NOVA1

Summary

NOVA1 (NOVA alternative splicing regulator 1, HGNC:7886) is a protein-coding gene on chromosome 14q12, encoding RNA-binding protein Nova-1 (P51513). RNA-binding protein which regulates alternative splicing of pre-mRNAs in the brain and spinal cord in a sequence-specific manner.

This gene encodes a neuron-specific RNA-binding protein, a member of the Nova family of paraneoplastic disease antigens, that is recognized and inhibited by paraneoplastic antibodies. These antibodies are found in the sera of patients with paraneoplastic opsoclonus-ataxia, breast cancer, and small cell lung cancer. Alternatively spliced transcripts encoding distinct isoforms have been described.

Source: NCBI Gene 4857 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 44 total — 2 pathogenic
• MANE Select transcript: NM_002515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7886
Approved symbol	NOVA1
Name	NOVA alternative splicing regulator 1
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	NOVA-1
Ensembl gene	ENSG00000139910
Ensembl biotype	protein_coding
OMIM	602157
Entrez	4857

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000344429, ENST00000347476, ENST00000449198, ENST00000465357, ENST00000483536, ENST00000539517, ENST00000546546, ENST00000547415, ENST00000547619, ENST00000549146, ENST00000549571, ENST00000551754, ENST00000574031

RefSeq mRNA: 12 — MANE Select: NM_002515 NM_001366390, NM_001366391, NM_001366392, NM_001366393, NM_001366394, NM_001366395, NM_001366396, NM_001366397, NM_001366398, NM_002515, NM_006489, NM_006491

CCDS: CCDS32060, CCDS32061, CCDS9635

Canonical transcript exons

ENST00000539517 — 5 exons

Exon	Start	End
ENSE00002303619	26597301	26598033
ENSE00002389416	26443090	26448963
ENSE00003543843	26479977	26480143
ENSE00003589396	26472320	26472391
ENSE00003675729	26595410	26595553

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 95.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.9559 / max 1937.7379, expressed in 1103 samples.

FANTOM5 promoters (22 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142678	4.8769	637
142679	3.5077	521
142682	2.7972	798
142680	1.3015	468
142673	0.9610	358
142671	0.9505	227
142665	0.9375	244
142675	0.6192	195
142667	0.5887	158
142676	0.4801	176

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	95.92	gold quality
cerebellum	UBERON:0002037	95.46	gold quality
cerebellar hemisphere	UBERON:0002245	95.43	gold quality
cerebellar cortex	UBERON:0002129	95.38	gold quality
hypothalamus	UBERON:0001898	94.48	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.48	gold quality
paraflocculus	UBERON:0005351	94.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	94.28	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.27	gold quality
prefrontal cortex	UBERON:0000451	93.99	gold quality
pons	UBERON:0000988	93.93	gold quality
synovial joint	UBERON:0002217	93.89	gold quality
ganglionic eminence	UBERON:0004023	93.83	gold quality
spinal cord	UBERON:0002240	93.68	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.64	gold quality
superior vestibular nucleus	UBERON:0007227	93.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.43	gold quality
Brodmann (1909) area 10	UBERON:0013541	93.09	gold quality
frontal cortex	UBERON:0001870	92.83	gold quality
cingulate cortex	UBERON:0003027	92.73	gold quality
anterior cingulate cortex	UBERON:0009835	92.67	gold quality
neocortex	UBERON:0001950	92.66	gold quality
postcentral gyrus	UBERON:0002581	92.66	gold quality
right frontal lobe	UBERON:0002810	92.57	gold quality
parietal lobe	UBERON:0001872	92.52	gold quality
substantia nigra	UBERON:0002038	92.50	gold quality
amygdala	UBERON:0001876	92.38	gold quality
midbrain	UBERON:0001891	92.37	gold quality
ventricular zone	UBERON:0003053	92.33	gold quality
cerebral cortex	UBERON:0000956	92.31	gold quality

Single-cell (SCXA)

Detected in 13 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-9435	yes	4500.81
E-HCAD-56	yes	2184.96
E-MTAB-7316	yes	1360.70
E-MTAB-8894	yes	945.44
E-GEOD-137537	yes	893.95
E-HCAD-35	yes	78.97
E-ANND-3	yes	37.47
E-HCAD-25	yes	26.61
E-GEOD-84465	yes	25.62
E-GEOD-93593	yes	12.33
E-HCAD-5	yes	10.91
E-GEOD-125970	yes	4.57
E-GEOD-83139	no	2.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

34 targeting NOVA1, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-942-5P	99.41	68.40	1977
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-488-5P	99.28	68.12	821
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-548L	99.06	70.90	2560
HSA-MIR-140-3P	99.04	67.69	1324
HSA-MIR-455-3P	98.94	67.68	878
HSA-MIR-487A-5P	98.85	69.37	993
HSA-MIR-487B-5P	98.85	69.48	987

Literature-anchored findings (GeneRIF, showing 37)

• Gene silencing and overexpression of the nELAV member HuD in motoneuronal NSC34 cells indicate that Nova1 mRNA stability and translation are positively and strongly controlled by the nELAV proteins (PMID:18218628)
• Semiquantitative estimation of circulating anti-Ri antibodies demonstrated a renewed increase in antibody levels preceding relapse of the cancer, as confirmed using F-fluorodeoxyglucose positron emission tomography (FDG-PET) (PMID:18822086)
• a regulation of LEDGF interaction with chromatin by cellular partners of its PWWP domain could be involved in several processes linked to LEDGF tethering properties, such as lentiviral integration, DNA repair or transcriptional regulation (PMID:24312278)
• High expression of NOVA1 correlates with poor prognosis in hepatocellular carcinoma. (PMID:24608171)
• MiR-181b-5p is a tumor suppressor in astrocytoma that inhibits tumor progression by targeting NOVA1. (PMID:25299073)
• Quantitative proteomic analysis was performed to help elucidate a molecular distinction between glioblastoma and oligodendroglioma; analysis showed HSPB1 and NOVA1 to be discriminating factors. (PMID:26108672)
• Data indicate RNA binding protein NOVA1 as a target of microRNA miR-339. (PMID:26391641)
• Loss of NOVA1 is associated with gastric cancer. (PMID:26673617)
• NOVA1 suppression was frequently noted in the gastric cancer microenvironment, and attenuated NOVA1 expression in tumor cells was associated with tumor progression and poor prognosis. (PMID:27318497)
• overexpression of miR-203a-3p leads to a decrease of NOVA1, counter-balanced by an increase of IKAP, supporting a potential interaction between NOVA1 and IKAP. (PMID:27483351)
• Nova1 interacts with GABAARgamma2 not only in the central nervous system but also in hepatocellular carcinoma. Nova1’s potential mechanism as an oncogene may due to its interaction with GABAA Rgamma2. (PMID:27733149)
• It regulates the alternative splicing of estrogen receptor beta in the aging brain. (PMID:29031089)
• NOVA1 acted as an oncogene in the development of melanoma partly through regulating FoxO3A expression. (PMID:29498217)
• NOVA1 has a role in regulating hTERT splicing and cell growth in non-small cell lung cancer (PMID:30082712)
• Bioinformatics prediction and a luciferase assay confirmed that NOVA1 was a direct functional target of miR-193a. Moreover, ectopic expression of NOVA1 could partially reverse the inhibitory effects of miR-193a-5p on glioma cell proliferation, colony formation, migration, and invasion. NOVA1 overexpression abrogated the inhibitory effect of miR-193a-5p on the PTEN/PI3k/AKT pathway. (PMID:30304561)
• Knockdown of PTBP1 increases the expression of PTBP2 which also interacts with NOVA1, potentially preventing the association of NOVA1 with hTERT pre-mRNA. (PMID:30568224)
• LncSNHG16 was highly expressed in osteosarcoma (OS) tissues and cell lines and negatively correlated with survival and positively with the tumor stage of OS patients. MicroRNA-146a-5p was predicted to be the target gene of lncSNHG16 and NOVA1 was predicted to be the target gene of microRNA-146a-5p. LncSNHG16 participates in the development of OS by downregulating microRNA-146a-5p to upregulate NOVA1 expression. (PMID:30657551)
• TATDN1 promotes the development and progression of breast cancer by targeting microRNA-140-3p. (PMID:31298381)
• NOVA1 induction by inflammation and NOVA1 suppression by epigenetic regulation in head and neck squamous cell carcinoma. (PMID:31375778)
• We also show that the TNIK protein isoforms including/excluding exon 15 differently regulate cell spreading in non-neuronal cells and neuritogenesis in primary cortical neurons. Our data suggest a complex regulation between the ubiquitous TDP-43 and the neuron-specific NOVA-1 splicing factors in the brain that may help better understand the pathobiology of both neurodegenerative diseases and schizophrenia. (PMID:31382054)
• The results indicated that the NEAT1/miR592/NOVA1 pathway may play regulatory roles in thyroid cancer malignancy in vitro and in vivo. Our findings may provide novel insight into the pathogenesis of thyroid cancer. (PMID:31524231)
• High NOVA1 expression is associated with metastasis of colorectal cancer. (PMID:31541909)
• miR-27-3p inhibition restore fibroblasts viability in diabetic wound by targeting NOVA1. (PMID:32589614)
• LncRNA MALAT1 mediates doxorubicin resistance of hepatocellular carcinoma by regulating miR-3129-5p/Nova1 axis. (PMID:32965597)
• MiR-582-5p inhibits the growth and invasion of osteosarcoma cell by targeting NOVA1. (PMID:33215417)
• MiR-146a functions as a potential tumor suppressor in retinoblastoma by negatively regulate neuro-oncological ventral antigen-1. (PMID:33340248)
• Reintroduction of the archaic variant of NOVA1 in cortical organoids alters neurodevelopment. (PMID:33574182)
• Roles of the microRNA3383p/NOVA1 axis in retinoblastoma. (PMID:33760207)
• Knockdown of NOVA1 inhibits inflammation and migration of asthmatic airway smooth muscle cells to regulate PTEN/Akt pathway by targeting PTBP1. (PMID:34332183)
• Aberrant NOVA1 function disrupts alternative splicing in early stages of amyotrophic lateral sclerosis. (PMID:35778567)
• Spliceosomic dysregulation unveils NOVA1 as a candidate actionable therapeutic target in pancreatic neuroendocrine tumors. (PMID:35882361)
• NOVA1 prevents overactivation of the unfolded protein response and facilitates chromatin access during human white adipogenesis. (PMID:37246706)
• Pattern of Brain Parenchymal Damage Related to Cerebral Small Vessel Disease in Carriers of Rare NOTCH3 Variants. (PMID:37775315)
• RNA-binding protein NOVA1 promotes acute T-lymphocyte leukemia progression by stabilizing USP44 mRNA. (PMID:37816258)
• Interaction of the C9orf72-Amyotrophic Lateral Sclerosis-Related Proline-Arginine Dipeptide Repeat Protein with the RNA-Binding Protein NOVA1 Causes Decreased Expression of UNC13A Due to Enhanced Inclusion of Cryptic Exons, Which Is Reversed by Betulin Treatment. (PMID:37887320)
• NOVA1 acts as an oncogenic RNA-binding protein to regulate cholesterol homeostasis in human glioblastoma cells. (PMID:38416679)
• Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer. (PMID:38657094)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	nova2	ENSDARG00000017673
danio_rerio	nova1	ENSDARG00000020178
mus_musculus	Nova1	ENSMUSG00000021047
rattus_norvegicus	Nova1	ENSRNOG00000031440
drosophila_melanogaster	ps	FBGN0261552
drosophila_melanogaster	mub	FBGN0262737
drosophila_melanogaster	Imp	FBGN0285926
caenorhabditis_elegans		WBGENE00003978
caenorhabditis_elegans		WBGENE00010908
caenorhabditis_elegans		WBGENE00013347
caenorhabditis_elegans		WBGENE00016489
caenorhabditis_elegans	fubl-4	WBGENE00019692

Paralogs (12): IGF2BP2 (ENSG00000073792), KHSRP (ENSG00000088247), PCBP4 (ENSG00000090097), NOVA2 (ENSG00000104967), FUBP3 (ENSG00000107164), IGF2BP3 (ENSG00000136231), IGF2BP1 (ENSG00000159217), FUBP1 (ENSG00000162613), HNRNPK (ENSG00000165119), PCBP1 (ENSG00000169564), PCBP3 (ENSG00000183570), PCBP2 (ENSG00000197111)

Protein

Protein identifiers

RNA-binding protein Nova-1 — P51513 (reviewed: P51513)

Alternative names: Neuro-oncological ventral antigen 1, Onconeural ventral antigen 1, Paraneoplastic Ri antigen, Ventral neuron-specific protein 1

All UniProt accessions (9): P51513, F8VW64, F8VWX1, F8VYI3, F8W659, G8JLA5, H0YHZ1, I3L2B5, J3KQU3

UniProt curated annotations — full annotation on UniProt →

Function. RNA-binding protein which regulates alternative splicing of pre-mRNAs in the brain and spinal cord in a sequence-specific manner. Binds to 5’-YCAY-3’ repeats, with a minimum of 2 to 3 repeats necessary for high-affinity binding. Mediates both exon inclusion and exclusion, depending upon the position of its binding site within the pre-mRNA. Binding to 5’-YCAY-3’ clusters results in a local and asymmetric action to regulate spliceosome assembly. Binding to an exonic 5’-YCAY-3’ cluster changes the protein complexes assembled on pre-mRNA, blocking U1 small nuclear ribonucleoprotein (snRNP) binding and inhibiting exon inclusion, whereas binding to an intronic 5’-YCAY-3’ repeat enhances spliceosome assembly and favors exon inclusion. Regulates the splicing of gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) and glycine receptor subunit alpha-2 (GLRA2) pre-mRNAs, among others. Autoregulates its own splicing. Binds to its own exon 4 and directs its exclusion, thus leading to NOVA1 isoform 3 production. May affect the splicing of many genes involved in vocal behavior.

Subunit / interactions. Directly interacts with PTBP2; this interaction inhibits NOVA-dependent activation of exon inclusion in glycine receptor subunit alpha-2 (GLRA2) pre-mRNA, when PTBP2 also binds to pre-mRNA.

Subcellular location. Nucleus.

Tissue specificity. Expressed in cerebellum, brain stem, hippocampus, and frontal cortex.

Disease relevance. Trigger of a neurological autoimmnue disorder, called paraneoplastic opsoclonus-myoclonus ataxia (POMA), that can cause extreme motor dysfunction. This disorder develops when tumor cells ectopically express NOVA1, that is normally restricted to the nervous system, triggering an anti-tumor immune response that breaches the blood-brain barrier, leading to autoimmune neurologic disease. POMA autoantibodies block NOVAl RNA binding.

Domain organisation. The KH domain consists of approximately 70 amino acids and includes a conserved hydrophobic core, an invariant Gly-X-X-Gly motif, and an additional variable segment. The third KH domain (KH3) binds a hairpin loop containing the 5’-YCAY-3’ motif on target pre-mRNAs. RNA binding by KH3 requires residues C-terminal to the KH domain.

Polymorphism. Valine at position 197 is unique to modern humans. Other mammalian species, including Neanderthals and Denisovans, have a isoleucine at this position. The variant p.Val197Ile is extremely rare in humans, with only one allele reported in gnomAD v4.1.0. When tested in transgenic mice, p.Ile197Val allele does not affect development, brain size, nor fertility and does not alter motor performance, but affects vocalization patterns in pups and adults. It has been proposed that this variant may have contributed to the development of neural systems involved in more complex vocal communication in modern humans.

Isoforms (3)

UniProt ID	Names	Canonical?
P51513-4	1	yes
P51513-2	2, Tumor
P51513-5	3

RefSeq proteins (12): NP_001353319, NP_001353320, NP_001353321, NP_001353322, NP_001353323, NP_001353324, NP_001353325, NP_001353326, NP_001353327, NP_002506, NP_006480, NP_006482 (=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 (36 total): helix 12, strand 9, domain 3, splice variant 3, region of interest 3, chain 1, sequence variant 1, turn 1, short sequence motif 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
2ANR	X-RAY DIFFRACTION	1.94
2ANN	X-RAY DIFFRACTION	2.3
1DT4	X-RAY DIFFRACTION	2.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51513-F1	64.13	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): 154

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 312 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, AAGCAAT_MIR137, TAATAAT_MIR126, MODULE_274, HNF3ALPHA_Q6, GCANCTGNY_MYOD_Q6, GOBP_ALTERNATIVE_MRNA_SPLICING_VIA_SPLICEOSOME, TATTATA_MIR374, ATGCAGT_MIR217, LHX3_01, CAGCTG_AP4_Q5, MORF_RAD51L3, FOXD3_01

GO Biological Process (8): regulation of alternative mRNA splicing, via spliceosome (GO:0000381), mRNA splicing, via spliceosome (GO:0000398), RNA processing (GO:0006396), nervous system development (GO:0007399), RNA splicing (GO:0008380), negative regulation of cold-induced thermogenesis (GO:0120163), mRNA processing (GO:0006397), regulation of RNA metabolic process (GO:0051252)

GO Molecular Function (6): RNA binding (GO:0003723), mRNA binding (GO:0003729), mRNA 3’-UTR binding (GO:0003730), sequence-specific mRNA binding (GO:1990825), nucleic acid binding (GO:0003676), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
mRNA binding	2
binding	2
nuclear lumen	2
cellular anatomical structure	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
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
system development	1
negative regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
mRNA metabolic process	1
RNA metabolic process	1
regulation of nucleobase-containing compound metabolic process	1
regulation of macromolecule metabolic process	1
nucleic acid binding	1
RNA binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NOVA1	PTBP2	Q9UKA9	861
NOVA1	FAM107B	Q9H098	847
NOVA1	GLRA2	P23416	845
NOVA1	UBR5	O95071	785
NOVA1	NRXN3	Q9Y4C0	754
NOVA1	PTBP1	P26599	746
NOVA1	NRXN2	Q9P2S2	693
NOVA1	ELAVL4	P26378	687
NOVA1	RBFOX1	Q9NWB1	685
NOVA1	RBFOX2	O43251	677
NOVA1	SRRM4	A7MD48	647
NOVA1	NRXN1	Q9ULB1	645
NOVA1	HNRNPC	P07910	634
NOVA1	SRSF1	Q07955	623
NOVA1	MBNL1	Q9NR56	622

IntAct

28 interactions, top by confidence:

A	B	Type	Score
NOVA1	HTR6	psi-mi:“MI:0915”(physical association)	0.600
NOVA1	HTR6	psi-mi:“MI:0403”(colocalization)	0.600
FOXP3	FOXP2	psi-mi:“MI:0914”(association)	0.530
NOVA1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
GABRG2	NOVA1	psi-mi:“MI:0915”(physical association)	0.400
NOVA1	Htr6	psi-mi:“MI:0915”(physical association)	0.400
NOVA1	NOVA2	psi-mi:“MI:0915”(physical association)	0.400
RPP14	NOVA1	psi-mi:“MI:0915”(physical association)	0.370
FOXB1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
FOXL1	DDX39A	psi-mi:“MI:0914”(association)	0.350
	TNFRSF10A	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
TP53BP1	PSMD14	psi-mi:“MI:2364”(proximity)	0.270
NOVA1	SMARCC2	psi-mi:“MI:0915”(physical association)	0.000
PCBP1	NOVA1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): NOVA1 (Co-fractionation), NOVA1 (Affinity Capture-MS), NOVA1 (Affinity Capture-MS), NOVA1 (Affinity Capture-MS), NOVA1 (Affinity Capture-MS), NOVA2 (Affinity Capture-MS), NOVA1 (Two-hybrid), NOVA1 (Affinity Capture-Western), NOVA1 (Affinity Capture-MS), NOVA1 (Two-hybrid), NOVA1 (Reconstituted Complex), HTR6 (Affinity Capture-Western), NOVA1 (Affinity Capture-Western), NOVA1 (Affinity Capture-RNA), NOVA2 (Affinity Capture-MS)

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
57745	GRCh38/hg38 14q11.2-21.2(chr14:20196945-45284802)x1	Pathogenic
980477	GRCh37/hg19 14q12(chr14:25172628-30285023)x1	Pathogenic

SpliceAI

2735 predictions. Top by Δscore:

Variant	Effect	Δscore
14:26470411:CAATT:C	donor_gain	1.0000
14:26479969:ACACT:A	donor_loss	1.0000
14:26479970:CACT:C	donor_loss	1.0000
14:26479971:ACTC:A	donor_loss	1.0000
14:26479972:CT:C	donor_loss	1.0000
14:26479973:TCA:T	donor_loss	1.0000
14:26479974:CACT:C	donor_loss	1.0000
14:26479975:A:AC	donor_gain	1.0000
14:26479975:A:C	donor_loss	1.0000
14:26479976:C:CA	donor_gain	1.0000
14:26479976:CTT:C	donor_gain	1.0000
14:26479976:CTTG:C	donor_gain	1.0000
14:26479976:CTTGT:C	donor_gain	1.0000
14:26480144:C:CC	acceptor_gain	1.0000
14:26480145:T:G	acceptor_loss	1.0000
14:26549679:CAGT:C	donor_gain	1.0000
14:26561449:T:TA	donor_gain	1.0000
14:26566794:T:TC	acceptor_gain	1.0000
14:26595554:C:CC	acceptor_gain	1.0000
14:26595561:A:AC	acceptor_gain	1.0000
14:26595561:A:C	acceptor_gain	1.0000
14:26597299:ACCGC:A	donor_gain	1.0000
14:26597300:CCGCC:C	donor_gain	1.0000
14:26448963:CCTG:C	acceptor_loss	0.9900
14:26448965:T:A	acceptor_loss	0.9900
14:26479976:CT:C	donor_gain	0.9900
14:26480139:AGTAC:A	acceptor_gain	0.9900
14:26480140:GTAC:G	acceptor_gain	0.9900
14:26480141:TAC:T	acceptor_gain	0.9900
14:26480142:AC:A	acceptor_gain	0.9900

AlphaMissense

3237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:26448020:A:C	I488S	1.000
14:26448020:A:T	I488N	1.000
14:26448032:G:T	A484D	1.000
14:26448033:C:G	A484P	1.000
14:26448056:C:A	G476V	1.000
14:26448056:C:T	G476E	1.000
14:26448057:C:G	G476R	1.000
14:26448057:C:T	G476R	1.000
14:26448062:A:C	I474S	1.000
14:26448062:A:G	I474T	1.000
14:26448062:A:T	I474N	1.000
14:26448068:A:T	V472E	1.000
14:26448074:C:A	R470L	1.000
14:26448074:C:G	R470P	1.000
14:26448074:C:T	R470Q	1.000
14:26448075:G:A	R470W	1.000
14:26448075:G:C	R470G	1.000
14:26448094:G:C	F463L	1.000
14:26448094:G:T	F463L	1.000
14:26448096:A:G	F463L	1.000
14:26448102:C:G	G461R	1.000
14:26448102:C:T	G461R	1.000
14:26448103:T:A	K460N	1.000
14:26448103:T:G	K460N	1.000
14:26448104:T:A	K460I	1.000
14:26448105:T:C	K460E	1.000
14:26448107:T:A	K459I	1.000
14:26448110:G:A	S458F	1.000
14:26448110:G:T	S458Y	1.000
14:26448111:A:G	S458P	1.000

dbSNP variants (sampled 300 via entrez): RS1000042839 (14:26590035 A>C), RS1000053150 (14:26573369 A>G), RS1000057635 (14:26596625 G>T), RS1000071489 (14:26459144 T>C), RS1000076989 (14:26443283 TA>T,TAA), RS1000086864 (14:26545546 T>C), RS1000089115 (14:26579490 C>T), RS1000093615 (14:26458834 A>G), RS1000109140 (14:26474430 A>G), RS1000153975 (14:26596410 C>A), RS1000164432 (14:26566263 CTT>C), RS1000193167 (14:26523281 A>G), RS1000233997 (14:26508947 T>C,G), RS1000252825 (14:26481124 C>A), RS1000260160 (14:26559123 C>A)

Disease associations

OMIM: gene MIM:602157 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST002570_1	Overweight status	6.000000e-07
GCST002697_6	Eosinophilic esophagitis	7.000000e-08
GCST002934_24	Zinc levels	9.000000e-06
GCST003075_47	Cognitive decline rate in late mild cognitive impairment	2.000000e-07
GCST003075_51	Cognitive decline rate in late mild cognitive impairment	4.000000e-07
GCST003986_14	Migraine	3.000000e-09
GCST004495_63	BMI (adjusted for smoking behaviour)	2.000000e-07
GCST004497_19	Body mass index (joint analysis main effects and smoking interaction)	3.000000e-07
GCST004499_88	BMI in non-smokers	9.000000e-06
GCST004904_173	Body mass index	6.000000e-13
GCST005830_70	Hand grip strength	4.000000e-09
GCST006039_8	Peanut allergy	3.000000e-06
GCST008368_2	Plasma anti-thyroid peroxidase levels	4.000000e-06
GCST008829_2	Neuritic plaque	7.000000e-08
GCST009391_972	Metabolite levels	7.000000e-06
GCST90010717_3	Finger osteoarthritis severity (hand Klsum)	3.000000e-07

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0005935	overweight body mass index status
EFO:0007710	cognitive decline measurement
EFO:0004318	smoking behavior
EFO:0004340	body mass index
EFO:0006941	grip strength measurement
EFO:0007017	peanut allergy measurement
EFO:0006798	neuritic plaque measurement

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, decreases expression, affects expression, decreases methylation	9
trichostatin A	affects cotreatment, decreases expression	3
entinostat	affects cotreatment, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Lead	affects splicing, decreases expression	2
Aflatoxin B1	decreases methylation, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
arsenite	increases methylation	1
butyraldehyde	decreases expression	1
beryllium sulfate	increases expression	1
nickel sulfate	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation, affects methylation, decreases methylation	1
Cadmium	decreases expression, increases abundance	1
Cisplatin	affects cotreatment, decreases expression	1
Cytarabine	increases expression	1
Dexamethasone	increases expression	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	increases expression	1
Tamoxifen	decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9LH	Ubigene HEK293 NOVA1 KO	Transformed cell line	Female

Clinical trials (associated diseases)

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