PROX1

prospero homeobox 1, the group of PROS class homeoboxes

Basic information

Region (hg38): 1:213983180-214041510

Links

ENSG00000117707 ∙ NCBI:5629 ∙ OMIM:601546 ∙ HGNC:9459 ∙ Uniprot:Q92786 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PROX1 gene.

• Inborn genetic diseases (17 variants)
• not provided (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PROX1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3		3
missense			17			17
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	17	3	0

Variants in PROX1

This is a list of pathogenic ClinVar variants found in the PROX1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-213996634-T-C			Likely benign (Jun 16, 2018)
1-213996711-T-C		not specified	Uncertain significance (Jul 09, 2021)
1-213996717-A-G		not specified	Uncertain significance (Oct 12, 2022)
1-213996718-T-C			Likely benign (Mar 01, 2024)
1-213996764-G-T		not specified	Uncertain significance (Dec 07, 2021)
1-213996771-C-T		not specified	Uncertain significance (Nov 07, 2022)
1-213996927-A-G		not specified	Uncertain significance (Sep 14, 2022)
1-213996953-T-C		not specified	Uncertain significance (Jan 18, 2023)
1-213997091-G-A		not specified	Uncertain significance (Jun 09, 2022)
1-213997119-C-T		not specified	Uncertain significance (Jul 12, 2022)
1-213997217-C-G		not specified	Uncertain significance (Jun 21, 2023)
1-213997241-C-T		not specified	Uncertain significance (Jul 12, 2023)
1-213997268-G-A		not specified	Uncertain significance (Feb 22, 2023)
1-213997435-C-T		PROX1-related disorder	Likely benign (Sep 18, 2019)
1-213997436-G-A		not specified	Uncertain significance (Oct 03, 2022)
1-213997437-A-G		not specified	Uncertain significance (Dec 28, 2022)
1-213997447-A-C		PROX1-related disorder	Likely benign (Dec 16, 2019)
1-213997477-G-C		PROX1-related disorder	Benign (May 28, 2019)
1-213997494-T-C		not specified	Uncertain significance (Oct 12, 2021)
1-213997542-A-C		PROX1-related disorder	Likely benign (Apr 11, 2023)
1-213997793-C-T		not specified	Uncertain significance (Sep 01, 2021)
1-213997799-G-A		not specified	Uncertain significance (Oct 26, 2022)
1-213997840-G-A			Likely benign (Jun 19, 2018)
1-213997883-C-A		not specified	Uncertain significance (Aug 30, 2022)
1-213997930-C-A		not specified	Uncertain significance (Jul 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PROX1	protein_coding	protein_coding	ENST00000366958	4	58072

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.00116	125708	0	1	125709	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.52	233	441	0.528	0.0000258	4890
Missense in Polyphen		73	186.27	0.3919		2048
Synonymous	0.931	163	179	0.911	0.0000113	1430
Loss of Function	4.59	2	28.4	0.0703	0.00000179	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription factor involved in developmental processes such as cell fate determination, gene transcriptional regulation and progenitor cell regulation in a number of organs. Plays a critical role in embryonic development and functions as a key regulatory protein in neurogenesis and the development of the heart, eye lens, liver, pancreas and the lymphatic system. Involved in the regulation of the circadian rhythm. Represses: transcription of the retinoid-related orphan receptor RORG, transcriptional activator activity of RORA and RORG and the expression of RORA/G-target genes including core clock components: ARNTL/BMAL1, NPAS2 and CRY1 and metabolic genes: AVPR1A and ELOVL3. {ECO:0000269|PubMed:23723244, ECO:0000303|PubMed:22733308}.
• Pathway: PTF1A related regulatory pathway;EMT transition in Colorectal Cancer (Consensus)

Recessive Scores

• pRec: 0.142

Intolerance Scores

• loftool: 0.0397
• rvis_EVS: -0.67
• rvis_percentile_EVS: 15.62

Haploinsufficiency Scores

• pHI: 0.500
• hipred: Y
• hipred_score: 0.875
• ghis: 0.507

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.536

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Prox1
• Phenotype: immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: prox1a
• Affected structure: vascular lymphangioblast
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;cell fate determination;kidney development;liver development;positive regulation of endothelial cell proliferation;lymphangiogenesis;lens development in camera-type eye;hepatocyte cell migration;brain development;circadian rhythm;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of gene expression;positive regulation of endothelial cell migration;dorsal spinal cord development;dentate gyrus development;cerebellar granule cell differentiation;neural tube development;skeletal muscle thin filament assembly;lung development;olfactory placode formation;pancreas development;response to nutrient levels;regulation of circadian rhythm;otic placode formation;negative regulation of DNA-binding transcription factor activity;negative regulation of viral genome replication;positive regulation of cyclin-dependent protein serine/threonine kinase activity;positive regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;optic placode formation involved in camera-type eye formation;venous blood vessel morphogenesis;ventricular cardiac myofibril assembly;atrial cardiac muscle tissue morphogenesis;ventricular cardiac muscle tissue morphogenesis;retina morphogenesis in camera-type eye;embryonic retina morphogenesis in camera-type eye;endocardium formation;positive regulation of sarcomere organization;ventricular septum morphogenesis;aorta smooth muscle tissue morphogenesis;positive regulation of heart growth;lymphatic endothelial cell differentiation;regulation of transcription involved in lymphatic endothelial cell fate commitment;branching involved in pancreas morphogenesis;lens fiber cell morphogenesis;hepatocyte differentiation;negative regulation of bile acid biosynthetic process;hepatocyte proliferation;acinar cell differentiation;neuronal stem cell population maintenance;positive regulation of cell cycle checkpoint;positive regulation of neural precursor cell proliferation;positive regulation of forebrain neuron differentiation
• Cellular component: nucleus;cytoplasm
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;nuclear receptor binding;transcription regulatory region DNA binding;DBD domain binding;LBD domain binding