TPRX2

Summary

TPRX2 (tetrapeptide repeat homeobox 2, HGNC:32175) is a protein-coding gene on chromosome 19q13.33, encoding Tetrapeptide repeat homeobox protein 2 (P0DV77). Transcription factor expressed after fertilization required for zygotic genome activation (ZGA), a critical event in early embryonic development during which the developmental control passes from maternally provided mRNAs to the expression of the zygotic genome after fertilizati…. It is a selective cancer dependency (DepMap: 25.0% of cell lines).

Homeobox genes encode DNA-binding proteins, many of which are thought to be involved in early embryonic development. Homeobox genes encode a DNA-binding domain of 60 to 63 amino acids referred to as the homeodomain. This pseudogene is a member of the TPRX homeobox gene family.

Source: NCBI Gene 503627 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• Cancer dependency (DepMap): dependent in 25.0% of screened cell lines
• MANE Select transcript: NM_001397347

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32175
Approved symbol	TPRX2
Name	tetrapeptide repeat homeobox 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TPRX2P1
Ensembl gene	ENSG00000259009
Ensembl biotype	protein_coding
OMIM	620360
Entrez	503627

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000535362, ENST00000699059, ENST00000699383

RefSeq mRNA: 3 — MANE Select: NM_001397347 NM_001397347, NM_001397348, NM_001397349

CCDS: CCDS92655, CCDS92656

Canonical transcript exons

ENST00000535362 — 3 exons

Exon	Start	End
ENSE00002304334	47860802	47861721
ENSE00003975556	47859235	47859271
ENSE00003976403	47860113	47860282

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 38.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	38.22	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
liver	UBERON:0002107	35.70	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	32.80	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
right lobe of liver	UBERON:0001114	29.03	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.21	gold quality
leukocyte	CL:0000738	26.12	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
monocyte	CL:0000576	25.97	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	24.89	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
pancreas	UBERON:0001264	24.01	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.16

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.0% of screened cell lines.

Cross-species orthologs

0 orthologs

Paralogs (1): TPRX1 (ENSG00000178928)

Protein

Protein identifiers

Tetrapeptide repeat homeobox protein 2 — P0DV77 (reviewed: P0DV77)

All UniProt accessions (3): P0DV77, A0A8V8TNP4, A0A8V8TPE6

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor expressed after fertilization required for zygotic genome activation (ZGA), a critical event in early embryonic development during which the developmental control passes from maternally provided mRNAs to the expression of the zygotic genome after fertilization. Binds and activates expression of key ZGA marker genes, such as NANOGNB, ZSCAN4, DUXB, KLF5 and DPPA3. Binds to regulatory DNA sequences containing a 5’-TAATCC-3’ sequence motif.

Subcellular location. Nucleus.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (3): NP_001384276, NP_001384277, NP_001384278 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF00046

UniProt features (8 total): region of interest 2, compositionally biased region 2, sequence conflict 2, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DV77-F1	64.66	0.22

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9819196	Zygotic genome activation (ZGA)

MSigDB gene sets: 9 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, REACTOME_MATERNAL_TO_ZYGOTIC_TRANSITION_MZT, REACTOME_ZYGOTIC_GENOME_ACTIVATION_ZGA, GOBP_MATERNAL_TO_ZYGOTIC_TRANSITION_OF_GENE_EXPRESSION, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, chr19q13

GO Biological Process (3): regulation of transcription by RNA polymerase II (GO:0006357), maternal-to-zygotic transition of gene expression (GO:0160021), 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)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
DNA-templated transcription	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

0 interactions, top by confidence (×1000):

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A0J9YXV3, A0A172M4N0, A2VE23, A5PL33, C7EMF5, E7EW31, F1NSM7, I3L273, O15027, O48582, O55189, O55196, O97939, P0C671, P0DV77, P14138, Q14D33, Q1XI13, Q28989, Q3B7M4, Q4R729, Q5R7U0, Q5SWP3, Q62840, Q63003, Q6E0U4, Q6H236, Q6NUN9, Q6UXA7, Q7Z2K8, Q86UU5, Q8BM15, Q8K4E0, Q8K4L6, Q8N1P7, Q8N3D4, Q96D09, Q96JG9, Q9BGL9, Q9D7G9

Diamond homologs: A1YEY5, A1YG57, A1YGA4, A2T733, A2T779, A2T7H5, A2T7T2, A9ZPC9, E9PXV9, F1Q4R9, G3X9P6, G3X9U1, G5EC89, O08686, O14627, O14813, O18381, O42250, O42356, O60479, O73917, P0DV77, P18111, P20009, P23813, P26630, P31277, P32442, P34684, P39020, P40764, P46692, P47237, P47902, P50221, P50574, P50575, P50576, P50577, P53544

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

1890 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000006591 (19:47861489 C>T), RS1000246365 (19:47860646 C>A,T), RS1000296079 (19:47860801 G>C), RS1000441513 (19:47861261 G>C,T), RS1000576391 (19:47859575 G>A), RS1001364704 (19:47860399 C>T), RS1001480656 (19:47860085 C>T), RS1001812700 (19:47859115 C>T), RS1002008815 (19:47859019 G>A), RS1003039931 (19:47859303 G>A), RS1003488547 (19:47858198 T>C), RS1004160309 (19:47862092 G>C), RS1004191583 (19:47861844 C>CT), RS1004523424 (19:47860563 C>T), RS1004820052 (19:47860069 G>A)

Disease associations

OMIM: gene MIM:620360 | disease phenotypes: MIM:120970

GenCC curated gene-disease

Mondo (1): cone-rod dystrophy 2 (MONDO:0007362)

Orphanet (1): Cone rod dystrophy (Orphanet:1872)

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: no

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

Clinical trials (associated diseases)

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