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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CSH2
chorionic somatomammotropin hormone 2
Chromosome 17 · 17q23.3
NCBI Gene: 1443Ensembl: ENSG00000213218.11HGNC: HGNC:2441UniProt: A0A0M6L0F6
31PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingvesicleendoplasmic reticulumresponse to nutrient levelsneurodegenerative diseasesenile cataractcancerAbnormality of the skeletal system
✦AI Summary

CSH2 (chorionic somatomammotropin hormone 2) is a placental hormone exclusively expressed during pregnancy 1. It stimulates lactation, promotes fetal growth, and regulates metabolism through activation of the prolactin receptor (PRLR) via zinc-induced dimerization, distinguishing it from growth hormone which utilizes the GH receptor 1. CSH2 belongs to the growth hormone/chorionic somatomammotropin gene cluster at chromosome 17.2, alongside pituitary GH and other placental variants 1. The gene exhibits complex evolutionary patterns shaped by hyperactive gene conversion and population-specific selective pressures, with signatures indicating functional specialization distinct from related cluster members 2. CSH2 undergoes alternative splicing, with isoform 3 particularly associated with cellular phenotypic characteristics in pituitary adenomas 3. While clinical significance remains largely unexplored in normal physiology, CSH2's altered expression patterns have been observed in somatotroph adenomas, where specific isoforms correlate with treatment response to somatostatin analogs 3. The restricted pregnancy-specific expression pattern and unique receptor signaling mechanism underscore CSH2's specialized role in feto-maternal physiological adaptation.

Sources cited
1
CSH2 is expressed in placenta during pregnancy; belongs to GH/CSH gene cluster at 17q24.2; activates prolactin receptor through zinc-induced dimerization
PMID: 24642386
2
CSH2 part of GH/CSH gene cluster; exhibits hyperactive gene conversion and population-specific selective pressures indicating functional specification
PMID: 18473352
3
CSH2 undergoes alternative splicing; CSH2 isoform 3 associated with epithelial phenotype and response to somatostatin analog treatment in somatotroph adenomas
PMID: 26071582
⚠Limited data available — This gene has 3 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.37Weak
senile cataractOpen Targets
0.12Weak
cancerOpen Targets
0.09Suggestive
Abnormality of the skeletal systemOpen Targets
0.08Suggestive
PituicytomaOpen Targets
0.06Suggestive
isolated growth hormone deficiency, type 4Open Targets
0.05Suggestive
Pituitary Gland AdenomaOpen Targets
0.05Suggestive
pituitary cancerOpen Targets
0.05Suggestive
Non-acquired isolated growth hormone deficiencyOpen Targets
0.05Suggestive
growth hormone-secreting pituitary adenomaOpen Targets
0.05Suggestive
short stature due to GHSR deficiencyOpen Targets
0.05Suggestive
short stature due to partial GHR deficiencyOpen Targets
0.05Suggestive
non-acquired combined pituitary hormone deficiency with spine abnormalitiesOpen Targets
0.05Suggestive
pituitary adenocarcinomaOpen Targets
0.05Suggestive
growth hormone secreting pituitary adenoma 1Open Targets
0.05Suggestive
ANE syndromeOpen Targets
0.05Suggestive
panhypopituitarismOpen Targets
0.05Suggestive
hypogonadotropic hypogonadism 6 with or without anosmiaOpen Targets
0.04Suggestive
isolated growth hormone deficiency type IIOpen Targets
0.04Suggestive
hyperprolactinemiaOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
EPOProtein interaction100%JAK2Protein interaction100%GHRLProtein interaction99%POMCProtein interaction97%THPOProtein interaction97%PSG3Protein interaction97%
Tissue Expression6 tissues
Brain
0%
Heart
0%
Lung
0%
Liver
0%
Bone Marrow
0%
Ovary
0%
Gene Interaction Network
Click a node to explore
CSH2EPOJAK2GHRLPOMCTHPOPSG3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt P0DML3
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.09LoF Tolerant
pLIⓘ
0.01Tolerant
Observed/Expected LoF0.63 [0.38–1.09]
RankingsWhere CSH2 stands among ~20K protein-coding genes
  • #11,694of 20,598
    Most Researched31
  • #11,141of 17,882
    Most Constrained (LOEUF)1.09
Genes detectedCSH2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.
PMID: 11992261
Am J Hum Genet · 2002
1.00
2
Gene signatures and genotype-phenotype correlations of sensorineural hearing loss in Noonan syndrome and related RASopathies.
PMID: 40204880
Sci Rep · 2025
0.90
3
Interaction of Calmodulin with the cSH2 Domain of the p85 Regulatory Subunit.
PMID: 29494137
Biochemistry · 2018
0.80
4
Calmodulin and IQGAP1 activation of PI3Kα and Akt in KRAS, HRAS and NRAS-driven cancers.
PMID: 29097261
Biochim Biophys Acta Mol Basis Dis · 2018
0.70
5
Calmodulin (CaM) Activates PI3Kα by Targeting the "Soft" CaM-Binding Motifs in Both the nSH2 and cSH2 Domains of p85α.
PMID: 30047727
J Phys Chem B · 2018
0.60