CGA

Summary

CGA (glycoprotein hormones, alpha polypeptide, HGNC:1885) is a protein-coding gene on chromosome 6q14.3, encoding Glycoprotein hormones alpha chain (P01215). Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH, follitropin/follicle stimulating hormone/FSH and choriogonadotropin/CG.

The four human glycoprotein hormones chorionic gonadotropin (CG), luteinizing hormone (LH), follicle stimulating hormone (FSH), and thyroid stimulating hormone (TSH) are dimers consisting of alpha and beta subunits that are associated noncovalently. The alpha subunits of these hormones are identical, however, their beta chains are unique and confer biological specificity. The protein encoded by this gene is the alpha subunit and belongs to the glycoprotein hormones alpha chain family. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 1081 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 13 total
• Druggable target: yes
• MANE Select transcript: NM_000735

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1885
Approved symbol	CGA
Name	glycoprotein hormones, alpha polypeptide
Location	6q14.3
Locus type	gene with protein product
Status	Approved
Aliases	HCG, GPHa, GPHA1, FSHA, LHA, TSHA, GPA1
Ensembl gene	ENSG00000135346
Ensembl biotype	protein_coding
OMIM	118850
Entrez	1081

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000369582, ENST00000610310, ENST00000625577, ENST00000627148, ENST00000627552, ENST00000630630

RefSeq mRNA: 2 — MANE Select: NM_000735 NM_000735, NM_001252383

CCDS: CCDS5007, CCDS75492

Canonical transcript exons

ENST00000627148 — 4 exons

Exon	Start	End
ENSE00000798148	87085498	87085833
ENSE00000798149	87086250	87086434
ENSE00000798150	87088113	87088207
ENSE00001450387	87095013	87095106

Expression profiles

Bgee: expression breadth ubiquitous, 156 present calls, max score 99.84.

FANTOM5 (CAGE): breadth broad, TPM avg 25.4249 / max 18792.1792, expressed in 190 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
74624	25.4092	190
74623	0.0157	10

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adenohypophysis	UBERON:0002196	99.84	gold quality
pituitary gland	UBERON:0000007	99.73	gold quality
placenta	UBERON:0001987	97.61	gold quality
buccal mucosa cell	CL:0002336	87.04	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.85	gold quality
cauda epididymis	UBERON:0004360	77.13	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	76.58	silver quality
amniotic fluid	UBERON:0000173	75.21	gold quality
decidua	UBERON:0002450	73.82	gold quality
islet of Langerhans	UBERON:0000006	63.70	gold quality
metanephros cortex	UBERON:0010533	61.31	gold quality
hair follicle	UBERON:0002073	60.99	silver quality
right coronary artery	UBERON:0001625	60.89	gold quality
right atrium auricular region	UBERON:0006631	60.22	gold quality
adult mammalian kidney	UBERON:0000082	59.90	gold quality
pancreas	UBERON:0001264	59.89	gold quality
thymus	UBERON:0002370	59.88	silver quality
gastrocnemius	UBERON:0001388	59.57	gold quality
body of pancreas	UBERON:0001150	59.44	gold quality
cardiac atrium	UBERON:0002081	59.33	gold quality
stromal cell of endometrium	CL:0002255	59.06	gold quality
left adrenal gland	UBERON:0001234	58.54	gold quality
left adrenal gland cortex	UBERON:0035825	57.74	gold quality
hindlimb stylopod muscle	UBERON:0004252	57.47	gold quality
secondary oocyte	CL:0000655	57.36	gold quality
pancreatic ductal cell	CL:0002079	57.33	silver quality
lower esophagus mucosa	UBERON:0035834	57.26	gold quality
skin of leg	UBERON:0001511	56.91	gold quality
right adrenal gland	UBERON:0001233	56.45	gold quality
metanephros	UBERON:0000081	56.12	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	273926.00
E-MTAB-6701	yes	100110.57
E-MTAB-9154	yes	54703.43
E-HCAD-24	yes	52379.70
E-HCAD-23	yes	31772.53
E-MTAB-10018	yes	22696.04
E-MTAB-3929	yes	5732.19
E-ANND-5	yes	1121.45
E-ANND-3	yes	3.74
E-MTAB-8060	no	198674.98

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NOTCH1	Activation

Upstream regulators (CollecTRI, top): AR, ASCL1, ATF1, ATF2, CREB1, DLX3, EGR1, ETS1, ETS2, FOXL2, GATA2, HESX1, JUN, LHX2, LHX3, LHX4, MSX1, NANOG, NCOR1, NFATC4, NFYA, NR3C1, NR5A1, OTX1, POU1F1, POU5F1, PROP1, SP1, TFAP2A, TFAP2C, THRA, THRB

miRNA regulators (miRDB)

27 targeting CGA, 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-12118	100.00	65.88	1270
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4499	99.62	67.29	1470
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914
HSA-MIR-1183	98.75	67.10	1116
HSA-MIR-508-3P	98.66	69.62	887
HSA-MIR-4463	98.56	66.05	1071
HSA-MIR-6516-5P	98.42	70.19	1551
HSA-MIR-4511	98.32	67.97	1500
HSA-MIR-1285-5P	98.01	68.71	779
HSA-MIR-34A-3P	96.80	67.70	805
HSA-MIR-1298-5P	95.96	64.81	573
HSA-MIR-362-5P	95.87	66.02	554
HSA-MIR-500B-5P	95.87	66.04	557

Literature-anchored findings (GeneRIF, showing 40)

• The ISOBM TD-7 Workshop on hCG and related molecules. Towards user-oriented standardization of pregnancy and tumor diagnosis (PMID:11893904)
• Review. The Asn52 and Asn78 glycosylation variants of human pituitary FSHA exhibit differential and divergent effects at the target cell level and that less sialylated, short-lived variants may exert significant effects in in vivo conditions. (PMID:11900895)
• Transcriptional regulation of the human glycoprotein hormone common alpha subunit gene by cAMP-response-element-binding protein (CREB)-binding protein (CBP)/p300 and p53. (PMID:12164786)
• Serum HCG beta, CA 72-4 and CEA are independent prognostic factors in colorectal cancer. (PMID:12237895)
• Expressed in human decidual tissue in patients during tubal pregnancy (PMID:12569177)
• Degree of alterations in maternal serum hCG and alpha-fetoprotein levels varied between fresh and frozen-thawed embryos and also between mode of fertilization. (PMID:12615827)
• induction of alphaGSU gene expression by peptide hormone signaling is coupled directly to the posttranslational status of SF-1 (PMID:12920232)
• Exposure of male mice to chronically elevated levels of hCG severely affects their urogenital tract function at multiple sites and causes infertility, but, unlike in LH/hCG overexpressing female mice, it is not tumorigenic. (PMID:12960071)
• x-ray crystallographic analysis shows that the FSH beta subunit is close to the N-terminal region and the alpha subunit is projected toward exoloop 3 in the endodomain (PMID:12963710)
• pituitary exit of LH and FSH occur via different secretion pathways, and are released spatially from the pituitary via different circulatory routes. (PMID:14585810)
• Human chorionic gonadotropin does not induce HOXA10 in Ishikawa cells. (PMID:14607569)
• LH and FSH have a dual effect on the cultured rat preovulatory follicle: an antiapoptotic effect on granulosa cells and a proapoptotic effect on theca-interstitial cells. (PMID:14726442)
• Decrease in molecular weight of dimeric chimeras digested with endoglycosidase-F was greater in Calpha than that in alphaC after treatment with neuraminidase, revealing that both chimeras have different numbers of sialic acids on O-linked carbohydrates. (PMID:15004409)
• contacts between the small seatbelt loop of alpha-human choriogonadotropin and the lutropin receptor involve its backbone atoms and possibly the side chain of residue betaAsp-99 (PMID:15304512)
• hCGalpha subunit gene activity is regulated by cAMP, which involves the binding of CREB and Ets-2 to discrete elements in the promoter as well as a physical interaction between the two proteins. (PMID:15637148)
• Overexpression of HCG alpha is associated with adenoma formation (PMID:16007123)
• The HCG profile is indicative of viable pregnancies conceived by in vitro fertilization. (PMID:16311298)
• There were no day/night differences in mean free alpha-subunit in younger or older post-menopausal women or in free alpha-subunit pulse frequency or amplitude (PMID:16461985)
• the Gly residue at site X(3) (G(3)) in the CXGXC motif of hCG is essential for heterodimer formation of glycoprotein hormones (PMID:16543672)
• The present findings indicate that the concentration of human placental lactogen (hPL) and human chorionic gonadotropin (beta hCG) mRNA is significantly higher in the cellular component of maternal blood samples than in the plasma component. (PMID:16950818)
• The strategy to produce a soluble FSH-FSHR complex that involves the co-secretion of a truncated FSHR ectodomain (FSHR(HB)) and a covalently linked FSHalphabeta heterodimer, is described. (PMID:17045735)
• hCGalpha is not derived from heterodimeric glycoprotein hormones suggesting hCG-independent functions of hCGalpha and hCGbeta in male and female fertility. (PMID:17097221)
• Chorionic gonadotropin produced during pregnancy could induce the biosynthesis of VEGF and by this means stimulate the development of breast cancer cells during pregnancy. (PMID:17112680)
• The approach of fusing the alpha and beta subunits of human Chorionic Gonadotropin (hCG) to produce a single chain hormone (phCGalphabeta) was used to investigate roles of critical residues of the alpha subunit in hormone receptor interaction. (PMID:17143726)
• characterization of the hourly secretion profile of hCG in early pregnancy after donor artificial insemination (PMID:17261286)
• The studies demonstrate the formation, in vivo dynamics of GPHalpha alpha homodimers, and the pathways of the cellular metabolism of variants of GPHalpha, monoglycosylated GPHalpha and large free GPHalpha. (PMID:17609437)
• Recombinant hCG overcomes in vitro the Trisomy 21 phenotype, allowing cytotrophoblasts to fuse and form a large syncytiotrophoblast. (PMID:17690166)
• Data shows that the GPHalpha in the hCG alphabeta-heterodimers decelerates the maturation of the hCGbeta portion in the heterodimer complex. (PMID:17761764)
• Endometrial IGF-I and -II are differentially regulated during decidualization and by human chorionic gonadotropin. (PMID:18022169)
• Chorionic gonadotropin promotes trophoblast invasion and migration through activation of ERK and AKT signaling involving their downstream effector MMP-2. (PMID:18063683)
• Follitropin beta and, more precisely, follitropin alfa suppress the spectral components and power of the myoelectrical signals, which provides uterine quiescence. (PMID:18068163)
• Gq- or G(s)-coupled receptors other than the classical GnRH receptor may play a role in the regulation of nonpituitary, nonplacental GPHalpha secretion under physiological and pathological conditions. (PMID:18079192)
• PI3-kinase may be involved in the negative regulation of alpha- and FSHbeta-subunit gene expression as well as cell proliferation. (PMID:18206295)
• Data show that mutations of the lutropin/choriogonadotropin receptor that do not activate the phosphoinositide cascade allow hCG to induce aromatase expression in immature rat granulosa cells. (PMID:18313839)
• Ghrelin suppresses the secretion of FSH in humans. (PMID:19054012)
• GnRH regulation of Jun transcription and its targets such as Cga, requires a functional interaction between TCF/LEF and beta-catenin. (PMID:19131506)
• FSH acts directly and indirectly to induce rapid changes in Sertoli cell and Leydig cell transcript levels in the hpg mouse but that effects on germ cell development must occur over a longer time-span. (PMID:19136570)
• The mannose receptor and hCG were colocalized on the surface of uterine natural killer cells. (PMID:19196802)
• Follitropin alfa FbM, a technologically modified formulation of r-hFSH, is as safe as follitropin alfa FbIU but requires a smaller dose over a shorter period to produce more oocytes and final embryos.(Review/Meta-analysis) (PMID:19344190)
• The utility of the tumour markers carcinoembryonic antigen, cancer antigen 125, carbohydrate antigen 19-9, carbohydrate antigen 15-3, alpha-fetoprotein and human chorionic gonadotropin for the diagnosis solitary pulmonary nodules, was investigated. (PMID:19383238)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cga	ENSDARG00000040479
danio_rerio	CGA	ENSDARG00000103345
mus_musculus	Cga	ENSMUSG00000028298
rattus_norvegicus	Cga	ENSRNOG00000009269

Protein

Protein identifiers

Glycoprotein hormones alpha chain — P01215 (reviewed: P01215)

Alternative names: Anterior pituitary glycoprotein hormones common subunit alpha, Choriogonadotropin alpha chain, Chorionic gonadotrophin subunit alpha, Follicle-stimulating hormone alpha chain, Follitropin alpha chain, Luteinizing hormone alpha chain, Lutropin alpha chain, Thyroid-stimulating hormone alpha chain, Thyrotropin alpha chain

All UniProt accessions (6): A0A087WYZ4, A0A0D9SFJ6, A0A0D9SGA7, A0A0R4J2F0, P01215, Q6I9S8

UniProt curated annotations — full annotation on UniProt →

Function. Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH, follitropin/follicle stimulating hormone/FSH and choriogonadotropin/CG. These hormones bind specific receptors on target cells that in turn activate downstream signaling pathways.

Subunit / interactions. Heterodimer. The active hormones thyrotropin, lutropin, follitropin and choriogonadotropin are heterodimers composed of CGA, a common alpha chain described here and a unique beta chain which confers their biological specificity to the hormones: TSHB for thyrotropin, LHB for lutropin, FSHB for follitropin and choriogonadotropin subunit beta/CGB for choriogonadotropin.

Subcellular location. Secreted.

Similarity. Belongs to the glycoprotein hormones subunit alpha family.

RefSeq proteins (2): NP_000726, NP_001239312 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000476	Glyco_hormone	Family
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00236

UniProt features (21 total): strand 7, disulfide bond 5, sequence conflict 2, helix 2, glycosylation site 2, signal peptide 1, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
9YXD	X-RAY DIFFRACTION	2.29
7UTZ	ELECTRON MICROSCOPY	2.4
4AY9	X-RAY DIFFRACTION	2.5
1HCN	X-RAY DIFFRACTION	2.6
8I2G	ELECTRON MICROSCOPY	2.8
4MQW	X-RAY DIFFRACTION	2.9
7T9I	ELECTRON MICROSCOPY	2.9
1XWD	X-RAY DIFFRACTION	2.92
7XW5	ELECTRON MICROSCOPY	2.96
1FL7	X-RAY DIFFRACTION	3
1HRP	X-RAY DIFFRACTION	3
7FIH	ELECTRON MICROSCOPY	3.2
1QFW	X-RAY DIFFRACTION	3.5
7FIG	ELECTRON MICROSCOPY	3.9
7FII	ELECTRON MICROSCOPY	4.3
1DZ7	SOLUTION NMR
1E9J	SOLUTION NMR
1HD4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P01215-F1	91.81	0.79

Antibody-complex structures (SAbDab): 6 — 1QFW, 7FIG, 7T9I, 7UTZ, 7XW5, 8I2G

Functional residue map

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

Disulfide bonds (5): 31–55, 34–84, 52–106, 56–108, 83–111

Glycosylation sites (2): 76, 102

Mutagenesis-validated functional residues (1):

Position	Phenotype
76	increases from 1 to 3 the number of fsh binding a single fshr receptor.

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-193048	Androgen biosynthesis
R-HSA-193993	Mineralocorticoid biosynthesis
R-HSA-209822	Glycoprotein hormones
R-HSA-209968	Thyroxine biosynthesis
R-HSA-375281	Hormone ligand-binding receptors
R-HSA-418555	G alpha (s) signalling events
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors
R-HSA-975578	Reactions specific to the complex N-glycan synthesis pathway

MSigDB gene sets: 217 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, MODULE_92, FREAC2_01, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, MODULE_64, GOBP_GROWTH, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_THYROID_HORMONE_METABOLIC_PROCESS, LHX3_01, PID_REG_GR_PATHWAY, NAGASHIMA_NRG1_SIGNALING_UP, CHX10_01, KORKOLA_CHORIOCARCINOMA

GO Biological Process (18): thyroid hormone generation (GO:0006590), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cell population proliferation (GO:0008284), hormone-mediated signaling pathway (GO:0009755), regulation of signaling receptor activity (GO:0010469), positive regulation of steroid biosynthetic process (GO:0010893), positive regulation of cell migration (GO:0030335), thyroid gland development (GO:0030878), luteinizing hormone secretion (GO:0032275), organ growth (GO:0035265), follicle-stimulating hormone signaling pathway (GO:0042699), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of organ growth (GO:0046621), follicle-stimulating hormone secretion (GO:0046884), signal transduction (GO:0007165), gonad development (GO:0008406), cellular response to hormone stimulus (GO:0032870), developmental growth (GO:0048589)

GO Molecular Function (3): hormone activity (GO:0005179), follicle-stimulating hormone activity (GO:0016913), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), Golgi lumen (GO:0005796), follicle-stimulating hormone complex (GO:0016914), pituitary gonadotropin complex (GO:0061696)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Metabolism of steroid hormones	2
Peptide hormone biosynthesis	1
Metabolism of amine-derived hormones	1
Class A/1 (Rhodopsin-like receptors)	1
GPCR downstream signalling	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1
N-glycan antennae elongation in the medial/trans-Golgi	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
signal transduction	2
gonadotropin secretion	2
thyroid hormone metabolic process	1
G protein-coupled receptor activity	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cellular response to hormone stimulus	1
regulation of signal transduction	1
signaling receptor activity	1
regulation of molecular function	1
steroid biosynthetic process	1
positive regulation of steroid metabolic process	1
positive regulation of lipid biosynthetic process	1
regulation of steroid biosynthetic process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
endocrine system development	1
gland development	1
multicellular organismal process	1
developmental growth	1
ovarian follicle development	1
G protein-coupled receptor signaling pathway	1
ovulation cycle process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
organ growth	1
regulation of organ growth	1
negative regulation of developmental growth	1
negative regulation of multicellular organismal process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
development of primary sexual characteristics	1
animal organ development	1
reproductive structure development	1

Protein interactions and networks

STRING

1160 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CGA	TSHB	P01222	981
CGA	GPHA2	Q96T91	955
CGA	CGB5	P01233	941
CGA	GPHB5	Q86YW7	886
CGA	FSHB	P01225	876
CGA	K7ELM3	K7ELM3	824
CGA	FSHR	P23945	808
CGA	SUCLG2	Q96I99	778
CGA	HARS1	P12081	761
CGA	HARS2	P49590	761
CGA	PIK3C3	Q8NEB9	688
CGA	GPR4	P46093	674
CGA	LHCGR	P22888	609
CGA	CSH1	P01243	592
CGA	CSH1	P01243	585

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CGA	FSHB	psi-mi:“MI:0407”(direct interaction)	0.760
FSHB	CGA	psi-mi:“MI:0915”(physical association)	0.760
FSHB	CGA	psi-mi:“MI:0407”(direct interaction)	0.760
CGA	CGB5	psi-mi:“MI:0407”(direct interaction)	0.590
CGA	CGB5	psi-mi:“MI:0915”(physical association)	0.590
PTPN12	CGA	psi-mi:“MI:0915”(physical association)	0.370
CGA	TRIO	psi-mi:“MI:0914”(association)	0.350
PTN	CGA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (27): CGA (Reconstituted Complex), PTN (Two-hybrid), FSHB (Co-crystal Structure), CGA (Affinity Capture-Western), BCKDHA (Affinity Capture-MS), MTMR12 (Affinity Capture-MS), RNF166 (Affinity Capture-MS), FN1 (Affinity Capture-MS), MTM1 (Affinity Capture-MS), EIF2AK3 (Affinity Capture-MS), ATP6V1G2 (Affinity Capture-MS), RBM22 (Affinity Capture-MS), PPT2 (Affinity Capture-MS), RNF114 (Affinity Capture-MS), ERLEC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2P1BSU3, A1BN60, A7VN14, A7VN15, A7VN16, A7VN17, B3F211, O02826, O08540, O42146, O57340, O97935, O97936, O97949, P01001, P01215, P01220, P01225, P01226, P01228, P04155, P08118, P0C552, P0C553, P0DKR6, P0DQG7, P16035, P16368, P25142, P49122, P58062, P83242, P97580, Q28767, Q2PUH2, Q3HRV5, Q3YC03, Q53B52, Q63467, Q863T4

Diamond homologs: O46642, P01215, P01216, P01217, P01218, P01219, P01220, P01221, P07474, P11962, P12836, P13152, P18857, P22762, P25329, P27794, P30970, P30983, P37036, P37037, P37204, P47744, P51499, P53542, P68241, P68242, P68267, P68268, P69062, P69063, P80051, P80665, Q19PY8, Q28365, Q3HRV5, Q3YC03, Q52R91, Q6YNX4, Q8HZS0, Q8JIE9

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
NANOG	“down-regulates quantity by repression”	CGA	“transcriptional regulation”
CGA	“form complex”	TSH	binding
LHX3	“up-regulates quantity by expression”	CGA	“transcriptional regulation”
CGA	up-regulates	TSHR	binding
LHX2	“up-regulates quantity by expression”	CGA	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

461 predictions. Top by Δscore:

Variant	Effect	Δscore
6:87086248:AC:A	donor_gain	1.0000
6:87086249:CC:C	donor_gain	1.0000
6:87088089:TGA:T	donor_gain	1.0000
6:87088111:AC:A	donor_gain	1.0000
6:87088112:CC:C	donor_gain	1.0000
6:87088220:A:C	acceptor_gain	1.0000
6:87088012:A:AC	donor_gain	0.9900
6:87088013:C:CC	donor_gain	0.9900
6:87088059:CAT:C	donor_gain	0.9900
6:87088061:T:TA	donor_gain	0.9900
6:87088078:T:TA	donor_gain	0.9900
6:87088224:C:CT	acceptor_gain	0.9900
6:87088225:A:T	acceptor_gain	0.9900
6:87085831:GACC:G	acceptor_loss	0.9800
6:87085832:ACC:A	acceptor_loss	0.9800
6:87085834:CT:C	acceptor_loss	0.9800
6:87086321:TGG:T	donor_gain	0.9800
6:87088086:A:AC	donor_gain	0.9800
6:87088087:C:CC	donor_gain	0.9800
6:87088108:CGCA:C	donor_loss	0.9800
6:87088110:CA:C	donor_loss	0.9800
6:87088219:CA:C	acceptor_gain	0.9800
6:87088220:A:AC	acceptor_gain	0.9800
6:87088106:CACG:C	donor_loss	0.9700
6:87088107:ACGC:A	donor_loss	0.9700
6:87095007:TATTA:T	donor_loss	0.9700
6:87095009:TTACC:T	donor_loss	0.9700
6:87095010:TACC:T	donor_loss	0.9700
6:87095012:C:CT	donor_loss	0.9700
6:87086244:TCTTA:T	donor_loss	0.9600

AlphaMissense

758 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:87086363:C:A	G54C	1.000
6:87085774:A:C	C111W	0.999
6:87085775:C:T	C111Y	0.999
6:87086271:A:C	C84W	0.999
6:87086272:C:G	C84S	0.999
6:87086272:C:T	C84Y	0.999
6:87086273:A:T	C84S	0.999
6:87086274:G:C	C83W	0.999
6:87086275:C:G	C83S	0.999
6:87086275:C:T	C83Y	0.999
6:87086276:A:T	C83S	0.999
6:87086355:G:C	C56W	0.999
6:87086363:C:G	G54R	0.999
6:87086367:G:C	C52W	0.999
6:87086368:C:G	C52S	0.999
6:87086369:A:T	C52S	0.999
6:87085775:C:A	C111F	0.998
6:87085775:C:G	C111S	0.998
6:87085776:A:G	C111R	0.998
6:87085776:A:T	C111S	0.998
6:87085789:G:C	C106W	0.998
6:87085790:C:G	C106S	0.998
6:87085790:C:T	C106Y	0.998
6:87085791:A:T	C106S	0.998
6:87086272:C:A	C84F	0.998
6:87086273:A:G	C84R	0.998
6:87086275:C:A	C83F	0.998
6:87086276:A:G	C83R	0.998
6:87086288:A:G	S79P	0.998
6:87086298:C:A	K75N	0.998

dbSNP variants (sampled 300 via entrez): RS1000087058 (6:87088358 T>C), RS1000517628 (6:87091572 G>A,C), RS1000547065 (6:87091199 G>A,T), RS1001045094 (6:87085315 A>G), RS1001057817 (6:87085029 A>C), RS1001198903 (6:87094295 G>A), RS1001229918 (6:87094071 A>T), RS1001332093 (6:87089100 C>G), RS1001730548 (6:87088005 A>C,G,T), RS1002258841 (6:87086314 G>A,C), RS1002432663 (6:87095238 C>T), RS1002597061 (6:87095638 C>T), RS1002879794 (6:87089301 C>T), RS1003013872 (6:87090250 C>A), RS1003430342 (6:87085242 A>T)

Disease associations

OMIM: gene MIM:118850 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006061_42	Atrial fibrillation	1.000000e-08
GCST006414_117	Atrial fibrillation	1.000000e-10
GCST007673_14	3-month functional outcome in ischaemic stroke (modified Rankin score)	8.000000e-07
GCST010653_27	Thyroid stimulating hormone levels	2.000000e-17

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009603	stroke outcome severity measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2146305 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Progesterone	affects cotreatment, increases secretion, decreases reaction, affects reaction, affects secretion (+2 more)	10
Cyclic AMP	increases secretion, affects cotreatment, increases abundance, increases activity, increases reaction (+3 more)	7
Testosterone	affects abundance, affects cotreatment, increases reaction, decreases reaction, increases secretion (+1 more)	7
Diethylhexyl Phthalate	affects cotreatment, decreases expression, increases expression, increases secretion, increases abundance (+3 more)	4
Estradiol	affects abundance, affects cotreatment, increases abundance, increases expression, decreases reaction	4
Valproic Acid	increases expression, affects cotreatment	4
mono-(2-ethylhexyl)phthalate	increases expression, increases secretion, affects expression, decreases reaction, increases abundance	3
butylbenzyl phthalate	affects expression, affects reaction, decreases expression, increases secretion, increases abundance (+3 more)	3
Benzo(a)pyrene	affects methylation, decreases reaction, increases abundance, increases expression	3
Dibutyl Phthalate	affects reaction, increases expression, decreases reaction, affects cotreatment, affects expression (+3 more)	3
Colforsin	increases abundance, increases reaction, increases expression, increases secretion, decreases reaction	3
diethyl phthalate	increases abundance, affects cotreatment, affects expression, affects reaction, decreases expression (+2 more)	2
diisononyl phthalate	affects reaction, decreases expression, increases expression, decreases reaction, increases abundance (+2 more)	2
diisobutyl phthalate	increases expression, decreases reaction, increases abundance, affects cotreatment, affects expression (+2 more)	2
monobutyl phthalate	affects expression, increases expression	2
perfluorooctane sulfonic acid	decreases reaction, increases expression, decreases expression	2
mono-benzyl phthalate	affects expression, increases expression, increases secretion	2
T0901317	increases reaction, increases secretion, increases abundance, affects cotreatment, increases expression (+1 more)	2
fatostatin	affects cotreatment, increases expression, decreases reaction, increases reaction, decreases expression (+3 more)	2
Resveratrol	affects cotreatment, decreases expression, increases secretion, decreases reaction, increases expression	2
Fulvestrant	decreases reaction, increases secretion, increases expression	2
Atrazine	affects cotreatment, decreases reaction, increases expression	2
DDT	increases reaction, decreases reaction, increases abundance, increases secretion, increases activity	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Theophylline	decreases stability, increases reaction, increases stability, affects cotreatment, increases expression (+1 more)	2
8-Bromo Cyclic Adenosine Monophosphate	affects reaction, decreases expression, increases expression, decreases reaction, affects cotreatment (+1 more)	2
Dinoprostone	decreases reaction, increases secretion, increases abundance, affects cotreatment, affects reaction	2
Thapsigargin	increases expression	2
Butyric Acid	affects cotreatment, decreases reaction, increases reaction, decreases stability, increases expression	2
propionaldehyde	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 1 functional, 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2114913	Functional	PubChem BioAssay. qHTS for Activators of Integrin-Mediated Alleviation for Muscular Dystrophy. (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL4312715	Binding	Activity at human TSH at 10 uM	3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977), a Hypoxia-Inducible Factor 2α (HIF-2α) Inhibitor for the Treatment of Clear Cell Renal Cell Carcinoma. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_6618	CSMalphabeta1h	Cancer cell line	Female
CVCL_6619	CSMalphabeta6C	Cancer cell line	Female

Clinical trials (associated diseases)

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