GH1

Summary

GH1 (growth hormone 1, HGNC:4261) is a protein-coding gene on chromosome 17q23.3, encoding Somatotropin (P01241). 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. This particular family member is expressed in the pituitary but not in placental tissue as is the case for the other four genes in the growth hormone locus. Mutations in or deletions of the gene lead to growth hormone deficiency and short stature.

Source: NCBI Gene 2688 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated growth hormone deficiency type IA (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 3
• Clinical variants (ClinVar): 34 total — 13 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 22
• MANE Select transcript: NM_000515

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4261
Approved symbol	GH1
Name	growth hormone 1
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	hGH, GH-N, GHN, GH, hGH-N
Ensembl gene	ENSG00000259384
Ensembl biotype	protein_coding
OMIM	139250
Entrez	2688

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000323322, ENST00000342364, ENST00000351388, ENST00000458650, ENST00000579711, ENST00000617086

RefSeq mRNA: 3 — MANE Select: NM_000515 NM_000515, NM_022559, NM_022560

CCDS: CCDS11653, CCDS11654, CCDS45760

Canonical transcript exons

ENST00000323322 — 5 exons

Exon	Start	End
ENSE00002220865	63917203	63917506
ENSE00002430246	63918346	63918506
ENSE00002498148	63918017	63918136
ENSE00002549577	63918767	63918839
ENSE00003464202	63917760	63917924

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 99.97.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 11.1012 / max 7190.8694, expressed in 11 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167529	11.1012	11
167521	1.7224	5
167530	0.7891	3
167528	0.2210	3
167522	0.1447	3
167531	0.0999	3
167524	0.0544	3
167527	0.0478	3
208317	0.0333	3
167525	0.0179	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pituitary gland	UBERON:0000007	99.97	gold quality
adenohypophysis	UBERON:0002196	99.95	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.83	silver quality
granulocyte	CL:0000094	78.69	gold quality
right coronary artery	UBERON:0001625	76.63	gold quality
lower esophagus mucosa	UBERON:0035834	75.37	gold quality
mucosa of stomach	UBERON:0001199	75.24	gold quality
right hemisphere of cerebellum	UBERON:0014890	71.08	gold quality
right uterine tube	UBERON:0001302	67.45	gold quality
descending thoracic aorta	UBERON:0002345	66.79	gold quality
endocervix	UBERON:0000458	63.58	gold quality
right ovary	UBERON:0002118	62.53	gold quality
ectocervix	UBERON:0012249	62.14	gold quality
right adrenal gland cortex	UBERON:0035827	61.77	gold quality
body of uterus	UBERON:0009853	61.52	gold quality
cerebellar hemisphere	UBERON:0002245	61.27	gold quality
gastrocnemius	UBERON:0001388	61.16	gold quality
spleen	UBERON:0002106	61.14	gold quality
right frontal lobe	UBERON:0002810	60.81	gold quality
cerebellar cortex	UBERON:0002129	60.42	gold quality
mucosa of transverse colon	UBERON:0004991	60.31	gold quality
left coronary artery	UBERON:0001626	60.16	gold quality
cerebellum	UBERON:0002037	60.08	gold quality
omental fat pad	UBERON:0010414	59.76	gold quality
body of pancreas	UBERON:0001150	58.96	gold quality
right lobe of liver	UBERON:0001114	58.69	gold quality
left adrenal gland	UBERON:0001234	58.65	gold quality
body of stomach	UBERON:0001161	58.35	gold quality
right adrenal gland	UBERON:0001233	58.21	gold quality
esophagus mucosa	UBERON:0002469	58.04	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.64

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
BCL2	Activation
CCND1	Activation
MYC	Activation

Upstream regulators (CollecTRI, top): AHR, AP1, AR, ATF3, BCL6, CEBPA, CEBPB, CEBPD, CEBPG, CREB1, DDIT3, DNMT1, DNMT3A, DNMT3B, EEF1A1, EGR1, ERF, ESR1, ETS1, FOS, FOXA2, GLI3, HNF4A, HOXB7, ID2, IKZF1, JUN, JUNB, LHX4, NCOR1, NEUROD1, NFKB1, NFKB, NKX2-1, NR1I2, NR3C1, ONECUT1, OTX1, PAX1, PAX6

miRNA regulators (miRDB)

8 targeting GH1, 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-4685-5P	99.25	65.99	1563
HSA-MIR-6837-5P	99.25	65.47	1632
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 40)

• A single determinant of the hGH locus control region has a critical, specific, and non-redundant role in facilitating promoter trans factor binding and activating transcription. (PMID:11864603)
• A novel and de novo splice-donor site mutation in intron 3 of the GH-1 gene in a patient with isolated growth hormone deficiency. (PMID:11914025)
• Effect of different growth hormone mutants on the regulation of GH-receptor gene transcription in a human hepatoma cell line. (PMID:11916628)
• 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)
• effect of interferon-gamma (IFN-gamma) on the activity of human growth hormone (hGH) gene promoter in rat pituitary GH(3) cells (PMID:12198566)
• GH-IGF-I axis in non-obese women with functional hyperandrogenism. (PMID:12240900)
• Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency (PMID:12428212)
• the human GH locus control region, an enhancer region of the GH-1 gene located approximately 15-32 kB upstream of the GH-1 coding region was shown to direct pituitary-specific, high-level GH expression in vivo (PMID:12435888)
• study provides evidence that cortisol, prolactin and growth hormone respond to psychological stress in humans (PMID:12445833)
• growth hormone signaling is inhibited when SOCS2 mediates the suppression of JAK2 phosphorylation by estrogen (PMID:12552091)
• ghrelin-induced growth hormone secretion was severely blunted in patients with active Cushing’s syndrome, in addition to a remarkable hyper-response in ACTH and cortisol secretion (PMID:12566947)
• The 5’-donor splice site of intron 3 of GH-1 is a mutational hot spot, and the IVS3 +1G>A mutation can be considered to be a common molecular defect in isolated growth hormone deficiency II in Russian patients. (PMID:12574219)
• The relationship between pituitary tumour transforming gene (PTTG) expression and in vitro growth hormone and vascular endothelial growth factor (VEGF) secretion from human pituitary adenomas. (PMID:12590639)
• results suggest that trunk fat attenuates the hormone replacement therapy-induced increase on growth hormone levels and is a significant determinant of low IGF-1 levels in postmenopausal women (PMID:12592062)
• An association is noted between adult height and the mean in vitro expression value corresponding to an individual’s GH1 promoter haplotype combination, although only 3.3% of the variance of adult height is explicable by reference to this parameter. (PMID:12655556)
• Heterozygous mutations have been identified disproportionately in individuals with short stature as compared to idiopathic growth hormone deficiency individuals and control group. (PMID:12655557)
• An 8-week training program consisting of continuous or extensive interval running has been effective on acute GH and cortisol secretion in 15-16 year-old male athletes. (PMID:12666876)
• Perturbations in the regulation of GH1 splicing cause IGHD II (Isolated Growth Hormone Deficiency type II) (PMID:12720086)
• data demonstrate differential regulation of leptin secretion and pulsatility in adipocytes and synchronicity between leptin and growth hormone, cortisol, and insulin (PMID:12721156)
• analysis of binding energetics of the regulatory step of growth hormone-induced receptor homodimerization (PMID:12930995)
• Reduced ghrelin, impaired growth hormone(GH) response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. (PMID:14559725)
• study showed decreased levels of serum insulin-like growth factor 1 (IGF-1) and increased levels of growth hormone (GH) in the hypoxic-ischemic (HI) brain of newborns (PMID:14631161)
• plasma levels of ET-1, ACE activities are elevated and associated with reduction of GH, NO and cGMP levels in the systemic and cavernous blood of erectile dysfunction patients. (PMID:14671660)
• These data implicate ETS-domain family members in the regulation of the GH locus in placenta and pituitary cells. (PMID:14673137)
• no significant differences between normal and reduced bone mineral density for serum growth hormone (PMID:14761840)
• Small interfering RNAs can be used to specifically degrade exon 3-skipped transcripts, potentially a new avenue of therapeutic intervention in isolated GH deficiency II and other dominant disorders. (PMID:14988388)
• Non-obese patients with PCOS have impaired GH secretion and some have impaired insulin sensitivity. These patients may also be at risk for cardiovascular diseases and diabetes mellitus. (PMID:14998943)
• In contrast to its ability to activate STAT 5 normally, activation of ERK by the Ile179Met variant was reduced to half that observed with wild type (PMID:15001589)
• Height velocity in the first year of treatment was significantly greater than the pretreatment value. Bone age advanced in the 12 months after commencing treatment. Use of hGH may be beneficial in treatment of Noonan syndrome. (PMID:15004410)
• GH and IGF-I can synergize in acute aspects of signaling and IGF-I enhances GH-induced assembly of conformationally active GHRs (PMID:15044591)
• Adults with GH insufficiency have abnormalities of body composition characteristic of GH deficiency; the degree of abnormality of body composition lies between that of healthy subjects and GHD adults and correlates with the IGF-I level (PMID:15070916)
• HGH acts directly on the neurons in the hypothalamus, and increases SOCS3 and CIS mRNAs, suggesting that these negative regulators may be involved in the mechanism that turns off the hGH action in the hypothalamic neurons. (PMID:15118263)
• genetic polymorphisms in the proximal promoter region and in the fourth intron of the GH1 gene are unrelated to breast carcinoma risk in Chinese women. (PMID:15241820)
• autocrine production of human growth hormone (hGH) results in a phenotypic conversion of mammary carcinoma cells such that they exhibit the morphological and molecular characteristics of a mesenchymal cell (PMID:15353581)
• common diversity in the GH1 region predisposes to osteoporosis via effects on the level of GH expression. (PMID:15472182)
• The data suggest that chronic GH treatment alters the early steps of the insulin signal transduction pathway, and may explain the changes in adipose tissue sensitivity to insulin. (PMID:15473132)
• Growth hormone attenuates the transcriptional activity of Runx2 by facilitating its physical association with Stat3beta (PMID:15476590)
• GH administration could exert beneficial effects against age-related changes in hepatocytes, mainly in males. (PMID:15545704)
• human growth hormone structural and mutational analysis (PMID:15591149)
• Effects of GH on physiological mechanisms of cardiovascular system are discussed, including effect of GH deficiency on cardiovascular disease risk. Also discussed are effects of long-term GH replacement therapy in this patient population. (Review) (PMID:15591764)

Cross-species orthologs

3 orthologs

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

Paralogs (5): GH2 (ENSG00000136487), CSH1 (ENSG00000136488), PRL (ENSG00000172179), CSHL1 (ENSG00000204414), CSH2 (ENSG00000213218)

Protein

Protein identifiers

Somatotropin — P01241 (reviewed: P01241)

Alternative names: Growth hormone, Growth hormone 1, Pituitary growth hormone

All UniProt accessions (5): B1A4G6, B1A4G7, B1A4G9, B1A4H0, P01241

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.

Disease relevance. Growth hormone deficiency, isolated, 1A (IGHD1A) [MIM:262400] An autosomal recessive, severe deficiency of growth hormone leading to dwarfism. Patients often develop antibodies to administered growth hormone. The disease is caused by variants affecting the gene represented in this entry. Growth hormone deficiency, isolated, 1B (IGHD1B) [MIM:612781] An autosomal recessive deficiency of growth hormone leading to short stature. Patients have low but detectable levels of growth hormone, significantly retarded bone age, and a positive response and immunologic tolerance to growth hormone therapy. The disease is caused by variants affecting the gene represented in this entry. Kowarski syndrome (KWKS) [MIM:262650] A syndrome clinically characterized by short stature associated with bioinactive growth hormone, normal or slightly increased growth hormone secretion, pathologically low insulin-like growth factor 1 levels, and normal catch-up growth on growth hormone replacement therapy. The disease is caused by variants affecting the gene represented in this entry. Growth hormone deficiency, isolated, 2 (IGHD2) [MIM:173100] An autosomal dominant deficiency of growth hormone leading to short stature. Clinical severity is variable. Patients have a positive response and immunologic tolerance to growth hormone therapy. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Circulating GH shows a great heterogeneity due to alternative splicing, differential post-translational modifications of monomeric forms, oligomerization, optional binding to 2 different GH-binding proteins, and potentially proteolytic processing.

Similarity. Belongs to the somatotropin/prolactin family.

Isoforms (5)

UniProt ID	Names	Canonical?
P01241-1	1, 22 kDa	yes
P01241-2	2, 20 kDa variant
P01241-3	3
P01241-4	4
P01241-5	5

RefSeq proteins (3): NP_000506, NP_072053, NP_072054 (=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 (51 total): sequence variant 20, helix 10, splice variant 4, turn 4, modified residue 4, binding site 2, sequence conflict 2, disulfide bond 2, signal peptide 1, chain 1, strand 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6QIO	X-RAY DIFFRACTION	1.95
1HUW	X-RAY DIFFRACTION	2
1AXI	X-RAY DIFFRACTION	2.1
1HGU	X-RAY DIFFRACTION	2.5
1HWG	X-RAY DIFFRACTION	2.5
1A22	X-RAY DIFFRACTION	2.6
1KF9	X-RAY DIFFRACTION	2.6
3HHR	X-RAY DIFFRACTION	2.8
1BP3	X-RAY DIFFRACTION	2.9
1HWH	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01241-F1	79.77	0.43

Functional residue map

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

Ligand- & substrate-binding residues (2): 44; 200

Post-translational modifications (4): 132, 163, 176, 178

Disulfide bonds (2): 79–191, 208–215

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1170546	Prolactin receptor signaling
R-HSA-422085	Synthesis, secretion, and deacylation of Ghrelin
R-HSA-982772	Growth hormone receptor signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-168256	Immune System
R-HSA-2980736	Peptide hormone metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 206 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_RECEPTOR_MEDIATED_ENDOCYTOSIS, GOBP_CELL_SURFACE_RECEPTOR_SIGNALING_PATHWAY_VIA_JAK_STAT

GO Biological Process (18): cell surface receptor signaling pathway via JAK-STAT (GO:0007259), positive regulation of D-glucose transmembrane transport (GO:0010828), cytokine-mediated signaling pathway (GO:0019221), response to nutrient levels (GO:0031667), response to estradiol (GO:0032355), positive regulation of multicellular organism growth (GO:0040018), positive regulation of MAPK cascade (GO:0043410), positive regulation of insulin-like growth factor receptor signaling pathway (GO:0043568), positive regulation of receptor signaling pathway via JAK-STAT (GO:0046427), animal organ development (GO:0048513), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), growth hormone receptor signaling pathway (GO:0060396), growth hormone receptor signaling pathway via JAK-STAT (GO:0060397), bone maturation (GO:0070977), cell surface receptor signaling pathway via STAT (GO:0097696), signal transduction (GO:0007165), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), negative regulation of growth hormone receptor signaling pathway (GO:0060400)

GO Molecular Function (8): cytokine activity (GO:0005125), growth hormone receptor binding (GO:0005131), prolactin receptor binding (GO:0005148), hormone activity (GO:0005179), growth factor activity (GO:0008083), metal ion binding (GO:0046872), growth hormone activity (GO:0070186), protein binding (GO:0005515)

GO Cellular Component (8): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), endosome lumen (GO:0031904), growth hormone receptor complex (GO:0070195), cytoplasm (GO:0005737), endomembrane system (GO:0012505), extracellular matrix (GO:0031012), vesicle (GO:0031982)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cytokine Signaling in Immune system	2
Peptide hormone metabolism	1
Immune System	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor ligand activity	3
cellular anatomical structure	3
cell surface receptor signaling pathway	2
positive regulation of intracellular signal transduction	2
growth hormone receptor signaling pathway	2
cytokine receptor binding	2
cell surface receptor signaling pathway via STAT	1
regulation of D-glucose transmembrane transport	1
positive regulation of transmembrane transport	1
D-glucose transmembrane transport	1
cellular response to cytokine stimulus	1
response to stimulus	1
response to lipid	1
response to oxygen-containing compound	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
MAPK cascade	1
regulation of MAPK cascade	1
positive regulation of signal transduction	1
regulation of insulin-like growth factor receptor signaling pathway	1
insulin-like growth factor receptor signaling pathway	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
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to growth hormone stimulus	1
animal organ maturation	1
bone development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1

Protein interactions and networks

STRING

898 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GH1	GHR	P10912	985
GH1	GHRH	P01286	926
GH1	IGF1	P01343	911
GH1	GHRHR	Q02643	909
GH1	GHSR	Q92847	877
GH1	SST	P01166	870
GH1	INS	P01308	813
GH1	POMC	P01189	802
GH1	IGFBP3	P17936	764
GH1	GHRL	Q9UBU3	761
GH1	GCG	P01275	730
GH1	PROP1	O75360	706
GH1	STH	Q8IWL8	696
GH1	POU1F1	P28069	671
GH1	GNRH1	P01148	628

IntAct

93 interactions, top by confidence:

A	B	Type	Score
GHR	GH1	psi-mi:“MI:0407”(direct interaction)	0.730
GH1	GHR	psi-mi:“MI:0407”(direct interaction)	0.730
BMP1	GH1	psi-mi:“MI:0915”(physical association)	0.400
CSH1	GH1	psi-mi:“MI:0914”(association)	0.350
FAM161A	GH1	psi-mi:“MI:0914”(association)	0.350
CSH2	GH1	psi-mi:“MI:0914”(association)	0.350
CSH1	H6PD	psi-mi:“MI:0914”(association)	0.350
GH1	CACYBP	psi-mi:“MI:0915”(physical association)	0.000
GH1		psi-mi:“MI:0915”(physical association)	0.000
YA61	GH1	psi-mi:“MI:0915”(physical association)	0.000
GH1	SARS1	psi-mi:“MI:0915”(physical association)	0.000
GH1	CYCS	psi-mi:“MI:0915”(physical association)	0.000
GH1	EEF1D	psi-mi:“MI:0915”(physical association)	0.000
GH1	PFDN5	psi-mi:“MI:0915”(physical association)	0.000
GH1	OTUB1	psi-mi:“MI:0915”(physical association)	0.000
GH1	FSCN1	psi-mi:“MI:0915”(physical association)	0.000
GH1	EIF2S3	psi-mi:“MI:0915”(physical association)	0.000
GH1	RANBP1	psi-mi:“MI:0915”(physical association)	0.000
RPS3A	GH1	psi-mi:“MI:0915”(physical association)	0.000
GH1	ADRM1	psi-mi:“MI:0915”(physical association)	0.000
GH1	EIF3L	psi-mi:“MI:0915”(physical association)	0.000
GH1	CAPZB	psi-mi:“MI:0915”(physical association)	0.000
GH1	SET	psi-mi:“MI:0915”(physical association)	0.000
GH1	TKT	psi-mi:“MI:0915”(physical association)	0.000
GH1	TMEM263	psi-mi:“MI:0915”(physical association)	0.000
GH1	H2BC10	psi-mi:“MI:0915”(physical association)	0.000
GH1	EIF6	psi-mi:“MI:0915”(physical association)	0.000
GH1	SEPTIN2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (16): GH1 (Affinity Capture-MS), LTA4H (Affinity Capture-MS), STRAP (Affinity Capture-MS), GH1 (Affinity Capture-MS), GH1 (Reconstituted Complex), GHR (Reconstituted Complex), GH1 (Protein-peptide), SHC1 (Biochemical Activity), GH1 (Affinity Capture-MS), GH1 (Affinity Capture-MS), GH1 (Affinity Capture-MS), S100P (Reconstituted Complex), GHR (Reconstituted Complex), S100A6 (Reconstituted Complex), GH1 (Affinity Capture-Luminescence)

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, O93566, P01241, P01244, P01245, P01246, P01248, P06880, P07064, P08591, P08899, P08998, P09113, P09537, P09538, P09539, P10298, P10607, P10766, P10813, P10814, P11228, P12855, P12856, P13391, P19795, P20332, P20391, P20392, P22077, P24363, P26773

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
POU1F1	“up-regulates quantity by expression”	GH1	“transcriptional regulation”
GH1	“up-regulates activity”	GHR	binding
GH1	“up-regulates quantity by expression”	MYC	“transcriptional regulation”
GH1	“up-regulates quantity by expression”	BCL2	“transcriptional regulation”
GH1	“up-regulates quantity by expression”	CCND1	“transcriptional regulation”
GH1	up-regulates	GHR	binding
GH1	up-regulates	PRLR	binding
ZNF292	“up-regulates quantity by expression”	GH1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 84 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Regulation of activated PAK-2p34 by proteasome mediated degradation	8	30.5×	1e-08
Hh mutants are degraded by ERAD	9	30.0×	3e-09
Regulation of ornithine decarboxylase (ODC)	8	29.8×	1e-08
Vpu mediated degradation of CD4	8	29.1×	1e-08
Autodegradation of the E3 ubiquitin ligase COP1	8	29.1×	1e-08
Ubiquitin-dependent degradation of Cyclin D	8	29.1×	1e-08
SPOP-mediated proteasomal degradation of PD-L1(CD274)	9	28.2×	4e-09
Cross-presentation of soluble exogenous antigens (endosomes)	8	27.8×	1e-08

GO biological processes:

GO term	Partners	Fold	FDR
translational initiation	5	22.1×	9e-04
cytoplasmic translation	5	11.4×	7e-03
proteasome-mediated ubiquitin-dependent protein catabolic process	11	7.1×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	13
Likely pathogenic	3
Uncertain significance	10
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (16)

Variant ID	HGVS	Classification
1072683	NC_000017.10:g.(?61994669)(61996136_?)del	Pathogenic
15962	NM_000515.5(GH1):c.245_246del (p.Glu82fs)	Pathogenic
15963	NM_000515.5(GH1):c.59G>A (p.Trp20Ter)	Pathogenic
15964	GH1, 6.7-KB DEL	Pathogenic
15965	NM_000515.5(GH1):c.52del (p.Leu18fs)	Pathogenic
15968	NM_000515.5(GH1):c.291+6T>C	Pathogenic
15972	NM_000515.5(GH1):c.291+28G>A	Pathogenic
15975	NM_000515.5(GH1):c.291+5G>A	Pathogenic
15979	NM_000515.5(GH1):c.172-2A>T	Pathogenic
15983	NM_000515.5(GH1):c.626G>A (p.Arg209His)	Pathogenic
15984	NM_000515.5(GH1):c.173A>C (p.Glu58Ala)	Pathogenic
2423184	NC_000017.10:g.(?61994669)(61996359_?)del	Pathogenic
2431647	NC_000017.11:g.(63914995_63921260)del	Pathogenic
1013138	NM_000515.5(GH1):c.178G>A (p.Ala60Thr)	Likely pathogenic
1702861	NM_000515.5(GH1):c.254C>T (p.Pro85Leu)	Likely pathogenic
998049	NM_000515.5(GH1):c.131A>C (p.His44Pro)	Likely pathogenic

SpliceAI

696 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63917505:CT:C	acceptor_gain	1.0000
17:63917507:C:T	acceptor_loss	1.0000
17:63917758:ACCC:A	donor_gain	1.0000
17:63917759:CCCC:C	donor_gain	1.0000
17:63917783:C:A	donor_gain	1.0000
17:63917788:AGGT:A	donor_gain	1.0000
17:63917791:T:TA	donor_gain	1.0000
17:63918345:CAAA:C	donor_gain	1.0000
17:63917502:AGCCT:A	acceptor_gain	0.9900
17:63917503:GCCT:G	acceptor_gain	0.9900
17:63917504:CCT:C	acceptor_gain	0.9900
17:63917504:CCTC:C	acceptor_gain	0.9900
17:63917505:CTC:C	acceptor_gain	0.9900
17:63917506:TCTGC:T	acceptor_gain	0.9900
17:63917507:C:CC	acceptor_gain	0.9900
17:63917508:T:A	acceptor_loss	0.9900
17:63917510:C:CT	acceptor_gain	0.9900
17:63917514:G:C	acceptor_gain	0.9900
17:63917514:G:GC	acceptor_gain	0.9900
17:63917758:AC:A	donor_gain	0.9900
17:63917759:CC:C	donor_gain	0.9900
17:63917761:C:CA	donor_gain	0.9900
17:63917782:T:A	donor_gain	0.9900
17:63917921:GGTT:G	acceptor_gain	0.9900
17:63917922:GTT:G	acceptor_gain	0.9900
17:63917922:GTTCT:G	acceptor_gain	0.9900
17:63917923:TT:T	acceptor_gain	0.9900
17:63917924:TC:T	acceptor_loss	0.9900
17:63917925:C:CC	acceptor_gain	0.9900
17:63917925:CT:C	acceptor_loss	0.9900

AlphaMissense

1421 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:63917788:A:G	L143P	0.971
17:63917388:A:G	F192S	0.968
17:63917882:A:G	W112R	0.967
17:63917882:A:T	W112R	0.967
17:63917880:C:A	W112C	0.965
17:63917880:C:G	W112C	0.965
17:63918346:A:C	F57L	0.964
17:63918346:A:T	F57L	0.964
17:63918348:A:G	F57L	0.964
17:63917357:G:C	F202L	0.957
17:63917357:G:T	F202L	0.957
17:63917359:A:G	F202L	0.957
17:63917914:A:G	L101P	0.957
17:63917355:A:G	L203P	0.956
17:63917340:C:G	C208S	0.954
17:63917341:A:T	C208S	0.954
17:63917387:G:C	F192L	0.949
17:63917387:G:T	F192L	0.949
17:63917389:A:G	F192L	0.949
17:63917379:T:G	D195A	0.939
17:63918347:A:C	F57C	0.938
17:63917388:A:C	F192C	0.934
17:63917341:A:G	C208R	0.932
17:63917380:C:G	D195H	0.930
17:63917797:A:G	L140P	0.927
17:63917911:A:G	L102P	0.925
17:63917911:A:T	L102H	0.924
17:63918368:G:T	A50D	0.924
17:63917902:G:A	S105F	0.923
17:63917400:A:G	L188P	0.922

dbSNP variants (sampled 300 via entrez): RS1000821103 (17:63919839 C>T), RS1000991694 (17:63916885 G>A), RS1001233703 (17:63920047 TCTC>T), RS1003856494 (17:63918041 G>C), RS1004651155 (17:63920483 T>G), RS1004825240 (17:63917137 GC>G), RS1005498274 (17:63918419 G>C), RS1005654521 (17:63919359 C>A), RS1010649071 (17:63919082 C>T), RS1012564466 (17:63917800 A>T), RS1013567260 (17:63916929 A>G), RS1013810726 (17:63919861 C>G,T), RS1014444452 (17:63919191 C>A,T), RS1015981398 (17:63920491 G>C), RS1016137386 (17:63916958 A>C,G)

Disease associations

OMIM: gene MIM:139250 | disease phenotypes: MIM:262400, MIM:173100, MIM:262650, MIM:612781

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated growth hormone deficiency type IA	Definitive	Autosomal recessive
isolated growth hormone deficiency type II	Strong	Autosomal dominant
short stature due to growth hormone qualitative anomaly	Strong	Autosomal recessive
isolated growth hormone deficiency type IB	Supportive	Autosomal recessive

Mondo (4): isolated growth hormone deficiency type IA (MONDO:0009876), isolated growth hormone deficiency type II (MONDO:0008250), short stature due to growth hormone qualitative anomaly (MONDO:0009879), isolated growth hormone deficiency type IB (MONDO:0013006)

Orphanet (5): Isolated growth hormone deficiency type IA (Orphanet:231662), Non-acquired isolated growth hormone deficiency (Orphanet:631), Isolated growth hormone deficiency type II (Orphanet:231679), Isolated growth hormone deficiency type IB (Orphanet:231671), Short stature due to growth hormone qualitative anomaly (Orphanet:629)

HPO phenotypes

22 total (22 of 22 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000348	High forehead
HP:0000457	Depressed nasal ridge
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000839	Pituitary dwarfism
HP:0001510	Growth delay
HP:0001939	Abnormality of metabolism/homeostasis
HP:0001943	Hypoglycemia
HP:0002650	Scoliosis
HP:0002750	Delayed skeletal maturation
HP:0003510	Severe short stature
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0004474	Persistent open anterior fontanelle
HP:0006579	Prolonged neonatal jaundice
HP:0010627	Anterior pituitary hypoplasia
HP:0011463	Childhood onset
HP:0030353	Decreased circulating serum insulin-like growth factor 1 concentration
HP:0031878	Acromicria
HP:0034323	Reduced circulating growth hormone concentration

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST010396_18	Gut microbiota (bacterial taxa, hurdle binary method)	9.000000e-06
GCST90000025_608	Appendicular lean mass	2.000000e-128
GCST90000025_609	Appendicular lean mass	8.000000e-81

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004980	appendicular lean mass

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
C567564	Isolated Growth Hormone Deficiency, Type IB (supp.)
C562704	Isolated Growth Hormone Deficiency, Type II (supp.)
C537505	Kowarski syndrome (supp.)
C537404	Pituitary dwarfism 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

58 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Octreotide	affects expression, decreases expression, decreases secretion	17
Bromocriptine	decreases expression, increases expression	5
Clonidine	increases expression, increases secretion, decreases reaction	5
Estradiol	decreases reaction, increases phosphorylation, increases expression, affects cotreatment, increases secretion	3
Apomorphine	increases expression, increases secretion	2
Cocaine	decreases reaction, increases secretion, increases expression	2
Ethinyl Estradiol	affects cotreatment, increases expression	2
Glucose	increases phosphorylation, increases reaction, decreases abundance, decreases reaction, increases secretion	2
Homocysteine	decreases abundance	2
Sodium	increases abundance	2
Thyroxine	decreases abundance	2
GSK-J4	increases expression	1
N-n-propylnorapomorphine	affects secretion	1
afimoxifene	increases phosphorylation, increases reaction	1
tetrabromobisphenol A	decreases expression, increases response to substance	1
hydroxymaprotilin	increases secretion	1
oxophenylarsine	decreases reaction, increases secretion	1
2-butanol	affects folding	1
L 657743	increases expression, decreases reaction	1
perfluorooctane sulfonic acid	increases expression	1
hexarelin	increases secretion	1
4-hydroxybutyric acid	increases secretion, decreases reaction	1
T0901317	increases expression, affects cotreatment, decreases expression	1
Pioglitazone	increases expression	1
Arsenic Trioxide	increases expression, increases response to substance, decreases activity, increases reaction, decreases expression	1
Adenosine Triphosphate	increases secretion, decreases reaction, affects reaction	1
Adrenocorticotropic Hormone	decreases reaction, increases secretion	1
Ethanol	affects folding	1
1-Propanol	affects folding	1
Benzo(a)pyrene	affects methylation	1

Cellosaurus cell lines

3 cell lines: 1 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_9V74	MCF-hGH	Cancer cell line	Female
CVCL_IR07	NeuCHO	Transformed cell line	Female
CVCL_RX03	Vero Mx13	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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