ZNF804A

Summary

ZNF804A (zinc finger protein 804A, HGNC:21711) is a protein-coding gene on chromosome 2q32.1, encoding Zinc finger protein 804A (Q7Z570).

The protein encoded by this gene is a zinc finger binding protein. Polymorphisms in this gene, especially rs1344706, are thought to confer increased susceptibility to schizophrenia, bipolar disorder, and heroin addiciton.

Source: NCBI Gene 91752 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Limited, GenCC)
• GWAS associations: 31
• Clinical variants (ClinVar): 200 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Transcription factor: yes — 10 downstream targets (CollecTRI)
• MANE Select transcript: NM_194250

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21711
Approved symbol	ZNF804A
Name	zinc finger protein 804A
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170396
Ensembl biotype	protein_coding
OMIM	612282
Entrez	91752

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000302277

RefSeq mRNA: 1 — MANE Select: NM_194250 NM_194250

CCDS: CCDS2291

Canonical transcript exons

ENST00000302277 — 4 exons

Exon	Start	End
ENSE00001164144	184935783	184939492
ENSE00001367674	184866369	184866512
ENSE00001385904	184598529	184599070
ENSE00002477059	184933603	184933733

Expression profiles

Bgee: expression breadth ubiquitous, 144 present calls, max score 80.55.

FANTOM5 (CAGE): breadth broad, TPM avg 5.1068 / max 206.2583, expressed in 819 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24075	4.3443	746
24076	0.3626	167
24074	0.3024	173
24073	0.0976	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	80.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	79.92	gold quality
Brodmann (1909) area 23	UBERON:0013554	79.37	gold quality
renal glomerulus	UBERON:0000074	78.67	gold quality
metanephric glomerulus	UBERON:0004736	78.22	gold quality
cortical plate	UBERON:0005343	77.16	gold quality
cerebellar vermis	UBERON:0004720	77.13	gold quality
middle temporal gyrus	UBERON:0002771	75.61	silver quality
stromal cell of endometrium	CL:0002255	74.87	gold quality
primary visual cortex	UBERON:0002436	73.99	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	73.97	gold quality
endothelial cell	CL:0000115	73.45	silver quality
prefrontal cortex	UBERON:0000451	72.90	gold quality
monocyte	CL:0000576	72.69	gold quality
ventricular zone	UBERON:0003053	72.63	gold quality
mononuclear cell	CL:0000842	72.48	gold quality
Brodmann (1909) area 46	UBERON:0006483	72.44	silver quality
leukocyte	CL:0000738	71.89	gold quality
frontal pole	UBERON:0002795	71.66	gold quality
paraflocculus	UBERON:0005351	71.22	silver quality
superior frontal gyrus	UBERON:0002661	70.85	gold quality
neocortex	UBERON:0001950	70.83	gold quality
occipital lobe	UBERON:0002021	70.68	gold quality
frontal cortex	UBERON:0001870	70.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	70.05	gold quality
cerebral cortex	UBERON:0000956	69.92	gold quality
cerebellum	UBERON:0002037	69.70	gold quality
cingulate cortex	UBERON:0003027	69.70	gold quality
anterior cingulate cortex	UBERON:0009835	69.63	gold quality
cerebellar cortex	UBERON:0002129	69.33	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	64.89
E-HCAD-25	yes	38.74
E-GEOD-81383	no	165.62
E-ANND-3	no	3.69

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

10 targets.

Target	Regulation
ANKRD1	Activation
BIRC3	Repression
CLIC2	Repression
DDIT3	Activation
DRD2
INHBE	Activation
MGAM	Repression
NLGN4X	Activation
PDE4B
PIK3AP1	Activation

Upstream regulators (CollecTRI, top): HSF2

miRNA regulators (miRDB)

57 targeting ZNF804A, 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-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-181B-2-3P	99.81	70.06	1646

Literature-anchored findings (GeneRIF, showing 40)

• genome-wide association study of schizophrenia; meta-analysis provided strongest evidence for association around ZNF804A (P = 1.61 x 10(-7)) and this strengthened when the affected phenotype included bipolar disorder (P = 9.96 x 10(-9)) (PMID:18677311)
• healthy carriers of rs1344706 risk genotype show no changes in regional activity but pronounced gene dosage-dependent alteration in functional coupling of dorsolateral prefrontal cortex across hemispheres & with hippocampus & abnormal coupling of amygdala (PMID:19407193)
• This study suggested that there is a consistent link between the A allele of rs1344706, increased expression of ZNF804A and risk for schizophrenia. (PMID:19844207)
• ZNF804A variants examined in this study confer risk of more than one category of disease. Rs1344706[T] is associated with both schizophrenia and bipolar disorder, and the copy number variants identified here suggest a connection with anxiety as well. (PMID:20048749)
• The allelic association at the ZNF804A locus is now one of the most compelling in schizophrenia to date, and supports the accumulating data suggesting overlapping genetic risk between schizophrenia and bipolar disorder. (PMID:20368704)
• This study further evidence for a positive association between the ZNF804A locus and schizophrenia, and support previous findings implicating that ZNF804A is likely a true susceptibility locus for schizophrenia. (PMID:20458322)
• This study suggested that significant association between ZNF804A status and the clinical symptomatology based on lifetime severity score for mania. (PMID:20538430)
• ZNF804A is predicted to have a role in phenotypes reflecting altered neural connectivity. (PMID:20664580)
• We conclude that ZNF804A is robustly, if modestly, associated with schizophrenia risk, with much work still remaining to elucidate its role in schizophrenia biology. (PMID:20688871)
• results do not support the hypothesis that moderately rare non-synonymous variants at the ZNF804A locus are involved in schizophrenia susceptibility (PMID:20862696)
• These data are consistent with our earlier behavioral data and suggest that ZNF804A is delineating a schizophrenia subtype characterized by relatively intact brain volume (PMID:20934520)
• Our findings confirm a key role for disturbed functional connectivity in the genetic risk architecture of schizophrenia (PMID:20946959)
• data suggest that rs1344706 may be related to memory dysfunction in schizophreni (PMID:20957649)
• genome-wide supported psychosis risk variant of ZNF804A is associated with altered executive control (larger conflict effect), which is a potential endophenotype of psychotic disorders (PMID:21040459)
• The results if this study suggested that a clinical and molecular modulation by sex of the association of ZNF804A ingle Nucleotide Polymorphism rs7597593 and risk of schizophrenia. (PMID:21349497)
• These results suggest that the genetic variation in ZNF804A might increase susceptibility not only for schizophrenia but also for schizotypal personality traits in healthy subjects. (PMID:21457757)
• The ZNF804A risk variant rs1344706 identifies neural mechanisms common to both schizophrenia and bipolar disorder through its potential effects on cortical thickness, white matter tract integrity, and cognitive function. (PMID:21525856)
• This study demonistrated that variation in ZNF804A contribute to the etiology or clinical schizophrenia in Chinese Han population. (PMID:21663974)
• nominal association of SNP rs1344706 with bipolar disorders and psychosis subphenotype (PMID:21767209)
• SNP rs1344706 associated with abnormal dorsolateral prefrontal cortex functional connectivity with other brain areas in schizophrenia (PMID:21810628)
• The results of this study demonistrated that ZNF804A was significantly associated with variation in interpersonal attributions in healthy participants but not in patients. (PMID:21876541)
• Our results suggest that ZNF804A is a common risk gene for schizophrenia in world populations and that the newly identified functional SNP (rs359895) is likely a risk SNP for schizophrenia. (PMID:21890790)
• The results of this study provided the further evidence that ZNF804A is of functional relevance to schizophrenia and indicates that ZNF804A may be a novel target for pharmacological interventions. (PMID:21892778)
• The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the white matter in the left prefrontal lobe together with other risk factors for schizophrenia. (PMID:21911029)
• using a PCR-RFKP method an association between ZNF804A rs1344706 variant and schizophrenia in a Turkish population was replicated (PMID:21988329)
• present study adds new evidence for an association between the conserved mammalian region of the ZNF804A gene and schizophrenia (PMID:21993378)
• The present data support fronto-hippocampal dysconnectivity as intermediate phenotype linking rs1344706 genotype for ZNF804A to psychosis (PMID:22042765)
• gene ontology analysis of differentially expressed genes indicated a significant effect of ZNF804A knockdown on expression of genes involved in cell adhesion, suggesting a role for ZNF804A in processes such as neural migration, neurite outgrowth and synapse formation (PMID:22080834)
• ZNF804A risk variant influence white matter integrity involving cortico-limbic brain regions in schizophrenia. (PMID:22328493)
• these results indicated that IQ may modulate the role of rs1344706 in the etiology of both schizophrenia and its cognitive impairments (PMID:22373944)
• ZNF804a regulates expression of the schizophrenia-associated genes PRSS16, COMT, PDE4B, and DRD2 (PMID:22384243)
• The ZNF804A rs1344706 variant was not associated with schizophrenia in the Romanian population from Cluj Napoca . (PMID:22775511)
• The present study provides evidence that ZNF804A might have a role in cognitive traits of relevance to reading and spelling. (PMID:22781169)
• analysis of a genomewide supported psychosis variant in ZNF804A and white matter integrity in the human brain (PMID:22840435)
• The results of this study that supporting the association between ZNF804A and schizophrenia in our Han Chinese sample. (PMID:22871346)
• ZNF804A may also contribute to schizophrenia susceptibility in Asians although the risk SNP is different from that in Europeans. (PMID:22887939)
• growing body of evidence suggests that the risk allele of rs1347706 is associated with a distinctive set of phenotypic features in healthy volunteers and individuals with schizophrenia. (PMID:22945618)
• The findings of this study suggested that ZNF804A is associated with a subtype of schizophrenia with better cognitive and neurological functioning (PMID:22948380)
• This study have identified a novel transcriptional variant of ZNF804A in human LCLs and postmortem brain samples. (PMID:23010486)
• results show that ZNF804A modulates mechanisms underlying cognitive control. (PMID:23032874)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	znf804a	ENSDARG00000027079
mus_musculus	Zfp804a	ENSMUSG00000070866
rattus_norvegicus	Zfp804a	ENSRNOG00000038004

Paralogs (2): ZNF804B (ENSG00000182348), GPATCH8 (ENSG00000186566)

Protein

Protein identifiers

Zinc finger protein 804A — Q7Z570 (reviewed: Q7Z570)

All UniProt accessions (1): Q7Z570

RefSeq proteins (1): NP_919226* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR052445	ZNF804A-like/GPATCH8	Family

UniProt features (19 total): sequence variant 9, compositionally biased region 4, sequence conflict 2, region of interest 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z570-F1	45.51	0.05

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 153 (showing top): GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_CELL_JUNCTION_ORGANIZATION, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_REGULATION_OF_SYNAPSE_STRUCTURE_OR_ACTIVITY, AACTTT_UNKNOWN, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOCC_NEURON_PROJECTION, GOBP_CELL_PROJECTION_ORGANIZATION, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_POSITIVE_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (4): positive regulation of gene expression (GO:0010628), regulation of neuron projection development (GO:0010975), positive regulation of neuron projection development (GO:0010976), positive regulation of dendritic spine maintenance (GO:1902952)

GO Molecular Function (2): zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (11): nucleus (GO:0005634), cytoplasm (GO:0005737), plasma membrane (GO:0005886), growth cone (GO:0030426), neuronal cell body (GO:0043025), dendritic spine (GO:0043197), dendritic shaft (GO:0043198), presynapse (GO:0098793), postsynapse (GO:0098794), dendritic microtubule (GO:1901588), axon (GO:0030424)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
dendrite	3
neuron projection development	2
positive regulation of cell projection organization	2
synapse	2
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of plasma membrane bounded cell projection organization	1
regulation of neuron projection development	1
dendritic spine maintenance	1
regulation of dendritic spine maintenance	1
transition metal ion binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
site of polarized growth	1
distal axon	1
somatodendritic compartment	1
cell body	1
neuron spine	1
postsynapse	1
microtubule	1
neuron projection	1

Protein interactions and networks

STRING

950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ZNF804A	DISC1	Q9NRI5	785
ZNF804A	DAOA	P59103	762
ZNF804A	DTNBP1	Q96EV8	735
ZNF804A	COMT	P21964	713
ZNF804A	CACNA1C	Q13936	699
ZNF804A	NRGN	Q92686	693
ZNF804A	VRK2	Q86Y07	669
ZNF804A	WBP1L	Q9NX94	659
ZNF804A	NRXN1	Q9ULB1	649
ZNF804A	ATXN1	P54253	647
ZNF804A	PPP3CC	P48454	613
ZNF804A	PRODH	O43272	610
ZNF804A	DAO	P14920	609
ZNF804A	CSMD1	Q96PZ7	607
ZNF804A	DRD2	P14416	599

IntAct

7 interactions, top by confidence:

A	B	Type	Score
CRK	ZNF804A	psi-mi:“MI:0407”(direct interaction)	0.440
ZNF804A	HSPA8	psi-mi:“MI:0915”(physical association)	0.400
ZNF804A	HNRNPC	psi-mi:“MI:0915”(physical association)	0.400
ZNF804A		psi-mi:“MI:0915”(physical association)	0.000
ATXN1	ZNF804A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): ZNF804A (Affinity Capture-MS), ZNF804A (Proximity Label-MS), ZNF804A (Proximity Label-MS), ZNF804A (Protein-peptide), ZNF804A (Cross-Linking-MS (XL-MS)), SET (Cross-Linking-MS (XL-MS)), RPLP2 (Cross-Linking-MS (XL-MS)), PKM (Cross-Linking-MS (XL-MS)), ZNF804A (Two-hybrid), ZNF804A (Two-hybrid)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: A2A6A1, A2AKY4, B2GV05, P52756, Q1RMU5, Q6DF57, Q6DGZ0, Q7Z570, Q91YE7, Q94C11, Q9UKJ3, A4D1E1

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
ZNF804A	“up-regulates activity”	STAT2	binding
ZNF804A	“up-regulates quantity by expression”	ANKRD1	“transcriptional regulation”
ZNF804A	“up-regulates quantity by expression”	INHBE	“transcriptional regulation”
ZNF804A	“up-regulates quantity by expression”	PIK3AP1	“transcriptional regulation”
ZNF804A	“up-regulates quantity by expression”	DDIT3	“transcriptional regulation”
ZNF804A	“down-regulates quantity by repression”	CLIC2	“transcriptional regulation”
ZNF804A	“down-regulates quantity by repression”	MGAM	“transcriptional regulation”
ZNF804A	“down-regulates quantity by repression”	BIRC3	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	158
Likely benign	20
Benign	15

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545252	NC_000002.12:g.(?184830819)(184884225_?)del	Likely pathogenic

SpliceAI

2507 predictions. Top by Δscore:

Variant	Effect	Δscore
2:184599026:G:GT	donor_gain	1.0000
2:184866360:A:AG	acceptor_gain	1.0000
2:184866361:T:G	acceptor_gain	1.0000
2:184866365:TCAG:T	acceptor_loss	1.0000
2:184866366:CAG:C	acceptor_loss	1.0000
2:184866367:A:G	acceptor_loss	1.0000
2:184866367:AG:A	acceptor_gain	1.0000
2:184866368:G:GA	acceptor_gain	1.0000
2:184866368:GG:G	acceptor_gain	1.0000
2:184866368:GGA:G	acceptor_gain	1.0000
2:184866368:GGAC:G	acceptor_gain	1.0000
2:184866368:GGACT:G	acceptor_gain	1.0000
2:184866509:GCAG:G	donor_gain	1.0000
2:184866512:GGTAA:G	donor_loss	1.0000
2:184866514:T:A	donor_loss	1.0000
2:184933598:A:AG	acceptor_gain	1.0000
2:184933599:A:G	acceptor_gain	1.0000
2:184933600:C:G	acceptor_gain	1.0000
2:184933601:A:AG	acceptor_gain	1.0000
2:184933601:AGAG:A	acceptor_gain	1.0000
2:184933602:G:GG	acceptor_gain	1.0000
2:184933602:GA:G	acceptor_gain	1.0000
2:184933602:GAGG:G	acceptor_gain	1.0000
2:184933602:GAGGC:G	acceptor_gain	1.0000
2:184933714:C:G	donor_gain	1.0000
2:184933729:GTATG:G	donor_gain	1.0000
2:184933730:TATG:T	donor_gain	1.0000
2:184933732:TG:T	donor_gain	1.0000
2:184933733:GG:G	donor_gain	1.0000
2:184933734:G:GC	donor_loss	1.0000

AlphaMissense

8038 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:184866426:T:C	F57L	1.000
2:184866428:T:A	F57L	1.000
2:184866428:T:G	F57L	1.000
2:184866432:T:C	C59R	1.000
2:184866433:G:A	C59Y	1.000
2:184866434:T:G	C59W	1.000
2:184866441:T:C	C62R	1.000
2:184866442:G:A	C62Y	1.000
2:184866442:G:T	C62F	1.000
2:184866443:T:G	C62W	1.000
2:184866471:T:C	F72L	1.000
2:184866472:T:C	F72S	1.000
2:184866472:T:G	F72C	1.000
2:184866473:T:A	F72L	1.000
2:184866473:T:G	F72L	1.000
2:184866480:C:G	H75D	1.000
2:184866482:C:A	H75Q	1.000
2:184866482:C:G	H75Q	1.000
2:184866504:C:G	H83D	1.000
2:184866509:G:C	K84N	1.000
2:184866509:G:T	K84N	1.000
2:184933605:G:C	R86S	1.000
2:184933605:G:T	R86S	1.000
2:184933607:T:C	L87P	1.000
2:184933616:T:C	L90P	1.000
2:184933620:A:C	K91N	1.000
2:184933620:A:T	K91N	1.000
2:184933630:T:C	F95L	1.000
2:184933631:T:C	F95S	1.000
2:184933631:T:G	F95C	1.000

dbSNP variants (sampled 300 via entrez): RS1000014329 (2:184934005 A>C), RS1000035923 (2:184668416 T>C), RS1000038672 (2:184867947 T>A), RS1000039615 (2:184617451 A>C,G), RS1000041866 (2:184687846 T>A,C), RS1000058276 (2:184897935 G>C), RS1000064109 (2:184860463 A>T), RS1000070697 (2:184790765 G>A,T), RS1000073033 (2:184688059 C>T), RS1000090720 (2:184867658 G>C), RS1000109479 (2:184643753 T>C), RS1000109758 (2:184617126 GTAGTTA>G), RS1000112903 (2:184640995 C>G,T), RS1000119811 (2:184641434 C>G), RS1000137102 (2:184621627 T>A)

Disease associations

OMIM: gene MIM:612282 | disease phenotypes: MIM:181500

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Limited	Autosomal dominant

Mondo (2): schizophrenia (MONDO:0005090), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (1): NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0100753	Schizophrenia

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000215_3	Schizophrenia	2.000000e-07
GCST001762_70	Obesity-related traits	4.000000e-06
GCST001877_61	Autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia (combined)	8.000000e-06
GCST002539_39	Schizophrenia	2.000000e-12
GCST002700_3	Cervical artery dissection	2.000000e-06
GCST003427_155	Alzheimer disease and age of onset	6.000000e-07
GCST003772_5	Loneliness (linear analysis)	7.000000e-06
GCST004521_67	Autism spectrum disorder or schizophrenia	7.000000e-09
GCST004946_1	Schizophrenia	9.000000e-11
GCST005081_2	Bipolar disorder lithium response (continuous) or schizophrenia	1.000000e-08
GCST005232_42	Neuroticism	1.000000e-07
GCST006624_78	Systolic blood pressure	6.000000e-10
GCST006803_77	Schizophrenia	5.000000e-09
GCST006940_9	Neurociticism	8.000000e-10
GCST006951_38	Feeling hurt	2.000000e-08
GCST007201_31	Schizophrenia	2.000000e-11
GCST007201_462	Schizophrenia	2.000000e-11
GCST007257_4	Broad depression or schizophrenia	3.000000e-12
GCST007576_370	Chronotype	4.000000e-09
GCST007576_95	Chronotype	4.000000e-09
GCST008103_76	Bipolar disorder	9.000000e-07
GCST008295_13	Number of decayed, missing and filled tooth surfaces or use of dentures	7.000000e-09
GCST008306_27	Dentures	2.000000e-08
GCST008555_3	Breakfast cereal skipping frequency	1.000000e-08
GCST008556_3	Breakfast skipping	1.000000e-08
GCST008595_60	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	5.000000e-11
GCST009600_75	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	8.000000e-12
GCST011377_2	Shoulder impingement or rotator cuff tear	2.000000e-08
GCST012354_8	Anxiety	4.000000e-07
GCST90000046_2	Age at first sexual intercourse	7.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0007865	loneliness measurement
EFO:0007660	neuroticism measurement
EFO:0006335	systolic blood pressure
EFO:0009599	feeling emotionally hurt measurement
EFO:0008328	chronotype measurement
EFO:0010078	dentures
EFO:0010129	breakfast skipping measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0009863	anxiety measurement
EFO:0009749	age at first sexual intercourse measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1344706	Efficacy	3	antipsychotics	Schizophrenia
rs62200793	Efficacy	3	lithium	Bipolar Disorder
rs7597593	Toxicity	3	opioids	Opioid-Related Disorders

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1344706	ZNF804A	3	2.00	1	antipsychotics
rs12693402	ZNF804A		0.00	0
rs62200793	ZNF804A	3	0.00	1	lithium
rs7597593	ZNF804A	3	2.00	1	opioids

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
sodium arsenite	increases expression	2
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
chromium hexavalent ion	affects expression, decreases expression, increases abundance	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
zinc chromate	decreases expression, increases abundance	1
ferrous chloride	decreases expression	1
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	1
monomethylarsonous acid	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
Panobinostat	affects cotreatment, increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Succimer	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Silicon Dioxide	decreases expression	1
Thiram	increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	increases expression	1
Acrylamide	increases expression	1
Particulate Matter	increases abundance, decreases expression	1
Magnetite Nanoparticles	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

302 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
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
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety