PROP1
protein-codingPROP paired-like homeobox 1, the group of PRD class homeoboxes and pseudogenes
Gene summary
This gene encodes a paired-like homeodomain transcription factor in the developing pituitary gland. Expression occurs prior to and is required for expression of pou domain transcription factor 1, which is responsible for pituitary development and hormone expression. Mutations in this gene have been associated with combined pituitary hormone deficiency-2 as well as deficiencies in luteinizing hormone, follicle-stimulating hormone, growth hormone, prolactin, and thyroid-stimulating hormone. [provided by RefSeq, Sep 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: Myriad Women's Health
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0019591
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: G2P
Inheritance Pattern: AD
Disease ID:MONDO:0013099
Submitter: Orphanet
Inheritance Pattern: AD
Disease ID:MONDO:0016411
Submitter: Orphanet
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0009878
Submitter: Natera
Clinical Genomic Database (CGD)
Manifestation: Endocrine
Intervention: Endocrine
Rationale: Hormone replacement therapy can be effective to treat multiple endocrinological deficiencies (eg, GH and thyroid hormone deficiency); Individuals may develop ACTH deficiency, and may require treatment including stress dose steroids; Medical interventions may be necessary to induce puberty
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PROP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006261.5. 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 | 4 | 115 | 119 | |||
| missense | 3 | 35 | 67 | 7 | 1 | 113 |
| nonsense | 5 | 8 | 1 | 14 | ||
| start loss | 1 | 3 | 4 | |||
| frameshift | 12 | 21 | 2 | 35 | ||
| splice donor/acceptor (+/-2bp) | 3 | 4 | 7 | |||
| Total | 24 | 71 | 74 | 122 | 1 | 292 |
Highest pathogenic variant AF is 0.00019148612
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006252.4 | 3 | MANE Select | |
| Ensembl | ENSP00000311290.2 | 3 | MANE Select |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| prop1 | Danio rerio | Structure: prolactin secreting cell Quality: spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- negative regulation of transcription by RNA polymerase II
- blood vessel development
- central nervous system development
- dorsal/ventral pattern formation
- cell migration
Molecular Function
- RNA polymerase II distal enhancer sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- chromatin binding
Cellular Component
- nucleus
- transcription factor complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000308304
- Coding exons
- 3
- Length
- 4008
- Individuals with no LoFs
- 125675
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 73
- Defined
- 125748
- p
- 0.000290
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.248 | 130 | 138 | 0.941 | 0.00000883 | 1416 |
| Missense (PolyPhen) | 50 | 44.389 | 1.1264 | 423 | ||
| Synonymous | -0.570 | 60 | 54.6 | 1.10 | 0.00000314 | 494 |
| Loss of Function | 1.78 | 3 | 8.63 | 0.348 | 6.40e-7 | 73 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00023 | 0.00023 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00051 | 0.00050 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Possibly involved in the ontogenesis of pituitary gonadotropes, as well as somatotropes, lactotropes and caudomedial thyrotropes.;
Intolerance Scores
- LoFtool
- 0.253
- RVIS EVS
- 0.28
- RVIS percentile EVS
- 71.27
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.488
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |