NES

Summary

NES (nestin, HGNC:7756) is a protein-coding gene on chromosome 1q23.1, encoding Nestin (P48681). Required for brain and eye development.

This gene encodes a member of the intermediate filament protein family and is expressed primarily in nerve cells.

Source: NCBI Gene 10763 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 263 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_006617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7756
Approved symbol	NES
Name	nestin
Location	1q23.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ21841
Ensembl gene	ENSG00000132688
Ensembl biotype	protein_coding
OMIM	600915
Entrez	10763

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000368223, ENST00000867897

RefSeq mRNA: 1 — MANE Select: NM_006617 NM_006617

CCDS: CCDS1151

Canonical transcript exons

ENST00000368223 — 4 exons

Exon	Start	End
ENSE00000959085	156675216	156675340
ENSE00001054729	156676482	156677407
ENSE00001074047	156673454	156673527
ENSE00001446624	156668763	156673205

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 98.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.0494 / max 972.7196, expressed in 1245 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15177	27.3204	1231
15169	0.3261	157
15170	0.3145	139
15168	0.3099	157
15163	0.2757	162
15171	0.2246	103
15172	0.1622	64
15167	0.1160	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	98.56	gold quality
gluteal muscle	UBERON:0002000	98.43	gold quality
apex of heart	UBERON:0002098	98.00	gold quality
vena cava	UBERON:0004087	97.66	gold quality
embryo	UBERON:0000922	97.48	gold quality
renal glomerulus	UBERON:0000074	97.36	gold quality
metanephric glomerulus	UBERON:0004736	97.34	gold quality
ganglionic eminence	UBERON:0004023	97.09	gold quality
saphenous vein	UBERON:0007318	96.98	gold quality
right atrium auricular region	UBERON:0006631	96.96	gold quality
heart right ventricle	UBERON:0002080	96.74	gold quality
cardiac atrium	UBERON:0002081	96.11	gold quality
cardiac ventricle	UBERON:0002082	95.84	gold quality
heart left ventricle	UBERON:0002084	95.80	gold quality
sural nerve	UBERON:0015488	95.55	gold quality
olfactory bulb	UBERON:0002264	95.41	gold quality
heart	UBERON:0000948	95.06	gold quality
cranial nerve II	UBERON:0000941	94.99	gold quality
diaphragm	UBERON:0001103	94.80	silver quality
dorsal root ganglion	UBERON:0000044	93.72	gold quality
trigeminal ganglion	UBERON:0001675	93.22	gold quality
pericardium	UBERON:0002407	93.02	gold quality
body of tongue	UBERON:0011876	92.94	gold quality
tibial nerve	UBERON:0001323	92.51	gold quality
left uterine tube	UBERON:0001303	92.39	gold quality
metanephros	UBERON:0000081	92.10	gold quality
triceps brachii	UBERON:0001509	91.76	gold quality
right lung	UBERON:0002167	91.54	gold quality
right coronary artery	UBERON:0001625	91.35	gold quality
myometrium	UBERON:0001296	91.17	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	715.86
E-MTAB-10485	yes	694.57
E-HCAD-13	yes	324.81
E-GEOD-98556	yes	324.35
E-GEOD-84465	yes	25.83
E-HCAD-5	yes	25.04
E-HCAD-10	yes	17.92
E-GEOD-93593	yes	14.29
E-MTAB-9388	yes	8.29
E-ANND-3	yes	7.73
E-GEOD-83139	yes	6.92
E-MTAB-11121	no	578.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, CTCF, DMTF1, EOMES, FOSB, FOXA1, HOXA1, MBD2, MYC, MYCN, NEUROD1, NKX2-1, NR2F1, NR5A1, PAX6, PITX3, POU2F1, POU3F2, POU3F3, POU5F1, PROX1, RARA, RBPJ, RXRA, RXRG, SATB1, SOX10, SOX17, SOX2, SOX9, SP1, SP3, TCF3, TTF1, VSX2, WT1, ZFHX3

miRNA regulators (miRDB)

17 targeting NES, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6799-5P	99.14	65.72	2093
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-374C-3P	98.47	67.93	451
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-509-3-5P	97.21	67.74	1517
HSA-MIR-509-5P	97.21	67.90	1512
HSA-MIR-1306-5P	97.11	64.04	755
HSA-MIR-4418	97.04	67.16	1372
HSA-MIR-658	88.20	67.03	178

Literature-anchored findings (GeneRIF, showing 40)

• Nestin-containing neurons occurred in hippocampus, septum, diagonal band, amygdala and basal nucleus of Meynert. Nestin-containing astrocytes occurred in the subependymal zone and dentate gyrus. (PMID:12101039)
• The tissue distribution of nestin has been studied in the muscularis propria of normal gastrointestinal autopsy material. (PMID:12172785)
• Beta-cell differentiation during human development does not rely on nestin-positive precursors (PMID:12187925)
• Nestin-immunoreactive cells colocalized with vimentin throughout the retina. Colocalized with mitotic Ki67 immunoreactive cells. (PMID:12786777)
• Demonstration of strong expression of nestin in Purkinje cells in pathologically advanced Creutzfeldt-Jakob disease correlates with the process that Purkinje cells undergo to promote survival. (PMID:14625035)
• detection of nestin-positive keratinocytes in the basal layer of cultured epidermis (PMID:15088413)
• nestin may be one mediator of N-myc-associated tumor aggressiveness of human neuroblastoma (PMID:15117961)
• In transgenic mice, nestin transgene expression in the olfactory bulb is limited to periglomerular neurons and is absent from granule cells, suggesting that this nestin promoter construct differentiates between the two interneuronal populations. (PMID:15176089)
• Nestin expression in tumor endothelium is enhanced by the first intron. (PMID:15502861)
• nestin has a role in multi-potentiality and regenerative potential [review] (PMID:15526158)
• nestin expression is recognized under all conditions of vascular development (PMID:15684833)
• Nestin is constantly expressed in situ in the cortex of normal human adrenal glands; a positive nestin immunoreaction could be useful in differential diagnosis of clear cell tumors in adrenal glands. (PMID:16136494)
• Data evaluate and compare the bcl2, bax, and nestin patterns in the frontal cortices of Alzheimer and multiple-infarct dementia patients, and in normal aging. (PMID:16186627)
• These results show that the pattern of nestin expression is related to the differentiation of epidermal stem cells. (PMID:16275024)
• Moderate to strong expression of nestin was observed in all tumors. (PMID:16487364)
• Nestin expression in adenomas cannot be viewed as a biologically relevant marker of cell proliferation and as a prognostic indicator in pituitary neoplasms. (PMID:16538520)
• Purkinje cells were immunoreactive with nestin regardless of the severity of degenerative cerebellar cortex. (PMID:16616189)
• cultured pancreatic islets contain nestin and Isl-1 positive mesenchymal stem cells with multipotential developmental capacity (PMID:16713999)
• Nestin-positive pancrease stem cells are in the stroma of human embryonic pancrease. (PMID:16736556)
• In a series of 40 surgical specimens, including gliomas, vascular malformations, abscesses and angiomas, nestin was poorly expressed in mature astrocytes and more expressed in developing reactive astrocytes, mainly in the cytoplasm. (PMID:16826367)
• The putative pancreatic stem cells expressed pdx-1 and nestin. (PMID:16874866)
• nestin is a survival determinant whose action is based upon a novel mode of Cdk5 regulation, affecting the targeting, activity, and turnover of the Cdk5/p35 signaling complex (PMID:17036052)
• Nestin is expressed in the human kidney from the first steps of glomerulogenesis within podocytes, mesangial, and endothelial cells. (PMID:17210924)
• The expression of nestin in the podocytes of normal and diseased kidneys of adolesscent and adult patients is reported. (PMID:17255215)
• nestin has a role in neovasculaturization in colorectal cancer (PMID:17273760)
• Nestin is more sensitive for malignant peripheral nerve sheath tumor (MPNST) than other neural markers, and immunostains for nestin in combination with other markers could be useful in the diagnosis of MPNST. (PMID:17300669)
• Transgenic mice in which the nestin neural enhancer drives expression of a green fluorescent protein reporter show that the regulation in Schwann cells is transcriptional. (PMID:17537965)
• The nestin(-) vimentin(+) fibroblasts may represent a novel type of multipotent adult stem cells in human dermis. (PMID:17652163)
• Nestin is expressed in podocytes of mature human glomerular tissues in quiescent states. (PMID:17784648)
• The extent of nestin-positive neuronal cells correlated with the appearance of tyrosine hydroxylase positive neurons. (PMID:17784840)
• Results specify a function for Nestin in cell motility and identify a novel pathway for prostate cancer metastasis. (PMID:17909025)
• enhanced expression of nestin in the injured myocardium might reflect spontaneous regenerative processes supposedly based on the differentiation of resident cardiac stem cells into diverse cardiac cell types. (PMID:17984177)
• Nestin is expressed in proliferating and metabolically active cells, such as endothelium, independent of developmental and neoplastic processes. (PMID:18265627)
• Nestin plays a crucial role in remodeling the cytoskeleton of cells in the human postinfarcted myocardium. (PMID:18546018)
• Dental follicle cells expressed the stem cell marker nestin in both serum-free and serum-containing cell culture media. (PMID:18618166)
• Nestin gene variants are associated with early-onset CHD. (PMID:18724036)
• Cyclosporin A induced renal injury recruits nestin-expressing cells to injured areas. (PMID:18724228)
• Nestin expression in pancreatic cancer cells may contribute to nerve and stromal invasion in this malignancy (PMID:18799194)
• SOX9 and SOX10 but not BRN2 seem to be required for nestin expression in human melanoma. (PMID:18923447)
• expression is detected in osteosarcomas (PMID:18925963)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nes	ENSMUSG00000004891
rattus_norvegicus	Nes	ENSRNOG00000018681

Paralogs (68): KRT33A (ENSG00000006059), VIM (ENSG00000026025), KRT31 (ENSG00000094796), NEFM (ENSG00000104722), KRT23 (ENSG00000108244), KRT37 (ENSG00000108417), KRT32 (ENSG00000108759), KRT18 (ENSG00000111057), LMNB1 (ENSG00000113368), KRT36 (ENSG00000126337), KRT17 (ENSG00000128422), GFAP (ENSG00000131095), KRT34 (ENSG00000131737), KRT33B (ENSG00000131738), PRPH (ENSG00000135406), KRT85 (ENSG00000135443), KRT7 (ENSG00000135480), KRT71 (ENSG00000139648), INA (ENSG00000148798), LMNTD1 (ENSG00000152936), LMNA (ENSG00000160789), KRT84 (ENSG00000161849), KRT82 (ENSG00000161850), KRT80 (ENSG00000167767), KRT1 (ENSG00000167768), KRT24 (ENSG00000167916), KRT8 (ENSG00000170421), KRT78 (ENSG00000170423), KRT86 (ENSG00000170442), KRT75 (ENSG00000170454), KRT6C (ENSG00000170465), KRT4 (ENSG00000170477), KRT74 (ENSG00000170484), KRT72 (ENSG00000170486), KRT83 (ENSG00000170523), BFSP2 (ENSG00000170819), KRT19 (ENSG00000171345), KRT15 (ENSG00000171346), KRT38 (ENSG00000171360), KRT13 (ENSG00000171401)

Protein

Protein identifiers

Nestin — P48681 (reviewed: P48681)

All UniProt accessions (1): P48681

UniProt curated annotations — full annotation on UniProt →

Function. Required for brain and eye development. Promotes the disassembly of phosphorylated vimentin intermediate filaments (IF) during mitosis and may play a role in the trafficking and distribution of IF proteins and other cellular factors to daughter cells during progenitor cell division. Required for survival, renewal and mitogen-stimulated proliferation of neural progenitor cells.

Subunit / interactions. Forms homodimers and homotetramers in vitro. In mixtures with other intermediate filament proteins such as vimentin and alpha-internexin, tis protein preferentially forms heterodimers which can assemble to form intermediate filaments if nestin does not exceed 25%. Interacts with FHOD3.

Tissue specificity. CNS stem cells.

Post-translational modifications. Constitutively phosphorylated. This increases during mitosis when the cytoplasmic intermediate filament network is reorganized.

Similarity. Belongs to the intermediate filament family.

RefSeq proteins (1): NP_006608* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018039	IF_conserved	Conserved_site
IPR031211	Nestin	Family
IPR039008	IF_rod_dom	Domain

Pfam: PF00038

UniProt features (104 total): modified residue 43, sequence conflict 23, compositionally biased region 16, region of interest 12, sequence variant 6, cross-link 2, chain 1, domain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48681-F1	49.18	0.15

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 (45): 1, 311, 315, 325, 338, 355, 358, 388, 398, 471, 476, 548, 564, 578, 588, 638, 680, 702, 746, 768 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 199 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_PROTEIN_BINDING, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, GOBP_CELL_CYCLE_PHASE_TRANSITION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, AP4_Q6, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_DISASSEMBLY, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, CAGCTG_AP4_Q5, GOBP_STEM_CELL_PROLIFERATION, GOBP_NEURAL_PRECURSOR_CELL_PROLIFERATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_BINDING, CHEN_LVAD_SUPPORT_OF_FAILING_HEART_UP, GOBP_POSITIVE_REGULATION_OF_NEURAL_PRECURSOR_CELL_PROLIFERATION

GO Biological Process (13): G2/M transition of mitotic cell cycle (GO:0000086), central nervous system development (GO:0007417), brain development (GO:0007420), positive regulation of intermediate filament depolymerization (GO:0030844), embryonic camera-type eye development (GO:0031076), negative regulation of protein binding (GO:0032091), negative regulation of catalytic activity (GO:0043086), negative regulation of neuron apoptotic process (GO:0043524), cell projection morphogenesis (GO:0048858), neuron apoptotic process (GO:0051402), stem cell proliferation (GO:0072089), positive regulation of neural precursor cell proliferation (GO:2000179), nervous system development (GO:0007399)

GO Molecular Function (3): intermediate filament binding (GO:0019215), CCR5 chemokine receptor binding (GO:0031730), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), intermediate filament (GO:0005882), intermediate filament cytoskeleton (GO:0045111)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
system development	2
binding	2
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
nervous system development	1
central nervous system development	1
animal organ development	1
head development	1
regulation of intermediate filament depolymerization	1
intermediate filament depolymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of protein depolymerization	1
camera-type eye development	1
embryonic organ development	1
protein binding	1
regulation of protein binding	1
negative regulation of binding	1
catalytic activity	1
negative regulation of molecular function	1
regulation of catalytic activity	1
negative regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
cell morphogenesis	1
anatomical structure morphogenesis	1
cell projection organization	1
apoptotic process	1
cell population proliferation	1
stem cell division	1
positive regulation of cell population proliferation	1
neural precursor cell proliferation	1
regulation of neural precursor cell proliferation	1
CCR chemokine receptor binding	1
intracellular anatomical structure	1
cellular anatomical structure	1
intermediate filament cytoskeleton	1
polymeric cytoskeletal fiber	1
cytoskeleton	1

Protein interactions and networks

STRING

4222 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NES	RBFOX3	A6NFN3	932
NES	SYNM	O15061	918
NES	CD44	P16070	888
NES	SOX2	P48431	883
NES	DCX	O43602	874
NES	PAX6	P26367	859
NES	OLIG2	Q13516	837
NES	PROM1	O43490	826
NES	POU5F1	P31359	825
NES	FGF2	P09038	825
NES	NANOG	Q9H9S0	820
NES	MAP2	P11137	801
NES	SOX1	O00570	791
NES	EGF	P01133	790
NES	CDK5	Q00535	790

IntAct

97 interactions, top by confidence:

A	B	Type	Score
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
GFAP	VIM	psi-mi:“MI:0914”(association)	0.830
VIM	NES	psi-mi:“MI:0915”(physical association)	0.800
NEFM	NEFL	psi-mi:“MI:0914”(association)	0.800
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
RSPRY1	NEFL	psi-mi:“MI:0914”(association)	0.530
MYOG	TCF4	psi-mi:“MI:0914”(association)	0.530
NEFM	EVI5	psi-mi:“MI:0914”(association)	0.530
NEFM	VWA8	psi-mi:“MI:0914”(association)	0.530
TRAK2	OGT	psi-mi:“MI:0914”(association)	0.530
TNIP3	NES	psi-mi:“MI:0915”(physical association)	0.400
EBF2	NES	psi-mi:“MI:0915”(physical association)	0.400
COL5A2	NES	psi-mi:“MI:0915”(physical association)	0.400
FAM81B	NES	psi-mi:“MI:0915”(physical association)	0.400
DNAH12	NES	psi-mi:“MI:0915”(physical association)	0.400
KRT8	NES	psi-mi:“MI:0915”(physical association)	0.400
CCSER2	NES	psi-mi:“MI:0915”(physical association)	0.400
Kat8	HCFC1	psi-mi:“MI:0914”(association)	0.350
TMEM132A	WWP2	psi-mi:“MI:0914”(association)	0.350
Plk2	NES	psi-mi:“MI:0914”(association)	0.350
Chmp2a	MEN1	psi-mi:“MI:0914”(association)	0.350
HIF1A	PIAS1	psi-mi:“MI:0914”(association)	0.350
NES	RPL10	psi-mi:“MI:0914”(association)	0.350
CCDC88A		psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (381): NES (Reconstituted Complex), NES (Affinity Capture-RNA), NES (Affinity Capture-MS), NES (Affinity Capture-MS), NES (Affinity Capture-MS), ADD1 (Affinity Capture-MS), CLTA (Affinity Capture-MS), CLTB (Affinity Capture-MS), FLII (Affinity Capture-MS), GART (Affinity Capture-MS), GOLGA2 (Affinity Capture-MS), HADHB (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), IDE (Affinity Capture-MS), IMPDH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GUA9, A2TJV2, A4FU49, A6NDB9, A6X8Z5, D3ZAQ5, P0C671, P10636, P10637, P48681, P58871, Q14676, Q2YDF7, Q3MI48, Q4R729, Q5EBJ4, Q5PSV9, Q5S6V2, Q5SWP3, Q5TM66, Q5TM68, Q5U2M8, Q5YCV9, Q5YCW0, Q5YCW1, Q640N3, Q68A65, Q68DA7, Q6NYC8, Q6ZW13, Q767L8, Q7YR40, Q7Z6I6, Q811Q2, Q8BHB9, Q8BHW6, Q8BQ30, Q8CB87, Q8CC96, Q8IXJ9

Diamond homologs: P21263, P48677, P48681, P86839, Q01550, Q5RA72, Q6P5H2, Q70IV5, Q9Z1Q1, P03995, P05786, P35616, P47819, P48671, P48672, Q04948, O15061, O77788, P07197, P08552, P08553, P12839, P16053, Q02916, A0A8C0N8E3, A0JND2, A1L595, A5A6M0, A6QQJ3, B4F721, O62654, O93532, P02533, P02540, P02541, P02542, P02543, P02544, P08776, P08779

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CDK5	unknown	NES	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Striated Muscle Contraction	5	18.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
centriole replication	5	33.9×	3e-04
intermediate filament organization	6	13.4×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	219
Likely benign	29
Benign	9

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
495229	Single allele	Likely pathogenic

SpliceAI

528 predictions. Top by Δscore:

Variant	Effect	Δscore
1:156673452:AC:A	donor_gain	1.0000
1:156673453:CC:C	donor_gain	1.0000
1:156675210:TCGTA:T	donor_loss	1.0000
1:156675211:CGTAC:C	donor_loss	1.0000
1:156675212:GTAC:G	donor_loss	1.0000
1:156675213:TACCT:T	donor_loss	1.0000
1:156675214:ACC:A	donor_loss	1.0000
1:156675223:TGGCC:T	donor_gain	1.0000
1:156675336:GCCAG:G	acceptor_gain	1.0000
1:156675337:CCAG:C	acceptor_gain	1.0000
1:156675337:CCAGC:C	acceptor_gain	1.0000
1:156675338:CAG:C	acceptor_gain	1.0000
1:156675338:CAGC:C	acceptor_gain	1.0000
1:156675339:AG:A	acceptor_gain	1.0000
1:156675340:GC:G	acceptor_loss	1.0000
1:156675341:C:CA	acceptor_loss	1.0000
1:156675341:C:CC	acceptor_gain	1.0000
1:156675342:T:A	acceptor_loss	1.0000
1:156676477:CTCA:C	donor_loss	1.0000
1:156676479:CACC:C	donor_loss	1.0000
1:156676480:ACCTG:A	donor_loss	1.0000
1:156676481:C:CT	donor_loss	1.0000
1:156673447:CTCTT:C	donor_loss	0.9900
1:156673448:TCTTA:T	donor_loss	0.9900
1:156673449:CTTA:C	donor_loss	0.9900
1:156673450:TTA:T	donor_loss	0.9900
1:156673451:TACC:T	donor_loss	0.9900
1:156673452:A:AC	donor_gain	0.9900
1:156673453:C:CC	donor_gain	0.9900
1:156673453:C:T	donor_loss	0.9900

AlphaMissense

10445 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:156677221:A:G	L15P	0.996
1:156677209:A:G	L19P	0.995
1:156669952:A:C	F1412L	0.993
1:156669952:A:T	F1412L	0.993
1:156669954:A:G	F1412L	0.993
1:156673522:A:G	L305P	0.993
1:156675226:C:G	A300P	0.993
1:156677212:C:G	R18P	0.993
1:156675252:A:G	L291P	0.992
1:156675240:A:G	L295P	0.991
1:156675220:A:C	Y302D	0.990
1:156677197:A:G	L23P	0.990
1:156675234:A:G	L297P	0.988
1:156675244:A:G	S294P	0.988
1:156675248:C:A	K292N	0.988
1:156675248:C:G	K292N	0.988
1:156677036:C:G	A77P	0.987
1:156673519:A:G	L306P	0.986
1:156675230:C:A	E298D	0.985
1:156675230:C:G	E298D	0.985
1:156677188:A:T	V26D	0.985
1:156677191:C:G	R25P	0.985
1:156677215:C:G	R17P	0.984
1:156677179:A:G	L29P	0.983
1:156673514:C:G	A308P	0.982
1:156675220:A:G	Y302H	0.981
1:156675261:A:G	L288P	0.980
1:156675303:A:G	L274P	0.980
1:156677221:A:T	L15H	0.980
1:156677230:A:G	M12T	0.980

dbSNP variants (sampled 300 via entrez): RS1000043642 (1:156670849 A>T), RS1000138137 (1:156671132 G>C), RS1000643984 (1:156674354 T>A), RS1000949570 (1:156676321 G>C,T), RS1001535998 (1:156679191 G>T), RS1001947132 (1:156669960 C>A,T), RS1002794491 (1:156679340 A>T), RS1003538771 (1:156675948 T>A), RS1004164330 (1:156674011 C>A,G,T), RS1004209351 (1:156677855 C>T), RS1004246471 (1:156674288 G>A), RS1004852916 (1:156672656 A>G), RS1005159932 (1:156668423 G>GC,GT), RS1005524906 (1:156678989 G>A), RS1005587278 (1:156672205 T>G)

Disease associations

OMIM: gene MIM:600915 | disease phenotypes: MIM:135700

GenCC curated gene-disease

Mondo (1): congenital fibrosis of extraocular muscles (MONDO:0007614)

Orphanet (1): Congenital fibrosis of extraocular muscles (Orphanet:45358)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580012	congenital fibrosis of the extraocular muscles (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066462 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	Kd	15.26	nM	CHEMBL3752910
7.09	Kd	81.5	nM	CHEMBL5653589
6.61	ED50	243.9	nM	CHEMBL3752910
5.88	ED50	1303	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 4 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148865: Binding affinity to human NES incubated for 45 mins by Kinobead based pull down assay	kd	0.0153	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148865: Binding affinity to human NES incubated for 45 mins by Kinobead based pull down assay	kd	0.0815	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases reaction, affects cotreatment, decreases expression, increases methylation, increases expression (+1 more)	9
Tretinoin	affects expression, decreases expression, increases reaction, affects cotreatment, increases expression	8
sodium arsenite	increases reaction, decreases expression, decreases reaction, affects methylation, increases expression	7
Valproic Acid	affects expression, decreases expression, increases expression, increases methylation	4
trichostatin A	affects cotreatment, decreases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	3
(+)-JQ1 compound	decreases expression	3
Resveratrol	decreases expression	3
lead acetate	decreases expression, decreases reaction, increases expression	2
decabromobiphenyl ether	affects cotreatment, decreases expression, increases expression	2
Vorinostat	affects cotreatment, decreases expression	2
Arsenic	decreases expression, increases methylation, affects expression	2
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation	2
Cannabidiol	affects cotreatment, increases expression	2
Cisplatin	affects cotreatment, increases expression, decreases response to substance	2
Dexamethasone	decreases expression, increases expression	2
Dimethyl Sulfoxide	decreases expression, increases expression	2
Estradiol	increases expression, affects cotreatment	2
Lead	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
moringin	affects cotreatment, increases expression	1
sotorasib	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
geldanamycin	increases expression	1
thymoquinone	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
methyleugenol	increases expression	1
arsenite	affects binding, increases reaction	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651907	Binding	Binding affinity to human NES incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_TA50	HAP1 NES (-) 1	Cancer cell line	Male
CVCL_XQ91	HAP1 NES (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03059420	Not specified	RECRUITING	Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies