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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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PROP1
PROP paired-like homeobox 1
Chromosome 5 Β· 5q35.3
NCBI Gene: 5626Ensembl: ENSG00000175325.2HGNC: HGNC:9455UniProt: A0A0G2JQ02
80PubMed Papers
1Diseases
0Drugs
95Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingsequence-specific double-stranded DNA bindingtranscription regulator complexDNA-binding transcription factor activity, RNA polymerase II-specificPituitary hormone deficiency, combined, 2
✦AI Summary

PROP1 (PROP paired-like homeobox 1) is a pituitary-specific transcription factor essential for anterior pituitary development and hormone production 1. As a paired-like homeodomain transcription factor, PROP1 controls pituitary ontogeny and regulates the differentiation of multiple pituitary cell types including somatotropes, lactotropes, thyrotropes, and gonadotropes 23. The protein functions through sequence-specific DNA binding and transcriptional regulation during central nervous system development. Biallelic mutations in PROP1 are currently the most frequently recognized genetic cause of combined pituitary hormone deficiency (CPHD) worldwide 4. Patients with PROP1 mutations typically present with deficiencies in growth hormone, thyroid-stimulating hormone, prolactin, and gonadotropins, with some developing late ACTH deficiency requiring lifelong surveillance 43. The condition is inherited in an autosomal recessive pattern and occurs more frequently among offspring of consanguineous parents 4. Neuroimaging typically shows a normal pituitary stalk and posterior lobe positioning, while the anterior pituitary may be hypoplastic, normal, or occasionally enlarged 4. PROP1 mutations also contribute to central hypothyroidism and hypogonadotropic hypogonadism 56.

Sources cited
1
PROP1 is one of the well-characterized transcription factors involved in pituitary development
PMID: 28476222
2
PROP1 is a paired-like homeodomain transcription factor that controls pituitary ontogeny
PMID: 39939491
3
PROP1 mutations are associated with combined pituitary hormone deficiency affecting multiple hormone types
PMID: 18174732
4
PROP1 mutations are the most common cause of autosomal recessive CPHD and patients may develop late ACTH deficiency
PMID: 31090814
5
PROP1 mutations cause central hypothyroidism
PMID: 11508826
6
PROP1 is among pituitary transcription factors involved in hypogonadotropic hypogonadism pathogenesis
PMID: 12536356
Disease Associationsβ“˜1
Pituitary hormone deficiency, combined, 2UniProt
Pathogenic Variants95
NM_006261.5(PROP1):c.301_302del (p.Leu102fs)Pathogenic
Pituitary hormone deficiency, combined, 2|Combined pituitary hormone deficiencies, genetic form|not provided|46,XY partial gonadal dysgenesis|PROP1-related disorder|Pituitary hormone deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 102
NM_006261.5(PROP1):c.349T>A (p.Phe117Ile)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided|Pituitary hormone deficiency
β˜…β˜…β˜†β˜†2026β†’ Residue 117
NM_006261.5(PROP1):c.2T>C (p.Met1Thr)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 1
NM_006261.5(PROP1):c.150del (p.Arg53fs)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided|See cases|Combined pituitary hormone deficiencies, genetic form
β˜…β˜…β˜†β˜†2026β†’ Residue 53
NM_006261.5(PROP1):c.296G>A (p.Arg99Gln)Pathogenic
Pituitary hormone deficiency, combined, 2|Inborn genetic diseases|not provided|Combined pituitary hormone deficiencies, genetic form
β˜…β˜…β˜†β˜†2026β†’ Residue 99
NM_006261.5(PROP1):c.358C>T (p.Arg120Cys)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2026β†’ Residue 120
NM_006261.5(PROP1):c.374G>A (p.Arg125Gln)Likely pathogenic
Combined pituitary hormone deficiencies, genetic form|Pituitary hormone deficiency, combined, 2
β˜…β˜…β˜†β˜†2025β†’ Residue 125
NM_006261.5(PROP1):c.343-1G>ALikely pathogenic
Pituitary hormone deficiency, combined, 2
β˜…β˜…β˜†β˜†2025
NM_006261.5(PROP1):c.46C>T (p.Arg16Ter)Pathogenic
Combined pituitary hormone deficiencies, genetic form|not provided|Pituitary hormone deficiency, combined, 2|PROP1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 16
NM_006261.5(PROP1):c.74_75dup (p.His26fs)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 26
NM_006261.5(PROP1):c.211C>T (p.Arg71Cys)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 71
NM_006261.5(PROP1):c.373C>T (p.Arg125Trp)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided|Pituitary hormone deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 125
NM_006261.5(PROP1):c.217C>T (p.Arg73Cys)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 73
NM_006261.5(PROP1):c.310del (p.Arg104fs)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 104
NM_006261.5(PROP1):c.295C>T (p.Arg99Ter)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 99
NM_006261.5(PROP1):c.611del (p.Gly204fs)Likely pathogenic
Pituitary hormone deficiency, combined, 2
β˜…β˜…β˜†β˜†2025β†’ Residue 204
NM_006261.5(PROP1):c.110-2A>GLikely pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025
NM_006261.5(PROP1):c.112_124del (p.Ser38fs)Pathogenic
Pituitary hormone deficiency, combined, 2|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 38
NM_006261.5(PROP1):c.629dup (p.Pro211fs)Likely pathogenic
Pituitary hormone deficiency, combined, 2
β˜…β˜…β˜†β˜†2025β†’ Residue 211
NM_006261.5(PROP1):c.629del (p.Pro210fs)Likely pathogenic
not provided|Pituitary hormone deficiency, combined, 2
β˜…β˜…β˜†β˜†2025β†’ Residue 210
View on ClinVar β†—
Related Genes
POMCProtein interaction97%GH1Protein interaction87%GHRProtein interaction87%GHRHProtein interaction87%GHRHRProtein interaction87%PRLProtein interaction87%
Tissue Expression

No tissue expression data available for this gene.

Gene Interaction Network
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PROP1POMCGH1GHRGHRHGHRHRPRL
PROTEIN STRUCTURE
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AlphaFoldAI-predicted Β· UniProt O75360
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.87LoF Tolerant
pLIβ“˜
0.01Tolerant
Observed/Expected LoF0.54 [0.34–0.87]
RankingsWhere PROP1 stands among ~20K protein-coding genes
  • #5,956of 20,598
    Most Researched80
  • #812of 5,498
    Most Pathogenic Variants95 Β· top quartile
  • #7,666of 17,882
    Most Constrained (LOEUF)0.87
Genes detectedPROP1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Pituitary Hypoplasia.
PMID: 28476222
Endocrinol Metab Clin North Am Β· 2017
1.00
2
Rathke's cleft cyst: From history to molecular genetics.
PMID: 39939491
Rev Endocr Metab Disord Β· 2025
0.90
3
Mutation spectrum analysis of 29 causative genes in 43 Chinese patients with congenital hypothyroidism.
PMID: 32319661
Mol Med Rep Β· 2020
0.80
4
Hypogonadotropic hypogonadism.
PMID: 12536356
Semin Reprod Med Β· 2002
0.70
5
Combined pituitary hormone deficiency caused by PROP1 mutations: update 20 years post-discovery.
PMID: 31090814
Arch Endocrinol Metab Β· 2019
0.60