SP4

Summary

SP4 (Sp4 transcription factor, HGNC:11209) is a protein-coding gene on chromosome 7p15.3, encoding Transcription factor Sp4 (Q02446). Binds to GT and GC boxes promoters elements.

The protein encoded by this gene is a transcription factor that can bind to the GC promoter region of a variety of genes, including those of the photoreceptor signal transduction system. The encoded protein binds to the same sites in promoter CpG islands as does the transcription factor SP1, although its expression is much more restricted compared to that of SP1. This gene may be involved in bipolar disorder and schizophrenia.

Source: NCBI Gene 6671 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 128 total
• Phenotypes (HPO): 1
• Transcription factor: yes — 53 downstream targets (CollecTRI)
• MANE Select transcript: NM_003112

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11209
Approved symbol	SP4
Name	Sp4 transcription factor
Location	7p15.3
Locus type	gene with protein product
Status	Approved
Aliases	SPR-1, HF1B, MGC130008, MGC130009
Ensembl gene	ENSG00000105866
Ensembl biotype	protein_coding
OMIM	600540
Entrez	6671

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000222584, ENST00000432066, ENST00000440636, ENST00000448246, ENST00000649633, ENST00000959244

RefSeq mRNA: 3 — MANE Select: NM_003112 NM_001326542, NM_001326543, NM_003112

CCDS: CCDS5373, CCDS94063

Canonical transcript exons

ENST00000222584 — 6 exons

Exon	Start	End
ENSE00000673233	21429289	21430843
ENSE00000831921	21428677	21428792
ENSE00001029037	21511022	21514822
ENSE00001668918	21428083	21428258
ENSE00003514845	21481924	21482123
ENSE00003678197	21477079	21477307

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 94.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.6293 / max 132.3765, expressed in 1645 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77549	5.3220	1307
77548	2.4977	891
77551	1.5313	803
77547	0.6136	359
77550	0.5908	295
77552	0.0741	19

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	94.29	gold quality
germinal epithelium of ovary	UBERON:0001304	93.62	gold quality
superficial temporal artery	UBERON:0001614	92.76	gold quality
pigmented layer of retina	UBERON:0001782	91.41	gold quality
retina	UBERON:0000966	91.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.39	gold quality
trabecular bone tissue	UBERON:0002483	90.25	gold quality
endothelial cell	CL:0000115	90.19	gold quality
mucosa of paranasal sinus	UBERON:0005030	89.77	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.48	gold quality
biceps brachii	UBERON:0001507	89.04	gold quality
heart right ventricle	UBERON:0002080	88.79	gold quality
urethra	UBERON:0000057	88.32	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	88.11	gold quality
ventricular zone	UBERON:0003053	87.46	gold quality
ganglionic eminence	UBERON:0004023	86.85	gold quality
middle temporal gyrus	UBERON:0002771	86.60	gold quality
cardia of stomach	UBERON:0001162	86.46	gold quality
cortical plate	UBERON:0005343	86.40	gold quality
visceral pleura	UBERON:0002401	86.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.12	gold quality
mammary duct	UBERON:0001765	85.44	gold quality
renal medulla	UBERON:0000362	85.24	gold quality
ventral tegmental area	UBERON:0002691	85.08	gold quality
synovial joint	UBERON:0002217	84.98	gold quality
subthalamic nucleus	UBERON:0001906	84.94	gold quality
inferior vagus X ganglion	UBERON:0005363	84.63	gold quality
trigeminal ganglion	UBERON:0001675	84.53	gold quality
skin of hip	UBERON:0001554	84.48	gold quality
epithelium of nasopharynx	UBERON:0001951	84.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

53 targets.

Target	Regulation
ABCA2	Activation
ADAM2
ADH5
ALDH7A1
ASS1	Activation
ATP1A1
ATP1A3
ATP1B1
BCL2
BIRC5	Unknown
CCND1	Unknown
CDC25A
CDKN1A	Unknown
CPOX
CREBBP
CTSB
CYP46A1
EGFR
ERBB2	Activation
ESR1
FGFR3	Unknown
FLT1
FOLR1	Activation
GNAS
GRIA1
GRIA2	Activation
GRIN1
GRIN2A
GRIN2B
GRIN2C	Activation

JASPAR motifs

Motif	Name	Family
MA0685.1	SP4	Three-zinc finger Kruppel-related
MA0685.2	SP4	Three-zinc finger Kruppel-related

JASPAR matrix evidence (PMIDs): PMID:23019068

Upstream regulators (CollecTRI, top): AP1, MAZ, SP1, SP3, SP4

miRNA regulators (miRDB)

260 targeting SP4, 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-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299

Literature-anchored findings (GeneRIF, showing 29)

• Sp4-mediated differential activation of the beta-PDE transcription defines the first specific Sp4 target gene reported (PMID:11943774)
• DIM-C-pPhCF3 induced p21 expression through a novel mechanism that involves PPARgamma interactions with both Sp1 and Sp4 proteins bound to the proximal GC-rich region of the p21 promoter. (PMID:15345676)
• has an intimate part in transcriptional regulation of the lh receptor gene. (PMID:15788387)
• Sp3 and Sp4 cooperatively interact with ERalpha to activate VEGFR2 (PMID:16574784)
• While digenic disease with the SP4 Asn306Ser and the GNB1 intronic variant alleles has not been established, neither has it been ruled out. This leaves open the possibility of a cooperative involvement of SP4 and GNB1 in the normal function of the retina. (PMID:17356515)
• Curcumin also decreased bladder tumor growth in athymic nude mice bearing KU7 cells as xenografts and this was accompanied by decreased Sp1, Sp3, and Sp4 protein levels in tumors. (PMID:18593936)
• Out of ten SNPs selected from the SP4 genomic locus, four displayed significant association with bipolar disorder in European Caucasian families. (PMID:19401786)
• Association of A80807T polymorphism of the transcriptional factor Sp4 gene with PT ICA was established. (PMID:19656107)
• Data show that Sp4 was constitutively bound to the GC-box in the proximal region of the AS promoter regardless of arginine availability in all three cell lines. (PMID:19934275)
• Results of Sp1, Sp3, and Sp4 knockdown by RNA interference demonstrate that both p50 and p65 are Sp-regulated genes. (PMID:20538607)
• Sp4 hypomorphic mice could therefore serve as a genetic model to investigate impaired NMDA functions resulting from loss-of-function mutations of human SP4 gene in schizophrenia and/or other psychiatric disorders. (PMID:20634195)
• Ascorbic acid decreased RKO and SW480 colon cancer cell proliferation and induced apoptosis and necrosis, accompanied by downregulation of Sp1, Sp3, and Sp4 proteins. (PMID:21919647)
• This study demonistrated that The transcription factor SP4 is reduced in postmortem cerebellum of bipolar disorder subjects. (PMID:22017217)
• Significantly increased SP4 relative expression levels are observed in patients with Alzheimer’s disease, compared with controls. (PMID:22614877)
• This study showed that SP1, SP3 and SP4 protein levels inversely correlated with negative symptoms in the cerebellum. (PMID:23540600)
• This study shows reduced SP4 protein levels in first-episode psychosis in lymphocytes, suggesting that these transcription factors are potential peripheral biomarkers of psychotic spectrum disorders in the early stages. (PMID:23941741)
• The results of this study suggest that SP4 and SP1 upregulation may be part of the mechanisms deregulated downstream of glutamate signalling pathways in schizophrenia (PMID:25175639)
• Results found that SP4 S770 phosphorylation was significantly increased in lymphocytes in first-episode psychosis compared to controls. (PMID:25915526)
• Results indicate that SP4 S770 phosphorylation is increased in the cerebellum in bipolar disorder that committed suicide and in severe schizophrenia, and may be part of a degradation signal that controls Sp4 abundance in cerebellar granule neurons (PMID:26049820)
• O-GlcNAc modification of Sp3 and Sp4, but not Sp2 transcription factors negatively regulates their transcriptional activities. (PMID:26431879)
• Common risk factors in the SP4 gene are associated with schizophrenia, although not with MDD, in the Han Chinese population. (PMID:26450579)
• Sp1, Sp3 and Sp4 are non-oncogene addiction (NOA) genes and are attractive drug targets for individual and combined cancer chemotherapies. (PMID:26967243)
• IN TMD patients, a novel locus at genome-wide level of significance (rs73460075, OR = 0.56, P = 3.8 x 10(-8)) in the intron of the dystrophin gene DMD (X chromosome), and a suggestive locus on chromosome 7 (rs73271865, P = 2.9 x 10(-7)) upstream of the Sp4 Transcription Factor ( SP4) gene were identified in the discovery cohort, but neither of these was replicated. (PMID:28081371)
• Over-representation of potential SP4 target genes within schizophrenia-risk genes. (PMID:34750502)
• The genetic polymorphisms in the SP4 gene and the risk of gastric cancer. (PMID:36346067)
• Common and rare variants within SP4 exert distinct molecular mechanisms contributing to the risk of schizophrenia. (PMID:36372009)
• Sp4 Regulates PTTG1IP Gene Transcription and Expression. (PMID:36383136)
• The FOXP4-AS1/miR-3130-3p/SP4 feedback loop is associated with prostate cancer. (PMID:37114256)
• SP4 Facilitates Esophageal Squamous Cell Carcinoma Progression by Activating PHF14 Transcription and Wnt/Beta-Catenin Signaling. (PMID:37768180)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	sp4	ENSDARG00000005186
mus_musculus	Sp4	ENSMUSG00000025323
rattus_norvegicus	Sp4	ENSRNOG00000005472

Paralogs (3): SP2 (ENSG00000167182), SP3 (ENSG00000172845), SP1 (ENSG00000185591)

Protein

Protein identifiers

Transcription factor Sp4 — Q02446 (reviewed: Q02446)

Alternative names: SPR-1

All UniProt accessions (4): Q02446, A0A3B3IRW4, C9JUS7, F8WB93

UniProt curated annotations — full annotation on UniProt →

Function. Binds to GT and GC boxes promoters elements. Probable transcriptional activator.

Subcellular location. Nucleus.

Tissue specificity. Abundant in brain.

Domain organisation. The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP4, the motif is inactive.

Similarity. Belongs to the Sp1 C2H2-type zinc-finger protein family.

RefSeq proteins (3): NP_001313471, NP_001313472, NP_003103* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR039938	Sp4-like	Family

Pfam: PF00096

UniProt features (21 total): compositionally biased region 9, zinc finger region 3, region of interest 3, sequence conflict 2, chain 1, modified residue 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02446-F1	39.58	0.00

Functional residue map

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

Post-translational modifications (1): 46

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 257 (showing top): RNGTGGGC_UNKNOWN, PAX4_01, GAANYNYGACNY_UNKNOWN, TTTGTAG_MIR520D, STEARMAN_LUNG_CANCER_EARLY_VS_LATE_DN, TATTATA_MIR374, GGGTGGRR_PAX4_03, ATGTTAA_MIR302C, CATTTCA_MIR203, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, ATTACAT_MIR3803P, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_6, ATTCTTT_MIR186, MODULE_123, TTGGAGA_MIR5155P_MIR519E

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (9): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
transition metal ion binding	1
protein binding	1
DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
cation binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

732 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SP4	HPS4	Q9NQG7	763
SP4	GJA5	P36382	720
SP4	HPS5	Q9UPZ3	689
SP4	HPS6	Q86YV9	688
SP4	HPS3	Q969F9	687
SP4	BLOC1S3	Q6QNY0	598
SP4	GJA1	P17302	573
SP4	LMNA	P02545	571
SP4	TMEM196	Q5HYL7	565
SP4	NRL	P54845	531
SP4	AP3B1	O00203	529
SP4	DTNBP1	Q96EV8	474
SP4	CRX	O43186	473
SP4	EMD	P50402	453
SP4	MYC	P01106	434

IntAct

136 interactions, top by confidence:

A	B	Type	Score
SP4		psi-mi:“MI:0915”(physical association)	0.720
SP4	CIB3	psi-mi:“MI:0915”(physical association)	0.720
	SP4	psi-mi:“MI:0915”(physical association)	0.720
SP4	FOXP2	psi-mi:“MI:0915”(physical association)	0.670
FOXP2	SP4	psi-mi:“MI:0915”(physical association)	0.670
POU2F1	SP4	psi-mi:“MI:0915”(physical association)	0.560
SP4	COL8A1	psi-mi:“MI:0915”(physical association)	0.560
PRR20C	SP4	psi-mi:“MI:0915”(physical association)	0.560
SP4	PRR20C	psi-mi:“MI:0915”(physical association)	0.560
SP4	ADAM15	psi-mi:“MI:0915”(physical association)	0.560
NRF1	SP4	psi-mi:“MI:0915”(physical association)	0.560
LOC730441	SP4	psi-mi:“MI:0915”(physical association)	0.560
SP4	LMO3	psi-mi:“MI:0915”(physical association)	0.560
ATXN7L1	SP4	psi-mi:“MI:0915”(physical association)	0.560
SP4	POU2F1	psi-mi:“MI:0915”(physical association)	0.560
ADAM15	SP4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (56): SP4 (Two-hybrid), SP4 (Two-hybrid), SP4 (Two-hybrid), ADAM15 (Two-hybrid), SERF2 (Two-hybrid), LMO3 (Two-hybrid), FOXP2 (Two-hybrid), CIB3 (Two-hybrid), PRR20A (Two-hybrid), ATXN7L1 (Two-hybrid), TRY2P (Two-hybrid), VRK3 (Affinity Capture-MS), PTPRA (Affinity Capture-MS), HIRA (Affinity Capture-MS), SP4 (Two-hybrid)

ESM2 similar proteins: A1Z9E2, B0R0I6, B5DE69, D3ZN95, E9Q7E2, P14859, P15143, P16143, P25425, P27699, P47825, P49848, P51610, P51611, Q02086, Q02446, Q03061, Q08CM4, Q09XV5, Q0IHV2, Q0P5K4, Q28BL7, Q29076, Q3TUF7, Q571G4, Q5E9U0, Q5F3U0, Q5R6A9, Q5RBN8, Q61191, Q62445, Q641Z1, Q68CP9, Q6MZP7, Q6P4L9, Q6ZPK0, Q7Z589, Q7ZUV7, Q7ZX03, Q86NP2

Diamond homologs: A5ABV9, O08876, O14901, O70494, O89090, O89091, P08047, P0CG40, P41696, Q01714, Q02446, Q02447, Q0VA40, Q13351, Q22678, Q3SY56, Q5XGT8, Q62445, Q64HY3, Q64HY5, Q6BEB4, Q6NW96, Q6P0J3, Q8BMJ8, Q8IXZ3, Q8K1S5, Q8TDD2, Q8VI67, Q90WR8, Q9ESX2, Q9JHX2, Q9TZ64, O08584, O35738, O35819, O43474, O62259, O75840, O95600, P46099

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
SP4	“up-regulates activity”	CRX	binding
SP4	“up-regulates quantity by expression”	RHO	“transcriptional regulation”
SP4	“up-regulates quantity by expression”	MAOB	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 44 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.

GO biological processes:

GO term	Partners	Fold	FDR
cell-cell signaling	6	11.0×	8e-04
angiogenesis	6	9.8×	1e-03
immune response	7	8.7×	8e-04
inflammatory response	8	7.9×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	113
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1995 predictions. Top by Δscore:

Variant	Effect	Δscore
7:21428256:GCG:G	donor_gain	1.0000
7:21477075:TTAG:T	acceptor_loss	1.0000
7:21477077:A:AG	acceptor_gain	1.0000
7:21477077:A:G	acceptor_loss	1.0000
7:21477078:G:GC	acceptor_gain	1.0000
7:21477078:GGTCA:G	acceptor_gain	1.0000
7:21477294:G:T	donor_gain	1.0000
7:21477303:GGAAG:G	donor_gain	1.0000
7:21477304:G:GT	donor_gain	1.0000
7:21477305:A:T	donor_gain	1.0000
7:21477305:AAG:A	donor_loss	1.0000
7:21477306:AG:A	donor_loss	1.0000
7:21477307:GG:G	donor_loss	1.0000
7:21477308:GT:G	donor_loss	1.0000
7:21477309:T:A	donor_loss	1.0000
7:21481918:T:TA	acceptor_gain	1.0000
7:21481922:A:AG	acceptor_gain	1.0000
7:21481923:G:GA	acceptor_gain	1.0000
7:21481923:GA:G	acceptor_gain	1.0000
7:21481923:GAGGC:G	acceptor_gain	1.0000
7:21482121:CAGG:C	donor_loss	1.0000
7:21482124:G:GA	donor_loss	1.0000
7:21482124:G:GG	donor_gain	1.0000
7:21482125:T:A	donor_loss	1.0000
7:21511258:G:GT	donor_gain	1.0000
7:21428254:GAGCG:G	donor_gain	0.9900
7:21428259:G:A	donor_loss	0.9900
7:21428259:G:GG	donor_gain	0.9900
7:21428260:T:G	donor_loss	0.9900
7:21428734:G:GT	donor_gain	0.9900

AlphaMissense

5077 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:21481961:T:A	C649S	1.000
7:21481961:T:C	C649R	1.000
7:21481962:G:A	C649Y	1.000
7:21481962:G:C	C649S	1.000
7:21481963:T:G	C649W	1.000
7:21481976:T:A	C654S	1.000
7:21481976:T:C	C654R	1.000
7:21481977:G:A	C654Y	1.000
7:21481977:G:C	C654S	1.000
7:21482007:T:C	L664S	1.000
7:21482015:C:A	H667N	1.000
7:21482015:C:G	H667D	1.000
7:21482017:T:A	H667Q	1.000
7:21482017:T:G	H667Q	1.000
7:21482019:T:C	L668P	1.000
7:21482021:C:A	R669S	1.000
7:21482027:C:G	H671D	1.000
7:21482029:T:A	H671Q	1.000
7:21482029:T:G	H671Q	1.000
7:21482045:T:C	F677L	1.000
7:21482047:T:A	F677L	1.000
7:21482047:T:G	F677L	1.000
7:21482051:T:A	C679S	1.000
7:21482051:T:C	C679R	1.000
7:21482052:G:A	C679Y	1.000
7:21482052:G:C	C679S	1.000
7:21482053:C:G	C679W	1.000
7:21482066:T:C	C684R	1.000
7:21482067:G:A	C684Y	1.000
7:21482068:T:G	C684W	1.000

dbSNP variants (sampled 300 via entrez): RS1000034310 (7:21496521 C>A,T), RS1000040570 (7:21439413 G>A), RS1000088740 (7:21502196 A>C), RS1000093762 (7:21491787 A>C), RS1000103671 (7:21462644 G>A,T), RS1000115581 (7:21428125 G>C), RS1000119124 (7:21507281 A>T), RS1000173673 (7:21482470 T>C), RS1000181738 (7:21443165 T>C), RS1000192388 (7:21476679 C>T), RS1000267279 (7:21445986 G>A,C), RS1000310638 (7:21459307 G>A), RS1000326991 (7:21497892 A>G), RS1000340584 (7:21454410 A>T), RS1000373199 (7:21454180 C>T)

Disease associations

OMIM: gene MIM:600540 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): dyslexia (MONDO:0005489), attention deficit-hyperactivity disorder (MONDO:0007743)

Orphanet (0):

HPO phenotypes

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

HPO	Term
HP:0010522	Dyslexia

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST000551_4	Major depressive disorder (broad)	8.000000e-07
GCST000578_9	Major depressive disorder	6.000000e-06
GCST001718_1	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	3.000000e-06
GCST001718_5	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	2.000000e-08
GCST001718_6	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	1.000000e-06
GCST001718_7	Multiple cancers (lung cancer, gastric cancer, and squamous cell carcinoma)	1.000000e-16
GCST002337_131	Amyotrophic lateral sclerosis (sporadic)	7.000000e-06
GCST004034_3	Temporomandibular joint disorder	3.000000e-07
GCST005315_1	Acute lymphoblastic leukemia (childhood)	2.000000e-08
GCST006269_1178	General cognitive ability	3.000000e-08
GCST007201_69	Schizophrenia	3.000000e-07
GCST008103_57	Bipolar disorder	4.000000e-07
GCST008467_12	Aspartate aminotransferase levels in non-alcoholic fatty liver disease	6.000000e-09
GCST008512_20	Multisite chronic pain	2.000000e-08
GCST010243_92	Apolipoprotein B levels	2.000000e-10
GCST010245_83	LDL cholesterol levels	2.000000e-08
GCST012332_82	Multisite chronic pain	3.000000e-08
GCST012465_50	Bipolar disorder	6.000000e-10
GCST90000047_134	Age at first sexual intercourse	5.000000e-12
GCST90002400_607	Plateletcrit	3.000000e-09

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0004736	aspartate aminotransferase measurement
EFO:0010100	multisite chronic pain
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0009749	age at first sexual intercourse measurement
EFO:0007985	platelet crit

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004410	Dyslexia	C10.597.606.150.500.300; C10.597.606.150.550.700.500; C23.888.592.604.150.500.300; C23.888.592.604.150.550.700.500; F03.625.374.188.700.500; F03.625.562.700.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, decreases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
sodium arsenite	affects expression, increases expression	2
Acetaminophen	increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Quercetin	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
quercitrin	increases expression	1
arsenite	affects binding, decreases reaction	1
hyperoside	decreases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
1,1-bis(3’-indolyl)-1-(4-trifluoromethylphenyl)methane	affects reaction, increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants, Occupational	affects expression	1
Ascorbic Acid	decreases expression	1
Caffeine	increases phosphorylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6P1	SEES3-1V human SP4, clone1	Embryonic stem cell	Male
CVCL_A6P2	SEES3-1V human SP4, clone2	Embryonic stem cell	Male
CVCL_A6P3	SEES3-1V human SP4, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00111371	PHASE4	UNKNOWN	Dopaminergic Enhancement of Learning and Memory in Healthy Adults and Patients With Dyslexia
NCT00607919	PHASE4	COMPLETED	Treatment of ADHD With Atomoxetine in Children & Adolescents With ADHD & Comorbid Dyslexia
NCT00716274	PHASE4	COMPLETED	Effects of Atomoxetine on Brain Activation During Attention & Reading Tasks in Participants With ADHD & Comorbid Dyslexia
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00181571	PHASE4	COMPLETED	A Double-Blind Comparison of Concerta and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181675	PHASE4	COMPLETED	A Double-Blind Comparison of Galantamine HBr and Placebo in Adults With Attention Deficit Hyperactivity Disorder
NCT00181714	PHASE4	COMPLETED	Prevention of Cigarette Smoking in Attention Deficit Hyperactivity Disorder (ADHD) Youth With Concerta
NCT00181948	PHASE4	COMPLETED	Strattera Treatment in Children With ADHD Who Have Poor Response to Stimulant Therapy
NCT00181987	PHASE4	COMPLETED	Concerta in the Treatment of ADHD in Youth and Adults With Bipolar Disorder
NCT00190736	PHASE4	COMPLETED	Efficacy and Safety of Once-Daily Atomoxetine Hydrochloride in Adults With ADHD Over an Extended Period of Time (6 Months)
NCT00190775	PHASE4	COMPLETED	A Randomized, Double-Blind Comparison of Placebo and Atomoxetine Hydrochloride Given Once a Day in Adults With Attention-Deficit/Hyperactivity Disorder (ADHD)
NCT00190879	PHASE4	COMPLETED	Placebo-Controlled Study of Atomoxetine Hydrochloride in the Treatment of Adults With ADHD and Comorbid Social Anxiety Disorder
NCT00190957	PHASE4	COMPLETED	Atomoxetine Treatment of Adults With ADHD and Comorbid Alcohol Abuse
NCT00191035	PHASE4	COMPLETED	Maintenance of Benefit With Atomoxetine Hydrochloride in Adolescents With ADHD
NCT00191048	PHASE4	COMPLETED	Treatment With Atomoxetine Hydrochloride in Children and Adolescents With ADHD
NCT00191633	PHASE4	COMPLETED	Study of Atomoxetine in Children With ADHD to Assess Symptomatic and Functional Outcomes
NCT00191906	PHASE4	COMPLETED	Comparison of Atomoxetine and Placebo in Children With Attention-Deficit/Hyperactivity Disorder (ADHD) and/or Reading Disorder (RD)
NCT00216918	PHASE4	COMPLETED	Neuropsychological Functioning in Children With Attention-Deficit/Hyperactivity Disorder.
NCT00221962	PHASE4	COMPLETED	Study of Aripiprazole (Abilify) in Children With ADHD (Attention Deficit Hyperactivity Disorder)
NCT00223561	PHASE4	COMPLETED	Methylphenidate and Driving Ability in Adult Patients With Attention-Deficit Hyperactivity Disorder
NCT00299234	PHASE4	TERMINATED	Atomoxetine for Children With Acquired Attentional Disorders Following Completion of Chemotherapy for ALL
NCT00302406	PHASE4	COMPLETED	Naturalistic Substitution of Concerta in Adult Subject With ADHD Receiving Immediate Release Methylphenidate
NCT00305370	PHASE4	COMPLETED	Aripiprazole Associated With Methylphenidate in Children and Adolescents With Bipolar Disorder and ADHD
NCT00381758	PHASE4	COMPLETED	The COMACS Study: A Comparison of Methylphenidates in an Analog Classroom Setting
NCT00406354	PHASE4	COMPLETED	Comparison of Atomoxetine Versus Placebo in Children and Adolescents With ADHD and Comorbid ODD in Germany
NCT00434213	PHASE4	COMPLETED	Characterization of Dermal Reactions in Pediatric Patients With ADHD Using DAYTRANA
NCT00468143	PHASE4	COMPLETED	A Within-Subject Cross-Over Comparison Between Immediate Release and Extended Release Adderall
NCT00471354	PHASE4	COMPLETED	A Study for Patients With Attention-Deficit/Hyperactivity Disorder Treated With Atomoxetine
NCT00483106	PHASE4	COMPLETED	Clinical and Pharmacogenetic Study of Attention Deficit With Hyperactivity Disorder (ADHD)
NCT00485849	PHASE4	COMPLETED	A Study of Atomoxetine for Attention Deficit and Hyperactive/Impulsive Behaviour Problems in Children With ASD
NCT00485875	PHASE4	COMPLETED	Safety and Efficacy of Switching From a Stimulant Medication to Atomoxetine in Children and Adolescents With ADHD
NCT00486122	PHASE4	COMPLETED	Evaluation of Continuous Symptom Treatment of ADHD
NCT00500071	PHASE4	COMPLETED	Dose-Optimization Study Evaluating the Efficacy, Safety and Tolerability of Vyvanse (Lisdexamfetamine Dimesylate) in Children Aged 6-12 Diagnosed With ADHD
NCT00506727	PHASE4	COMPLETED	Analog Classroom Study Comparison of ADDERALL XR With STRATTERA in Children Aged 6-12 With ADHD
NCT00510276	PHASE4	COMPLETED	Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) With Atomoxetine in Young Adults and Its Effects on Functional Outcomes
NCT00517504	PHASE4	COMPLETED	Methylphenidate Study in Young Children With Developmental Disorders
NCT00517647	PHASE4	COMPLETED	Atomoxetine Pilot Study in Preschool Children With ADHD
NCT00518232	PHASE4	COMPLETED	A Study to Determine Effective and Tolerable Titration Scheme for OROS-Methylphenidate in Children With Attention-deficit Hyperactivity Disorder
NCT00530257	PHASE4	COMPLETED	Study of the Effects of Osmotic-Release Oral System (OROS) Methylphenidate (Concerta) on Attention and Memory
NCT00536419	PHASE4	UNKNOWN	Impact of Attention Deficit/Hyperactivity Disorder and Substance Use Disorder on Motorcycle Traffic Accidents