PRRX2

Summary

PRRX2 (paired related homeobox 2, HGNC:21338) is a protein-coding gene on chromosome 9q34.11, encoding Paired mesoderm homeobox protein 2 (Q99811). May play a role in the scarless healing of cutaneous wounds during the first two trimesters of development.

The DNA-associated protein encoded by this gene is a member of the paired family of homeobox proteins. Expression is localized to proliferating fetal fibroblasts and the developing dermal layer, with downregulated expression in adult skin. Increases in expression of this gene during fetal but not adult wound healing suggest a possible role in mechanisms that control mammalian dermal regeneration and prevent formation of scar response to wounding. The expression patterns provide evidence consistent with a role in fetal skin development and a possible role in cellular proliferation.

Source: NCBI Gene 51450 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total
• MANE Select transcript: NM_016307

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21338
Approved symbol	PRRX2
Name	paired related homeobox 2
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	PRX2, PMX2
Ensembl gene	ENSG00000167157
Ensembl biotype	protein_coding
OMIM	604675
Entrez	51450

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000372469, ENST00000911261

RefSeq mRNA: 1 — MANE Select: NM_016307 NM_016307

CCDS: CCDS6926

Canonical transcript exons

ENST00000372469 — 4 exons

Exon	Start	End
ENSE00001110386	129720596	129720774
ENSE00001110387	129719231	129719418
ENSE00001457888	129722217	129722674
ENSE00001457889	129665647	129666126

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 94.72.

FANTOM5 (CAGE): breadth broad, TPM avg 10.1953 / max 171.8858, expressed in 774 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98946	5.0876	700
98945	4.9642	574
98944	0.1435	89

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
olfactory bulb	UBERON:0002264	94.72	silver quality
type B pancreatic cell	CL:0000169	92.44	gold quality
ascending aorta	UBERON:0001496	91.87	gold quality
thoracic aorta	UBERON:0001515	91.78	gold quality
periodontal ligament	UBERON:0008266	91.31	gold quality
descending thoracic aorta	UBERON:0002345	90.96	gold quality
aorta	UBERON:0000947	89.17	gold quality
cervix squamous epithelium	UBERON:0006922	88.46	silver quality
gingival epithelium	UBERON:0001949	88.04	gold quality
diaphragm	UBERON:0001103	87.92	gold quality
hair follicle	UBERON:0002073	87.82	silver quality
tibial artery	UBERON:0007610	87.31	gold quality
popliteal artery	UBERON:0002250	87.26	gold quality
vena cava	UBERON:0004087	86.85	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.43	gold quality
skin of leg	UBERON:0001511	86.17	gold quality
endocervix	UBERON:0000458	85.79	gold quality
gingiva	UBERON:0001828	85.68	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	85.56	gold quality
cartilage tissue	UBERON:0002418	85.12	gold quality
right coronary artery	UBERON:0001625	85.07	gold quality
ectocervix	UBERON:0012249	84.56	gold quality
zone of skin	UBERON:0000014	84.21	gold quality
tongue squamous epithelium	UBERON:0006919	84.19	silver quality
left coronary artery	UBERON:0001626	83.83	gold quality
skin of abdomen	UBERON:0001416	83.80	gold quality
coronary artery	UBERON:0001621	83.76	gold quality
cervix epithelium	UBERON:0004801	83.73	silver quality
pericardium	UBERON:0002407	83.46	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	83.27	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	376.06
E-ANND-3	yes	7.87

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
CEL
FSHB
TNC

JASPAR motifs

Motif	Name	Family
MA0075.3	PRRX2	Paired-related HD factors
MA0075.4	PRRX2	Paired-related HD factors

JASPAR matrix evidence (PMIDs): PMID:7901837

miRNA regulators (miRDB)

12 targeting PRRX2, 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-4283	100.00	66.42	2097
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-208A-5P	99.42	70.83	1913
HSA-MIR-208B-5P	99.42	70.83	1952
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-212-5P	96.83	67.43	950

Literature-anchored findings (GeneRIF, showing 8)

• Encodes homeobox transcription factors that are expressed during vasculogenesis. (PMID:11893718)
• Valsartan, a selective Ang II type 1 (AT1) receptor blocker, and N-acetylcysteine, an antioxidant, inhibited both of these modifications, indicating the contribution of AT1 receptor and reactive oxygen species to oxidation of Prx2. (PMID:17964282)
• Model for the exceptional reactivity of peroxiredoxins 2 and 3 with hydrogen peroxide: a kinetic and computational study. (PMID:21385867)
• These data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-beta-induced invasion and epithelial mesenchymal transition in breast cancer. (PMID:26824226)
• Attenuation of PRRX2 and HEY2 enables efficient conversion of adult human skin fibroblasts to neurons. (PMID:31255287)
• PRRX2 inhibition may reduce invasive and migrating abilities to hinder epithelial-mesenchymal transition (EMT), and suppress colon cancer liver metastasis through inactivation of Wnt/beta-catenin pathway. (PMID:31471104)
• Silencing Prrx2 expression can effectively inhibit the proliferation and growth of breast cancer (PMID:32234171)
• CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis. (PMID:36266731)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prrx2	ENSMUSG00000039476
rattus_norvegicus	Prrx2	ENSRNOG00000058329

Paralogs (50): ARX (ENSG00000004848), PAX6 (ENSG00000007372), PAX7 (ENSG00000009709), ALX4 (ENSG00000052850), GSC2 (ENSG00000063515), PITX1 (ENSG00000069011), PAX2 (ENSG00000075891), RHOXF1 (ENSG00000101883), CRX (ENSG00000105392), EVX1 (ENSG00000106038), PAX4 (ENSG00000106331), NOBOX (ENSG00000106410), PITX3 (ENSG00000107859), PHOX2B (ENSG00000109132), OTX1 (ENSG00000115507), PRRX1 (ENSG00000116132), VSX2 (ENSG00000119614), ESX1 (ENSG00000123576), PAX8 (ENSG00000125618), PAX1 (ENSG00000125813), RHOXF2 (ENSG00000131721), GSC (ENSG00000133937), RAX (ENSG00000134438), PAX3 (ENSG00000135903), ALX3 (ENSG00000156150), HESX1 (ENSG00000163666), PITX2 (ENSG00000164093), UNCX (ENSG00000164853), PHOX2A (ENSG00000165462), OTX2 (ENSG00000165588), DRGX (ENSG00000165606), SHOX2 (ENSG00000168779), OTP (ENSG00000171540), RAX2 (ENSG00000173976), EVX2 (ENSG00000174279), PROP1 (ENSG00000175325), ISX (ENSG00000175329), ALX1 (ENSG00000180318), MIXL1 (ENSG00000185155), SHOX (ENSG00000185960)

Protein

Protein identifiers

Paired mesoderm homeobox protein 2 — Q99811 (reviewed: Q99811)

Alternative names: Paired-related homeobox protein 2

All UniProt accessions (2): A0A140VJS2, Q99811

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in the scarless healing of cutaneous wounds during the first two trimesters of development.

Subcellular location. Nucleus.

Tissue specificity. In fetal skin, highest expression found in cells of mesodermal origin within the dermal papilla of the developing hair shaft. Not detected in epidermis or dermis. In adult skin, weakly expressed within the basal layers of the epidermis. Not expressed in dermis.

Similarity. Belongs to the paired homeobox family.

RefSeq proteins (1): NP_057391* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003654	OAR_dom	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR043378	PRRX1/2	Family

Pfam: PF00046, PF03826

UniProt features (12 total): compositionally biased region 5, sequence conflict 2, region of interest 2, chain 1, DNA-binding region 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9LYV	X-RAY DIFFRACTION	1.52

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99811-F1	68.21	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): TGACCTY_ERR1_Q2, COUP_01, WANG_RESPONSE_TO_BEXAROTENE_UP, HOWLIN_PUBERTAL_MAMMARY_GLAND, HNF4_DR1_Q3, HNF4_01, MODULE_123, PPAR_DR1_Q2, AACTTT_UNKNOWN, MODULE_98, SIMBULAN_PARP1_TARGETS_UP, MARKEY_RB1_ACUTE_LOF_UP, BURTON_ADIPOGENESIS_7, CAIRO_LIVER_DEVELOPMENT_UP, PPARG_01

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): 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 factor activity (GO:0003700), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	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
transcription cis-regulatory region binding	1
transcription regulator activity	1
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1094 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRRX2	HOXB13	Q92826	829
PRRX2	PAX9	P55771	826
PRRX2	ARID3A	Q99856	563
PRRX2	GATA2	P23769	507
PRRX2	RXRA	P19793	482
PRRX2	FGF8	P55075	466
PRRX2	TP53I11	O14683	441
PRRX2	ATOH8	Q96SQ7	437
PRRX2	KLF4	P78338	437
PRRX2	SNAI2	O43623	423
PRRX2	MRGPRF	Q96AM1	415
PRRX2	COPZ2	Q9P299	414
PRRX2	MYCN	P04198	413
PRRX2	TGFB3	P10600	395
PRRX2	COL6A1	P12109	392

IntAct

1 interactions, top by confidence:

A	B	Type	Score
	TK2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): PRRX2 (Synthetic Lethality)

ESM2 similar proteins: A1YEV8, A1YF08, A1YG25, A1YG85, A2RU54, A2T711, A2T756, A8MTQ0, O14813, O15522, O35160, O35602, O43763, O70218, P28360, P42580, P43687, P50223, P52945, P52946, P52947, P70118, P70354, P81062, Q06348, Q2VL79, Q2VL84, Q2VL85, Q2VL87, Q2VL88, Q61663, Q62066, Q62782, Q6XYB7, Q7YRX0, Q96IS3, Q99811, Q9DED6, Q9ER42, Q9GK08

Diamond homologs: A1A546, A1YEV8, A1YG25, A2T711, A6NJT0, A6NNA5, A6YP92, G5EC89, G5EDS1, L8E946, O08934, O09113, O14813, O15266, O18381, O35085, O35137, O35602, O35690, O35750, O42115, O42201, O42250, O42356, O42357, O42358, O42477, O42567, O60902, O70137, O73917, O95076, O97039, P0DMV5, P23759, P23760, P24610, P26367, P26630, P29506

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

866 predictions. Top by Δscore:

Variant	Effect	Δscore
9:129666122:GGATG:G	donor_gain	1.0000
9:129666123:GATGG:G	donor_gain	1.0000
9:129666125:TG:T	donor_gain	1.0000
9:129666126:GG:G	donor_gain	1.0000
9:129666127:G:GG	donor_gain	1.0000
9:129666127:G:T	donor_loss	1.0000
9:129666128:T:A	donor_loss	1.0000
9:129719228:CA:C	acceptor_loss	1.0000
9:129719229:AG:A	acceptor_gain	1.0000
9:129719229:AGGT:A	acceptor_gain	1.0000
9:129719230:GG:G	acceptor_gain	1.0000
9:129719230:GGT:G	acceptor_gain	1.0000
9:129719230:GGTG:G	acceptor_gain	1.0000
9:129719230:GGTGA:G	acceptor_gain	1.0000
9:129719416:CAGG:C	donor_loss	1.0000
9:129719419:G:GG	donor_gain	1.0000
9:129719420:T:A	donor_loss	1.0000
9:129720774:GGTG:G	donor_loss	1.0000
9:129720775:G:GA	donor_loss	1.0000
9:129720776:T:G	donor_loss	1.0000
9:129666123:GATG:G	donor_gain	0.9900
9:129666131:G:GG	donor_gain	0.9900
9:129719220:A:AG	acceptor_gain	0.9900
9:129719221:A:G	acceptor_gain	0.9900
9:129720595:GGT:G	acceptor_gain	0.9900
9:129720595:GGTC:G	acceptor_gain	0.9900
9:129720595:GGTCT:G	acceptor_gain	0.9900
9:129722215:A:AG	acceptor_gain	0.9900
9:129722216:G:GG	acceptor_gain	0.9900
9:129722216:GCACA:G	acceptor_gain	0.9900

AlphaMissense

1634 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:129719293:C:A	R108S	1.000
9:129719302:T:A	F111I	1.000
9:129719302:T:C	F111L	1.000
9:129719302:T:G	F111V	1.000
9:129719303:T:C	F111S	1.000
9:129719303:T:G	F111C	1.000
9:129719304:C:A	F111L	1.000
9:129719304:C:G	F111L	1.000
9:129719316:A:C	Q115H	1.000
9:129719316:A:T	Q115H	1.000
9:129719318:T:C	L116P	1.000
9:129719327:T:A	L119Q	1.000
9:129719327:T:C	L119P	1.000
9:129719338:T:A	F123I	1.000
9:129719338:T:C	F123L	1.000
9:129719338:T:G	F123V	1.000
9:129719339:T:C	F123S	1.000
9:129719339:T:G	F123C	1.000
9:129719340:C:A	F123L	1.000
9:129719340:C:G	F123L	1.000
9:129719350:C:G	H127D	1.000
9:129719353:T:C	Y128H	1.000
9:129719353:T:G	Y128D	1.000
9:129719354:A:G	Y128C	1.000
9:129719356:C:A	P129T	1.000
9:129719356:C:T	P129S	1.000
9:129719357:C:A	P129H	1.000
9:129719357:C:G	P129R	1.000
9:129719363:C:A	A131D	1.000
9:129719365:T:C	F132L	1.000

dbSNP variants (sampled 300 via entrez): RS1000022897 (9:129702490 G>T), RS1000029259 (9:129707511 C>T), RS1000042261 (9:129672351 A>G), RS1000086474 (9:129703711 C>T), RS1000089438 (9:129718569 G>A), RS1000269827 (9:129687821 T>C,G), RS1000272732 (9:129681779 T>A), RS1000276422 (9:129719986 C>A,G), RS1000281094 (9:129671136 G>T), RS1000318026 (9:129719619 G>A), RS1000344890 (9:129671556 T>C), RS1000442073 (9:129693117 T>C), RS1000447622 (9:129713632 C>T), RS1000448726 (9:129676371 C>T), RS1000460264 (9:129676027 C>T)

Disease associations

OMIM: gene MIM:604675 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003207_3	Response to exercise (triglyceride level interaction)	7.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007681	triglyceride change measurement
EFO:0007768	response to exercise

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases methylation	2
Dexamethasone	decreases expression, affects cotreatment	2
Valproic Acid	increases expression, increases methylation, affects expression	2
propionaldehyde	increases expression	1
bisphenol A	affects methylation, affects cotreatment, decreases methylation	1
sulforaphane	decreases expression	1
butyraldehyde	increases expression	1
zinc chromate	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
pentanal	increases expression	1
chromium hexavalent ion	increases abundance, decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
ICG 001	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	affects response to substance	1
Zoledronic Acid	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Aldehydes	increases expression	1
Carmustine	affects response to substance	1
Diethylhexyl Phthalate	decreases expression	1
Estradiol	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methapyrilene	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Silicon Dioxide	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1

Clinical trials (associated diseases)

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