HIVEP3

Summary

HIVEP3 (HIVEP zinc finger 3, HGNC:13561) is a protein-coding gene on chromosome 1p34.2, encoding Transcription factor HIVEP3 (Q5T1R4). Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation.

This gene encodes a member of the human immunodeficiency virus type 1 enhancer-binding protein family. Members of this protein family contain multiple zinc finger and acid-rich (ZAS) domains and serine-threonine rich regions. This protein acts as a transcription factor and is able to regulate nuclear factor kappaB-mediated transcription by binding the kappaB motif in target genes. This protein also binds the recombination signal sequence that flanks the V, D, and J regions of immunoglobulin and T-cell receptors. Alternate splicing results in both coding and non-coding transcript variants.

Source: NCBI Gene 59269 — RefSeq curated summary.

At a glance

• GWAS associations: 36
• Clinical variants (ClinVar): 113 total
• Dosage sensitivity (ClinGen): haploinsufficiency little evidence, triplosensitivity no evidence
• MANE Select transcript: NM_024503

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13561
Approved symbol	HIVEP3
Name	HIVEP zinc finger 3
Location	1p34.2
Locus type	gene with protein product
Status	Approved
Aliases	KRC, KBP1, KBP-1, SHN3, FLJ16752, KIAA1555, ZAS3, Schnurri-3, ZNF40C
Ensembl gene	ENSG00000127124
Ensembl biotype	protein_coding
OMIM	606649
Entrez	59269

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 protein_coding_CDS_not_defined, 3 protein_coding

ENST00000372583, ENST00000372584, ENST00000460604, ENST00000479350, ENST00000489103, ENST00000491442, ENST00000643665

RefSeq mRNA: 2 — MANE Select: NM_024503 NM_001127714, NM_024503

CCDS: CCDS44124, CCDS463

Canonical transcript exons

ENST00000372583 — 9 exons

Exon	Start	End
ENSE00000870144	41524735	41524910
ENSE00001146673	41579737	41585318
ENSE00001391323	41628749	41628947
ENSE00001458149	41506365	41511266
ENSE00001458150	41700916	41700995
ENSE00001458151	41918413	41918922
ENSE00003615146	41575544	41575689
ENSE00003635014	41512816	41513750
ENSE00003665456	41518402	41518488

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 95.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.8468 / max 162.8225, expressed in 1280 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11959	1.5970	675
11972	1.0806	648
11958	0.9727	490
11971	0.5289	247
11969	0.4567	137
11970	0.1207	27
11968	0.0901	42

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	95.00	gold quality
endothelial cell	CL:0000115	93.25	gold quality
Brodmann (1909) area 23	UBERON:0013554	87.79	gold quality
cartilage tissue	UBERON:0002418	83.02	gold quality
cortical plate	UBERON:0005343	82.66	gold quality
parietal pleura	UBERON:0002400	82.39	gold quality
primary visual cortex	UBERON:0002436	82.21	gold quality
granulocyte	CL:0000094	81.26	gold quality
middle temporal gyrus	UBERON:0002771	81.24	gold quality
entorhinal cortex	UBERON:0002728	80.98	gold quality
germinal epithelium of ovary	UBERON:0001304	80.96	gold quality
occipital lobe	UBERON:0002021	80.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.04	gold quality
pleura	UBERON:0000977	80.04	gold quality
cerebellar vermis	UBERON:0004720	79.97	gold quality
skin of abdomen	UBERON:0001416	79.61	gold quality
right lung	UBERON:0002167	79.40	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	78.95	gold quality
visceral pleura	UBERON:0002401	78.45	gold quality
spinal cord	UBERON:0002240	78.12	gold quality
upper lobe of left lung	UBERON:0008952	78.02	gold quality
skin of leg	UBERON:0001511	77.95	gold quality
left lobe of thyroid gland	UBERON:0001120	77.83	gold quality
thyroid gland	UBERON:0002046	77.55	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.45	gold quality
right lobe of thyroid gland	UBERON:0001119	77.38	gold quality
upper lobe of lung	UBERON:0008948	77.38	gold quality
cerebellar cortex	UBERON:0002129	77.35	gold quality
cerebellum	UBERON:0002037	77.26	gold quality
cerebellar hemisphere	UBERON:0002245	77.23	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	27.19
E-ANND-3	yes	5.34
E-MTAB-6075	no	458.21

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

6 targets.

Target	Regulation
IL17A
IL2	Unknown
PRKD2
RUNX2	Unknown
TNF	Unknown
WWP1

Upstream regulators (CollecTRI, top): NR1I2, RUNX1

miRNA regulators (miRDB)

156 targeting HIVEP3, 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-4425	100.00	67.59	1049
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-515-5P	99.92	69.82	2343

Functional genomics

ClinGen dosage: haploinsufficiency 1 (little evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 11)

• Overexpression of KRC in transformed and primary T cells leads to increased IL-2 production. (PMID:14707112)
• Single nucleotide polymorphisms strongly support HIVEP3 as a candidate for PARK10 in Parkinson disease. (PMID:17388942)
• An interaction between ZAS3 and Smad proteins enhances transforming growth factor beta signaling. (PMID:20732416)
• DNA competition by ZAS3 is sufficient to repress transcription activated by NF-kappaB and that ZAS3 is an endogenous kappaB-motif competitor with ininsic repression activity. (PMID:21189157)
• The inhibitory effect of ZAS3 on NF-kappa B activity is mediated by neither direct association with N-kappa B nor disrupting nuclear localization of NFvarkappaB. (PMID:21524353)
• ZAS3 expression is directly regulated by estrogen and is overexpressed in lupus. Its upregulation by estrogen could play a critical role in female-biased autoimmune disorders. (PMID:23178823)
• Transdifferentiation of VSMC into calcifying vascular cells is enhanced by LPC and attenuated by Schnurri-3. (PMID:23500015)
• rheumatoid arthritis-fibroblast-like synoviocytes were more sensitive to the synergistic increase of Schnurri-3 expression. (PMID:27072520)
• The identification and structural analysis of potential 14-3-3 interaction sites on the bone regulator protein Schnurri-3. (PMID:34341191)
• HIVEP3 cooperates with ferroptosis gene signatures to confer adverse prognosis in acute myeloid leukemia. (PMID:35535739)
• HIVEP3 as a potential prognostic factor promotes the development of acute myeloid leukemia. (PMID:36571205)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	hivep3b	ENSDARG00000037154
danio_rerio	hivep3a	ENSDARG00000075928
mus_musculus	Hivep3	ENSMUSG00000028634
rattus_norvegicus	Hivep3	ENSRNOG00000009341

Paralogs (14): HIVEP2 (ENSG00000010818), HIVEP1 (ENSG00000095951), SALL4 (ENSG00000101115), ZNF516 (ENSG00000101493), SALL1 (ENSG00000103449), BCL11A (ENSG00000119866), ZNF831 (ENSG00000124203), RREB1 (ENSG00000124782), BCL11B (ENSG00000127152), ZNF219 (ENSG00000165804), SALL2 (ENSG00000165821), ZNF217 (ENSG00000171940), ZNF536 (ENSG00000198597), SALL3 (ENSG00000256463)

Protein

Protein identifiers

Transcription factor HIVEP3 — Q5T1R4 (reviewed: Q5T1R4)

Alternative names: Human immunodeficiency virus type I enhancer-binding protein 3, Kappa-B and V(D)J recombination signal sequences-binding protein, Kappa-binding protein 1, Zinc finger protein ZAS3

All UniProt accessions (1): Q5T1R4

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role of transcription factor; binds to recognition signal sequences (Rss heptamer) for somatic recombination of immunoglobulin and T-cell receptor gene segments; Also binds to the kappa-B motif of gene such as S100A4, involved in cell progression and differentiation. Kappa-B motif is a gene regulatory element found in promoters and enhancers of genes involved in immunity, inflammation, and growth and that responds to viral antigens, mitogens, and cytokines. Involvement of HIVEP3 in cell growth is strengthened by the fact that its down-regulation promotes cell cycle progression with ultimate formation of multinucleated giant cells. Strongly inhibits TNF-induced NF-kappa-B activation; Interferes with nuclear factor NF-kappa-B by several mechanisms: as transcription factor, by competing for Kappa-B motif and by repressing transcription in the nucleus; through a non transcriptional process, by inhibiting nuclear translocation of RELA by association with TRAF2, an adapter molecule in the tumor necrosis factor signaling, which blocks the formation of IKK complex. Interaction with TRAF proteins inhibits both NF-Kappa-B-mediated and c-Jun N-terminal kinase/JNK-mediated responses that include apoptosis and pro-inflammatory cytokine gene expression. Positively regulates the expression of IL2 in T-cell. Essential regulator of adult bone formation.

Subunit / interactions. Interacts with TRAF1 and TRAF2 as well as with JUN. Forms a multimeric complex with RUNX2 and E3 ubiquitin ligase WWP1.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylated on threonine and serine residues.

Domain organisation. The ZAS2 domain binds DNA as dimers, tetramers, and multiple of tetramers and readily forms highly ordered DNA-protein structures.

Induction. By 12-O-tetradecanoylphorbol-13 acetate (TPA).

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T1R4-1	1, HIVEP3S	yes
Q5T1R4-2	2

RefSeq proteins (2): NP_001121186, NP_078779* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013087	Znf_C2H2_type	Domain
IPR034729	Znf_CCHC_HIVEP	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051969

Pfam: PF00096

UniProt features (93 total): compositionally biased region 32, region of interest 22, sequence conflict 15, sequence variant 9, repeat 6, zinc finger region 5, chain 1, coiled-coil region 1, short sequence motif 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T1R4-F1	37.25	0.02

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8939902	Regulation of RUNX2 expression and activity

MSigDB gene sets: 340 (showing top): GOBP_MUSCLE_TISSUE_DEVELOPMENT, GCANCTGNY_MYOD_Q6, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, ATGCAGT_MIR217, HEIDENBLAD_AMPLICON_8Q24_DN, CAGCTG_AP4_Q5, GTGCCTT_MIR506, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, TGCTGAY_UNKNOWN, BACH2_01, GOBP_SKELETAL_MUSCLE_ORGAN_DEVELOPMENT, WTGAAAT_UNKNOWN, chr1p34, HP1SITEFACTOR_Q6, TGACATY_UNKNOWN

GO Biological Process (4): regulation of transcription by RNA polymerase II (GO:0006357), skeletal muscle cell differentiation (GO:0035914), positive regulation of DNA-templated transcription (GO:0045893), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (6): 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), DNA binding (GO:0003677), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): nucleus (GO:0005634), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transcriptional regulation by RUNX2	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription by RNA polymerase II	1
skeletal muscle tissue development	1
cell differentiation	1
positive regulation of RNA biosynthetic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	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
nucleic acid binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1416 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HIVEP3	WWP1	Q9H0M0	885
HIVEP3	CDCP2	Q5VXM1	847
HIVEP3	USP24	Q9UPU5	799
HIVEP3	RUNX2	Q13950	757
HIVEP3	ELAVL4	P26378	729
HIVEP3	EIF2B3	Q9NR50	655
HIVEP3	RAG2	P55895	442
HIVEP3	REL	Q04864	440
HIVEP3	TYRP1	P17643	436
HIVEP3	ADAMTS18	Q8TE60	428
HIVEP3	KRTCAP3	Q53RY4	426
HIVEP3	MAST2	Q6P0Q8	422
HIVEP3	HSPB3	Q12988	421
HIVEP3	SPATC1L	Q9H0A9	418
HIVEP3	TRAF2	Q12933	407
HIVEP3	DYNLT4	Q5JR98	407

IntAct

14 interactions, top by confidence:

A	B	Type	Score
SFN	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.620
YWHAG	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.560
YWHAH	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAB	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAQ	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAE	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.440
YWHAZ	HIVEP3	psi-mi:“MI:0407”(direct interaction)	0.440
HIVEP3	JUN	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (34): HIVEP3 (Affinity Capture-MS), HIVEP3 (Proximity Label-MS), TRAF1 (Two-hybrid), TRAF2 (Two-hybrid), HIVEP3 (Affinity Capture-RNA), HIVEP3 (Affinity Capture-RNA), HIVEP3 (Proximity Label-MS), HIVEP3 (Affinity Capture-RNA), TRAF2 (Affinity Capture-Western), TRAF1 (Affinity Capture-Western), HIVEP3 (Affinity Capture-MS), HIVEP3 (Two-hybrid), HIVEP3 (Affinity Capture-RNA), PNN (Cross-Linking-MS (XL-MS)), CRABP2 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2A884, F1QQA8, O08696, O43151, O94993, P08651, P09414, P15822, P17923, P21999, P31629, P55200, Q00900, Q01538, Q03164, Q03172, Q08050, Q08D57, Q12857, Q1LY77, Q2M1Z3, Q3UHF7, Q3UTJ2, Q498L0, Q499E5, Q5DTJ9, Q5SW79, Q5T1R4, Q5ZKH6, Q62255, Q62417, Q66J90, Q69Z38, Q6A065, Q86V15, Q8BG87, Q8C5W0, Q8CFC2, Q8CGW4, Q8CH77

Diamond homologs: A1L2U9, A2A884, A2ANX9, A7Y7X5, B0X9H6, B0YDH7, B1WAZ8, B1WBU4, O35615, O62836, O77459, P08048, P10925, P15822, P17010, P17012, P20662, P31505, P31629, P60319, P78871, P80944, Q00900, Q01611, Q02031, Q03172, Q0IH98, Q0VCJ6, Q292R5, Q29419, Q3UHF7, Q52V16, Q5JPB2, Q5T1R4, Q6B4Z5, Q7JM44, Q811F1, Q86UZ6, Q8BID6, Q8CII0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	42
Benign	44

Top pathogenic / likely-pathogenic (0)

SpliceAI

4684 predictions. Top by Δscore:

Variant	Effect	Δscore
1:41513748:TTC:T	acceptor_gain	1.0000
1:41513749:TC:T	acceptor_gain	1.0000
1:41513750:CC:C	acceptor_gain	1.0000
1:41513751:C:CA	acceptor_loss	1.0000
1:41513751:C:CC	acceptor_gain	1.0000
1:41513758:C:CT	acceptor_gain	1.0000
1:41518396:TGTTA:T	donor_loss	1.0000
1:41518397:GTTAC:G	donor_loss	1.0000
1:41518398:TTA:T	donor_loss	1.0000
1:41518399:TA:T	donor_loss	1.0000
1:41518401:CCTT:C	donor_gain	1.0000
1:41518485:TTCC:T	acceptor_gain	1.0000
1:41518487:CC:C	acceptor_gain	1.0000
1:41518488:CC:C	acceptor_gain	1.0000
1:41518489:C:CC	acceptor_gain	1.0000
1:41575699:C:CT	acceptor_gain	1.0000
1:41646187:C:A	donor_gain	1.0000
1:41799084:A:T	acceptor_gain	1.0000
1:41918407:CCCTA:C	donor_loss	1.0000
1:41918408:CCTAC:C	donor_loss	1.0000
1:41918409:CTA:C	donor_loss	1.0000
1:41918410:TA:T	donor_loss	1.0000
1:41918411:ACCTT:A	donor_loss	1.0000
1:41512959:T:TA	donor_gain	0.9900
1:41512960:C:A	donor_gain	0.9900
1:41513747:GTTC:G	acceptor_gain	0.9900
1:41518404:T:A	donor_gain	0.9900
1:41518486:TCC:T	acceptor_gain	0.9900
1:41518487:CCC:C	acceptor_gain	0.9900
1:41518488:CCTAG:C	acceptor_loss	0.9900

AlphaMissense

15507 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:41518465:A:G	S1803P	1.000
1:41518472:G:C	H1800Q	1.000
1:41518472:G:T	H1800Q	1.000
1:41518473:T:C	H1800R	1.000
1:41518473:T:G	H1800P	1.000
1:41518474:G:C	H1800D	1.000
1:41518474:G:T	H1800N	1.000
1:41518475:C:A	K1799N	1.000
1:41518475:C:G	K1799N	1.000
1:41518477:T:C	K1799E	1.000
1:41518482:A:G	L1797P	1.000
1:41518484:A:C	N1796K	1.000
1:41518484:A:T	N1796K	1.000
1:41518486:T:C	N1796D	1.000
1:41518488:C:T	G1795E	1.000
1:41524735:C:A	G1795W	1.000
1:41524735:C:G	G1795R	1.000
1:41524735:C:T	G1795R	1.000
1:41524742:T:A	K1792N	1.000
1:41524742:T:G	K1792N	1.000
1:41524743:T:A	K1792I	1.000
1:41524744:T:C	K1792E	1.000
1:41524745:A:C	F1791L	1.000
1:41524745:A:T	F1791L	1.000
1:41524746:A:C	F1791C	1.000
1:41524746:A:G	F1791S	1.000
1:41524747:A:G	F1791L	1.000
1:41524747:A:T	F1791I	1.000
1:41524751:A:C	F1789L	1.000
1:41524751:A:T	F1789L	1.000

dbSNP variants (sampled 300 via entrez): RS1000007641 (1:41547074 C>T), RS1000010462 (1:41735969 A>T), RS1000013004 (1:41666996 G>A), RS1000021010 (1:41925945 A>C), RS1000033530 (1:41857019 C>T), RS1000034093 (1:41888184 C>T), RS1000043164 (1:41893542 A>G), RS1000048295 (1:41989648 A>G,T), RS1000053951 (1:41945747 C>T), RS1000055294 (1:41539127 A>G), RS1000058928 (1:41609529 C>T), RS1000061064 (1:41513394 C>G), RS1000061642 (1:41651325 C>T), RS1000064324 (1:41736224 T>C), RS1000065468 (1:41776742 G>A)

Disease associations

OMIM: gene MIM:606649 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

36 associations (top):

Study	Trait	p-value
GCST002104_7	Bronchopulmonary dysplasia	9.000000e-06
GCST002479_4	Lupus nephritis in systemic lupus erythematosus	2.000000e-06
GCST002941_9	Airway imaging phenotypes	9.000000e-07
GCST003542_104	Night sleep phenotypes	9.000000e-07
GCST003854_8	Gut microbiota (functional units)	3.000000e-08
GCST004600_59	Eosinophil percentage of white cells	2.000000e-13
GCST004606_181	Eosinophil count	1.000000e-14
GCST004617_53	Eosinophil percentage of granulocytes	2.000000e-12
GCST004623_146	Neutrophil percentage of granulocytes	1.000000e-09
GCST004624_206	Sum eosinophil basophil counts	2.000000e-12
GCST004722_3	Left ventricular obstructive tract defect (maternal effect)	8.000000e-07
GCST004750_95	Squamous cell lung carcinoma	2.000000e-06
GCST004988_660	Breast cancer	4.000000e-08
GCST005170_14	Intraocular pressure	5.000000e-11
GCST006258_1	Diastolic blood pressure	2.000000e-07
GCST006259_33	Systolic blood pressure	5.000000e-12
GCST006291_94	Spherical equivalent or myopia (age of diagnosis)	6.000000e-09
GCST006979_875	Heel bone mineral density	5.000000e-11
GCST007095_49	Systolic blood pressure	3.000000e-08
GCST007095_50	Systolic blood pressure	1.000000e-06
GCST007096_25	Pulse pressure	3.000000e-16
GCST007097_102	Pulse pressure	1.000000e-07
GCST007097_103	Pulse pressure	8.000000e-11
GCST007099_10	Systolic blood pressure	3.000000e-14
GCST007267_172	Systolic blood pressure	1.000000e-11
GCST007269_11	Pulse pressure	5.000000e-10
GCST007325_26	General risk tolerance (MTAG)	4.000000e-08
GCST007667_5	Treatment resistant depression	5.000000e-06
GCST009307_16	Spatial memory	7.000000e-06
GCST010002_356	Refractive error	5.000000e-36

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0007627	airway imaging measurement
EFO:0007874	gut microbiome measurement
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007996	eosinophil percentage of granulocytes
EFO:0007994	neutrophil percentage of granulocytes
EFO:0005090	basophil count
EFO:0004695	intraocular pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0006335	systolic blood pressure
EFO:0004847	age at onset
EFO:0009270	heel bone mineral density
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0009854	treatment resistant depression
EFO:0004874	memory performance
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression	3
sodium arsenite	increases expression	2
entinostat	decreases expression, affects cotreatment	2
bisphenol S	decreases methylation, affects cotreatment, decreases expression	2
Air Pollutants	increases expression, decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	increases methylation, affects methylation	2
Dexamethasone	affects cotreatment, decreases expression, increases expression	2
Estradiol	affects expression, increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases expression	1
bufotalin	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
mono-(2-ethylhexyl)phthalate	decreases methylation, increases abundance	1
sulforaphane	decreases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

202 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,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice