GH2

Summary

GH2 (growth hormone 2, HGNC:4262) is a protein-coding gene on chromosome 17q23.3, encoding Growth hormone variant (P01242). Plays an important role in growth control.

The protein encoded by this gene is a member of the somatotropin/prolactin family of hormones which play an important role in growth control. The gene, along with four other related genes, is located at the growth hormone locus on chromosome 17 where they are interspersed in the same transcriptional orientation; an arrangement which is thought to have evolved by a series of gene duplications. The five genes share a remarkably high degree of sequence identity. Alternative splicing generates additional isoforms of each of the five growth hormones, leading to further diversity and potential for specialization. As in the case of its pituitary counterpart, growth hormone 1, the predominant isoform of this particular family member shows similar somatogenic activity, with reduced lactogenic activity. Mutations in this gene lead to placental growth hormone/lactogen deficiency.

Source: NCBI Gene 2689 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_002059

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4262
Approved symbol	GH2
Name	growth hormone 2
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	GH-V, GHV, GHL, hGH-V
Ensembl gene	ENSG00000136487
Ensembl biotype	protein_coding
OMIM	139240
Entrez	2689

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000332800, ENST00000423893, ENST00000449787, ENST00000456543, ENST00000622506

RefSeq mRNA: 4 — MANE Select: NM_002059 NM_002059, NM_022556, NM_022557, NM_022558

CCDS: CCDS11647, CCDS11648, CCDS45757, CCDS45758

Canonical transcript exons

ENST00000423893 — 5 exons

Exon	Start	End
ENSE00002225272	63881029	63881148
ENSE00002443150	63880772	63880936
ENSE00002457996	63881359	63881519
ENSE00003728271	63880215	63880518
ENSE00003844433	63881792	63881944

Expression profiles

Bgee: expression breadth broad, 56 present calls, max score 94.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4548 / max 443.7714, expressed in 19 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167503	0.4266	15
167504	0.0153	5
167502	0.0068	3
167505	0.0060	3

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	94.58	gold quality
pituitary gland	UBERON:0000007	88.23	gold quality
adenohypophysis	UBERON:0002196	87.89	gold quality
decidua	UBERON:0002450	72.59	silver quality
vena cava	UBERON:0004087	57.83	gold quality
diaphragm	UBERON:0001103	56.46	gold quality
epithelium of nasopharynx	UBERON:0001951	52.81	gold quality
choroid plexus epithelium	UBERON:0003911	51.04	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
quadriceps femoris	UBERON:0001377	50.32	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
hair follicle	UBERON:0002073	50.13	gold quality
thymus	UBERON:0002370	50.05	gold quality
myocardium	UBERON:0002349	49.70	gold quality
vastus lateralis	UBERON:0001379	49.50	gold quality
deltoid	UBERON:0001476	49.45	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.25	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
epithelial cell of pancreas	CL:0000083	48.81	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
oviduct epithelium	UBERON:0004804	48.21	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.66

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXF1, FOXF2, POU1F1, SP1

miRNA regulators (miRDB)

6 targeting GH2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-891B	99.59	69.81	1083
HSA-MIR-1322	97.98	68.96	625
HSA-MIR-541-3P	96.07	66.11	1271
HSA-MIR-654-5P	96.07	66.18	1280

Literature-anchored findings (GeneRIF, showing 14)

• report that autocrine hGH production by mammary carcinoma cells specifically results in the transcriptional repression of the p53-regulated placental transforming growth factor-beta gene (Placental growth factor-beta; TGF-beta) (PMID:11994274)
• GH-V plays a major role in affecting target cells expressing the GH receptor, thus potentially exerting significant GH-like effects on maternal physiology during pregnancy. (PMID:12213191)
• Data show that improved binding affinity of human growth hormone (hGH(v)) results from numerous small contributions distributed broadly over the interface. (PMID:12946357)
• Using a mutagenesis-scanning analysis of 81 single and 32 pairwise double mutations, it is shown that the GHv hormone’s two spatially distal receptor binding sites (Site1 and Site2) are allosterically coupled (PMID:15563602)
• results offer the first evidence for a placental role of human placental growth hormone(hPGH) and suggest an autocrine/paracrine role of hPGH in the regulation of trophoblast invasion (PMID:15718272)
• PGH may play a role in the mechanisms of disease in preeclampsia and fetal growth restriction. (PMID:17701665)
• Placental growth hormone (PGH) secretion by BeWo cells is regulated by hormonal factors and adipokines. Elevated insulin and leptin levels might down-regulate PGH secretion. (PMID:18356738)
• early first trimester maternal serum marker for Down syndrome (PMID:19844941)
• The hGH-V promoter activity and the endogenous mRNA expression in human placental choriocarcinoma cell line JAR in the presence of glucose and demethylating genome conditions, were compared. (PMID:20005926)
• These results suggest that the normal PGH-IGF-I-IGFBP3 axis in pregnancy is abnormal in Type 1 Diabetic pregnancies. (PMID:22363400)
• results are consistent with a pleiotropic effect of placental hGH/CSH genes at the maternal-fetal interface relating to the regulation of fetal growth and the risk of affected maternal metabolism. (PMID:22387044)
• Maternal serum PGH at 11-13 weeks’ gestation is unlikely to be a useful biochemical marker for early prediction of small for gestational age neonates. (PMID:22489624)
• genetic association studies in populations in Estonia, Czech Republic, and Bashkortostan/Russia: Data suggest an SNP in GH2 (rs2006123) is associated with adult height (not body mass index); A-allele is associated with taller stature. [META-ANALYSIS] (PMID:24035309)
• Type 1 diabetic women delivering large for gestational age infants had lower placental GH levels in early pregnancy. (PMID:26589570)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	gh1	ENSDARG00000038185
mus_musculus	Gh	ENSMUSG00000020713
rattus_norvegicus	Gh1	ENSRNOG00000011207

Paralogs (5): CSH1 (ENSG00000136488), PRL (ENSG00000172179), CSHL1 (ENSG00000204414), CSH2 (ENSG00000213218), GH1 (ENSG00000259384)

Protein

Protein identifiers

Growth hormone variant — P01242 (reviewed: P01242)

Alternative names: Growth hormone 2, Placenta-specific growth hormone

All UniProt accessions (3): A0A087WXJ5, A0A0M6L0J9, P01242

UniProt curated annotations — full annotation on UniProt →

Function. Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.

Subunit / interactions. Monomer, dimer, trimer, tetramer and pentamer, disulfide-linked or non-covalently associated, in homomeric and heteromeric combinations. Can also form a complex either with GHBP or with the alpha2-macroglobulin complex.

Subcellular location. Secreted.

Tissue specificity. Expressed in the placenta.

Similarity. Belongs to the somatotropin/prolactin family.

Isoforms (4)

UniProt ID	Names	Canonical?
P01242-1	1, GH-V1	yes
P01242-2	2, GH-V2
P01242-3	3
P01242-4	4

RefSeq proteins (4): NP_002050, NP_072050, NP_072051, NP_072052 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001400	Somatotropin/Prolactin	Family
IPR009079	4_helix_cytokine-like_core	Homologous_superfamily
IPR018116	Somatotropin_CS	Conserved_site
IPR034975	Somatotropin	Family

Pfam: PF00103

UniProt features (13 total): splice variant 3, sequence conflict 2, modified residue 2, disulfide bond 2, signal peptide 1, chain 1, sequence variant 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01242-F1	80.98	0.42

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2): 132, 176

Disulfide bonds (2): 79–191, 208–215

Glycosylation sites (1): 166

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1170546	Prolactin receptor signaling
R-HSA-982772	Growth hormone receptor signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System

MSigDB gene sets: 89 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GCM_RING1, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, GOBP_RESPONSE_TO_GROWTH_HORMONE, KEGG_NEUROACTIVE_LIGAND_RECEPTOR_INTERACTION, MODULE_99, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_HORMONE, GNF2_KISS1, GNF2_CDKN1C

GO Biological Process (5): response to nutrient levels (GO:0031667), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), animal organ development (GO:0048513), growth hormone receptor signaling pathway (GO:0060396), signal transduction (GO:0007165)

GO Molecular Function (4): growth hormone receptor binding (GO:0005131), hormone activity (GO:0005179), growth factor activity (GO:0008083), metal ion binding (GO:0046872)

GO Cellular Component (6): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endosome lumen (GO:0031904), cytoplasm (GO:0005737), endomembrane system (GO:0012505), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Cytokine Signaling in Immune system	2
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
receptor ligand activity	2
response to stimulus	1
cell surface receptor signaling pathway via JAK-STAT	1
regulation of receptor signaling pathway via JAK-STAT	1
positive regulation of receptor signaling pathway via STAT	1
anatomical structure development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to growth hormone stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine receptor binding	1
hormone receptor binding	1
cation binding	1
endosome	1
intracellular organelle lumen	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
membrane-bounded organelle	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

4 interactions, top by confidence:

A	B	Type	Score
GH2	METAP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (10): ISCA1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), UBR2 (Affinity Capture-MS), S100P (Reconstituted Complex), S100A6 (Reconstituted Complex), GH2 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8QHQ6, A0A3Q1LRJ2, A0A8M9PDM1, B4ER10, B5DFM7, B6ZK77, B8JI67, E1B9E5, E9Q8Q8, E9Q9F6, O35256, O35257, P01241, P01242, P05402, P06880, P08998, P09321, P09586, P09611, P0DJF3, P0DP43, P11228, P18121, P22077, P37886, P58343, P58757, Q0VCB1, Q14406, Q14956, Q5SY80, Q6AXW8, Q6AY06, Q6NXM3, Q6P7C7, Q6P7N7, Q6PVW7, Q6X782, Q6X784

Diamond homologs: O12980, O13188, O18938, O62754, O70615, O73848, O73849, O93359, O93360, P01241, P01242, P01244, P01245, P01246, P01248, P06880, P07064, P08591, P08899, P08998, P09113, P09538, P0DML2, P0DML3, P10298, P10607, P10766, P10813, P10814, P11228, P12855, P12856, P19795, P20332, P20391, P20392, P22077, P26773, P26774, P29971

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FOXF1	“up-regulates quantity by expression”	GH2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	40
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

671 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63880514:AGCCT:A	acceptor_gain	1.0000
17:63880515:GCCT:G	acceptor_gain	1.0000
17:63880516:CCTC:C	acceptor_gain	1.0000
17:63880517:CT:C	acceptor_gain	1.0000
17:63880518:TC:T	acceptor_loss	1.0000
17:63880519:C:CC	acceptor_gain	1.0000
17:63880520:T:G	acceptor_loss	1.0000
17:63880771:CCCA:C	donor_gain	1.0000
17:63880774:A:AC	donor_gain	1.0000
17:63880775:C:CC	donor_gain	1.0000
17:63880775:CAT:C	donor_gain	1.0000
17:63880794:T:A	donor_gain	1.0000
17:63880795:C:A	donor_gain	1.0000
17:63880800:AGGT:A	donor_gain	1.0000
17:63880803:T:TA	donor_gain	1.0000
17:63881786:GCTTA:G	donor_loss	1.0000
17:63881787:CTTAC:C	donor_loss	1.0000
17:63881788:TTA:T	donor_loss	1.0000
17:63881789:TAC:T	donor_loss	1.0000
17:63881790:A:AT	donor_loss	1.0000
17:63880516:CCT:C	acceptor_gain	0.9900
17:63880517:CTC:C	acceptor_gain	0.9900
17:63880518:TCT:T	acceptor_gain	0.9900
17:63880522:CAAAG:C	acceptor_gain	0.9900
17:63880526:G:C	acceptor_gain	0.9900
17:63880526:G:GC	acceptor_gain	0.9900
17:63880770:A:AC	donor_gain	0.9900
17:63880770:AC:A	donor_gain	0.9900
17:63880771:C:CC	donor_gain	0.9900
17:63880771:CC:C	donor_gain	0.9900

AlphaMissense

1411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63880369:G:C	F202L	0.933
17:63880369:G:T	F202L	0.933
17:63880371:A:G	F202L	0.933
17:63881359:A:C	F57L	0.931
17:63881359:A:T	F57L	0.931
17:63881361:A:G	F57L	0.931
17:63880399:G:C	F192L	0.920
17:63880399:G:T	F192L	0.920
17:63880401:A:G	F192L	0.920
17:63880892:C:A	W112C	0.910
17:63880892:C:G	W112C	0.910
17:63880400:A:G	F192S	0.900
17:63880859:G:C	F123L	0.884
17:63880859:G:T	F123L	0.884
17:63880861:A:G	F123L	0.884
17:63880800:A:G	L143P	0.882
17:63880894:A:G	W112R	0.879
17:63880894:A:T	W112R	0.879
17:63880926:A:G	L101P	0.875
17:63880400:A:C	F192C	0.868
17:63880914:G:A	S105F	0.860
17:63880367:A:G	L203P	0.849
17:63881080:G:C	F80L	0.849
17:63881080:G:T	F80L	0.849
17:63881082:A:G	F80L	0.849
17:63880352:C:G	C208S	0.845
17:63880353:A:T	C208S	0.845
17:63881360:A:C	F57C	0.839
17:63880809:A:G	L140P	0.830
17:63880923:A:T	L102H	0.821

dbSNP variants (sampled 300 via entrez): RS1001582760 (17:63881305 GA>G), RS1002621337 (17:63880025 G>A,C), RS1004835047 (17:63882497 A>C,G,T), RS1005032173 (17:63881602 T>TC,TCTC), RS1006034625 (17:63880557 G>A,C), RS1007173475 (17:63879750 C>A,T), RS1007965773 (17:63883196 G>A), RS1008833082 (17:63881868 C>G,T), RS1009939312 (17:63881255 A>C,T), RS1010945626 (17:63880178 C>A,T), RS1010972151 (17:63879991 G>A,T), RS1011492966 (17:63882528 T>A,C,G), RS1011867055 (17:63883613 G>C), RS1013284009 (17:63882375 G>A), RS1015325991 (17:63882407 G>A)

Disease associations

OMIM: gene MIM:139240 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004639_30	Prudent dietary pattern	6.000000e-06
GCST008839_218	Height	4.000000e-46
GCST012226_809	Waist circumference adjusted for body mass index	2.000000e-10
GCST90013466_21	Height	1.000000e-52
GCST90013466_72	Height	1.000000e-15
GCST90013468_20	Height	8.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0008111	diet measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

11 total (human), top 11 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2,4,6-tribromophenol	decreases expression	1
bisphenol A	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
Benzo(a)pyrene	affects methylation	1
Silicon Dioxide	decreases expression, increases expression	1
Valproic Acid	increases methylation	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.