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GeneE
26 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
GHR
growth hormone receptor
Chromosome 5 Β· 5p13.1-p12
NCBI Gene: 2690Ensembl: ENSG00000112964.14HGNC: HGNC:4263UniProt: A0A087X0H5
347PubMed Papers
22Diseases
6Drugs
58Pathogenic Variants
FUNCTIONAL ROLE
Receptor
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein homodimerization activityplasma membraneGO:0005615cell surfaceLaron syndromeshort stature due to partial GHR deficiencyTurner syndromepituitary dwarfism
✦AI Summary

The growth hormone receptor (GHR) is a cell surface receptor that mediates the pleiotropic effects of growth hormone (GH) on growth, metabolism, and cellular function. Upon GH binding, GHR undergoes dimerization and recruits the cytoplasmic tyrosine kinase JAK2, initiating a phosphorylation cascade 1. This activation leads to recruitment of signal transducers and activators of transcription (STATs), mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3-kinase (PI3K) pathways that regulate transcription of GH-responsive genes and control metabolic effects 2. The circulating GH-binding protein (GHBP) is a proteolytic product of GHR that serves as a marker of receptor number and function 3. GHR signaling promotes insulin-like growth factor-I (IGF-I) synthesis, the principal growth-promoting product of GH action 4. Loss-of-function GHR mutations cause severe growth hormone insensitivity syndromes, including Laron syndrome, characterized by post-natal growth failure and IGF-I deficiency 35. Conversely, GHR signaling excess in acromegaly associates with increased cancer and type 2 diabetes risk, suggesting GHR-derived IGF-I independently influences neoplastic progression through effects on DNA damage and apoptosis 4.

Sources cited
1
GHR dimerization activates JAK2 and downstream signaling through STATs, Shc, and IRSs
PMID: 9255227
2
GHR promotes STAT, MAPK, and PI3K activation to regulate GH-responsive gene transcription
PMID: 12099386
3
GHR mutations cause severe GH insensitivity; GHBP is a proteolytic receptor product serving as functional marker
PMID: 10905371
4
GHR/IGF-I signaling influences growth, metabolism, and is implicated in cancer and diabetes pathogenesis
PMID: 29395968
5
GHR gene defects cause growth hormone insensitivity syndrome with IGF-I deficiency
PMID: 33029712
Disease Associationsβ“˜22
Laron syndromeOpen Targets
0.83Strong
short stature due to partial GHR deficiencyOpen Targets
0.78Strong
Turner syndromeOpen Targets
0.60Moderate
pituitary dwarfismOpen Targets
0.60Moderate
acromegalyOpen Targets
0.59Moderate
Growth delayOpen Targets
0.57Moderate
Prader-Willi syndromeOpen Targets
0.57Moderate
chronic kidney diseaseOpen Targets
0.55Moderate
endocrine system diseaseOpen Targets
0.54Moderate
gonadal dysgenesisOpen Targets
0.53Moderate
HIV infectionOpen Targets
0.53Moderate
short bowel syndromeOpen Targets
0.52Moderate
pituitary gland diseaseOpen Targets
0.52Moderate
growth hormone insensitivity syndromeOpen Targets
0.51Moderate
response to growth hormoneOpen Targets
0.50Moderate
Abnormality of the skeletal systemOpen Targets
0.50Moderate
hypercholesterolemia, familial, 1Open Targets
0.49Moderate
growthOpen Targets
0.49Moderate
atrial fibrillationOpen Targets
0.46Moderate
obesityOpen Targets
0.43Moderate
Growth hormone insensitivity, partialUniProt
Laron syndromeUniProt
Pathogenic Variants58
NM_000163.5(GHR):c.703C>T (p.Arg235Ter)Pathogenic
Laron-type isolated somatotropin defect|not provided|Short stature due to partial GHR deficiency;Hypercholesterolemia, familial, 1;Laron-type isolated somatotropin defect
β˜…β˜…β˜†β˜†2026β†’ Residue 235
NM_000163.5(GHR):c.266+83G>TPathogenic
not provided
β˜…β˜…β˜†β˜†2026
NM_000163.5(GHR):c.618+792A>GPathogenic
Laron-type isolated somatotropin defect|not provided|Growth hormone insensitivity syndrome
β˜…β˜…β˜†β˜†2025
NM_000163.5(GHR):c.440-1G>APathogenic
not provided
β˜…β˜…β˜†β˜†2025
NM_000163.5(GHR):c.476T>A (p.Leu159Ter)Pathogenic
See cases|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 159
NM_000163.5(GHR):c.335G>T (p.Cys112Phe)Pathogenic
not provided|Laron-type isolated somatotropin defect
β˜…β˜…β˜†β˜†2024β†’ Residue 112
NM_000163.5(GHR):c.594A>G (p.Glu198=)Pathogenic
Laron-type isolated somatotropin defect|not provided|Short stature due to partial GHR deficiency;Hypercholesterolemia, familial, 1;Laron-type isolated somatotropin defect
β˜…β˜…β˜†β˜†2024β†’ Residue 198
NM_000163.5(GHR):c.344A>C (p.Asn115Thr)Pathogenic
Laron-type isolated somatotropin defect|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 115
NM_000163.5(GHR):c.192_193del (p.Ser65fs)Pathogenic
not provided|Laron-type isolated somatotropin defect|Growth hormone insensitivity syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 65
NM_000163.5(GHR):c.181C>T (p.Arg61Ter)Pathogenic
Laron-type isolated somatotropin defect|not provided|Short stature due to partial GHR deficiency;Hypercholesterolemia, familial, 1;Laron-type isolated somatotropin defect
β˜…β˜…β˜†β˜†2024β†’ Residue 61
NM_000163.5(GHR):c.168C>A (p.Cys56Ter)Pathogenic
Laron-type isolated somatotropin defect|Growth hormone insensitivity syndrome|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 56
NM_000163.5(GHR):c.267-2A>GPathogenic
Laron-type isolated somatotropin defect|not provided
β˜…β˜…β˜†β˜†2023
NM_000163.5(GHR):c.3G>A (p.Met1Ile)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 1
NM_000163.5(GHR):c.619-1G>TPathogenic
Laron-type isolated somatotropin defect|not provided
β˜…β˜†β˜†β˜†2026
NM_000163.5(GHR):c.334T>C (p.Cys112Arg)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 112
NM_000163.5(GHR):c.1687G>T (p.Glu563Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2026β†’ Residue 563
NM_000163.5(GHR):c.1641_1645del (p.Pro548fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 548
NM_000163.5(GHR):c.372_378del (p.Tyr125fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 125
NM_000163.5(GHR):c.731G>T (p.Ser244Ile)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 244
NM_000163.5(GHR):c.1369C>T (p.Gln457Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 457
View on ClinVar β†—
Drug Targets6
LONAPEGSOMATROPINApproved
Growth hormone receptor agonist
Growth delay
PEGVISOMANTApproved
Growth hormone receptor antagonist
acromegaly
SOMAPACITANApproved
Growth hormone receptor agonist
SOMATREMApproved
Growth hormone receptor agonist
SOMATROGONApproved
Growth hormone receptor agonist
SOMATROPINApproved
Growth hormone receptor agonist
chronic kidney disease
Related Genes
IL6Protein interaction100%JAK3Protein interaction100%GHRLProtein interaction100%IL7Protein interaction100%SOCS3Protein interaction99%JAK1Protein interaction99%
Tissue Expression6 tissues
Liver
100%
Heart
20%
Lung
8%
Ovary
7%
Brain
2%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
GHRIL6JAK3GHRLIL7SOCS3JAK1
PROTEIN STRUCTURE
Preparing viewer…
PDB6I5N Β· 1.98 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.65LoF Tolerant
pLIβ“˜
0.16Tolerant
Observed/Expected LoF0.43 [0.29–0.65]
RankingsWhere GHR stands among ~20K protein-coding genes
  • #920of 20,598
    Most Researched347 Β· top 5%
  • #258of 1,025
    FDA-Approved Drug Targets6
  • #1,194of 5,498
    Most Pathogenic Variants58 Β· top quartile
  • #4,710of 17,882
    Most Constrained (LOEUF)0.65
Genes detectedGHR
Sources retrieved26 papers
Response timeβ€”
πŸ“„ Sources
26β–Ό
1
GH and GHR signaling in human disease.
PMID: 29395968
Growth Horm IGF Res Β· 2018
1.00
2
GHR/PRLR Heteromultimer Is Composed of GHR Homodimers and PRLR Homodimers.
PMID: 27003442
Mol Endocrinol Β· 2016
0.92
3
Growth-hormone signal transduction.
PMID: 9255227
J Pediatr Β· 1997
0.90
4
Physiology and disorders of the growth hormone receptor (GHR) and GH-GHR signal transduction.
PMID: 10905371
Endocrine Β· 2000
0.80
5
Human growth hormone receptor (GHR) expression in obesity: I. GHR mRNA expression in omental and subcutaneous adipose tissues of obese women.
PMID: 21386804
Int J Obes (Lond) Β· 2011
0.72