GPHA2 (glycoprotein hormone subunit alpha 2)

Gene

• Entrez ID: 170589
• Gene name: Glycoprotein hormone subunit alpha 2
• Gene symbol: GPHA2
• Synonyms (NCBI Gene): A2, GPA2, ZSIG51
• Chromosome: 11
• Chromosome location: 11q13.1
• Summary: GPHA2 is a cystine knot-forming polypeptide and a subunit of the dimeric glycoprotein hormone family (Hsu et al., 2002 [PubMed 12089349]).[supplied by OMIM, Mar 2008]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT649023	hsa-miR-125a-3p	HITS-CLIP	23824327
MIRT649022	hsa-miR-764	HITS-CLIP	23824327
MIRT649021	hsa-miR-3934-5p	HITS-CLIP	23824327
MIRT649019	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT649020	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT649018	hsa-miR-877-3p	HITS-CLIP	23824327
MIRT649017	hsa-miR-3664-3p	HITS-CLIP	23824327
MIRT649016	hsa-miR-1266-5p	HITS-CLIP	23824327
MIRT649015	hsa-miR-4518	HITS-CLIP	23824327
MIRT649014	hsa-miR-942-5p	HITS-CLIP	23824327
MIRT649013	hsa-miR-3185	HITS-CLIP	23824327
MIRT649012	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT460403	hsa-miR-4476	PAR-CLIP	23592263
MIRT460402	hsa-miR-6876-5p	PAR-CLIP	23592263
MIRT460401	hsa-miR-1915-3p	PAR-CLIP	23592263
MIRT460400	hsa-miR-6764-5p	PAR-CLIP	23592263
MIRT460399	hsa-miR-1180-5p	PAR-CLIP	23592263
MIRT460398	hsa-miR-7114-3p	PAR-CLIP	23592263
MIRT460397	hsa-miR-4533	PAR-CLIP	23592263
MIRT460396	hsa-miR-766-5p	PAR-CLIP	23592263
MIRT460394	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT460395	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT460393	hsa-miR-7973	PAR-CLIP	23592263
MIRT460392	hsa-miR-7111-5p	PAR-CLIP	23592263
MIRT649023	hsa-miR-125a-3p	HITS-CLIP	23824327
MIRT649022	hsa-miR-764	HITS-CLIP	23824327
MIRT649021	hsa-miR-3934-5p	HITS-CLIP	23824327
MIRT649019	hsa-miR-6887-3p	HITS-CLIP	23824327
MIRT649020	hsa-miR-6795-3p	HITS-CLIP	23824327
MIRT649018	hsa-miR-877-3p	HITS-CLIP	23824327
MIRT649017	hsa-miR-3664-3p	HITS-CLIP	23824327
MIRT649016	hsa-miR-1266-5p	HITS-CLIP	23824327
MIRT649015	hsa-miR-4518	HITS-CLIP	23824327
MIRT649014	hsa-miR-942-5p	HITS-CLIP	23824327
MIRT649013	hsa-miR-3185	HITS-CLIP	23824327
MIRT649012	hsa-miR-6826-3p	HITS-CLIP	23824327
MIRT460403	hsa-miR-4476	PAR-CLIP	23592263
MIRT460402	hsa-miR-6876-5p	PAR-CLIP	23592263
MIRT460401	hsa-miR-1915-3p	PAR-CLIP	23592263
MIRT460400	hsa-miR-6764-5p	PAR-CLIP	23592263
MIRT460399	hsa-miR-1180-5p	PAR-CLIP	23592263
MIRT460398	hsa-miR-7114-3p	PAR-CLIP	23592263
MIRT460397	hsa-miR-4533	PAR-CLIP	23592263
MIRT460396	hsa-miR-766-5p	PAR-CLIP	23592263
MIRT460394	hsa-miR-7106-5p	PAR-CLIP	23592263
MIRT460395	hsa-miR-6825-5p	PAR-CLIP	23592263
MIRT460393	hsa-miR-7973	PAR-CLIP	23592263
MIRT460392	hsa-miR-7111-5p	PAR-CLIP	23592263
MIRT1029283	hsa-miR-1272	CLIP-seq
MIRT1029284	hsa-miR-3662	CLIP-seq
MIRT1029285	hsa-miR-583	CLIP-seq
MIRT2237992	hsa-miR-1207-5p	CLIP-seq
MIRT2237993	hsa-miR-145	CLIP-seq
MIRT2237994	hsa-miR-1827	CLIP-seq
MIRT2237995	hsa-miR-2467-3p	CLIP-seq
MIRT2237996	hsa-miR-3127-5p	CLIP-seq
MIRT2237997	hsa-miR-3154	CLIP-seq
MIRT2237998	hsa-miR-3667-3p	CLIP-seq
MIRT2237999	hsa-miR-3918	CLIP-seq
MIRT2238000	hsa-miR-4328	CLIP-seq
MIRT2238001	hsa-miR-4446-3p	CLIP-seq
MIRT2238002	hsa-miR-4448	CLIP-seq
MIRT2238003	hsa-miR-4514	CLIP-seq
MIRT2238004	hsa-miR-4640-5p	CLIP-seq
MIRT2238005	hsa-miR-4645-5p	CLIP-seq
MIRT2238006	hsa-miR-4673	CLIP-seq
MIRT2238007	hsa-miR-4692	CLIP-seq
MIRT2238008	hsa-miR-4726-5p	CLIP-seq
MIRT2238009	hsa-miR-4755-3p	CLIP-seq
MIRT2238010	hsa-miR-4763-3p	CLIP-seq
MIRT2238011	hsa-miR-940	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005179	Function	Hormone activity	IEA
GO:0005515	Function	Protein binding	IPI	12045258
GO:0005576	Component	Extracellular region	IDA	12089349
GO:0005576	Component	Extracellular region	IEA
GO:0005576	Component	Extracellular region	TAS
GO:0005615	Component	Extracellular space	IBA
GO:0007166	Process	Cell surface receptor signaling pathway	IBA
GO:0007166	Process	Cell surface receptor signaling pathway	IMP	12045258
GO:0007189	Process	Adenylate cyclase-activating G protein-coupled receptor signaling pathway	IMP	12045258
GO:0031531	Function	Thyrotropin-releasing hormone receptor binding	IBA
GO:0031531	Function	Thyrotropin-releasing hormone receptor binding	IMP	12045258
GO:0046982	Function	Protein heterodimerization activity	IDA	12045258

Other IDs

• MIM: 609651
• HGNC: 18054
• e!Ensembl: ENSG00000149735

Protein

• UniProt ID: Q96T91
• Protein name: Glycoprotein hormone alpha-2 (Putative secreted protein Zsig51) (Thyrostimulin subunit alpha)
• Protein function: Functions as a heterodimeric glycoprotein hormone with GPHB5 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production (PubMed:12045258). Plays a central role in controlling thyroid cell meta
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF03045	DAN	16 → 124	DAN domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Found in a variety of tissues. {ECO:0000269|PubMed:12089349}.
• Sequence:

  MPMASPQTLVLYLLVLAVTEAWGQEAVIPGCHLHPFNVTVRSDRQGTCQGSHVAQACVGH
  CESSAFPSRYSVLVASGYRHNITSVSQCCTISGLKKVKVQLQCVGSRREELEIFTARACQ
  CDMCRLSRY

• Sequence length: 129

Pathways

KEGG:

cAMP signaling pathway
Neuroactive ligand-receptor interaction

Reactome:

Hormone ligand-binding receptors
G alpha (s) signalling events
ADORA2B mediated anti-inflammatory cytokines production

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
MELANOMA	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
alpha Thalassemia	Alpha thalassemia	Pubtator	14508795, 14587048, 23368878, 23614625, 2473806, 25730315, 26377141, 31060505, 31478238, 34247821, 3680504, 36902239, 3771577, 6255436, 6894931, 6946451, 8611658, 8781536	Associate	★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	22691495	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Hemolytic	Hemolytic anemia	Pubtator	9029003	Associate	★☆☆☆☆ Found in Text Mining only
Anemia Sickle Cell	Sickle cell anemia	Pubtator	1177281, 3337900, 8781536	Associate	★☆☆☆☆ Found in Text Mining only
Anodontia	Anodontia	Pubtator	8781536	Associate	★☆☆☆☆ Found in Text Mining only
Arthritis Rheumatoid	Rheumatoid arthritis	Pubtator	2510617	Associate	★☆☆☆☆ Found in Text Mining only
Asthma	Asthma	Pubtator	23160057	Associate	★☆☆☆☆ Found in Text Mining only
Autosomal Dominant Nocturnal Frontal Lobe Epilepsy	Nocturnal frontal lobe epilepsy	Pubtator	17900292	Associate	★☆☆☆☆ Found in Text Mining only
beta Thalassemia	Beta thalassemia	Pubtator	2473806, 36902239	Associate	★☆☆☆☆ Found in Text Mining only
Blood Platelet Disorders	Platelet disorder	Pubtator	10449749, 30545930	Associate	★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain Neoplasms	BEFREE	30113464		★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	18787945, 22644305, 26903292	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	8276836	Inhibit	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	34559939	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	18398683	Associate	★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	31795149	Associate	★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	15063740, 37116137	Inhibit	★☆☆☆☆ Found in Text Mining only
Crohn Disease	Crohn disease	Pubtator	10623652	Associate	★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus Type 2	Diabetes mellitus, type 2	Pubtator	33426802	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathies	Diabetic neuropathy	Pubtator	22343787	Inhibit	★☆☆☆☆ Found in Text Mining only
Fabry Disease	Fabry disease	Pubtator	23614625	Associate	★☆☆☆☆ Found in Text Mining only
Glaucoma	Glaucoma	BEFREE	31275629		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	34207114	Stimulate	★☆☆☆☆ Found in Text Mining only
Graves Ophthalmopathy	Graves ophthalmopathy	Pubtator	34889904	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobin C Disease	Hemoglobin c disease	Pubtator	23368878	Associate	★☆☆☆☆ Found in Text Mining only
Hemoglobinopathies	Hemoglobinopathy	Pubtator	2981252	Associate	★☆☆☆☆ Found in Text Mining only
Hydrops Fetalis	Hydrops fetalis	Pubtator	20642338	Associate	★☆☆☆☆ Found in Text Mining only
Idiopathic Pulmonary Fibrosis	Idiopathic pulmonary fibrosis	Pubtator	26006016	Associate	★☆☆☆☆ Found in Text Mining only
IgA Deficiency	Selective immunoglobulin a deficiency	Pubtator	19153537	Associate	★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	29129073, 8385084	Associate	★☆☆☆☆ Found in Text Mining only
Malformations of Cortical Development	Cortical development malformation	Pubtator	24613745	Associate	★☆☆☆☆ Found in Text Mining only
Marfan Syndrome	Marfan syndrome	Pubtator	6950413	Associate	★☆☆☆☆ Found in Text Mining only
melanoma	Melanoma	CTD_human_DG	22535842		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Melanoma	Melanoma	Pubtator	8868467	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Mouth Diseases	Mouth disease	Pubtator	26006016	Associate	★☆☆☆☆ Found in Text Mining only
Myocardial Infarction	Myocardial infarction	Pubtator	15978110	Associate	★☆☆☆☆ Found in Text Mining only
Nasopharyngeal carcinoma	Nasopharyngeal Carcinoma	BEFREE	18998154		★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	28358117	Associate	★☆☆☆☆ Found in Text Mining only
Prion Diseases	Prion disease	Pubtator	21552571	Associate	★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	23242739, 25137483	Associate	★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	34290711	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	36289103	Associate	★☆☆☆☆ Found in Text Mining only
Status Epilepticus	Status epilepticus	Pubtator	24613745	Associate	★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	33947960	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	10339462	Associate	★☆☆☆☆ Found in Text Mining only
Urinary Bladder Neoplasms	Urinary bladder neoplasms	Pubtator	8178925	Associate	★☆☆☆☆ Found in Text Mining only