TPRX1

Summary

TPRX1 (tetrapeptide repeat homeobox 1, HGNC:32174) is a protein-coding gene on chromosome 19q13.33, encoding Tetra-peptide repeat homeobox protein 1 (Q8N7U7). 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….

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 gene is a member of the TPRX homeobox gene family.

Source: NCBI Gene 284355 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 96 total
• MANE Select transcript: NM_001397346

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32174
Approved symbol	TPRX1
Name	tetrapeptide repeat homeobox 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40321
Ensembl gene	ENSG00000178928
Ensembl biotype	protein_coding
OMIM	611166
Entrez	284355

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000322175, ENST00000535759, ENST00000698655

RefSeq mRNA: 2 — MANE Select: NM_001397346 NM_001397346, NM_198479

CCDS: CCDS33066, CCDS92654

Canonical transcript exons

ENST00000698655 — 3 exons

Exon	Start	End
ENSE00003974338	47803504	47803673
ENSE00003974339	47801232	47802980
ENSE00003974340	47804515	47804551

Expression profiles

Bgee: expression breadth tissue_specific, 8 present calls, max score 52.00.

Top tissues by expression

128 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	52.00	gold quality
left testis	UBERON:0004533	45.45	gold quality
right testis	UBERON:0004534	45.20	gold quality
testis	UBERON:0000473	45.11	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
bone marrow cell	CL:0002092	36.16	gold quality
sural nerve	UBERON:0015488	35.87	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
muscle tissue	UBERON:0002385	32.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
monocyte	CL:0000576	30.18	gold quality
prefrontal cortex	UBERON:0000451	29.99	gold quality
leukocyte	CL:0000738	29.95	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.71	gold quality
vermiform appendix	UBERON:0001154	29.36	gold quality
duodenum	UBERON:0002114	28.14	gold quality
smooth muscle tissue	UBERON:0001135	27.61	gold quality
lymph node	UBERON:0000029	27.57	gold quality
cerebellum	UBERON:0002037	27.28	silver quality
cerebellar hemisphere	UBERON:0002245	27.19	silver quality
cerebellar cortex	UBERON:0002129	27.12	silver quality
tonsil	UBERON:0002372	27.05	gold quality
superior frontal gyrus	UBERON:0002661	26.94	gold quality
descending thoracic aorta	UBERON:0002345	26.89	gold quality
myometrium	UBERON:0001296	26.81	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-36552	yes	923.85
E-ANND-3	no	1.14

Regulation

Is transcription factor: yes

JASPAR motifs

Motif	Name	Family
MA2600.1	TPRX1	Paired-related HD

JASPAR matrix evidence (PMIDs): PMID:39605530

miRNA regulators (miRDB)

34 targeting TPRX1, 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-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-6507-5P	99.36	70.46	2524
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6769B-5P	98.73	64.91	1092
HSA-MIR-7977	98.65	66.18	2590
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-3155A	98.16	66.09	965
HSA-MIR-3155B	98.16	66.09	965
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-6881-5P	98.16	67.38	665
HSA-MIR-211-3P	98.14	66.77	1052

Cross-species orthologs

0 orthologs

Paralogs (1): TPRX2 (ENSG00000259009)

Protein

Protein identifiers

Tetra-peptide repeat homeobox protein 1 — Q8N7U7 (reviewed: Q8N7U7)

All UniProt accessions (3): A0A8V8TM49, A0A8V8TMK4, D2CFI5

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N7U7-1	1	yes
Q8N7U7-2	2

RefSeq proteins (2): NP_001384275, NP_940881 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily

UniProt features (17 total): compositionally biased region 7, region of interest 4, sequence conflict 3, chain 1, DNA-binding region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N7U7-F1	47.45	0.04

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 24 (showing top): GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GLI1_TARGET_GENES, ZNF146_TARGET_GENES, ZNF486_TARGET_GENES, MIR607, MIR4262, MIR3671, MIR181A_5P_MIR181B_5P, MIR181D_5P, MIR181C_5P, MIR1252_5P, MIR3123, MIR12128, MIR1226_3P, MIR3936

GO Biological Process (3): maternal-to-zygotic transition of gene expression (GO:0160021), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (2): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA binding (GO:0003677)

GO Cellular Component (3): chromatin (GO:0000785), nucleoplasm (GO:0005654), nucleus (GO:0005634)

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
cellular anatomical structure	2
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
chromosome	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

408 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TPRX1	CRX	O43186	879
TPRX1	DPRX	A6NFQ7	818
TPRX1	ARGFX	A6NJG6	797
TPRX1	DUXB	A0A1W2PPF3	768
TPRX1	LEUTX	A8MZ59	729
TPRX1	DUXA	A6NLW8	705
TPRX1	NANOGNB	Q7Z5D8	667
TPRX1	RHOXF2B	P0C7M4	570
TPRX1	LBX1	P52954	527
TPRX1	ANHX	E9PGG2	463
TPRX1	RHOXF2	Q9BQY4	419
TPRX1	DUX4L2	P0CJ85	409
TPRX1	ZMAT1	Q5H9K5	408
TPRX1	UNCX	A6NJT0	404
TPRX1	DRGX	A6NNA5	403

IntAct

2 interactions, top by confidence:

A	B	Type	Score
TPRX1	PARP4	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (20): TPRX1 (Two-hybrid), TPRX1 (Two-hybrid), TPRX1 (Two-hybrid), TPRX1 (Two-hybrid), TPRX1 (Two-hybrid), TPRX1 (Two-hybrid), MKRN3 (Two-hybrid), KRTAP6-2 (Two-hybrid), NELFB (Two-hybrid), INCA1 (Two-hybrid), GOLGA6L9 (Two-hybrid), PRR20B (Two-hybrid), PRR20A (Two-hybrid), FANCG (Two-hybrid), PRR20D (Two-hybrid)

ESM2 similar proteins: A0A0J9YWL9, A0A0J9YY54, A0A0U1RQI7, A0A494C071, A6NNC1, A6QL64, B3KS81, D3YZV8, E2RYF7, E9Q6E9, F1LWT0, F8W0I5, O60732, P0C8Z4, P0DKJ7, P0DKJ8, P0DKL2, P0DPF3, P18751, P20930, P43537, P53353, P59797, P62521, Q01456, Q08AG5, Q12816, Q3BBV2, Q5H9R4, Q5HY64, Q5JPF3, Q6P902, Q6ZQX7, Q86T75, Q86VE3, Q86VQ3, Q8BGJ3, Q8N307, Q8N7U7, Q8N7X1

Diamond homologs: A1YEV8, A1YEY5, A1YFI3, A1YG25, A1YG57, A1YGA2, A2T711, A2T733, A2T777, A2T7P4, A6YP92, F1NEA7, G3X9P6, G3X9U1, O14813, O15499, O35085, O35160, O42115, O43186, O43316, O54751, O73592, O75364, O93385, O97670, P06601, P09082, P09083, P0DV77, P10181, P18264, P20270, P21711, P22810, P29454, P32242, P32243, P50223, P53544

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	77
Likely benign	19
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

571 predictions. Top by Δscore:

Variant	Effect	Δscore
19:47802978:CAC:C	acceptor_gain	1.0000
19:47803498:TCAGA:T	donor_loss	1.0000
19:47803499:CAGA:C	donor_loss	1.0000
19:47803500:AGAC:A	donor_loss	1.0000
19:47803501:GAC:G	donor_loss	1.0000
19:47803502:AC:A	donor_loss	1.0000
19:47803503:C:CT	donor_loss	1.0000
19:47803518:C:CA	donor_gain	1.0000
19:47803670:GGGC:G	acceptor_gain	1.0000
19:47803671:GGC:G	acceptor_gain	1.0000
19:47803672:GC:G	acceptor_gain	1.0000
19:47803673:CC:C	acceptor_gain	1.0000
19:47803674:C:CC	acceptor_gain	1.0000
19:47803674:CTGG:C	acceptor_loss	1.0000
19:47803675:T:C	acceptor_loss	1.0000
19:47802976:CACAC:C	acceptor_gain	0.9900
19:47802977:ACAC:A	acceptor_gain	0.9900
19:47802978:CACC:C	acceptor_gain	0.9900
19:47802982:T:C	acceptor_loss	0.9900
19:47802989:C:CT	acceptor_gain	0.9900
19:47802990:A:T	acceptor_gain	0.9900
19:47803506:G:A	donor_gain	0.9900
19:47803509:G:C	donor_gain	0.9900
19:47803669:AGGGC:A	acceptor_gain	0.9900
19:47803680:G:C	acceptor_gain	0.9900
19:47803680:G:GC	acceptor_gain	0.9900
19:47818967:CTCAC:C	donor_loss	0.9900
19:47818968:TCAC:T	donor_loss	0.9900
19:47818969:CACCT:C	donor_loss	0.9900
19:47818970:A:C	donor_loss	0.9900

AlphaMissense

2909 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:47802969:C:A	K14N	0.985
19:47802969:C:G	K14N	0.985
19:47803508:A:G	L9P	0.957
19:47802964:C:G	R16P	0.955
19:47802970:T:A	K14M	0.955
19:47802972:G:C	F13L	0.955
19:47802972:G:T	F13L	0.955
19:47802974:A:G	F13L	0.955
19:47802975:C:A	W12C	0.953
19:47802975:C:G	W12C	0.953
19:47802973:A:G	F13S	0.950
19:47802977:A:G	W12R	0.948
19:47802977:A:T	W12R	0.948
19:47803517:T:A	E6V	0.946
19:47802965:G:T	R16S	0.939
19:47802959:C:G	A18P	0.933
19:47802954:T:A	K19N	0.926
19:47802954:T:G	K19N	0.926
19:47802968:T:C	N15D	0.923
19:47802970:T:G	K14T	0.923
19:47802967:T:C	N15S	0.921
19:47802962:G:T	R17S	0.917
19:47803518:C:T	E6K	0.911
19:47802967:T:G	N15T	0.908
19:47802967:T:A	N15I	0.906
19:47802971:T:C	K14E	0.906
19:47802961:C:G	R17P	0.903
19:47802966:A:C	N15K	0.900
19:47802966:A:T	N15K	0.900
19:47802980:C:T	V11M	0.876

dbSNP variants (sampled 300 via entrez): RS1000067162 (19:47814000 A>C), RS1000241886 (19:47808271 T>C), RS1000299028 (19:47820997 C>A,T), RS1000574795 (19:47817930 C>T), RS1000645890 (19:47819154 T>G), RS1000777598 (19:47801393 A>G), RS1000862751 (19:47805122 A>G), RS1001025614 (19:47810677 T>G), RS1001037778 (19:47816213 C>T), RS1001088667 (19:47816033 C>T), RS1001149556 (19:47803036 T>A,G), RS1001268673 (19:47809515 T>C), RS1001280507 (19:47813225 G>A), RS1001331956 (19:47810873 G>A,C), RS1001361224 (19:47818927 T>A)

Disease associations

OMIM: gene MIM:611166 | 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)

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
CGP 52608	affects binding, increases reaction	1

Clinical trials (associated diseases)

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