NOVA2

Summary

NOVA2 (NOVA alternative splicing regulator 2, HGNC:7887) is a protein-coding gene on chromosome 19q13.32, encoding RNA-binding protein Nova-2 (Q9UNW9). Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion.

Enables sequence-specific mRNA binding activity. Involved in neuron differentiation and regulation of alternative mRNA splicing, via spliceosome. Predicted to be active in cytoplasm and nucleus.

Source: NCBI Gene 4858 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 124 total — 10 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_002516

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7887
Approved symbol	NOVA2
Name	NOVA alternative splicing regulator 2
Location	19q13.32
Locus type	gene with protein product
Status	Approved
Aliases	ANOVA, NOVA-2
Ensembl gene	ENSG00000104967
Ensembl biotype	protein_coding
OMIM	601991
Entrez	4858

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263257, ENST00000596784, ENST00000599462, ENST00000676183

RefSeq mRNA: 1 — MANE Select: NM_002516 NM_002516

CCDS: CCDS12679

Canonical transcript exons

ENST00000263257 — 4 exons

Exon	Start	End
ENSE00000858269	45973267	45973865
ENSE00001112712	45933734	45940945
ENSE00003601100	45961010	45961153
ENSE00003634238	45953780	45953946

Expression profiles

Bgee: expression breadth ubiquitous, 222 present calls, max score 93.42.

FANTOM5 (CAGE): breadth broad, TPM avg 9.1129 / max 277.8255, expressed in 664 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
181596	6.4430	619
181594	2.0135	499
181593	0.4799	209
181595	0.1765	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	93.42	gold quality
ganglionic eminence	UBERON:0004023	89.57	gold quality
tendon of biceps brachii	UBERON:0008188	88.05	gold quality
entorhinal cortex	UBERON:0002728	86.64	gold quality
cervix squamous epithelium	UBERON:0006922	86.43	gold quality
type B pancreatic cell	CL:0000169	85.65	gold quality
olfactory bulb	UBERON:0002264	85.61	gold quality
postcentral gyrus	UBERON:0002581	85.61	gold quality
parietal lobe	UBERON:0001872	85.25	gold quality
prefrontal cortex	UBERON:0000451	84.88	gold quality
superior frontal gyrus	UBERON:0002661	84.76	gold quality
right frontal lobe	UBERON:0002810	84.75	gold quality
frontal cortex	UBERON:0001870	84.42	gold quality
frontal lobe	UBERON:0016525	84.41	gold quality
nucleus accumbens	UBERON:0001882	84.09	gold quality
neocortex	UBERON:0001950	84.05	gold quality
medial globus pallidus	UBERON:0002477	83.75	gold quality
Brodmann (1909) area 10	UBERON:0013541	83.57	silver quality
temporal lobe	UBERON:0001871	83.33	gold quality
cerebellar vermis	UBERON:0004720	83.11	gold quality
superficial temporal artery	UBERON:0001614	83.02	gold quality
ventricular zone	UBERON:0003053	83.02	gold quality
cerebral cortex	UBERON:0000956	82.89	gold quality
occipital lobe	UBERON:0002021	82.69	gold quality
cingulate cortex	UBERON:0003027	82.63	gold quality
telencephalon	UBERON:0001893	82.49	gold quality
anterior cingulate cortex	UBERON:0009835	82.42	gold quality
buccal mucosa cell	CL:0002336	82.26	silver quality
globus pallidus	UBERON:0001875	82.21	gold quality
male germ cell	CL:0000015	82.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.41

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

304 targeting NOVA2, 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-200C-3P	100.00	73.35	2685
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-4745-5P	99.98	65.95	1028

Literature-anchored findings (GeneRIF, showing 13)

• SCN1A polymorphism has a dramatic effect on the proportions of neonate and adult alternative transcripts of SCN1A in adult brain tissue and, the effect of the polymorphism also appears to be modified by Nova2 expression levels. (PMID:17436242)
• Here, the authors report that endothelial cells (ECs) express a novel isoform of the cell-surface adhesion molecule L1CAM, termed L1-DeltaTM. The splicing factor NOVA2, which binds directly to L1CAM pre-mRNA, is necessary and sufficient for the skipping of L1CAM transmembrane domain in ECs, leading to the release of soluble L1-DeltaTM. (PMID:30829570)
• Authors identify a mechanism whereby Nova2-regulated splicing constrains Erk signaling, thus limiting lymphatic progenitor cell specification. (PMID:31014480)
• MiR-7-5p suppresses tumor metastasis of non-small cell lung cancer by targeting NOVA2. (PMID:31832068)
• The NOVA2 variant protein shows decreased ability to bind target RNA sequences. (PMID:32197073)
• PART1 destabilized by NOVA2 regulates blood-brain barrier permeability in endothelial cells via STAU1-mediated mRNA degradation. (PMID:34990795)
• Circ_0016760 Serves as a Cancer Promoter in Non-small Cell Lung Cancer Through miR-876-3p/NOVA2 Axis. (PMID:35239092)
• De novo truncating NOVA2 variants affect alternative splicing and lead to heterogeneous neurodevelopmental phenotypes. (PMID:35607920)
• Neuro-oncological Ventral Antigen 2 Regulates Splicing of Vascular Endothelial Growth Factor Receptor 1 and Is Required for Endothelial Function. (PMID:35927413)
• Alternative Splicing Changes Promoted by NOVA2 Upregulation in Endothelial Cells and Relevance for Gastric Cancer. (PMID:37175811)
• METTL14 reverses liver fibrosis by inhibiting NOVA2 through an m6A-YTHDF2-dependent mechanism. (PMID:37534933)
• Circ_0102231 inactivates the PI3K/AKT signaling pathway by regulating the miR-635/NOVA2 pathway to promote the progression of non-small cell lung cancer. (PMID:37864285)
• Circ_0004140 promotes lung adenocarcinoma progression by upregulating NOVA2 via sponging miR-330-5p. (PMID:37920146)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nova2	ENSMUSG00000030411
rattus_norvegicus	Nova2	ENSRNOG00000013847
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), NOVA1 (ENSG00000139910), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

RNA-binding protein Nova-2 — Q9UNW9 (reviewed: Q9UNW9)

Alternative names: Astrocytic NOVA1-like RNA-binding protein, Neuro-oncological ventral antigen 2

All UniProt accessions (3): A0A6Q8PFC2, Q9UNW9, M0R1A0

UniProt curated annotations — full annotation on UniProt →

Function. Functions to regulate alternative splicing in neurons by binding pre-mRNA in a sequence-specific manner to activate exon inclusion or exclusion. It binds specifically to the sequences 5’-YCAY-3’ and regulates splicing in only a subset of regulated exons. Binding to an exonic 5’-YCAY-3’ cluster changes the protein complexes assembled on pre-mRNA, blocking U1 snRNP binding and exon inclusion, whereas binding to an intronic 5’-YCAY-3’ cluster enhances spliceosome assembly and exon inclusion. With NOVA1, they perform unique biological functions in different brain areas and cell types. Uniquely regulates alternative splicing events of a series of axon guidance related genes during cortical development, being essential for central nervous system development by regulating neural networks wiring. Regulates differentially alternative splicing on the same transcripts expressed in different neurons. This includes functional differences in transcripts expressed in cortical and cerebellar excitatory versus inhibitory neurons where is required for, respectively, development of laminar structure and motor coordination and synapse formation. Also the regulation the regulation of intron retention can sequester the trans-acting splicing factor PTBP2, acting as a variable cis-acting scaffolding platform for PTBP2 across various natural conditions.

Subunit / interactions. Interacts with PTBP2; the interaction is direct.

Subcellular location. Nucleus.

Tissue specificity. Brain. Expression restricted to astrocytes.

Disease relevance. Neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (NEDASB) [MIM:618859] An early-onset neurodevelopmental disorder characterized by intellectual disability, motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and structural brain abnormalities including cerebral atrophy, cerebellar atrophy, and/or thin corpus callosum. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The third KH domain (KH3) recognizes specifically 5’-YCAY-3'.

RefSeq proteins (1): NP_002507* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004087	KH_dom	Domain
IPR004088	KH_dom_type_1	Domain
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR047274	KH-I_NOVA_rpt3	Domain
IPR047275	KH-I_NOVA_rpt1	Domain
IPR047276	KH-I_NOVA_rpt2	Domain

Pfam: PF00013

UniProt features (17 total): helix 4, domain 3, strand 3, sequence conflict 2, chain 1, turn 1, short sequence motif 1, cross-link 1, mutagenesis site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
1DTJ	X-RAY DIFFRACTION	2
1EC6	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UNW9-F1	65.60	0.22

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): 112

Mutagenesis-validated functional residues (1):

Position	Phenotype
231–492	loss of alternative splicing regulation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 245 (showing top): BENPORATH_ES_WITH_H3K27ME3, CMYB_01, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_NEUROGENESIS, GOBP_REGULATION_OF_AXON_GUIDANCE, SHEPARD_BMYB_MORPHOLINO_DN, MODULE_66, GOBP_TAXIS, IRF7_01, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, ATF1_Q6, GOBP_CENTRAL_NERVOUS_SYSTEM_NEURON_DIFFERENTIATION, GOBP_RNA_SPLICING, TGACATY_UNKNOWN

GO Biological Process (10): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), central nervous system neuron development (GO:0021954), neuron differentiation (GO:0030182), regulation of RNA metabolic process (GO:0051252), negative regulation of cold-induced thermogenesis (GO:0120163), regulation of axon guidance (GO:1902667), mRNA processing (GO:0006397), nervous system development (GO:0007399), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), sequence-specific mRNA binding (GO:1990825), nucleic acid binding (GO:0003676)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
alternative mRNA splicing, via spliceosome	1
regulation of mRNA splicing, via spliceosome	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
central nervous system neuron differentiation	1
neuron development	1
cell differentiation	1
generation of neurons	1
RNA metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
regulation of macromolecule metabolic process	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
axon guidance	1
regulation of neuron projection development	1
regulation of chemotaxis	1
mRNA metabolic process	1
system development	1
nucleic acid binding	1
RNA binding	1
mRNA binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1036 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOVA2	PTBP2	Q9UKA9	888
NOVA2	FAM107B	Q9H098	853
NOVA2	HNRNPC	P07910	716
NOVA2	KCNF1	Q9H3M0	686
NOVA2	SCN1A	P35498	682
NOVA2	PTBP1	P26599	671
NOVA2	RBFOX2	O43251	670
NOVA2	RBFOX1	Q9NWB1	665
NOVA2	SRRM4	A7MD48	636
NOVA2	NEO1	Q92859	617
NOVA2	KCNG1	Q9UIX4	617
NOVA2	FMR1	Q06787	603
NOVA2	GLRA2	P23416	600
NOVA2	FXR2	P51116	576
NOVA2	SRSF1	Q07955	574

IntAct

7 interactions, top by confidence:

A	B	Type	Score
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
NOVA1	NOVA2	psi-mi:“MI:0915”(physical association)	0.400
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350

BioGRID (15): NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Proximity Label-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA2 (Protein-RNA)

ESM2 similar proteins: A0A1W2P872, A1L1C7, A4IIM2, B2RYD2, F1LQ48, O57406, O88532, O95319, P14866, P28659, P51513, P57723, P57724, Q28HE9, Q2PFW9, Q32PX7, Q3U0V1, Q3US41, Q4QQT3, Q4R535, Q58A45, Q5F3T7, Q5NVC8, Q5R8Y8, Q5R995, Q5U231, Q640Q5, Q6DGV1, Q6GPM1, Q6NXG1, Q6P0B1, Q6PF35, Q792H5, Q7T2T1, Q7TSY6, Q7ZXE2, Q80WA4, Q8R081, Q8UVD9, Q91WJ8

Diamond homologs: A0A0B4KGY6, A0A1W2P872, O19048, O19049, O73932, O74919, P51513, P57721, P57722, P60335, P61978, P61979, P61980, Q15365, Q15366, Q2PFW9, Q32PX7, Q3T0D0, Q4R4M6, Q5E9A3, Q5R5H8, Q5RB68, Q5SF07, Q5ZIQ3, Q5ZLP8, Q61990, Q80WA4, Q8UVD9, Q91WJ8, Q96AE4, Q96I24, Q9JKN6, Q9LZ82, Q9SZH4, Q9UNW9, Q9Y6M1, O00425, P38151, P57723, P57724

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CAMK4	unknown	NOVA2	phosphorylation
CAMK4	“up-regulates quantity”	NOVA2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	3
Uncertain significance	74
Likely benign	25
Benign	2

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
1298775	NM_002516.4(NOVA2):c.755_764del (p.Leu252fs)	Pathogenic
1699936	NM_002516.4(NOVA2):c.729del (p.Ala244fs)	Pathogenic
1802596	NM_002516.4(NOVA2):c.523del (p.Leu175fs)	Pathogenic
3068386	NM_002516.4(NOVA2):c.987del (p.Tyr330fs)	Pathogenic
812085	NM_002516.4(NOVA2):c.782del (p.Val261fs)	Pathogenic
870455	NM_002516.4(NOVA2):c.710_711dup (p.Leu238fs)	Pathogenic
870456	NM_002516.4(NOVA2):c.701_720dup (p.Ala241fs)	Pathogenic
870457	NM_002516.4(NOVA2):c.709_748del (p.Val237fs)	Pathogenic
870458	NM_002516.4(NOVA2):c.781del (p.Val261fs)	Pathogenic
870459	NM_002516.4(NOVA2):c.720_721insCCGCGGATGTGCTTCCAGCC (p.Ala241fs)	Pathogenic
1326304	NM_002516.4(NOVA2):c.826del (p.Leu276fs)	Likely pathogenic
2630361	NM_002516.4(NOVA2):c.1104_1134del (p.Gly369fs)	Likely pathogenic
4526493	NM_002516.4(NOVA2):c.656del (p.Gly219fs)	Likely pathogenic

SpliceAI

996 predictions. Top by Δscore:

Variant	Effect	Δscore
19:45939897:C:CA	donor_gain	1.0000
19:45961004:GCTCA:G	donor_loss	1.0000
19:45961005:CTCA:C	donor_loss	1.0000
19:45961006:TCA:T	donor_loss	1.0000
19:45961008:A:AC	donor_gain	1.0000
19:45961009:C:CC	donor_gain	1.0000
19:45973263:TCACC:T	donor_loss	1.0000
19:45973264:CACC:C	donor_loss	1.0000
19:45973265:ACCT:A	donor_gain	1.0000
19:45973265:ACCTC:A	donor_gain	1.0000
19:45973266:CCT:C	donor_gain	1.0000
19:45973266:CCTC:C	donor_gain	1.0000
19:45973266:CCTCC:C	donor_gain	1.0000
19:45973268:T:TA	donor_gain	1.0000
19:45973269:C:A	donor_gain	1.0000
19:45939894:ACTC:A	donor_gain	0.9900
19:45939895:CTCC:C	donor_gain	0.9900
19:45940942:TGGC:T	acceptor_gain	0.9900
19:45940943:GGCCT:G	acceptor_loss	0.9900
19:45940944:GCCTG:G	acceptor_loss	0.9900
19:45940946:C:CC	acceptor_gain	0.9900
19:45940947:T:A	acceptor_loss	0.9900
19:45940949:C:CT	acceptor_gain	0.9900
19:45940950:G:C	acceptor_gain	0.9900
19:45942655:T:TA	donor_gain	0.9900
19:45953830:C:CT	donor_gain	0.9900
19:45961150:TCCT:T	acceptor_gain	0.9900
19:45961151:CCTC:C	acceptor_gain	0.9900
19:45961152:CT:C	acceptor_gain	0.9900
19:45961154:C:CC	acceptor_gain	0.9900

AlphaMissense

3107 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:45939915:C:G	R476P	1.000
19:45939918:T:G	Q475P	1.000
19:45939924:A:C	I473S	1.000
19:45939924:A:G	I473T	1.000
19:45939924:A:T	I473N	1.000
19:45939927:A:G	L472P	1.000
19:45939936:G:T	A469D	1.000
19:45939937:C:G	A469P	1.000
19:45939960:C:A	G461V	1.000
19:45939960:C:T	G461D	1.000
19:45939961:C:A	G461C	1.000
19:45939961:C:G	G461R	1.000
19:45939966:A:C	I459S	1.000
19:45939966:A:G	I459T	1.000
19:45939966:A:T	I459N	1.000
19:45939972:A:T	V457D	1.000
19:45939978:C:A	R455L	1.000
19:45939978:C:G	R455P	1.000
19:45939978:C:T	R455Q	1.000
19:45939979:G:A	R455W	1.000
19:45939979:G:C	R455G	1.000
19:45939998:G:C	F448L	1.000
19:45939998:G:T	F448L	1.000
19:45940000:A:G	F448L	1.000
19:45940006:C:G	G446R	1.000
19:45940007:C:A	K445N	1.000
19:45940007:C:G	K445N	1.000
19:45940014:G:A	S443F	1.000
19:45940015:A:G	S443P	1.000
19:45940017:A:C	I442S	1.000

dbSNP variants (sampled 300 via entrez): RS1000223550 (19:45975554 C>T), RS1000299650 (19:45969858 AG>A), RS1000346128 (19:45933808 T>G), RS1000348891 (19:45939795 G>A,C,T), RS1000401402 (19:45940685 G>A,T), RS1000482032 (19:45964161 T>C), RS1000494530 (19:45964698 C>G,T), RS1000600698 (19:45958498 A>T), RS1000649228 (19:45947280 G>A), RS1000665138 (19:45952779 C>T), RS1001064237 (19:45958625 G>C), RS1001078099 (19:45957609 T>G), RS1001108926 (19:45964304 G>A), RS1001159197 (19:45955598 G>A), RS1001204258 (19:45975381 C>A,T)

Disease associations

OMIM: gene MIM:601991 | disease phenotypes: MIM:618859

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (2): neurodevelopmental disorder with or without autistic features and/or structural brain abnormalities (MONDO:0030024), intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000248	Brachycephaly
HP:0000463	Anteverted nares
HP:0000490	Deeply set eye
HP:0000494	Downslanted palpebral fissures
HP:0000729	Autistic behavior
HP:0000748	Inappropriate laughter
HP:0000750	Delayed speech and language development
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001270	Motor delay
HP:0001290	Generalized hypotonia
HP:0001488	Bilateral ptosis
HP:0002002	Deep philtrum
HP:0002079	Hypoplasia of the corpus callosum
HP:0002120	Cerebral cortical atrophy
HP:0002714	Downturned corners of mouth
HP:0007099	Chiari type I malformation
HP:0009890	High anterior hairline
HP:0011968	Feeding difficulties
HP:0100023	Recurrent hand flapping

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007576_412	Chronotype	2.000000e-08
GCST010245_198	LDL cholesterol levels	2.000000e-31
GCST010796_1145	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008328	chronotype measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	2
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
propionaldehyde	increases expression	1
trichostatin A	decreases expression	1
butyraldehyde	increases expression	1
aflatoxin B2	decreases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
pentanal	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
LDN 193189	increases expression, affects cotreatment	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	decreases expression, affects cotreatment	1
Aldehydes	increases expression	1
Allergens	decreases expression	1
Atrazine	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment, decreases expression	1
Niclosamide	increases expression	1
Phenylmercuric Acetate	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Tetrachlorodibenzodioxin	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

2 cell lines: 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D6HZ	FDCHi014-A	Induced pluripotent stem cell	Female
CVCL_D9LI	Ubigene HEK293 NOVA2 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT03479476	PHASE2/PHASE3	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome
NCT02616796	PHASE1/PHASE2	COMPLETED	Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome
NCT06860672	EARLY_PHASE1	RECRUITING	Clinical Trial of the Dual Vector Base Editor for the Treatment of the CHD3-R1025W Mutation
NCT00597948	Not specified	COMPLETED	Healthy Lifestyles for People With Intellectual Disabilities
NCT01087320	Not specified	RECRUITING	Genome Medical Sequencing for Gene Discovery
NCT01652963	Not specified	UNKNOWN	Picture-based Computerised Assessment and Training of Cognitive Behaviour Therapy Skills
NCT01695395	Not specified	COMPLETED	Mental Health Care Provision for Adults With Intellectual Disability and a Mental Disorder
NCT01867554	Not specified	COMPLETED	Research and Characterization of New Genes Involved in Intellectual Disability
NCT01915381	Not specified	COMPLETED	Improving Adherence Healthy Lifestyle With a Smartphone Application Based on Adults With Intellectual Disabilities
NCT01988623	Not specified	COMPLETED	Pivotal Response Treatment for Individuals With Intellectual Disabilities
NCT02099773	Not specified	COMPLETED	Support Staff-client Interactions With Augmentative and Alternative Communication
NCT02136849	Not specified	COMPLETED	Inter-regional Project of the Great Western Exploration Approach for Exome Molecular Causes Severe Intellectual Disability Isolated or Syndromic
NCT02225041	Not specified	COMPLETED	Sedation Strategy and Cognitive Outcome After Critical Illness in Early Childhood
NCT02414438	Not specified	COMPLETED	Establishing the Clinical Utility of First StepDx PLUS and NextStepDx PLUS Study
NCT02451761	Not specified	COMPLETED	Apparently Balanced Chromosomal Translocation/ Next-generation Sequencing/ Intellectual Disability
NCT02461420	Not specified	ACTIVE_NOT_RECRUITING	Mapping the Genotype, Phenotype, and Natural History of Phelan-McDermid Syndrome
NCT02461459	Not specified	ACTIVE_NOT_RECRUITING	Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC)
NCT02486081	Not specified	COMPLETED	Development and Application-Smart Football for Movement Evaluation and Training in the Special Education Population
NCT02504502	Not specified	COMPLETED	Enhancing Genomic Laboratory Reports to Enhance Communication and Empower Patients
NCT02513277	Not specified	COMPLETED	Diabetes Screening & Prevention for People With Learning (Intellectual) Disabilities:STOP Diabetes Study
NCT02561754	Not specified	COMPLETED	Weight Management for Adolescents With IDD
NCT02591446	Not specified	COMPLETED	Transcranial Magnetic Stimulation Studies in Autism Spectrum Disorders
NCT02714868	Not specified	COMPLETED	Evaluation of Project TEAM (Teens Making Environmental and Activity Modifications)
NCT02721394	Not specified	UNKNOWN	FCT With Young Children With ID in the UK: A Feasibility Project V.1
NCT02746614	Not specified	COMPLETED	Psychomotor Therapy Effects in Adaptive Behavior and Motor Proficiency in Intellectual Disability
NCT02836405	Not specified	COMPLETED	TMS for the Investigation of Brain Plasticity in Autism Spectrum Disorders