PROP1
Chr 5ARPROP paired-like homeobox 1
Also known as: CPHD2, PROP-1
This gene encodes a paired-like homeodomain transcription factor required for normal pituitary development and expression of multiple pituitary hormones including growth hormone, prolactin, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone. Biallelic mutations cause autosomal recessive combined pituitary hormone deficiency with deficiencies in multiple anterior pituitary hormones. The gene shows low constraint against loss-of-function variants in the general population (pLI 0.09, LOEUF 0.90).
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
400 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 17 | 3 | 42 | 0 | 62 |
Likely Pathogenic | 31 | 36 | 4 | 0 | 71 |
VUS | 2 | 65 | 22 | 4 | 93 |
Likely Benign | 0 | 3 | 31 | 105 | 139 |
Benign | 0 | 3 | 11 | 1 | 15 |
Conflicting | — | 19 | |||
| Total | 50 | 110 | 110 | 110 | 399 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
PROP1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools