NANOGP8

Summary

NANOGP8 (Nanog homeobox retrogene P8, HGNC:23106) is a protein-coding gene on chromosome 15q14, encoding Homeobox protein NANOGP8 (Q6NSW7). May act as a transcription regulator.

This gene represents a transcribed retrogene of the Nanog homeobox gene. The putative encoded protein may participate in reprogramming of cancer cells. In vitro studies using a recombinant protein have shown that the protein localizes to the nucleus and can promote cell proliferation, similar to the Nanog protein.

Source: NCBI Gene 388112 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_001355281

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23106
Approved symbol	NANOGP8
Name	Nanog homeobox retrogene P8
Location	15q14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000255192
Ensembl biotype	protein_coding
OMIM	621215
Entrez	388112

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000528386

RefSeq mRNA: 1 — MANE Select: NM_001355281 NM_001355281

CCDS: CCDS86444

Canonical transcript exons

ENST00000528386 — 1 exons

Exon	Start	End
ENSE00002194661	35083410	35085295

Expression profiles

Bgee: expression breadth broad, 72 present calls, max score 81.81.

Top tissues by expression

93 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	81.81	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.56	silver quality
sural nerve	UBERON:0015488	55.46	gold quality
bone marrow cell	CL:0002092	47.44	gold quality
adrenal tissue	UBERON:0018303	46.97	silver quality
cortex of kidney	UBERON:0001225	46.43	silver quality
metanephros cortex	UBERON:0010533	46.01	gold quality
right adrenal gland cortex	UBERON:0035827	44.96	gold quality
calcaneal tendon	UBERON:0003701	44.72	silver quality
right adrenal gland	UBERON:0001233	44.42	gold quality
cortical plate	UBERON:0005343	43.65	gold quality
endometrium	UBERON:0001295	43.63	silver quality
tonsil	UBERON:0002372	43.27	gold quality
ectocervix	UBERON:0012249	42.56	gold quality
nucleus accumbens	UBERON:0001882	42.17	silver quality
smooth muscle tissue	UBERON:0001135	42.01	silver quality
mucosa of stomach	UBERON:0001199	41.51	silver quality
adrenal gland	UBERON:0002369	41.26	silver quality
kidney	UBERON:0002113	41.20	silver quality
myometrium	UBERON:0001296	41.00	silver quality
apex of heart	UBERON:0002098	40.94	silver quality
body of uterus	UBERON:0009853	40.81	silver quality
tibial nerve	UBERON:0001323	40.58	silver quality
body of pancreas	UBERON:0001150	40.33	silver quality
lower esophagus mucosa	UBERON:0035834	40.29	silver quality
left adrenal gland	UBERON:0001234	40.21	silver quality
left adrenal gland cortex	UBERON:0035825	40.20	silver quality
putamen	UBERON:0001874	40.08	silver quality
uterine cervix	UBERON:0000002	40.06	silver quality
pancreas	UBERON:0001264	39.75	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	90.55
E-ANND-3	no	0.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
BMP5	Repression
FGFR2	Repression
JUN	Repression
KDM3A	Repression

Literature-anchored findings (GeneRIF, showing 13)

• NANOGP8 is expressed in primary human glioblastoma and is required for glioblastoma growth in xenograft assay in mice (PMID:20581802)
• conclude that eNANOG is not exclusively expressed in undifferentiated cells and that both embryonic NANOG and NANOGP8 may function as transcription factors in a cell type-specific manner (PMID:21136380)
• these data indicate that nanog1 and nanogp8 are differentially expressed in colon cancer cells, and suggest that their expression contributes to proliferation of colon cancer cells. (PMID:22079639)
• A comparative genomic approach identifies a series of retrotranspositional and mutational events that allowed NANOGP8 to evolve as a human-specific retro-oncogene. (PMID:23173096)
• These results show that cancer-associated NANOGP8 can contribute to promote de-differentiation and/or cellular plasticity. (PMID:23752184)
• High levels of NanogP8 may disrupt normal developmental programs and inhibit tumor development by depleting stem cells. (PMID:23839044)
• Unique biochemical properties of Nanog1 in embryonal carcinoma cells and NanogP8 in somatic cancer cells. (PMID:24598770)
• NANOGP8 has a close relationship with the proliferation, cycle, apoptosis, migration and invasion of SGC-7901 gastric cancer cells (PMID:26062418)
• Results indicate that NANOG and NANOGP8 proteins are expressed in prostate cancer cell lines, and NANOG and NANOGP8 equally contribute to the high malignant potential of prostate cancer. (PMID:26087476)
• LGR5-expressing fraction of CD54+ cells represents gastric cancer CSCs, in which LGR5 is closely associated with stemness and EMT core genes (PMID:28033430)
• studies demonstrated a paracrine role for endothelial cells in regulating the cancer stem cells phenotype and chemoresistance in colorectal cancer cells by AKT-mediated induction of NANOGP8. (PMID:28453235)
• NANOGP8 is the main regulator of gastric cancer stem cells. NANOGP8 is correlated with cell proliferation, migration, invasion, clonogenic capacity, beta-catenin accumulation in nucleus, and chemoresistance in gastric cancer. (PMID:29689047)
• A Restriction Endonuclease-Based Assay to Distinguish NANOGP8 Retrogene from Parental NANOG. (PMID:34165720)

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), NANOG (ENSG00000111704), DLX2 (ENSG00000115844), DLX1 (ENSG00000144355), VENTX (ENSG00000151650), BSX (ENSG00000188909)

Protein

Protein identifiers

Homeobox protein NANOGP8 — Q6NSW7 (reviewed: Q6NSW7)

All UniProt accessions (1): Q6NSW7

UniProt curated annotations — full annotation on UniProt →

Function. May act as a transcription regulator. When overexpressed, promotes entry of cells into S phase and cell proliferation.

Subcellular location. Nucleus.

Similarity. Belongs to the Nanog homeobox family.

RefSeq proteins (1): NP_001342210* (*=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 (30 total): sequence variant 15, repeat 8, region of interest 4, chain 1, compositionally biased region 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NSW7-F1	58.04	0.20

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOBP_CELL_CYCLE_PHASE_TRANSITION, chr15q14, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_MAINTENANCE_OF_CELL_NUMBER, GOBP_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE, GOBP_CELL_CYCLE_PROCESS, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_POSITIVE_REGULATION_OF_CELL_POPULATION_PROLIFERATION

GO Biological Process (6): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), stem cell population maintenance (GO:0019827), cell differentiation (GO:0030154), positive regulation of cell cycle G1/S phase transition (GO:1902808), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (3): 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 (GO:0003677)

GO Cellular Component (2): nucleus (GO:0005634), nucleoplasm (GO:0005654)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
multicellular organismal process	1
maintenance of cell number	1
cellular developmental process	1
cell cycle G1/S phase transition	1
positive regulation of cell cycle phase transition	1
regulation of cell cycle G1/S phase transition	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1

Protein interactions and networks

STRING

290 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NANOGP8	SCN11A	Q9UI33	602
NANOGP8	SCN8A	Q9UQD0	591
NANOGP8	POU5F1B	Q06416	589
NANOGP8	POU5F1	P31359	567
NANOGP8	SCN10A	Q9Y5Y9	510
NANOGP8	LIN28A	Q9H9Z2	486
NANOGP8	SOX2	P48431	450
NANOGP8	SLC2A14	Q8TDB8	398
NANOGP8	GFER	P55789	385
NANOGP8	NR0B1	P51843	379
NANOGP8	NXNL1	Q96CM4	370
NANOGP8	POU5F2	Q8N7G0	359
NANOGP8	FBXO15	Q8NCQ5	356
NANOGP8	APP	P05067	349
NANOGP8	PROM1	O43490	305

IntAct

3 interactions, top by confidence:

A	B	Type	Score
NANOGP8	RBPMS	psi-mi:“MI:0915”(physical association)	0.490
RBPMS	NANOGP8	psi-mi:“MI:0915”(physical association)	0.490

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

4 interactions.

A	Effect	B	Mechanism
NANOGP8	“down-regulates quantity by repression”	BMP5	“transcriptional regulation”
NANOGP8	“down-regulates quantity by repression”	FGFR2	“transcriptional regulation”
NANOGP8	“down-regulates quantity by repression”	JUN	“transcriptional regulation”
NANOGP8	“down-regulates quantity by repression”	KDM3A	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

143 predictions. Top by Δscore:

Variant	Effect	Δscore
15:35084650:TGC:T	donor_gain	0.8600
15:35084652:C:CT	donor_gain	0.8500
15:35084653:C:CT	donor_gain	0.8400
15:35084693:TC:T	donor_gain	0.6200
15:35084848:T:TA	donor_gain	0.6100
15:35084379:T:A	donor_gain	0.5800
15:35084296:T:TA	donor_gain	0.5700
15:35084297:C:A	donor_gain	0.5400
15:35084374:T:TA	donor_gain	0.5400
15:35084706:G:C	donor_gain	0.5400
15:35084268:A:AC	donor_gain	0.5200
15:35084289:AAGG:A	donor_gain	0.5200
15:35084308:T:TA	donor_gain	0.5200
15:35084325:G:C	donor_gain	0.5200
15:35084402:T:A	donor_gain	0.5200
15:35084463:CCAGG:C	donor_gain	0.5200
15:35084651:G:GC	donor_gain	0.5200
15:35084920:T:TA	donor_gain	0.5100
15:35084284:A:AC	donor_gain	0.4900
15:35084285:C:CC	donor_gain	0.4900
15:35084196:CACGT:C	donor_gain	0.4800
15:35084649:CTG:C	donor_gain	0.4700
15:35084417:T:TA	donor_gain	0.4600
15:35084560:CC:C	acceptor_gain	0.4600
15:35084561:CCTGG:C	acceptor_gain	0.4600
15:35084565:G:C	acceptor_gain	0.4600
15:35084691:CT:C	donor_gain	0.4600
15:35084692:TT:T	donor_gain	0.4600
15:35084557:CATCC:C	acceptor_gain	0.4400
15:35084560:C:A	donor_gain	0.4400

AlphaMissense

2060 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:35084682:G:C	F143L	1.000
15:35084682:G:T	F143L	1.000
15:35084684:A:G	F143L	1.000
15:35084769:A:C	F114L	1.000
15:35084769:A:T	F114L	1.000
15:35084771:A:G	F114L	1.000
15:35084670:T:A	R147S	0.999
15:35084670:T:G	R147S	0.999
15:35084678:T:C	N145D	0.999
15:35084679:C:A	Q144H	0.999
15:35084679:C:G	Q144H	0.999
15:35084683:A:G	F143S	0.999
15:35084687:A:G	W142R	0.999
15:35084687:A:T	W142R	0.999
15:35084691:C:A	K140N	0.999
15:35084691:C:G	K140N	0.999
15:35084710:A:G	L134P	0.999
15:35084728:A:G	L128P	0.999
15:35084756:A:G	Y119H	0.999
15:35084770:A:G	F114S	0.999
15:35084782:A:G	L110P	0.999
15:35084782:A:T	L110H	0.999
15:35084805:G:C	F102L	0.999
15:35084805:G:T	F102L	0.999
15:35084807:A:G	F102L	0.999
15:35084666:T:C	K149E	0.998
15:35084671:C:G	R147T	0.998
15:35084676:G:C	N145K	0.998
15:35084676:G:T	N145K	0.998
15:35084677:T:C	N145S	0.998

dbSNP variants (sampled 300 via entrez): RS1000321677 (15:35086864 AG>A), RS1000621328 (15:35087132 A>G), RS1000695606 (15:35085802 C>T), RS1003543951 (15:35085539 T>A,C), RS1003827656 (15:35083004 G>A), RS1003955462 (15:35084362 G>A,T), RS1004425019 (15:35083195 C>G,T), RS1004760966 (15:35086590 T>C), RS1005058322 (15:35084856 T>C,G), RS1006044424 (15:35086510 C>A,T), RS1006498666 (15:35085491 A>G), RS1006529665 (15:35085161 AG>A), RS1007060788 (15:35086641 C>T), RS1007986453 (15:35085562 A>G), RS1010815111 (15:35084332 G>A)

Disease associations

OMIM: gene MIM:621215 | disease phenotypes: MIM:148300

GenCC curated gene-disease

Mondo (1): keratoconus (MONDO:0015486)

Orphanet (2): OBSOLETE: Keratoconus (Orphanet:156071), NON RARE IN EUROPE: Isolated keratoconus (Orphanet:2335)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000563	Keratoconus

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007640	Keratoconus	C11.204.627

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Resveratrol	affects cotreatment, decreases expression	1
Copper	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01485211	PHASE4	COMPLETED	Corneal Thickness Changes During Corneal Collagen Cross-linking With Ultraviolet-A Irradiation and Riboflavin
NCT02119039	PHASE4	COMPLETED	Effect of CACICOL20 on Corneal Epithelial Healing After Cross-linking in Patients With Keratoconus
NCT03245853	PHASE4	COMPLETED	Epi-On Corneal Crosslinking for Keratoconus
NCT03429569	PHASE4	UNKNOWN	Cross-Linking ACcéléré Iontophorèse Confocal kératocONE
NCT04427956	PHASE4	COMPLETED	Corneal Crosslinking Treatment Study
NCT07474870	PHASE4	NOT_YET_RECRUITING	Outcomes of CTAK Surgery
NCT00371202	PHASE3	UNKNOWN	Comparison of Penetrating Keratoplasty and Deep Lamellar Keratoplasty With the Big Bubble Technique for Keratoconus
NCT00647699	PHASE3	COMPLETED	Corneal Collagen Cross-linking for Progressive Keratoconus
NCT00815256	PHASE3	UNKNOWN	Safety and Effectiveness of Collagen Cross Linking in Progressive Mild and Moderate Keratoconus
NCT00887900	PHASE3	COMPLETED	Deep Anterior Lamellar Keratoplasty (DALK)
NCT01112072	PHASE3	UNKNOWN	Corneal Collagen Crosslinking and Intacs for Keratoconus and Ectasia
NCT01152541	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Progressive Keratoconus and Ectasia Using Riboflavin/Dextran and Hypotonic Riboflavin
NCT01190306	PHASE3	TERMINATED	Safety Study of the VEGA UV-A System to Treat Keratoconus
NCT01344187	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01459679	PHASE3	TERMINATED	Safety & Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus or Corneal Ectasia After Refractive Surgery
NCT01464268	PHASE3	UNKNOWN	Transepithelial Corneal Collagen Crosslinking for Keratoconus and Corneal Ectasia
NCT01604135	PHASE3	ACTIVE_NOT_RECRUITING	Collagen Crosslinking for Keratoconus - a Randomized Controlled Clinical Trial
NCT01643226	PHASE3	COMPLETED	Safety and Efficacy Study of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT01672814	PHASE3	COMPLETED	Microwave Treatment and Corneal Collagen Crosslinking for Keratoconus
NCT01682993	PHASE3	TERMINATED	Corneal Cross Linking and Topography Guided Excimer Laser Treatment
NCT01972854	PHASE3	TERMINATED	Safety and Efficacy of Corneal Collagen Cross-Linking in Eyes With Keratoconus
NCT02613780	PHASE3	UNKNOWN	Refractive Treatment of Early Keratoconus
NCT02638376	PHASE3	UNKNOWN	Evaluating the Safety and Efficacy of the KXL System for Corneal Collagen Cross-Linking in Eyes Having Keratoconus
NCT03080077	PHASE3	UNKNOWN	Safety and Effectiveness of Corneal Crosslinking (CXL): Keratoconus and Post-Refractive Ectasia
NCT03187912	PHASE3	COMPLETED	Accelerated Corneal Cross-linking With Different Riboflavin Solutions
NCT03442751	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Epi-on Corneal Cross-linking in Eyes With Progressive Keratoconus
NCT03858036	PHASE3	UNKNOWN	Corneal Collagen Cross-Linking (CXL) Performed With Epi-ON Versus Epi-OFF in Eyes With Keratoconus and Other Corneal Ectatic Disorders
NCT04897503	PHASE3	UNKNOWN	Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Riboflavin/Dextran or Riboflavin/Methylcellulose
NCT04905108	PHASE3	UNKNOWN	Transepithelial (Epi-on) Corneal Collagen Crosslinking to Treat Keratoconus and Corneal Ectasia
NCT05027295	PHASE3	UNKNOWN	Accelerated Corneal Collagen Crosslinking for Keratoconus and Ectasia Using Pulse or Continuous UV-A Light
NCT06100939	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age With Keratoconus
NCT06100952	PHASE3	ACTIVE_NOT_RECRUITING	Epithelium-On Corneal Cross-linking in Subjects 8 to 45 Years of Age with Keratoconus
NCT06450470	PHASE3	RECRUITING	Use of a Freeze-dried Amniotic Membrane Post Crosslinking in Subjects With Progressive Keratoconus
NCT06601101	PHASE3	RECRUITING	Effects of Topical Insulin on Corneal Epithelium Healing After Corneal Crosslinking in Patients With Keratoconus
NCT07124910	PHASE3	RECRUITING	Comparison of Epi-ON Corneal Collagen Crosslinking Performed Using an 18-Minute UVA Exposure vs. a 24-Minute UVA Exposure on Eyes With Ectatic Corneal Diseases
NCT07135167	PHASE3	RECRUITING	Compassionate Use Study of Epi-ON Corneal Collagen Crosslinking Performed Using UVA Exposure on Eyes With Ectatic Corneal Diseases for Subjects With Down Syndrome
NCT00409955	PHASE2	COMPLETED	Lamellar Transplant With Lyophilized Corneas
NCT00925327	PHASE2	UNKNOWN	Safety and Effectiveness of the UV-X System for Corneal Collagen Cross-Linking for Compassionate Treatment in Pediatric Patients With Progressive Keratoconus
NCT01143389	PHASE2	COMPLETED	Corneal Crosslinking in Patients With Keratoconus and Post-Refractive Ectasia
NCT01181219	PHASE2	COMPLETED	Transepithelial Corneal Collagen Cross-linking (CXL) in Treatment of Keratoconus