NANOG

Summary

NANOG (Nanog homeobox, HGNC:20857) is a protein-coding gene on chromosome 12p13.31, encoding Homeobox protein NANOG (Q9H9S0). Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal.

The protein encoded by this gene is a DNA binding homeobox transcription factor involved in embryonic stem (ES) cell proliferation, renewal, and pluripotency. The encoded protein can block ES cell differentiation and can also autorepress its own expression in differentiating cells. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 79923 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• Transcription factor: yes — 65 downstream targets (CollecTRI)
• MANE Select transcript: NM_024865

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20857
Approved symbol	NANOG
Name	Nanog homeobox
Location	12p13.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12581, FLJ40451
Ensembl gene	ENSG00000111704
Ensembl biotype	protein_coding
OMIM	607937
Entrez	79923

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000229307, ENST00000526286, ENST00000526434, ENST00000541267, ENST00000933164, ENST00000933165

RefSeq mRNA: 2 — MANE Select: NM_024865 NM_001297698, NM_024865

CCDS: CCDS31736, CCDS73436

Canonical transcript exons

ENST00000229307 — 4 exons

Exon	Start	End
ENSE00000716537	7792950	7793212
ENSE00000867802	7789402	7789765
ENSE00001426852	7794679	7799146
ENSE00001746619	7794457	7794543

Expression profiles

Bgee: expression breadth broad, 74 present calls, max score 86.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.3887 / max 498.8093, expressed in 88 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123923	1.1595	78
123924	1.1008	72
123922	0.1284	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.27	gold quality
cerebellar vermis	UBERON:0004720	78.49	silver quality
sperm	CL:0000019	77.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.54	gold quality
kidney epithelium	UBERON:0004819	76.38	gold quality
vena cava	UBERON:0004087	75.41	silver quality
upper arm skin	UBERON:0004263	75.28	gold quality
epithelial cell of pancreas	CL:0000083	73.15	gold quality
pericardium	UBERON:0002407	72.76	silver quality
vastus lateralis	UBERON:0001379	72.50	gold quality
myocardium	UBERON:0002349	72.41	gold quality
quadriceps femoris	UBERON:0001377	72.18	gold quality
cardia of stomach	UBERON:0001162	71.34	silver quality
thymus	UBERON:0002370	70.83	gold quality
pharyngeal mucosa	UBERON:0000355	70.52	silver quality
cardiac muscle of right atrium	UBERON:0003379	70.38	gold quality
ventral tegmental area	UBERON:0002691	70.28	silver quality
layer of synovial tissue	UBERON:0007616	70.21	gold quality
left ventricle myocardium	UBERON:0006566	70.12	gold quality
body of tongue	UBERON:0011876	69.86	silver quality
tongue	UBERON:0001723	69.42	silver quality
secondary oocyte	CL:0000655	69.38	gold quality
superior surface of tongue	UBERON:0007371	69.20	silver quality
trigeminal ganglion	UBERON:0001675	68.79	silver quality
pons	UBERON:0000988	68.76	silver quality
lateral nuclear group of thalamus	UBERON:0002736	68.73	gold quality
synovial joint	UBERON:0002217	68.64	silver quality
cartilage tissue	UBERON:0002418	68.00	gold quality
decidua	UBERON:0002450	67.99	silver quality
oocyte	CL:0000023	67.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	384.33
E-ANND-3	yes	5.15

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

65 targets.

Target	Regulation
AFP	Repression
AHR
ATF3
BCL6
BMI1
CCND1	Unknown
CCND2
CCND3
CCNE1
CDC25A	Repression
CDK1
CDK6	Repression
CDX2	Repression
CEL
CGA	Repression
CGB3	Repression
CUL3
CXCR4	Activation
DKK1	Unknown
DNMT1	Activation
DPPA4	Activation
E2F1
EPCAM	Activation
ESRRB	Unknown
FGF4	Activation
FOXA2	Repression
GATA2	Repression
GATA4	Repression
GATA6	Repression
GDF3	Unknown

Upstream regulators (CollecTRI, top): CTCF, CTNNB1, DACH1, EPAS1, ESRRB, FEZF1, FOXC1, FOXD3, GATA4, GATA6, JUN, KDM2A, KLF4, LEF1, MBD2, NANOG, NFKB, NR0B1, NR2C1, NR2C2, PAX6, PBX1, POU5F1, RARG, SALL4, SATB1, SATB2, SNAI1, SOX2, SP1, SP3, STAT3, TBXT, TCF3, TCF7L1, TP53, ZIC3, ZNF143, ZNF281, ZNF322

miRNA regulators (miRDB)

30 targeting NANOG, 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-3613-3P	100.00	76.36	7965
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-652-5P	99.91	67.49	505
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6808-5P	99.31	66.23	2150
HSA-MIR-6893-5P	99.31	66.25	2119
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-154-5P	98.92	66.65	733
HSA-MIR-605-5P	98.79	68.24	1161
HSA-MIR-6771-3P	98.20	66.53	971
HSA-MIR-4457	98.09	67.12	1274
HSA-MIR-4733-5P	97.75	67.44	866
HSA-MIR-376A-5P	97.70	65.61	863
HSA-MIR-585-5P	97.54	69.02	955
HSA-MIR-6824-5P	97.41	68.43	583
HSA-MIR-3157-5P	97.41	67.61	998
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-4509	96.19	65.80	900
HSA-MIR-5186	94.63	66.76	627

Literature-anchored findings (GeneRIF, showing 40)

• mouse and human Nanog and Nanog2 genes may have a common role in the maintenance of pluripotency in both species (PMID:15108323)
• Ten processed NANOG pseudogenes are identified in the complete human genome. (PMID:15233988)
• demonstrated changes in DNA methylation in the promoter regions of Nanog and Oct-4 in a human cell line during retinoic acid-induced differentiation (PMID:15615706)
• Gene knockdown of Nanog promotes differentiation, thereby demonstrating a role for these factors in human embryonic stem cell self-renewal. (PMID:15749924)
• NANOG is a new marker for testicular carcinoma in situ and germ cell tumours. (PMID:15982323)
• findings suggest that NANOG acts as a gatekeeper of pluripotency in human embryonic stem and carcinoma cells by preventing their differentiation to extraembryonic endoderm and trophectoderm lineages (PMID:15983365)
• The NANOG protein co-occupy a substantial portion of its target genes, and collaborate to form regulatory circuitry consisting of autoregulatory and feedforward loops. (PMID:16153702)
• We conclude that, despite the difference in primary structure and expression pattern in various stem cells, the alternatively-spliced variant of Nanog has similar activity to that of the full length version. (PMID:16391521)
• NANOG overexpression in human embryonic stem cells enables their propagation for multiple passages during which the cells remain pluripotent (PMID:16501172)
• Nanog possesses an oncogenic potential that may be related to the role it plays in germ cell tumors and to its function in self renewal of ES cells. (PMID:16540082)
• These results suggest that NANOG plays a crucial role in maintaining the pluripotent state of primate embryonic stem cells. (PMID:16923129)
• A series of deletion and site-directed mutagenesis within the homeodomain revealed that two basic NLS motifs are located at the N-terminus and C-terminus of the homeodomain and that both motifs are required for complete hNanog nuclear localization. (PMID:17196939)
• Nanog is described in this review as a unique homeobox transcription factor and key downstream effector of extrinsic signals of embryonic stem cell self-renewal and pluripotency. (PMID:17211451)
• reprogramming of DNA methylation and histone modifications on regulatory regions of the developmentally regulated OCT4 and NANOG genes (PMID:17314394)
• knock-downs of NANOG produced a proliferation rather than a differentiation phenotype in EC cells (PMID:17506876)
• Hence, Nanog does not inhibit terminal differentiation of committed cells but it is an inhibitor of trans-differentiation that is dependent on de-novo activation of gene transcription. (PMID:18039466)
• the CD2 domain of Nanog is a unique transactivator that utilizes aromatic residues to confer specific activity absolutely required for ES self-renewal. (PMID:18086680)
• Sox2-expressing MSCs showed consistent proliferation and osteogenic capability in culture media containing bFGF (PMID:18187129)
• The human primordial germ cells is the first primary cell type described to express POU5F1 and NANOG but not SOX2. (PMID:18199879)
• Sox2, Oct4 and Nanog are linked together in a pluripotent regulatory network (PMID:18388306)
• SMAD 2/3 signaling directly supports NANOG expression, while SMAD 1/5/8 activation moderately represses SOX2. (PMID:18393632)
• may be involved in carcinogenesis of the cervix and progression of cervical carcinoma (PMID:18419830)
• Immunohistochemical localization of nanog in stem cell compartments of human sacrococcygeal teratomas. (PMID:18439155)
• HA binding to tumor cells promotes Nanog protein association with CD44 followed by Nanog activation and the expression of pluripotent stem cell regulators, and forms a complex with Stat-3 in the nucleus leading to Stat-3 and MDR1 activation (PMID:18441325)
• Oct-4 and Nanog may have roles in oral cancer stem-like cells and high-grade oral squamous cell carcinoma (PMID:18593985)
• an essential role in sustaining human embryonic stem cells self-renewal (PMID:18682241)
• These findings suggest that NANOG is involved in the pathogenesis and clinical progress of gestational trophoblastic disease, likely through its effect on apoptosis, cell migration, and invasion. (PMID:18772339)
• Identification of the OCT4-pg1 retrogene and NANOG gene expression in the human embryonic eye (PMID:18946985)
• Esrrb coordinates with Nanog and Oct4 to activate the internal machinery of ES cells (PMID:18957414)
• Effects of ectopic Nanog and Oct4 overexpression on mesenchymal stem cells. (PMID:19102659)
• NANOG regulates S-phase entry in human embryonic stem cells (hESCs) via transcriptional regulation of cell cycle regulatory components. (PMID:19139263)
• Results identified two distinct transactivation domains in the C-terminal domain of human NANOG, which function in a synergistic manner to activate transcription in pluripotent human embryonic carcinoma cells. (PMID:19229867)
• Nanog in turn prevents neuroectoderm differentiation induced by FGF signalling and limits the transcriptional activity of the Smad2/3 cascade, blocking progression along the endoderm lineage (PMID:19279133)
• a detailed characterization of the functional domains in the human (h) NANOG protein (PMID:19350681)
• NANOG, a cell-fate regulatory molecule known to be important for embryonic stem cell self-renewal, also plays a novel role in tumor development. (PMID:19415763)
• Studies show that the expression of genes belonging to the OCT3/SOX2/NANOG/KLF4 core circuitry that acts at the highest level in regulating stem cell biology. (PMID:19458492)
• This study evaluates the use of the markers, podoplanin, SOX2, NANOG, and OCT3/4 in ovarian tumors (PMID:19483629)
• Data showed that both KLF4 and PBX1 mRNA and protein expression were downregulated during hESC differentiation. Overexpression of KLF4 and PBX1 upregulated NANOG promoter activity and NANOG protein expression. (PMID:19522013)
• Findings indicate that overexpression of stemness gene Nanog in NCCIT cells is associated with maintaining stem cell-like phenotype and suggest that targeting Nanog might be an approach for improved therapy of poorly differentiated tumors. (PMID:19567677)
• Results indicate that HA binding to CD44 promotes PKCepsilon activation, increases the phosphorylation of the stem cell marker, Nanog, leads to microRNA-21 (miR-21) production and PDCD4 reduction. (PMID:19633292)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nanog	ENSDARG00000075113
mus_musculus	Nanog	ENSMUSG00000012396
rattus_norvegicus	Nanog	ENSRNOG00000008368
drosophila_melanogaster	Dll	FBGN0000157
caenorhabditis_elegans		WBGENE00000463

Paralogs (9): DLX6 (ENSG00000006377), DLX3 (ENSG00000064195), DLX5 (ENSG00000105880), DLX4 (ENSG00000108813), DLX2 (ENSG00000115844), DLX1 (ENSG00000144355), VENTX (ENSG00000151650), BSX (ENSG00000188909), NANOGP8 (ENSG00000255192)

Protein

Protein identifiers

Homeobox protein NANOG — Q9H9S0 (reviewed: Q9H9S0)

Alternative names: Homeobox transcription factor Nanog

All UniProt accessions (2): Q9H9S0, F5GZI2

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator involved in inner cell mass and embryonic stem (ES) cells proliferation and self-renewal. Imposes pluripotency on ES cells and prevents their differentiation towards extraembryonic endoderm and trophectoderm lineages. Blocks bone morphogenetic protein-induced mesoderm differentiation of ES cells by physically interacting with SMAD1 and interfering with the recruitment of coactivators to the active SMAD transcriptional complexes. Acts as a transcriptional activator or repressor. Binds optimally to the DNA consensus sequence 5’-TAAT[GT][GT]-3’ or 5’-[CG][GA][CG]C[GC]ATTAN[GC]-3’. Binds to the POU5F1/OCT4 promoter. Able to autorepress its expression in differentiating (ES) cells: binds to its own promoter following interaction with ZNF281/ZFP281, leading to recruitment of the NuRD complex and subsequent repression of expression. When overexpressed, promotes cells to enter into S phase and proliferation.

Subunit / interactions. Interacts with SMAD1. Interacts with SALL4. Interacts with ZNF281/ZFP281. Interacts with PCGF1. Interacts with ESRRB; reciprocally modulates their transcriptional activities. Interacts with NSD2.

Subcellular location. Nucleus.

Tissue specificity. Expressed in testicular carcinoma and derived germ cell tumors (at protein level). Expressed in fetal gonads, ovary and testis. Also expressed in ovary teratocarcinoma cell line and testicular embryonic carcinoma. Not expressed in many somatic organs and oocytes.

Miscellaneous. Exists an other tandem duplicated non-processed pseudogene (NANOGP1) and 10 other NANOG-related nucleotide sequences located on different chromosomes, all of which are processed pseudogenes lacking introns (NANOGP2 to NANOGP11); except NANOGP8 which is a retrogene.

Similarity. Belongs to the Nanog homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9H9S0-1	1	yes
Q9H9S0-2	2, Nanog-delta 48

RefSeq proteins (2): NP_001284627, NP_079141* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR050460	Distal-less_Homeobox_TF	Family

Pfam: PF00046

UniProt features (36 total): mutagenesis site 13, repeat 8, region of interest 5, helix 3, compositionally biased region 2, chain 1, splice variant 1, sequence variant 1, strand 1, DNA-binding region 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4RBO	X-RAY DIFFRACTION	3.3
2KT0	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H9S0-F1	58.23	0.19

Functional residue map

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

Mutagenesis-validated functional residues (13):

Position	Phenotype
102	no effect on pou5f1 promoter dna-binding.
122	increased pou5f1 promoter dna-binding and protein stability.
124	decreased pou5f1 promoter dna-binding and protein stability.
125	decreased pou5f1 promoter dna-binding and protein stability.
136	decreased pou5f1 promoter dna-binding and protein stability.
137	inhibits pou5f1 promoter dna-binding.
140	decreased pou5f1 promoter dna-binding and protein stability.
141	inhibits pou5f1 promoter dna-binding.
144	no effect on pou5f1 promoter dna-binding. decreased protein stability.
145	inhibits pou5f1 promoter dna-binding.
147	inhibits pou5f1 promoter dna-binding.
148	no effect on pou5f1 promoter dna-binding. increased protein stability.
151	decreased pou5f1 promoter dna-binding and protein stability.

Function

Pathways and Gene Ontology

Reactome pathways

13 pathways

ID	Pathway
R-HSA-2892245	POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation
R-HSA-2892247	POU5F1 (OCT4), SOX2, NANOG activate genes related to proliferation
R-HSA-452723	Transcriptional regulation of pluripotent stem cells
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-9754189	Germ layer formation at gastrulation
R-HSA-9823739	Formation of the anterior neural plate
R-HSA-9827857	Specification of primordial germ cells
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1474165	Reproduction
R-HSA-168256	Immune System
R-HSA-449147	Signaling by Interleukins
R-HSA-9758941	Gastrulation

MSigDB gene sets: 113 (showing top): GOBP_SOMATIC_STEM_CELL_POPULATION_MAINTENANCE, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_STEM_CELL_PROLIFERATION, MUELLER_PLURINET, GOBP_CELL_FATE_COMMITMENT_INVOLVED_IN_FORMATION_OF_PRIMARY_GERM_LAYER, KORKOLA_EMBRYONAL_CARCINOMA_UP, GOBP_GASTRULATION, GOBP_ENDODERM_DEVELOPMENT, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_STEM_CELL_PROLIFERATION, BENPORATH_NOS_TARGETS, GOBP_ENDODERM_FORMATION, GOBP_EMBRYO_DEVELOPMENT, CONRAD_STEM_CELL

GO Biological Process (12): endodermal cell fate specification (GO:0001714), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), regulation of gene expression (GO:0010468), stem cell population maintenance (GO:0019827), cell differentiation (GO:0030154), somatic stem cell population maintenance (GO:0035019), regulation of cell differentiation (GO:0045595), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of stem cell proliferation (GO:2000648), negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of cell population proliferation (GO:0008284)

GO Molecular Function (9): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription repressor activity, RNA polymerase II-specific (GO:0001227), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transcriptional regulation of pluripotent stem cells	2
Developmental Biology	2
Gastrulation	2
Signaling by Interleukins	1
Reproduction	1
Immune System	1
Cytokine Signaling in Immune system	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
regulation of transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
nuclear lumen	2
cell fate specification	1
endodermal cell fate commitment	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
multicellular organismal process	1
maintenance of cell number	1
cellular developmental process	1
stem cell population maintenance	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
positive regulation of DNA-templated transcription	1
positive regulation of cell population proliferation	1
stem cell proliferation	1
regulation of stem cell proliferation	1
negative regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
transcription regulatory region nucleic acid binding	1
sequence-specific double-stranded DNA binding	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
negative regulation of transcription by RNA polymerase II	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription repressor activity	1
nucleic acid binding	1
transcription regulator activity	1
double-stranded DNA binding	1

Protein interactions and networks

STRING

4726 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NANOG	POU5F1	P31359	999
NANOG	SOX2	P48431	999
NANOG	SALL4	Q9UJQ4	997
NANOG	TET1	Q8NFU7	991
NANOG	KLF4	P78338	975
NANOG	TET2	Q6N021	960
NANOG	STAT3	P40763	952
NANOG	LIN28A	Q9H9Z2	947
NANOG	MYC	P01106	915
NANOG	GJB2	P29033	914
NANOG	ESRRB	O95718	909
NANOG	SALL1	Q9NSC2	908
NANOG	CD44	P16070	883
NANOG	TET3	O43151	876
NANOG	TBX3	O15119	874
NANOG	KDM1A	O60341	874

IntAct

5 interactions, top by confidence:

A	B	Type	Score
IFNA10	NANOG	psi-mi:“MI:0915”(physical association)	0.370
NANOG	RHOXF2	psi-mi:“MI:0915”(physical association)	0.370
KPNA2	PARP1	psi-mi:“MI:0403”(colocalization)	0.350
L1TD1	SOX2	psi-mi:“MI:0914”(association)	0.350

BioGRID (277): NANOG (Biochemical Activity), NANOG (Affinity Capture-Western), NANOG (Affinity Capture-Western), NANOG (Co-purification), ACACB (Affinity Capture-MS), ACOT9 (Affinity Capture-MS), AKAP8L (Affinity Capture-MS), AKAP9 (Affinity Capture-MS), ALYREF (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), ANAPC4 (Affinity Capture-MS), ANGEL2 (Affinity Capture-MS), ARGLU1 (Affinity Capture-MS), ARID1B (Affinity Capture-MS), ARID3A (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PPF3, A0A1W2PPM1, A1A546, A1YGI6, A2T763, A5YC49, A6NFQ7, A6NJG6, D2HQI1, G3X9P6, O42173, O57374, P09632, P0C7M4, P10242, P14837, P17278, P31272, P31538, Q1KKS8, Q28ET4, Q28G02, Q3LTE0, Q3UT54, Q4JM65, Q4KL20, Q5TM83, Q5TM84, Q5W1J6, Q68EH7, Q6NSW7, Q80Z64, Q8IUE1, Q8JH55, Q8JIT7, Q8JJ26, Q8MIB7, Q8MIB8, Q8MIE9, Q91685

Diamond homologs: A1L2P5, A1YF16, A1YG92, A1YG93, A2T763, A7Y7W3, A8XJD0, O08686, O42368, O43711, O55144, O60479, O88181, O93353, O93366, O93367, P09026, P14651, P18867, P20009, P22544, P22808, P23410, P23682, P28362, P31314, P35548, P35993, P40764, P42583, P43345, P50574, P50575, P50576, P50577, P52953, P53770, P53771, P53772, P53774

SIGNOR signaling

36 interactions.

A	Effect	B	Mechanism
SMAD2/SMAD4	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
SMAD3/SMAD4	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
NANOG	up-regulates	Pluripotency
NANOG	“up-regulates quantity by expression”	DNMT1	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	GATA6	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	GATA4	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	PAX6	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	FOXA2	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	SOX17	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	AFP	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	CDX2	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	CGA	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	“CGB Family”	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	GATA2	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	LAMB1	“transcriptional regulation”
POU5F1	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
SALL4	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
NANOG	“up-regulates quantity by expression”	NANOG	“transcriptional regulation”
KDM5B	“down-regulates quantity by repression”	NANOG	“transcriptional regulation”
PTK2	“up-regulates activity”	NANOG	phosphorylation
PRKCE	“up-regulates activity”	NANOG	phosphorylation
MAPK3	down-regulates	NANOG	phosphorylation
“Av/b1 integrin”	“up-regulates quantity by expression”	NANOG

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	28
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

698 predictions. Top by Δscore:

Variant	Effect	Δscore
12:7789761:GACTG:G	donor_gain	1.0000
12:7792946:ACAG:A	acceptor_loss	1.0000
12:7792947:CA:C	acceptor_loss	1.0000
12:7792948:A:AG	acceptor_gain	1.0000
12:7792949:G:GG	acceptor_gain	1.0000
12:7792949:G:GT	acceptor_loss	1.0000
12:7792949:GT:G	acceptor_gain	1.0000
12:7792949:GTC:G	acceptor_gain	1.0000
12:7792949:GTCT:G	acceptor_gain	1.0000
12:7792949:GTCTC:G	acceptor_gain	1.0000
12:7792970:AT:A	acceptor_gain	1.0000
12:7792970:ATG:A	acceptor_gain	1.0000
12:7792971:T:G	acceptor_gain	1.0000
12:7792971:T:TA	acceptor_gain	1.0000
12:7792972:G:A	acceptor_gain	1.0000
12:7793211:AGG:A	donor_loss	1.0000
12:7793213:G:GG	donor_gain	1.0000
12:7793213:G:T	donor_loss	1.0000
12:7794452:T:A	acceptor_gain	1.0000
12:7794452:TGCAG:T	acceptor_loss	1.0000
12:7794454:CAGGT:C	acceptor_loss	1.0000
12:7794455:A:AG	acceptor_gain	1.0000
12:7794455:AG:A	acceptor_gain	1.0000
12:7794455:AGGT:A	acceptor_gain	1.0000
12:7794456:G:GT	acceptor_gain	1.0000
12:7794456:GG:G	acceptor_gain	1.0000
12:7794456:GGT:G	acceptor_gain	1.0000
12:7794456:GGTG:G	acceptor_gain	1.0000
12:7794456:GGTGA:G	acceptor_gain	1.0000
12:7794542:AG:A	donor_loss	1.0000

AlphaMissense

2057 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:7794469:T:C	F143L	1.000
12:7794470:T:C	F143S	1.000
12:7794471:C:A	F143L	1.000
12:7794471:C:G	F143L	1.000
12:7794474:G:C	Q144H	1.000
12:7794474:G:T	Q144H	1.000
12:7794483:A:C	R147S	1.000
12:7794483:A:T	R147S	1.000
12:7793102:T:C	F102L	0.999
12:7793103:T:C	F102S	0.999
12:7793104:C:A	F102L	0.999
12:7793104:C:G	F102L	0.999
12:7793127:T:A	L110H	0.999
12:7793127:T:C	L110P	0.999
12:7793138:T:C	F114L	0.999
12:7793139:T:C	F114S	0.999
12:7793140:T:A	F114L	0.999
12:7793140:T:G	F114L	0.999
12:7793153:T:C	Y119H	0.999
12:7793199:T:C	L134P	0.999
12:7794462:G:C	K140N	0.999
12:7794462:G:T	K140N	0.999
12:7794466:T:A	W142R	0.999
12:7794466:T:C	W142R	0.999
12:7794469:T:A	F143I	0.999
12:7794469:T:G	F143V	0.999
12:7794470:T:G	F143C	0.999
12:7794475:A:G	N145D	0.999
12:7794476:A:G	N145S	0.999
12:7794482:G:C	R147T	0.999

dbSNP variants (sampled 300 via entrez): RS1000041624 (12:7794284 G>A,T), RS1000470220 (12:7796063 T>A), RS1000595703 (12:7799205 C>A,T), RS1000831779 (12:7796402 C>G), RS1001028548 (12:7799443 T>G), RS1001477808 (12:7788267 A>C), RS1001645432 (12:7796343 A>T), RS1001927998 (12:7793551 CTT>C,CT,CTTT), RS1001957409 (12:7793853 TG>T), RS1001988426 (12:7796149 G>A), RS1002382405 (12:7788699 T>C), RS1003100166 (12:7791009 C>T), RS1003633919 (12:7795511 CG>C), RS1003915573 (12:7798377 A>G), RS1004266209 (12:7798220 T>C)

Disease associations

OMIM: gene MIM:607937 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3580527 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression, decreases reaction	8
sodium arsenite	affects cotreatment, increases expression, increases reaction, decreases expression, decreases reaction (+1 more)	7
Cisplatin	affects cotreatment, increases expression, decreases expression, decreases response to substance, affects expression (+1 more)	6
Tretinoin	affects cotreatment, decreases expression, affects expression	5
bisphenol A	affects cotreatment, decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	4
Resveratrol	decreases expression, decreases reaction, affects cotreatment, decreases response to substance	4
Arsenic Trioxide	affects cotreatment, decreases expression, increases expression, affects reaction	4
methylmercuric chloride	increases expression	3
diallyl trisulfide	decreases reaction, increases expression, decreases expression	3
(+)-JQ1 compound	decreases expression	3
Benzo(a)pyrene	increases expression, increases reaction, affects methylation, decreases expression, decreases methylation (+1 more)	3
Quercetin	decreases expression	3
napabucasin	decreases expression	2
perfluorooctanoic acid	increases expression, affects cotreatment, decreases expression	2
perfluorooctane sulfonic acid	decreases expression, increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, decreases reaction, increases expression, increases reaction	2
Chir 99021	affects cotreatment, increases expression, decreases expression	2
belinostat	increases expression, affects cotreatment	2
bisphenol S	affects cotreatment, decreases expression, increases expression	2
Sunitinib	decreases expression, increases expression	2
Vorinostat	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Gemcitabine	decreases expression	2
Acetylcysteine	decreases expression, decreases reaction	2
Cadmium	increases abundance, increases expression, decreases expression	2
Deoxyglucose	decreases reaction, increases expression, decreases expression	2
Estradiol	increases expression	2
Nicotine	decreases reaction, affects cotreatment, increases expression	2

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3584483	Binding	Activation of human Nanog in NCCIT cells transfected with firefly luciferase gene assessed as relative luciferase activity up to 72 hrs by luminometer plate reader relative to DMSO control	Identification of 2-[4-[(4-Methoxyphenyl)methoxy]-phenyl]acetonitrile and Derivatives as Potent Oct3/4 Inducers. — J Med Chem

Cellosaurus cell lines

9 cell lines: 5 embryonic stem cell, 3 cancer cell line, 1 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A4J7	SEES3-1V human NANOG, clone1	Embryonic stem cell	Male
CVCL_A4J8	SEES3-1V human NANOG, clone2	Embryonic stem cell	Male
CVCL_A4J9	SEES3-1V human NANOG, clone3	Embryonic stem cell	Male
CVCL_B8L4	Abcam HCT 116 NANOG KO	Cancer cell line	Male
CVCL_B9NB	Abcam A-549 NANOG KO	Cancer cell line	Male
CVCL_D2GI	Abcam MCF-7 NANOG KO	Cancer cell line	Female
CVCL_F0SJ	H1 NANOG	Embryonic stem cell	Male
CVCL_F0SK	H9 NANOG	Induced pluripotent stem cell	Female
CVCL_F0SL	hES-NCL1 NANOG	Embryonic stem cell	Female

Clinical trials (associated diseases)

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