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] See more...

Aliases for GPHA2 Gene

Aliases for GPHA2 Gene

  • Glycoprotein Hormone Subunit Alpha 2 2 3 5
  • Thyrostimulin Subunit Alpha 2 3 4
  • Putative Secreted Protein Zsig51 3 4
  • Glycoprotein Hormone Alpha-2 3 4
  • Glycoprotein Hormone Alpha 2 2 3
  • Cysteine Knot Protein 2 3
  • Glycoprotein Alpha 2 2 3
  • ZSIG51 3 4
  • GPA2 3 4
  • A2 3

External Ids for GPHA2 Gene

Previous GeneCards Identifiers for GPHA2 Gene

  • GC11M067217
  • GC11M066383
  • GC11M064952
  • GC11M064477
  • GC11M064458
  • GC11M064701
  • GC11M061028
  • GC11M064980
  • GC11M064984
  • GC11M064991
  • GC11M064949
  • GC11M064958
  • GC11M064964
  • GC11M064974

Summaries for GPHA2 Gene

Entrez Gene Summary for GPHA2 Gene

  • 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]

GeneCards Summary for GPHA2 Gene

GPHA2 (Glycoprotein Hormone Subunit Alpha 2) is a Protein Coding gene. Diseases associated with GPHA2 include Norrie Disease and Malignant Skin Fibrous Histiocytoma. Among its related pathways are Signaling by GPCR and Peptide ligand-binding receptors. Gene Ontology (GO) annotations related to this gene include hormone activity.

UniProtKB/Swiss-Prot Summary for GPHA2 Gene

  • 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 metabolism (PubMed:12045258).

Gene Wiki entry for GPHA2 Gene

Additional gene information for GPHA2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GPHA2 Gene

Genomics for GPHA2 Gene

GeneHancer (GH) Regulatory Elements for GPHA2 Gene

Promoters and enhancers for GPHA2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J064934 Promoter/Enhancer 1.5 EPDnew Ensembl ENCODE CraniofacialAtlas 505.2 +2.8 2832 2.6 POLR2G ZIC2 TGIF2 ZBTB7A POLR2A SIN3A MYNN KLF9 ZBTB17 KAT7 GPHA2 MAJIN CDC42BPG EHD1 ENSG00000270775 NEAT1 BATF2 CAPN1 PPP2R5B lnc-PPP2R5B-1
GH11J064970 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE CraniofacialAtlas 15.4 -33.3 -33332 2.5 NRF1 JUND RFX1 MYC HDAC2 GTF2F1 NFIC CREB3L1 POLR2A FOS MAJIN ARL2 GPHA2 SNX15 EHD1 ENSG00000270775 CCDC88B PPP2R5B CAPN1 piR-53177-006
GH11J064846 Promoter/Enhancer 1.9 FANTOM5 Ensembl ENCODE dbSUPER 10.4 +81.2 81153 20.8 RXRA ZBTB40 ZNF217 CTCF SIN3A TCF12 MYC USF1 SP1 JUND EHD1 MAP4K2 MIR192 MEN1 MAJIN GPHA2 MAP3K11 CDC42EP2 CDC42BPG NEAT1
GH11J064914 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 4.5 +21.1 21085 4.3 FOXK2 ZBTB40 ZNF217 CTCF SIN3A TCF12 NRF1 USF1 POLR2G SP1 ATG2A PPP2R5B lnc-PPP2R5B-1 SPDYC ARL2 GPHA2 POLA2 MIR6749
GH11J064973 Enhancer 0.4 Ensembl 15.5 -36.4 -36369 2.2 RBM25 IRF1 ZMYM3 ZFP36 ZNF7 ARL2 GPHA2 SNX15 EHD1 ENSG00000270775 PPP2R5B BATF2 MAJIN piR-34822-054
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GPHA2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GPHA2

Top Transcription factor binding sites by QIAGEN in the GPHA2 gene promoter:
  • aMEF-2
  • C/EBPalpha
  • CUTL1
  • E47
  • FOXC1
  • FOXD1
  • MEF-2A
  • MyoD
  • Nkx2-5
  • Pax-6

Genomic Locations for GPHA2 Gene

Genomic Locations for GPHA2 Gene
chr11:64,934,471-64,938,132
(GRCh38/hg38)
Size:
3,662 bases
Orientation:
Minus strand
chr11:64,701,943-64,703,360
(GRCh37/hg19)
Size:
1,418 bases
Orientation:
Minus strand

Genomic View for GPHA2 Gene

Genes around GPHA2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GPHA2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GPHA2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GPHA2 Gene

Proteins for GPHA2 Gene

  • Protein details for GPHA2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q96T91-GPHA2_HUMAN
    Recommended name:
    Glycoprotein hormone alpha-2
    Protein Accession:
    Q96T91
    Secondary Accessions:
    • Q52LE2

    Protein attributes for GPHA2 Gene

    Size:
    129 amino acids
    Molecular mass:
    14163 Da
    Quaternary structure:
    • Heterodimer with GPHB5; this heterodimer interacts with thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP production.

neXtProt entry for GPHA2 Gene

Post-translational modifications for GPHA2 Gene

Other Protein References for GPHA2 Gene

No data available for DME Specific Peptides for GPHA2 Gene

Domains & Families for GPHA2 Gene

Gene Families for GPHA2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted secreted proteins

Protein Domains for GPHA2 Gene

Blocks:
  • Growth factor cystine knot superfamily signature
  • Glycoprotein hormones alpha chain
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GPHA2 Gene

GenScript: Design optimal peptide antigens:
  • Thyrostimulin subunit alpha (GPHA2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q96T91

UniProtKB/Swiss-Prot:

GPHA2_HUMAN :
  • Belongs to the glycoprotein hormones subunit alpha family.
Family:
  • Belongs to the glycoprotein hormones subunit alpha family.
genes like me logo Genes that share domains with GPHA2: view

Function for GPHA2 Gene

Molecular function for GPHA2 Gene

UniProtKB/Swiss-Prot 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 metabolism (PubMed:12045258).

Phenotypes From GWAS Catalog for GPHA2 Gene

Gene Ontology (GO) - Molecular Function for GPHA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005179 hormone activity IEA --
GO:0005515 protein binding IPI 12045258
GO:0031531 thyrotropin-releasing hormone receptor binding IMP,IBA 12045258
GO:0046982 protein heterodimerization activity IDA 12045258
GO:0051427 hormone receptor binding IBA 21873635
genes like me logo Genes that share ontologies with GPHA2: view
genes like me logo Genes that share phenotypes with GPHA2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for GPHA2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GPHA2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for GPHA2 Gene

Localization for GPHA2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for GPHA2 Gene

Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GPHA2 gene
Compartment Confidence
extracellular 5
plasma membrane 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
nucleus 1
endoplasmic reticulum 1
endosome 1
cytosol 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for GPHA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IDA,TAS --
GO:0005615 extracellular space IBA 21873635
genes like me logo Genes that share ontologies with GPHA2: view

Pathways & Interactions for GPHA2 Gene

genes like me logo Genes that share pathways with GPHA2: view

SIGNOR curated interactions for GPHA2 Gene

Activates:

Gene Ontology (GO) - Biological Process for GPHA2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007165 signal transduction IEA --
GO:0007166 cell surface receptor signaling pathway IMP 12045258
GO:0007186 G protein-coupled receptor signaling pathway TAS --
GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway IMP 12045258
genes like me logo Genes that share ontologies with GPHA2: view

Drugs & Compounds for GPHA2 Gene

(2) Drugs for GPHA2 Gene - From: HMDB and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
genes like me logo Genes that share compounds with GPHA2: view

Transcripts for GPHA2 Gene

mRNA/cDNA for GPHA2 Gene

1 REFSEQ mRNAs :
4 NCBI additional mRNA sequence :
3 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GPHA2

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for GPHA2 Gene

ExUns: 1 ^ 2a · 2b ^ 3 ^ 4a · 4b
SP1: -
SP2:

Relevant External Links for GPHA2 Gene

GeneLoc Exon Structure for
GPHA2

Expression for GPHA2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GPHA2 Gene

mRNA differential expression in normal tissues according to GTEx for GPHA2 Gene

This gene is overexpressed in Pancreas (x28.1), Pituitary (x14.4), and Testis (x5.2).

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GPHA2

SOURCE GeneReport for Unigene cluster for GPHA2 Gene:

Hs.436119

mRNA Expression by UniProt/SwissProt for GPHA2 Gene:

Q96T91-GPHA2_HUMAN
Tissue specificity: Found in a variety of tissues.

Evidence on tissue expression from TISSUES for GPHA2 Gene

  • Nervous system(4.2)
  • Pancreas(2)
genes like me logo Genes that share expression patterns with GPHA2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , Protein differential expression in normal tissues , Protein expression , Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for GPHA2 Gene

Orthologs for GPHA2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for GPHA2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GPHA2 31 30
  • 100 (n)
OneToOne
cow
(Bos Taurus)
Mammalia GPHA2 31 30
  • 90.18 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Gpha2 30
  • 85.16 (n)
mouse
(Mus musculus)
Mammalia Gpha2 17 31 30
  • 82.55 (n)
oppossum
(Monodelphis domestica)
Mammalia GPHA2 31
  • 76 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia GPA2 31
  • 74 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia gpha2 30
  • 70.3 (n)
zebrafish
(Danio rerio)
Actinopterygii gpha2 31 30
  • 63.3 (n)
OneToOne
Species where no ortholog for GPHA2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for GPHA2 Gene

ENSEMBL:
Gene Tree for GPHA2 (if available)
TreeFam:
Gene Tree for GPHA2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GPHA2: view image

Paralogs for GPHA2 Gene

No data available for Paralogs for GPHA2 Gene

Variants for GPHA2 Gene

Additional dbSNP identifiers (rs#s) for GPHA2 Gene

Structural Variations from Database of Genomic Variants (DGV) for GPHA2 Gene

Variant ID Type Subtype PubMed ID
nsv526181 CNV gain 19592680
nsv555208 CNV loss 21841781

Variation tolerance for GPHA2 Gene

Residual Variation Intolerance Score: 68.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.44; 9.59% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GPHA2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
GPHA2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GPHA2 Gene

Disorders for GPHA2 Gene

MalaCards: The human disease database

(6) MalaCards diseases for GPHA2 Gene - From: DISEASES and GeneCards

Disorder Aliases PubMed IDs
norrie disease
  • nd
malignant skin fibrous histiocytoma
  • malignant fibrous histiocytoma of skin
malignant dermis tumor
  • malignant neoplasm of dermis
voyeurism
cone-rod dystrophy 2
  • cord2
- elite association - COSMIC cancer census association via MalaCards
Search GPHA2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GPHA2

genes like me logo Genes that share disorders with GPHA2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GPHA2 Gene

Publications for GPHA2 Gene

  1. A glycoprotein hormone expressed in corticotrophs exhibits unique binding properties on thyroid-stimulating hormone receptor. (PMID: 16210345) Okada SL … Webster PJ (Molecular endocrinology (Baltimore, Md.) 2006) 2 3 23 54
  2. Evolution of glycoprotein hormone subunit genes in bilateral metazoa: identification of two novel human glycoprotein hormone subunit family genes, GPA2 and GPB5. (PMID: 12089349) Hsu SY … Bhalla A (Molecular endocrinology (Baltimore, Md.) 2002) 2 3 4 54
  3. Biochemical roles of the oligosaccharide chains in thyrostimulin, a heterodimeric hormone of glycoprotein hormone subunits alpha 2 (GPA2) and beta 5 (GPB5). (PMID: 18433898) Okajima Y … Oiso Y (Regulatory peptides 2008) 3 23 54
  4. The LIM domain homeobox gene isl-1 is a positive regulator of glycoprotein alpha 2 (GPA2), a subunit of thyrostimulin. (PMID: 17363077) Suzuki C … Oiso Y (Regulatory peptides 2007) 3 23 54
  5. Heterodimeric fly glycoprotein hormone-alpha2 (GPA2) and glycoprotein hormone-beta5 (GPB5) activate fly leucine-rich repeat-containing G protein-coupled receptor-1 (DLGR1) and stimulation of human thyrotropin receptors by chimeric fly GPA2 and human GPB5. (PMID: 15890769) Sudo S … Hsueh AJ (Endocrinology 2005) 3 23 54

Products for GPHA2 Gene

Sources for GPHA2 Gene