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): 264 total — 1 likely-pathogenic
• GTEx eGene: eQTL in 11 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.26 (unconstrained)
• MANE Select transcript: NM_006617
• Interaction hub: 3,336 STRING partners (top 2% of genes corpus-wide)
• Notable: 264 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 4 — 3 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000368223

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1

ENST00000368223, ENST00000867897, ENST00001123256, ENST00001145915

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.

Highest expression (Bgee): ventricular zone, gluteal muscle, apex of heart, vena cava, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NES is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 11 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Testis	eqtl	3.6e-09	+0.27	1:156663731:T:G
Skin Sun Exposed Lower leg	eqtl	7.9e-05	+0.53	1:156667356:C:T
Skin Not Sun Exposed Suprapubic	eqtl	9.3e-05	+0.52	1:156667356:C:T
Cells Cultured fibroblasts	eqtl	4.2e-04	+0.10	1:156661854:G:C
Brain Spinal cord cervical c-1	eqtl	3.5e-03	+0.36	1:156677793:T:G
Liver	eqtl	1.1e-02	-1.05	1:156748361:C:T
Brain Cerebellum	eqtl	1.1e-02	-0.27	1:156682011:A:C
Nerve Tibial	eqtl	1.1e-02	+0.19	1:156921062:C:G
Brain Hippocampus	eqtl	2.1e-02	+0.20	1:157378066:G:A
Heart Left Ventricle	eqtl	3.3e-02	-0.14	1:156666005:C:CCCGT
Muscle Skeletal	eqtl	5.0e-02	+0.11	1:156664847:A:G

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

showing 100 of 284 tissues 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
spleen	UBERON:0002106	90.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.85	gold quality
mammary duct	UBERON:0001765	90.76	gold quality
upper lobe of lung	UBERON:0008948	90.69	gold quality
upper lobe of left lung	UBERON:0008952	90.66	gold quality
stromal cell of endometrium	CL:0002255	90.56	gold quality
lower lobe of lung	UBERON:0008949	90.38	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.31	gold quality
myocardium	UBERON:0002349	90.29	gold quality
body of uterus	UBERON:0009853	90.27	gold quality
cauda epididymis	UBERON:0004360	90.26	gold quality
cortex of kidney	UBERON:0001225	90.15	gold quality
gastrocnemius	UBERON:0001388	89.99	gold quality
cardia of stomach	UBERON:0001162	89.89	silver quality
muscle of leg	UBERON:0001383	89.80	gold quality
smooth muscle tissue	UBERON:0001135	89.69	gold quality
omental fat pad	UBERON:0010414	89.64	gold quality
peritoneum	UBERON:0002358	89.61	gold quality
spinal cord	UBERON:0002240	89.60	gold quality
epithelium of mammary gland	UBERON:0003244	89.42	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.40	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.37	gold quality
lung	UBERON:0002048	89.27	gold quality
tongue	UBERON:0001723	89.13	gold quality
muscle organ	UBERON:0001630	88.95	gold quality
adult mammalian kidney	UBERON:0000082	88.83	gold quality
kidney epithelium	UBERON:0004819	88.77	gold quality
biceps brachii	UBERON:0001507	88.70	gold quality
inferior vagus X ganglion	UBERON:0005363	88.30	gold quality
renal medulla	UBERON:0000362	88.22	gold quality
urethra	UBERON:0000057	88.14	gold quality
kidney	UBERON:0002113	88.09	gold quality
cardiac muscle of right atrium	UBERON:0003379	87.94	gold quality
superficial temporal artery	UBERON:0001614	87.82	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.62	gold quality
muscle tissue	UBERON:0002385	87.62	gold quality
coronary artery	UBERON:0001621	87.60	gold quality
nipple	UBERON:0002030	87.43	gold quality
mammary gland	UBERON:0001911	87.40	gold quality
thoracic mammary gland	UBERON:0005200	87.32	gold quality
skeletal muscle tissue	UBERON:0001134	87.24	gold quality
endocervix	UBERON:0000458	87.20	gold quality
metanephros cortex	UBERON:0010533	87.05	gold quality
right lobe of thyroid gland	UBERON:0001119	87.04	gold quality
vastus lateralis	UBERON:0001379	86.94	silver quality
periodontal ligament	UBERON:0008266	86.84	gold quality
uterus	UBERON:0000995	86.79	gold quality
left coronary artery	UBERON:0001626	86.78	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.65	gold quality
colonic epithelium	UBERON:0000397	86.61	gold quality
adipose tissue	UBERON:0001013	86.52	gold quality
ventral tegmental area	UBERON:0002691	86.44	gold quality
left ventricle myocardium	UBERON:0006566	86.28	gold quality
connective tissue	UBERON:0002384	86.17	gold quality
quadriceps femoris	UBERON:0001377	86.05	silver quality
superior surface of tongue	UBERON:0007371	85.98	gold quality
subthalamic nucleus	UBERON:0001906	85.69	gold quality
medulla oblongata	UBERON:0001896	85.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.40	gold quality
medial globus pallidus	UBERON:0002477	85.35	gold quality
lower esophagus	UBERON:0013473	85.30	gold quality
ascending aorta	UBERON:0001496	84.84	gold quality
synovial joint	UBERON:0002217	84.82	gold quality
endometrium	UBERON:0001295	84.80	gold quality
thoracic aorta	UBERON:0001515	84.77	gold quality
globus pallidus	UBERON:0001875	84.60	gold quality
tendon	UBERON:0000043	84.54	gold quality
calcaneal tendon	UBERON:0003701	84.50	gold quality
prostate gland	UBERON:0002367	84.46	gold quality
midbrain	UBERON:0001891	84.15	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Heart muscle	tissue	151.3	medium
Skeletal muscle	tissue	52.2	low
Tongue	tissue	44.2
Spleen	tissue	38.8	not detected
Adipose tissue	tissue	37.5	not detected
Seminal vesicle	tissue	34.0	not detected
Smooth muscle	tissue	28.3	low
Lung	tissue	25.7	not detected
Spinal cord	tissue	23.5
Endometrium 1	tissue	22.4	not detected
Cervix	tissue	22.1	not detected
Prostate	tissue	19.9	not detected
Kidney	tissue	19.1	high
Breast	tissue	17.6	high
Vagina	tissue	17.6	not detected
Hippocampus	tissue	17.4	not detected
Placenta	tissue	15.7	not detected
Locus coeruleus	tissue	13.4
Fallopian tube	tissue	13.1	not detected
Appendix	tissue	13.0	not detected
Nucleus accumbens	tissue	12.5
Pituitary gland	tissue	12.4
Postcentral gyrus	tissue	12.4
Epididymis	tissue	12.2	not detected
Gallbladder	tissue	10.6	not detected
Urinary bladder	tissue	10.5	not detected
Thyroid gland	tissue	9.8	not detected
Parathyroid gland	tissue	9.7	not detected
Superior colliculi	tissue	9.5
Choroid plexus	tissue	8.6
Ovary	tissue	8.3	not detected
Esophagus	tissue	7.7	not detected
Colon	tissue	7.7	low
Retina	tissue	7.6
Thalamus	tissue	7.1
Substantia nigra	tissue	6.9
Adrenal gland	tissue	6.8	not detected
Small intestine	tissue	6.6	not detected
Rectum	tissue	6.2	not detected
Salivary gland	tissue	5.4	not detected
Caudate putamen	tissue	5.4
Stomach 1	tissue	5.0	not detected
Hypothalamus	tissue	5.0
Duodenum	tissue	5.0	not detected
Testis	tissue	4.7	high
Pons	tissue	4.7
Lymph node	tissue	4.5	not detected
Liver	tissue	4.5	not detected
Septum	tissue	4.5
Cerebral cortex	tissue	4.4	low
Motor cortex	tissue	4.4
Hippocampal formation	tissue	4.4
Entorhinal cortex	tissue	4.4
Olfactory bulb	tissue	4.4
Medulla oblongata	tissue	4.1
Prefrontal cortex	tissue	4.0
Midbrain	tissue	4.0
Temporal cortex	tissue	3.9
Insular cortex	tissue	3.9
Frontal cortex	tissue	3.8

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Area postrema (43.7), Dorsal funiculus (white matter) (38.0), Cervical spinal cord, central gray (37.7), Cervical spinal cord, ventral horn (37.7), Inferior olive (34.1).

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)

Targeting NES by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

17 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 3.22e-09, LOEUF 1.26, missense Z 0.665 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000368223 — one region, missense o/e 0.94.

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), KRT9 (ENSG00000171403), KRT20 (ENSG00000171431), KRT27 (ENSG00000171446), KRT2 (ENSG00000172867), KRT28 (ENSG00000173908), DES (ENSG00000175084), LMNB2 (ENSG00000176619), SYNM (ENSG00000182253), KRT76 (ENSG00000185069), KRT6B (ENSG00000185479), KRT79 (ENSG00000185640), KRT73 (ENSG00000186049), KRT5 (ENSG00000186081), KRT26 (ENSG00000186393), KRT10 (ENSG00000186395), KRT3 (ENSG00000186442), KRT16 (ENSG00000186832), KRT14 (ENSG00000186847), KRT12 (ENSG00000187242), KRT77 (ENSG00000189182)

+8 more (showing top 60).

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:101784) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 15 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal neuromuscular synapse morphology	1
impaired coordination	1
decreased embryo size	1
increased heart weight	1
increased circulating chloride level	1
nervous system phenotype	1
decreased neuronal precursor cell number	1
decreased circulating cholesterol level	1
growth/size/body region phenotype	1
embryo phenotype	1
decreased birth body size	1
abnormal neuron differentiation	1
lethality at weaning, incomplete penetrance	1
embryonic lethality between implantation and placentation, incomplete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Mesocricetus auratus	Q9Z1Q1	63.3%	Diamond
Xenopus laevis	Q01550	50.0%	Diamond
Danio rerio	P86839	33.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
BCAN-AS2	ncRNA	126568844
NAXE	protein-coding	128240
GPATCH4	protein-coding	54865
HAPLN2	protein-coding	60484
BCAN	protein-coding	63827
CRABP2	protein-coding	1382
METTL25B	protein-coding	51093
ISG20L2	protein-coding	81875
HDGF	protein-coding	3068
MRPL24	protein-coding	79590
PRCC	protein-coding	5546

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): intermediate filaments

Antibody reliability (HPA): IH enhanced · IF enhanced

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)

Type	Positions
N-acetylmethionine	1
Phosphoserine	311, 325, 355, 358, 398, 471, 476, 548, 564, 578, 588, 638, 680, 702, 746, 768, 790, 820, 831, 842, 894, 905, 913, 934, 1016, 1261, 1282, 1286, 1310, 1347, 1409, 1418, 1452, 1496, 1498, 1577, 1617, 1618
Phosphothreonine	315, 338, 388, 851
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	811
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	811

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

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 (10): 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), 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

33 GO namespaces:

Category	Terms
system development	2
animal gross anatomical part developmental process	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
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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
G2/M transition of mitotic cell cycle	BP	direct assay
negative regulation of catalytic activity	BP	direct assay
negative regulation of protein binding	BP	direct assay
stem cell proliferation	BP	mutant phenotype
cytoplasm	CC	direct assay
intermediate filament cytoskeleton	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 3,336 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NES	RBFOX3	A6NFN3	917
NES	SOX2	P48431	881
NES	PAX6	P26367	879
NES	DCX	O43602	868
NES	OLIG2	Q13516	825
NES	NANOG	Q9H9S0	821
NES	FGF2	P09038	814
NES	BDNF	P23560	813
NES	PROM1	O43490	802
NES	POU5F1	P31359	799
NES	MAP2	P11137	785
NES	EGF	P01133	779
NES	SOX1	O00570	770
NES	TBR1	Q16650	752
NES	SOX17	Q9H6I2	751

IntAct

Human interaction partners of NES in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

14 partners by confidence:

Partner	Interaction type	MIscore	Records
VIM	physical association	0.800	1
CCSER2	physical association	0.400	1
COL5A2	physical association	0.400	1
DNAH12	physical association	0.400	1
EBF2	physical association	0.400	1
FAM81B	physical association	0.400	1
KRT8	physical association	0.400	1
TNIP3	physical association	0.400	1
EGR1	association	0.350	1
KRT23	association	0.350	1
KRT31	association	0.350	1
RPL10	association	0.350	1
SYNM	association	0.350	1
ZNF10	association	0.350	1

BioGRID (385 interactions; top human partners by supporting records): VIM (Affinity Capture-MS; 8 records), CDK5 (Biochemical Activity; 3 records), GFAP (Affinity Capture-MS; 3 records), IDE (Reconstituted Complex; 3 records), MYC (Affinity Capture-MS; 3 records), NEFM (Affinity Capture-MS; 3 records), TUBB2A (Affinity Capture-Western; 3 records), FAM167A (Affinity Capture-MS; 2 records), GPATCH4 (Affinity Capture-MS; 2 records), KEAP1 (Affinity Capture-Western; 2 records), KRT18 (Proximity Label-MS; 2 records), KRT31 (Affinity Capture-MS; 2 records), MYF6 (Affinity Capture-MS; 2 records), MYOG (Affinity Capture-MS; 2 records), PRDX2 (Affinity Capture-MS; 2 records)

SIGNOR signaling

showing 1 of 2 signaling interactions:

A	Effect	B	Mechanism
CDK5	unknown	NES	phosphorylation

Disease & clinical

Genetic variants

Variant evidence for NES: 264 ClinVar records (1 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	220
Likely benign	29
Benign	9

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
495229	Single allele	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore NES’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 230):

Position(s)	Effect	Δscore	Sites
1:156675214–156675215	donor_loss	1.0000	4
1:156675341–156675342	acceptor_loss	1.0000	3
1:156676480–156676481	donor_loss	1.0000	5
1:156673452–156673453	donor_loss	0.9900	6
1:156673528–156673529	acceptor_loss	0.9900	6
1:156675215	donor_loss	0.9900
1:156675341–156675342	acceptor_loss	0.9900	3
1:156675350	acceptor_gain	0.9800
1:156675339	acceptor_gain	0.9700
1:156675345	acceptor_gain	0.9700

AlphaMissense

731 missense substitutions predicted likely pathogenic (of 10,445 scored), across 268 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M293	9	0.827	0.959
N16	8	0.917	0.973
D1410	8	0.829	0.920
N33	8	0.821	0.933
D1414	8	0.810	0.911
E298	7	0.961	0.985
F1412	7	0.954	0.993
M12	7	0.931	0.980
W186	7	0.926	0.977
F260	7	0.906	0.968
W71	7	0.889	0.954
R303	7	0.888	0.974
W13	7	0.835	0.962
E8	7	0.824	0.899
W250	7	0.781	0.891
E201	7	0.765	0.862
D82	7	0.740	0.864
D1297	7	0.716	0.821
K292	6	0.918	0.988
K74	6	0.905	0.961

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme, Skin Cutaneous Melanoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00015
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000783

Disease associations

OMIM: gene MIM:600915 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066462 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

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	decreases reaction, affects methylation, increases expression, increases reaction, decreases expression	7
Valproic Acid	decreases expression, increases expression, increases methylation, affects expression	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	affects cotreatment, increases expression, decreases 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	affects cotreatment, increases expression	2
Lead	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
moringin	increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.

1 trials:

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NES across ~30M SureChEMBL compounds — explore on Sugi Predict.