), RS1000938659 (16:30981607 T>C), RS1001071168 (16:30965534 G>A,C,T), RS1001094974 (16:30976600 G>A), RS1001123633 (16:30965127 C>A,G), RS1001274114 (16:30975309 C>CA)

Disease associations

OMIM: gene MIM:611052 | disease phenotypes: MIM:618832, MIM:619056, MIM:181500, MIM:617755

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with speech impairment and dysmorphic facies	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant
epilepsy, early-onset, with or without developmental delay	Limited	Autosomal dominant

Mondo (7): neurodevelopmental disorder (MONDO:0700092), epilepsy, early-onset, with or without developmental delay (MONDO:0030005), neurodevelopmental disorder with speech impairment and dysmorphic facies (MONDO:0033630), schizophrenia (MONDO:0005090), autism spectrum disorder (MONDO:0005258), neurodevelopmental disorder with dysmorphic facies and distal limb anomalies (MONDO:0060596), intellectual disability (MONDO:0001071)

Orphanet (4): BPTF-related intellectual disability-facial dysmorphism-skeletal anomalies syndrome (Orphanet:686482), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000034	Hydrocele testis
HP:0000154	Wide mouth
HP:0000256	Macrocephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000445	Wide nose
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000687	Widely spaced teeth
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001363	Craniosynostosis
HP:0001382	Joint hypermobility
HP:0001513	Obesity
HP:0001562	Oligohydramnios

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004630_201	Mean corpuscular hemoglobin	2.000000e-13
GCST005537_107	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	1.000000e-10
GCST009325_22	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	5.000000e-20
GCST009512_7	Parkinson’s disease	6.000000e-06
GCST009597_241	Multiple sclerosis	5.000000e-06
GCST90002390_83	Mean corpuscular hemoglobin	1.000000e-38
GCST90002392_500	Mean corpuscular volume	1.000000e-35
GCST90002396_585	Mean reticulocyte volume	3.000000e-42
GCST90002397_237	Mean spheric corpuscular volume	9.000000e-39
GCST90002403_673	Red blood cell count	3.000000e-39

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0010701	mean reticulocyte volume
EFO:0004305	erythrocyte count

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): CHEMBL4105954 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 2.1.1.43 Histone methyltransferases (HMTs)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.30	IC50	50	nM	MOLIBRESIB
7.28	Kd	53	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178490: Inhibition of SETD1A (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression, decreases expression	3
sodium arsenite	increases abundance, increases expression, decreases expression	2
Cisplatin	affects expression, decreases expression	2
Cadmium Chloride	increases abundance, decreases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
coumarin	decreases phosphorylation	1
ICG 001	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Ethanol	decreases expression	1
Arsenic	increases abundance, increases expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Deferoxamine	increases expression	1
Diuron	decreases expression	1
Estradiol	increases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	decreases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Dronabinol	increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4017388	Binding	Inhibition of SET1a (unknown origin) H3K4 methyltransferase activity using biotinyl-H3 peptide (1 to 21 residues) and using [3H]-S adenosylmethionine as methyl donor up to 100 uM after 1 hr by scintillation counting	Discovery of a Highly Potent, Cell-Permeable Macrocyclic Peptidomimetic (MM-589) Targeting the WD Repeat Domain 5 Protein (WDR5)-Mixed Lineage Leukemia (MLL) Protein-Protein Interaction. — J Med Chem

Clinical trials (associated diseases)

300 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,
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia