PROX2

protein-coding

prospero homeobox 2, the group of PROS class homeoboxes

Gene summary

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. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_001243007.2

Inheritance

—

ClinVar variants

U:63B:5

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.16

Max pathogenic AF

—

Genomic locus

chr14:74,852,871-74,876,154

External References & Databases

Ensembl (ENSG00000119608)

Transcript & Mutation Effects

hg38 • Region Span ~23.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PROX2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 5

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001243007.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous					1 clinvar	1
missense			62 clinvar	2 clinvar	2 clinvar	66
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	63	2	3	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001243007.2	RefSeq	NP_001229936.1	4	MANE Select
ENST00000556489.4	Ensembl	ENSP00000451223.2	4	MANE Select
NM_001080408.3	RefSeq	NP_001073877.2	3	Standard
NM_001384314.1	RefSeq	NP_001371243.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of transcription by RNA polymerase II
lymphangiogenesis
positive regulation of transcription by RNA polymerase II
lymphatic endothelial cell differentiation
lens fiber cell morphogenesis

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
DNA binding

Cellular Component

nucleus

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000556084
Coding exons: 3
Length: 10802
Individuals with no LoFs: 124592
Homozygous LoFs: 0
Heterozygous LoFs: 63
Defined: 124655
p: 0.000253

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.519	176	196	0.896	0.0000104	2380
Missense (PolyPhen)		50	55.444	0.90181		742
Synonymous	0.590	68	74.5	0.913	0.00000400	719
Loss of Function	-0.554	16	13.8	1.16	7.44e-7	151

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00040	0.00039	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.00025	0.00023	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00028	0.00026	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription regulator. Does not seem to be essential for embryonic development and postnatal survival (By similarity). {ECO:0000250}.;

Intolerance Scores

RVIS EVS: -0.11
RVIS percentile EVS: 45.49

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0377

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium