PROX2

Summary

PROX2 (prospero homeobox 2, HGNC:26715) is a protein-coding gene on chromosome 14q24.3, encoding Prospero homeobox protein 2 (Q3B8N5). Transcription regulator.

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 283571 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 57 total
• MANE Select transcript: NM_001243007

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26715
Approved symbol	PROX2
Name	prospero homeobox 2
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36749
Ensembl gene	ENSG00000119608
Ensembl biotype	protein_coding
OMIM	615094
Entrez	283571

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000556489, ENST00000619947, ENST00000673765

RefSeq mRNA: 3 — MANE Select: NM_001243007 NM_001080408, NM_001243007, NM_001384314

CCDS: CCDS45136, CCDS73663

Canonical transcript exons

ENST00000556489 — 6 exons

Exon	Start	End
ENSE00000808246	74856801	74856995
ENSE00002259765	74871103	74871237
ENSE00002435005	74858407	74858514
ENSE00002472312	74853033	74855302
ENSE00002513655	74862530	74864008
ENSE00003920954	74875895	74876145

Expression profiles

Bgee: expression breadth ubiquitous, 139 present calls, max score 78.67.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0175 / max 8.2010, expressed in 6 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144087	0.0175	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.67	silver quality
pancreatic ductal cell	CL:0002079	67.54	silver quality
stromal cell of endometrium	CL:0002255	65.03	gold quality
granulocyte	CL:0000094	63.36	gold quality
bone marrow cell	CL:0002092	57.61	gold quality
ileal mucosa	UBERON:0000331	57.27	silver quality
colonic epithelium	UBERON:0000397	56.73	gold quality
tibialis anterior	UBERON:0001385	55.70	silver quality
right ovary	UBERON:0002118	55.63	gold quality
epithelial cell of pancreas	CL:0000083	55.56	gold quality
cortical plate	UBERON:0005343	55.34	silver quality
left ovary	UBERON:0002119	55.04	gold quality
ganglionic eminence	UBERON:0004023	55.04	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
endocervix	UBERON:0000458	54.20	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
ovary	UBERON:0000992	52.51	gold quality
right uterine tube	UBERON:0001302	52.33	gold quality
right lobe of thyroid gland	UBERON:0001119	52.11	gold quality
deltoid	UBERON:0001476	51.67	gold quality
body of uterus	UBERON:0009853	51.26	gold quality
prefrontal cortex	UBERON:0000451	51.10	gold quality
uterine cervix	UBERON:0000002	51.07	gold quality
right coronary artery	UBERON:0001625	50.80	gold quality
left lobe of thyroid gland	UBERON:0001120	50.79	gold quality
lymph node	UBERON:0000029	50.70	gold quality
tonsil	UBERON:0002372	50.47	gold quality
endometrium	UBERON:0001295	50.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

95 targeting PROX2, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-548A-3P	99.76	70.58	3524

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prox2	ENSDARG00000041952
mus_musculus	Prox2	ENSMUSG00000042320
rattus_norvegicus	Prox2	ENSRNOG00000005054
drosophila_melanogaster	pros	FBGN0004595
caenorhabditis_elegans		WBGENE00000448

Paralogs (1): PROX1 (ENSG00000117707)

Protein

Protein identifiers

Prospero homeobox protein 2 — Q3B8N5 (reviewed: Q3B8N5)

Alternative names: Homeobox prospero-like protein PROX2

All UniProt accessions (3): Q3B8N5, A0A0G2JMC2, G3V3G0

UniProt curated annotations — full annotation on UniProt →

Function. Transcription regulator. Does not seem to be essential for embryonic development and postnatal survival.

Subcellular location. Nucleus.

Domain organisation. The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain.

Similarity. Belongs to the Prospero homeodomain family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3B8N5-1	1	yes
Q3B8N5-2	2

RefSeq proteins (3): NP_001073877, NP_001229936, NP_001371243 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR023082	Homeo_prospero_dom	Domain
IPR037131	Homeo_prospero_dom_sf	Homologous_superfamily
IPR039350	Prospero_homeodomain	Family

Pfam: PF05044

UniProt features (18 total): region of interest 6, compositionally biased region 4, sequence conflict 3, domain 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3B8N5-F1	60.97	0.32

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_LENS_FIBER_CELL_DIFFERENTIATION, GOBP_HEPATICOBILIARY_SYSTEM_DEVELOPMENT, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_EPITHELIAL_CELL_DEVELOPMENT, GOBP_PANCREAS_DEVELOPMENT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, chr14q24, GOBP_ENDOTHELIUM_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT, GOBP_SENSORY_ORGAN_DEVELOPMENT, GOBP_SENSORY_ORGAN_MORPHOGENESIS, GOBP_LENS_MORPHOGENESIS_IN_CAMERA_TYPE_EYE, GOBP_LYMPH_VESSEL_DEVELOPMENT, GOBP_RETINA_DEVELOPMENT_IN_CAMERA_TYPE_EYE

GO Biological Process (12): regulation of transcription by RNA polymerase II (GO:0006357), central nervous system development (GO:0007417), pancreas development (GO:0031016), tube development (GO:0035295), cell fate commitment (GO:0045165), anatomical structure formation involved in morphogenesis (GO:0048646), embryonic retina morphogenesis in camera-type eye (GO:0060059), lymphatic endothelial cell differentiation (GO:0060836), lens fiber cell morphogenesis (GO:0070309), hepatocyte differentiation (GO:0070365), regulation of DNA-templated transcription (GO:0006355), positive regulation of cell cycle (GO:0045787)

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 (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
nervous system development	1
system development	1
animal organ development	1
multicellular organism development	1
anatomical structure development	1
cell differentiation	1
cellular developmental process	1
anatomical structure morphogenesis	1
developmental process	1
embryonic morphogenesis	1
retina morphogenesis in camera-type eye	1
lymph vessel development	1
endothelial cell differentiation	1
cell morphogenesis	1
lens morphogenesis in camera-type eye	1
lens fiber cell development	1
liver development	1
epithelial cell differentiation	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell cycle	1
positive regulation of cellular process	1
regulation of cell cycle	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
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

530 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PROX2	VRTN	Q9H8Y1	726
PROX2	AREL1	O15033	598
PROX2	SYNDIG1L	A6NDD5	542
PROX2	YLPM1	P49750	521
PROX2	RPS6KL1	Q9Y6S9	518
PROX2	CATSPER1	Q8NEC5	455
PROX2	SWI5	Q1ZZU3	455
PROX2	IFT80	Q9P2H3	447
PROX2	NBPF6	Q5VWK0	447
PROX2	CTXN1	P60606	437
PROX2	HEATR4	Q86WZ0	436
PROX2	FLRT2	O43155	430
PROX2	FCF1	Q9Y324	419
PROX2	TMEM236	Q5W0B7	413
PROX2	NISCH	Q9Y2I1	411

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GVQ3, A0A1W2PPK0, A0A1W2PPM1, A2A9I7, A6NCI8, A6QQS3, A7XCE8, E9PI22, E9PXT9, O15016, O91083, P09414, P0DMB1, P17923, P18804, P20879, P35965, P49750, Q0P670, Q12857, Q1RMX6, Q32LN6, Q32MG2, Q3B8N5, Q3T016, Q3V0A6, Q4JK59, Q5BI31, Q5T035, Q5ZKH6, Q642A3, Q6AXV6, Q6IMN6, Q6P1W5, Q6PEX7, Q6X4T0, Q80YD3, Q86UF4, Q8BII1, Q8C5V0

Diamond homologs: P29617, P34522, P48437, Q3B8N5, Q8BII1, Q91018, Q92786, Q9U6A1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	2
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

601 predictions. Top by Δscore:

Variant	Effect	Δscore
14:74855322:C:CT	acceptor_gain	0.9900
14:74855322:C:T	acceptor_gain	0.9900
14:74856992:TGAA:T	acceptor_gain	0.9900
14:74856996:C:CC	acceptor_gain	0.9900
14:74863408:G:C	donor_gain	0.9900
14:74856795:TCTTA:T	donor_loss	0.9800
14:74856796:CTTA:C	donor_loss	0.9800
14:74856797:TTA:T	donor_loss	0.9800
14:74856798:TACCT:T	donor_loss	0.9800
14:74856799:A:C	donor_loss	0.9800
14:74856800:C:CA	donor_loss	0.9800
14:74856991:TTGAA:T	acceptor_gain	0.9800
14:74863153:T:A	donor_gain	0.9800
14:74856794:GTCTT:G	donor_loss	0.9700
14:74856993:GAA:G	acceptor_gain	0.9700
14:74856995:ACT:A	acceptor_loss	0.9500
14:74856996:C:A	acceptor_loss	0.9500
14:74857006:A:T	acceptor_loss	0.9500
14:74855312:C:CT	acceptor_gain	0.9400
14:74855212:T:TA	donor_gain	0.9300
14:74856998:G:C	acceptor_gain	0.9300
14:74856994:AA:A	acceptor_gain	0.9200
14:74856814:C:A	donor_gain	0.9100
14:74863363:C:A	donor_gain	0.9100
14:74863343:T:TA	donor_gain	0.9000
14:74863456:T:TA	donor_gain	0.9000
14:74863138:C:A	donor_gain	0.8900
14:74857002:A:T	acceptor_loss	0.8800
14:74855313:A:T	acceptor_gain	0.8700
14:74857001:CAAA:C	acceptor_loss	0.8700

AlphaMissense

3870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:74855210:C:A	K567N	0.997
14:74855210:C:G	K567N	0.997
14:74855215:A:G	W566R	0.997
14:74855215:A:T	W566R	0.997
14:74856939:A:C	F490L	0.997
14:74856939:A:T	F490L	0.997
14:74856941:A:G	F490L	0.997
14:74856954:G:C	S485R	0.997
14:74856954:G:T	S485R	0.997
14:74856956:T:G	S485R	0.997
14:74856962:A:G	W483R	0.997
14:74856962:A:T	W483R	0.997
14:74856913:G:T	A499D	0.996
14:74856947:G:T	R488S	0.996
14:74856957:G:C	F484L	0.996
14:74856957:G:T	F484L	0.996
14:74856959:A:G	F484L	0.996
14:74855255:G:C	F552L	0.995
14:74855255:G:T	F552L	0.995
14:74855257:A:G	F552L	0.995
14:74856946:C:G	R488P	0.995
14:74856963:C:A	K482N	0.995
14:74856963:C:G	K482N	0.995
14:74858464:A:C	F452L	0.995
14:74858464:A:T	F452L	0.995
14:74858466:A:G	F452L	0.995
14:74855213:C:A	W566C	0.994
14:74855213:C:G	W566C	0.994
14:74856965:T:C	K482E	0.994
14:74858473:T:A	K449N	0.994

dbSNP variants (sampled 300 via entrez): RS1000042726 (14:74858335 G>A), RS1000114281 (14:74868745 A>G), RS1000174504 (14:74871340 TAAA>T,TAA,TAAAA), RS1000215899 (14:74865172 A>G), RS1000232943 (14:74864301 C>T), RS1000436204 (14:74858145 C>A,G), RS1000490074 (14:74872020 A>T), RS1000510905 (14:74869831 T>G), RS1000544990 (14:74869547 G>A), RS1000600751 (14:74856309 G>A), RS1000610145 (14:74870993 G>A,T), RS1000686958 (14:74858006 C>T), RS1000720491 (14:74856692 C>G,T), RS1000777150 (14:74863363 C>T), RS1000801306 (14:74856376 G>A)

Disease associations

OMIM: gene MIM:615094 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST005237_3	Mood instability	1.000000e-06
GCST005238_3	Mood instability	3.000000e-09
GCST005839_15	Depression	4.000000e-09
GCST006697_23	Parental longevity (combined parental attained age, Martingale residuals)	2.000000e-08
GCST006701_14	Parental longevity (father’s attained age)	2.000000e-07
GCST009145_7	Total cholesterol levels	1.000000e-07
GCST90000514_22	Gastroesophageal reflux disease	2.000000e-09
GCST90002393_488	Monocyte count	8.000000e-17

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008475	mood instability measurement
EFO:0007796	parental longevity
EFO:0004574	total cholesterol measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	affects cotreatment, decreases methylation	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Malathion	decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	increases methylation	1

Clinical trials (associated diseases)

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