WBP4

Summary

WBP4 (WW domain binding protein 4, HGNC:12739) is a protein-coding gene on chromosome 13q14.11, encoding WW domain-binding protein 4 (O75554). Involved in pre-mRNA splicing as a component of the spliceosome.

This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A.

Source: NCBI Gene 11193 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 86 total — 1 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 67
• MANE Select transcript: NM_007187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12739
Approved symbol	WBP4
Name	WW domain binding protein 4
Location	13q14.11
Locus type	gene with protein product
Status	Approved
Aliases	FBP21, MGC117310
Ensembl gene	ENSG00000120688
Ensembl biotype	protein_coding
OMIM	604981
Entrez	11193

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000379487, ENST00000916033, ENST00000916034, ENST00000953016, ENST00000953017

RefSeq mRNA: 1 — MANE Select: NM_007187 NM_007187

CCDS: CCDS9375

Canonical transcript exons

ENST00000379487 — 10 exons

Exon	Start	End
ENSE00000680991	41065016	41065078
ENSE00000680992	41065164	41065287
ENSE00000680993	41068561	41068737
ENSE00000680994	41071527	41071573
ENSE00000680995	41072782	41072857
ENSE00000680997	41080646	41080809
ENSE00000817202	41062644	41062716
ENSE00000817203	41076044	41076237
ENSE00001481264	41082704	41084006
ENSE00001481275	41061509	41061675

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.29.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.9662 / max 617.2054, expressed in 1775 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
134833	17.7751	1775
134834	0.1911	55

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	96.29	gold quality
secondary oocyte	CL:0000655	93.29	gold quality
amniotic fluid	UBERON:0000173	92.51	gold quality
tendon	UBERON:0000043	92.18	gold quality
biceps brachii	UBERON:0001507	91.96	gold quality
calcaneal tendon	UBERON:0003701	91.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.63	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.57	gold quality
gastrocnemius	UBERON:0001388	90.97	gold quality
muscle of leg	UBERON:0001383	90.95	gold quality
muscle organ	UBERON:0001630	90.70	gold quality
vastus lateralis	UBERON:0001379	90.36	gold quality
quadriceps femoris	UBERON:0001377	90.17	gold quality
tendon of biceps brachii	UBERON:0008188	90.14	gold quality
deltoid	UBERON:0001476	90.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	89.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.78	gold quality
skeletal muscle tissue	UBERON:0001134	89.49	gold quality
medial globus pallidus	UBERON:0002477	89.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.99	gold quality
tibialis anterior	UBERON:0001385	88.64	gold quality
diaphragm	UBERON:0001103	88.58	gold quality
heart right ventricle	UBERON:0002080	88.52	gold quality
postcentral gyrus	UBERON:0002581	88.23	gold quality
globus pallidus	UBERON:0001875	87.98	gold quality
muscle tissue	UBERON:0002385	87.90	gold quality
orbitofrontal cortex	UBERON:0004167	87.89	gold quality
ventricular zone	UBERON:0003053	87.73	gold quality
heart left ventricle	UBERON:0002084	87.70	gold quality
cardiac ventricle	UBERON:0002082	87.67	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.02
E-MTAB-7249	no	986.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

91 targeting WBP4, 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-5692A	100.00	74.40	6850
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548A-5P	99.94	71.27	3482
HSA-MIR-548AD-5P	99.94	71.23	3502
HSA-MIR-548AE-5P	99.94	71.23	3502
HSA-MIR-548AK	99.94	71.24	3488
HSA-MIR-548AM-5P	99.94	71.24	3488
HSA-MIR-548AP-5P	99.94	71.14	3489
HSA-MIR-548AQ-5P	99.94	71.34	3426
HSA-MIR-548AR-5P	99.94	71.28	3515
HSA-MIR-548AS-5P	99.94	71.22	3482
HSA-MIR-548AU-5P	99.94	71.24	3488
HSA-MIR-548AY-5P	99.94	71.23	3502
HSA-MIR-548B-5P	99.94	71.23	3502

Literature-anchored findings (GeneRIF, showing 4)

• analysis of the Structure and function of the two tandem WW domains of the pre-mRNA splicing factor FBP21 (formin-binding protein 21) (PMID:19592703)
• formin-binding protein 21 (FBP21)-tandem-WW domain binding fosters protein recognition in the pre-spliceosome (PMID:21917930)
• Biochemical and biophysical analyses revealed that an intrinsically disordered region of FBP21 binds to an extended surface of the C-terminal Sec63 unit of Brr2. Additional contacts in the C-terminal helicase cassette are required for allosteric inhibition of Brr2 helicase activity. (PMID:28838205)
• FBP21’s C-Terminal Domain Remains Dynamic When Wrapped around the c-Sec63 Unit of Brr2 Helicase (PMID:30558886)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Wbp4	ENSMUSG00000022023
rattus_norvegicus	Wbp4	ENSRNOG00000011678
drosophila_melanogaster	CG4291	FBGN0031287

Protein

Protein identifiers

WW domain-binding protein 4 — O75554 (reviewed: O75554)

Alternative names: Formin-binding protein 21, WW domain-containing-binding protein 4

All UniProt accessions (1): O75554

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as a component of the spliceosome. May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex.

Subunit / interactions. Component of the spliceosome B complex. Associated with U2 snRNPs. Binds splicing factors SNRPB, SNRPC and SF1. Interacts via the WW domains with the Pro-rich domains of KHDRBS1/SAM68. Interacts via the WW domains with the Pro-rich domains of WBP11. Interacts with SNRNP200.

Subcellular location. Nucleus. Nucleus speckle.

Disease relevance. Neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities (NEDHFDB) [MIM:620852] An autosomal recessive, severe disorder apparent from infancy and characterized by global developmental delay, poor or absent speech, severe intellectual disability, hypotonia, and musculoskeletal and gastrointestinal abnormalities. Brain imaging shows aplasia or hypoplasia of corpus callosum in most patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WW domain recognizes the proline, glycine and methionine-rich (PGM) motif present in the splicing factors, as well as the Arg/Gly-rich-flanked Pro-rich domains found in several WW domain-binding proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
O75554-1	1	yes
O75554-2	2

RefSeq proteins (1): NP_009118* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000690	Matrin/U1-C_Znf_C2H2	Domain
IPR001202	WW_dom	Domain
IPR003604	Matrin/U1-like-C_Znf_C2H2	Domain
IPR013085	U1-CZ_Znf_C2H2	Domain
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR040023	WBP4	Family

Pfam: PF00397, PF06220

UniProt features (40 total): strand 9, compositionally biased region 8, modified residue 4, turn 4, region of interest 4, domain 2, sequence variant 2, mutagenesis site 2, helix 2, chain 1, splice variant 1, zinc finger region 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
8Q7N	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
7OS1	ELECTRON MICROSCOPY	3.3
6AHD	ELECTRON MICROSCOPY	3.8
8QZS	ELECTRON MICROSCOPY	4.1
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
2DK1	SOLUTION NMR
2JXW	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75554-F1	66.86	0.25

Functional residue map

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

Post-translational modifications (4): 220, 227, 229, 262

Mutagenesis-validated functional residues (2):

Position	Phenotype
150	nearly abolishes activation of pre-mrna splicing. abolishes interaction with wbp11.
191	nearly abolishes activation of pre-mrna splicing. abolishes interaction with wbp11.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 334 (showing top): MORF_MSH3, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, MORF_BRCA1, TGACCTY_ERR1_Q2, FOXO1_01, CAGCTG_AP4_Q5, MORF_RAD51L3, COUP_01, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, TGCTGAY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, GARY_CD5_TARGETS_DN, REACTOME_MRNA_SPLICING, NRF2_Q4

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), RNA splicing (GO:0008380), mRNA cis splicing, via spliceosome (GO:0045292), mRNA processing (GO:0006397)

GO Molecular Function (6): RNA binding (GO:0003723), zinc ion binding (GO:0008270), proline-rich region binding (GO:0070064), nucleic acid binding (GO:0003676), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), precatalytic spliceosome (GO:0071011), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
binding	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
mRNA metabolic process	1
nucleic acid binding	1
transition metal ion binding	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
spliceosomal complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WBP4	SNRPB	P14678	897
WBP4	SNRPB2	P08579	855
WBP4	FMN1	Q68DA7	822
WBP4	ZMAT2	Q96NC0	777
WBP4	MFAP1	P55081	747
WBP4	SNRPC	P09234	742
WBP4	PRPF38A	Q8NAV1	741
WBP4	FNBP4	Q8N3X1	687
WBP4	SNRNP200	O75643	659
WBP4	SF1	Q15637	629
WBP4	SF3B4	Q15427	616
WBP4	FMNL3	Q8IVF7	606
WBP4	FMNL1	O95466	605
WBP4	DAAM2	Q86T65	585
WBP4	SMU1	Q2TAY7	583

IntAct

120 interactions, top by confidence:

A	B	Type	Score
MED17	MED19	psi-mi:“MI:0914”(association)	0.840
SART1	PRPF3	psi-mi:“MI:0914”(association)	0.720
SNRNP200	WBP4	psi-mi:“MI:0915”(physical association)	0.690
SNRNP200	WBP4	psi-mi:“MI:0407”(direct interaction)	0.690
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670
WBP4	KHDRBS1	psi-mi:“MI:0407”(direct interaction)	0.670
KHDRBS1	WBP4	psi-mi:“MI:0407”(direct interaction)	0.670
KHDRBS1	WBP4	psi-mi:“MI:0915”(physical association)	0.670
WBP4	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.670
PRPF31	PRPF4	psi-mi:“MI:0914”(association)	0.640
WBP4	RBM45	psi-mi:“MI:0915”(physical association)	0.620
	WBP4	psi-mi:“MI:0882”(atpase reaction)	0.610
	WBP4	psi-mi:“MI:0915”(physical association)	0.610
WBP4		psi-mi:“MI:0407”(direct interaction)	0.610
WBP4	SF3A2	psi-mi:“MI:0915”(physical association)	0.590
SF3A2	WBP4	psi-mi:“MI:0915”(physical association)	0.590

BioGRID (145): WBP4 (Proximity Label-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), RBM45 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), FSTL5 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), WBP4 (Affinity Capture-MS), HIST1H2BH (Proximity Label-MS), SF3A2 (Proximity Label-MS), WBP4 (Proximity Label-MS)

ESM2 similar proteins: A5DUN2, A6ZZI5, B3LQW4, B5RTE0, C4Y2J3, C4YIM0, C5M6H7, G2TRU5, O36031, O42921, O59799, O74347, O75012, O75554, P0CM70, P0CM71, P34415, P36064, P38824, P45967, Q02772, Q04341, Q05809, Q12287, Q17Q91, Q21551, Q28GG4, Q2KHZ4, Q2TAP8, Q54P46, Q552P9, Q5A884, Q5BJN5, Q61712, Q63ZK1, Q6BKN1, Q6C4R1, Q6CIT9, Q6DEI8, Q6FML0

Diamond homologs: O60138, O75554, Q5F457, Q5HZF2, Q61048, Q7XA66

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 89 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
Metabolism of non-coding RNA	5	48.1×	1e-06
mRNA Splicing - Minor Pathway	11	37.3×	1e-13
mRNA Splicing	22	36.6×	1e-27
Processing of Capped Intron-Containing Pre-mRNA	26	32.4×	2e-31
mRNA Polyadenylation	24	31.9×	9e-29
mRNA Splicing - Major Pathway	38	31.5×	2e-47
CHD1 and CHD2 subfamily	15	24.7×	7e-16
RNA Polymerase II Transcription Termination	6	20.0×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	12	92.5×	2e-19
RNA splicing, via transesterification reactions	9	69.3×	4e-13
spliceosomal snRNP assembly	9	64.6×	6e-13
mRNA splicing, via spliceosome	36	40.7×	2e-47
spliceosomal complex assembly	5	37.1×	1e-05
RNA splicing	21	22.9×	7e-21
mRNA processing	16	15.6×	4e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	4
Uncertain significance	56
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
4537930	NM_007187.5(WBP4):c.340_347del (p.Lys114fs)	Pathogenic
2500811	NC_000013.11:g.41074134_41090164del	Likely pathogenic
2500812	NM_007187.5(WBP4):c.668C>G (p.Ser223Ter)	Likely pathogenic
2500814	NM_007187.5(WBP4):c.440-1G>A	Likely pathogenic
4845694	NM_007187.5(WBP4):c.15del (p.Tyr4_Trp5insTer)	Likely pathogenic

SpliceAI

1484 predictions. Top by Δscore:

Variant	Effect	Δscore
13:41062872:GCT:G	donor_gain	1.0000
13:41065007:A:AG	acceptor_gain	1.0000
13:41065008:T:G	acceptor_gain	1.0000
13:41065013:A:AG	acceptor_gain	1.0000
13:41065014:A:G	acceptor_gain	1.0000
13:41065015:GA:G	acceptor_gain	1.0000
13:41065015:GAGT:G	acceptor_gain	1.0000
13:41065161:T:G	acceptor_gain	1.0000
13:41065162:A:AG	acceptor_gain	1.0000
13:41065163:G:GC	acceptor_gain	1.0000
13:41065163:GA:G	acceptor_gain	1.0000
13:41065163:GATT:G	acceptor_gain	1.0000
13:41065163:GATTA:G	acceptor_gain	1.0000
13:41065283:GTCAG:G	donor_gain	1.0000
13:41065284:TCAGG:T	donor_loss	1.0000
13:41065285:CAGGT:C	donor_loss	1.0000
13:41065288:GTA:G	donor_loss	1.0000
13:41065289:T:A	donor_loss	1.0000
13:41066580:T:G	donor_gain	1.0000
13:41068556:TTTA:T	acceptor_loss	1.0000
13:41068558:TAG:T	acceptor_loss	1.0000
13:41068559:A:AG	acceptor_gain	1.0000
13:41068559:AGAA:A	acceptor_loss	1.0000
13:41068560:G:GC	acceptor_gain	1.0000
13:41068560:GA:G	acceptor_gain	1.0000
13:41068560:GAA:G	acceptor_gain	1.0000
13:41080639:A:AG	acceptor_gain	1.0000
13:41080645:GGAAA:G	acceptor_gain	1.0000
13:41080805:TCTCA:T	donor_gain	1.0000
13:41080806:CTCAG:C	donor_loss	1.0000

AlphaMissense

2474 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:41062654:T:A	W5R	1.000
13:41062654:T:C	W5R	1.000
13:41062656:G:C	W5C	1.000
13:41062656:G:T	W5C	1.000
13:41062678:T:A	C13S	1.000
13:41062678:T:C	C13R	1.000
13:41062679:G:A	C13Y	1.000
13:41062679:G:C	C13S	1.000
13:41062679:G:T	C13F	1.000
13:41062687:T:A	C16S	1.000
13:41062687:T:C	C16R	1.000
13:41062688:G:A	C16Y	1.000
13:41062688:G:C	C16S	1.000
13:41062696:T:A	W19R	1.000
13:41062696:T:C	W19R	1.000
13:41062698:G:C	W19C	1.000
13:41062698:G:T	W19C	1.000
13:41065025:T:C	F29L	1.000
13:41065027:T:A	F29L	1.000
13:41065027:T:G	F29L	1.000
13:41065028:C:A	H30N	1.000
13:41065028:C:G	H30D	1.000
13:41065046:C:G	H36D	1.000
13:41062655:G:C	W5S	0.999
13:41062675:T:C	F12L	0.999
13:41062677:C:A	F12L	0.999
13:41062677:C:G	F12L	0.999
13:41062680:T:G	C13W	0.999
13:41062688:G:T	C16F	0.999
13:41062689:C:G	C16W	0.999

dbSNP variants (sampled 300 via entrez): RS1000167851 (13:41075423 C>A), RS1000213153 (13:41062587 G>A,C,T), RS1000242875 (13:41062349 T>A,C), RS1000401406 (13:41075156 C>A,G), RS1000436321 (13:41068965 C>A,T), RS1000541227 (13:41075589 C>T), RS1000572914 (13:41067578 T>G), RS1000739495 (13:41073814 T>A), RS1000897815 (13:41074810 C>T), RS1000903667 (13:41065334 A>G), RS1000934207 (13:41064922 T>C,G), RS1000968239 (13:41071539 A>G), RS1001094957 (13:41076810 C>T), RS1001161854 (13:41060736 C>A,G,T), RS1001239170 (13:41064420 G>A,C,T)

Disease associations

OMIM: gene MIM:604981 | disease phenotypes: MIM:620852

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal recessive
neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities	Moderate	Autosomal recessive

Mondo (2): neurodevelopmental disorder (MONDO:0700092), neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities (MONDO:0971043)

Orphanet (0):

HPO phenotypes

67 total (30 of 67 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000126	Hydronephrosis
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000262	Turricephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000319	Smooth philtrum
HP:0000322	Short philtrum
HP:0000341	Narrow forehead
HP:0000369	Low-set ears
HP:0000402	Stenosis of the external auditory canal
HP:0000407	Sensorineural hearing impairment
HP:0000411	Protruding ear
HP:0000426	Prominent nasal bridge
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000520	Proptosis
HP:0000582	Upslanted palpebral fissure
HP:0000678	Dental crowding
HP:0000718	Aggressive behavior
HP:0000729	Autistic behavior
HP:0000733	Motor stereotypy
HP:0000750	Delayed speech and language development
HP:0000752	Hyperactivity
HP:0001249	Intellectual disability

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001785_3	Crohn’s disease	8.000000e-09
GCST005331_8	CSF tryptophan concentration in tuberculous meningitis	2.000000e-06
GCST005580_307	Intraocular pressure	4.000000e-09
GCST009067_3	Mosaic loss of chromosome Y (Y chromosome dosage)	9.000000e-10
GCST009375_18	Mosaic loss of chromosome Y (Y chromosome dosage)	9.000000e-10
GCST90013442_21	Keratoconus	6.000000e-35

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008534	tryptophan measurement
EFO:0004695	intraocular pressure measurement
EFO:0007783	mosaic loss of chromosome Y measurement

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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	3
sodium arsenite	affects expression, affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
borrelidin	affects binding, affects splicing, decreases reaction	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
Bortezomib	increases expression	1
Resveratrol	increases expression, affects cotreatment	1
Air Pollutants	increases abundance, decreases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Copper	affects binding, increases expression	1
Succimer	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	affects expression	1
Gold	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methyl Methanesulfonate	increases 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