CGB2

Summary

CGB2 (chorionic gonadotropin subunit beta 2, HGNC:16722) is a protein-coding gene on chromosome 19q13.33, encoding Choriogonadotropin subunit beta variant 2 (Q6NT52).

The beta subunit of chorionic gonadotropin (CGB) is encoded by six highly homologous and structurally similar genes that are arranged in tandem and inverted pairs on chromosome 19q13.3, and contiguous with the luteinizing hormone beta (LHB) subunit gene. The CGB genes are primarily distinguished by differences in the 5’ untranscribed region. This gene was originally thought to be one of the two pseudogenes (CGB1 and CGB2) of CGB subunit, however, detection of CGB1 and CGB2 transcripts in vivo, and their presence on the polysomes, suggested that these transcripts are translated. To date, a protein product corresponding to CGB2 has not been isolated. The deduced sequence of the hypothetical protein of 132 aa does not share any similarity with that of functional CGB subunits (PMID:8954017). However, a 163 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits.

Source: NCBI Gene 114336 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• MANE Select transcript: NM_033378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16722
Approved symbol	CGB2
Name	chorionic gonadotropin subunit beta 2
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000104818
Ensembl biotype	protein_coding
OMIM	608824
Entrez	114336

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000359342, ENST00000474913

RefSeq mRNA: 2 — MANE Select: NM_033378 NM_001319065, NM_033378

CCDS: CCDS12750

Canonical transcript exons

ENST00000359342 — 3 exons

Exon	Start	End
ENSE00001710927	49031890	49032104
ENSE00002474564	49032907	49033238
ENSE00003528686	49032504	49032671

Expression profiles

Bgee: expression breadth broad, 42 present calls, max score 94.51.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.68	gold quality
right testis	UBERON:0004534	44.81	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.46	gold quality
putamen	UBERON:0001874	42.06	gold quality
skeletal muscle tissue	UBERON:0001134	41.86	silver quality
left testis	UBERON:0004533	41.59	gold quality
testis	UBERON:0000473	41.48	gold quality
placenta	UBERON:0001987	40.09	gold quality
caudate nucleus	UBERON:0001873	38.88	gold quality
apex of heart	UBERON:0002098	38.45	silver quality
Ammon’s horn	UBERON:0001954	37.78	gold quality
muscle tissue	UBERON:0002385	37.30	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
hypothalamus	UBERON:0001898	36.98	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	36.44	gold quality
nucleus accumbens	UBERON:0001882	36.20	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
mucosa of stomach	UBERON:0001199	36.14	silver quality
gastrocnemius	UBERON:0001388	35.58	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle of leg	UBERON:0001383	35.38	gold quality
pituitary gland	UBERON:0000007	33.47	gold quality
skin of abdomen	UBERON:0001416	32.91	gold quality
zone of skin	UBERON:0000014	32.62	gold quality
amygdala	UBERON:0001876	32.47	gold quality
temporal lobe	UBERON:0001871	32.46	gold quality
skin of leg	UBERON:0001511	32.34	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.63

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• In silico prediction of putative transcription factor binding sites supports the hypothesis that CGB1 and CGB2 gene products are expressed in, and may contribute to, implantation and placental development. (PMID:17055150)
• The presence of CGB1 and CGB2 transcripts in 41% of analyzed ovarian cancer cases, is reported. (PMID:23774837)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Gpb5	FBGN0063368

Paralogs (9): LHB (ENSG00000104826), CGB3 (ENSG00000104827), FSHB (ENSG00000131808), TSHB (ENSG00000134200), GPHB5 (ENSG00000179600), CGB5 (ENSG00000189052), CGB7 (ENSG00000196337), CGB8 (ENSG00000213030), CGB1 (ENSG00000267631)

Protein

Protein identifiers

Choriogonadotropin subunit beta variant 2 — Q6NT52 (reviewed: Q6NT52)

All UniProt accessions (2): Q6NT52, M0R0E6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expressed in placenta, testis and pituitary.

Miscellaneous. Encoded by a cluster of genes that have evolved by duplication from LHB. HCG-beta is encoded by six non-allelic genes (CGB) clustered on chromosome 19q13.3 and named CGB1, CGB2, CGB3, CGB5, CGB7 and CGB8. Two specific hCGb proteins that differ by three amino acids in positions 2,4 and 117 have been described: type 1 (CGB7) and type 2 (CGB3, CGB5, CGB8). The CGB gene first arose in the common ancestor of the anthropoid primates.

Similarity. Belongs to the glycoprotein hormones subunit beta family.

RefSeq proteins (2): NP_001305994, NP_203696* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001545	Gonadotropin_bsu	Family
IPR006208	Glyco_hormone_CN	Domain
IPR018245	Gonadotropin_bsu_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00007

UniProt features (12 total): disulfide bond 6, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6NT52-F1	78.22	0.41

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 (6): 56–108, 111–118, 27–75, 41–90, 44–128, 52–106

Glycosylation sites (2): 31, 48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): CCTGTGA_MIR513, GGARNTKYCCA_UNKNOWN, TGGNNNNNNKCCAR_UNKNOWN, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_HORMONE_ACTIVITY, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, DIDO1_TARGET_GENES, KAT2A_TARGET_GENES, SKIL_TARGET_GENES, TERT_TARGET_GENES, ZFHX3_TARGET_GENES, BDP1_TARGET_GENES, CC2D1A_TARGET_GENES, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY

GO Biological Process (2): G protein-coupled receptor signaling pathway (GO:0007186), signal transduction (GO:0007165)

GO Molecular Function (2): hormone activity (GO:0005179), signaling receptor binding (GO:0005102)

GO Cellular Component (3): obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
G protein-coupled receptor activity	1
signal transduction	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
receptor ligand activity	1
protein binding	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

224 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CGB2	ACTL7A	Q9Y615	507
CGB2	ODF4	Q2M2E3	446
CGB2	MAGEB4	O15481	396
CGB2	ETS2	P15036	355
CGB2	TSGA10	Q9BZW7	348
CGB2	CIMAP1A	Q96PU9	302
CGB2	RUVBL2	Q9Y230	287
CGB2	INSL4	Q14641	270
CGB2	PASD1	Q8IV76	269
CGB2	SPATA19	Q7Z5L4	268
CGB2	CSH1	P01243	258
CGB2	KCNA7	Q96RP8	251
CGB2	OIP5	O43482	250
CGB2	CSH1	P01243	248
CGB2	AURKC	Q9UQB9	246

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CGB2	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CGB2	CGB1	psi-mi:“MI:0914”(association)	0.350
CGB2	PMPCB	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A6NKQ9, B1AWI6, G7PWZ3, I6M4H4, O09108, O46482, O46483, O46641, O77805, O77835, P01229, P01230, P01231, P01232, P04651, P07434, P08751, P0DN86, P0DN87, P17490, P19794, P27767, P30984, P43021, P45646, P45657, P51500, Q04997, Q1L6U9, Q2Q1P0, Q2Q1P1, Q2Q1P2, Q3HRV3, Q3S2X5, Q6EV78, Q6HA10, Q6NT52, Q6PX77, Q7ZZV4, Q8CB67

Diamond homologs: A1BN60, A1BN61, A6NKQ9, O09108, O13050, O46430, O46482, O46483, O46641, O57340, O73824, O77805, O77835, P01222, P01223, P01224, P01225, P01226, P01227, P01228, P01229, P01230, P01231, P01232, P01235, P04651, P04652, P04837, P07434, P07732, P08751, P0DN86, P0DN87, P10256, P10257, P12656, P12837, P18427, P19794, P25330

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	31
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

286 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49032498:TCCCA:T	acceptor_loss	1.0000
19:49032499:CCCAG:C	acceptor_loss	1.0000
19:49032500:CCAGG:C	acceptor_loss	1.0000
19:49032501:CAGGG:C	acceptor_loss	1.0000
19:49032502:A:C	acceptor_loss	1.0000
19:49032503:G:GC	acceptor_loss	1.0000
19:49032672:G:GG	donor_gain	1.0000
19:49032672:GT:G	donor_loss	1.0000
19:49032673:T:A	donor_loss	1.0000
19:49032271:G:GG	donor_gain	0.9900
19:49032502:AG:A	acceptor_gain	0.9900
19:49032503:GG:G	acceptor_gain	0.9900
19:49032667:CCATG:C	donor_gain	0.9900
19:49032670:TG:T	donor_gain	0.9900
19:49032671:GG:G	donor_gain	0.9900
19:49032897:C:G	acceptor_gain	0.9900
19:49032502:A:AG	acceptor_gain	0.9800
19:49032502:AGG:A	acceptor_gain	0.9800
19:49032502:AGGG:A	acceptor_gain	0.9800
19:49032503:G:GG	acceptor_gain	0.9800
19:49032503:GGG:G	acceptor_gain	0.9800
19:49032503:GGGG:G	acceptor_gain	0.9800
19:49032669:ATG:A	donor_gain	0.9800
19:49032674:GAGCT:G	donor_loss	0.9800
19:49032894:ACAC:A	acceptor_gain	0.9800
19:49032896:AC:A	acceptor_gain	0.9800
19:49032896:ACG:A	acceptor_gain	0.9800
19:49032897:C:CA	acceptor_gain	0.9800
19:49032898:G:A	acceptor_gain	0.9800
19:49032668:CATG:C	donor_gain	0.9700

AlphaMissense

1025 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49032952:T:A	C75S	0.996
19:49032953:G:A	C75Y	0.996
19:49032953:G:C	C75S	0.996
19:49032654:G:T	G54C	0.995
19:49032649:G:A	C52Y	0.994
19:49032648:T:A	C52S	0.993
19:49032649:G:C	C52S	0.993
19:49032650:T:G	C52W	0.993
19:49032997:T:A	C90S	0.993
19:49032998:G:C	C90S	0.993
19:49033046:G:A	C106Y	0.993
19:49032952:T:C	C75R	0.992
19:49032953:G:T	C75F	0.992
19:49032959:A:G	Y77C	0.992
19:49033045:T:A	C106S	0.992
19:49033046:G:C	C106S	0.992
19:49033060:T:A	C111S	0.992
19:49033061:G:C	C111S	0.992
19:49033081:T:A	C118S	0.992
19:49033082:G:C	C118S	0.992
19:49032573:T:A	C27S	0.991
19:49032574:G:C	C27S	0.991
19:49032954:C:G	C75W	0.991
19:49033047:T:G	C106W	0.991
19:49032648:T:C	C52R	0.990
19:49032660:T:A	C56S	0.990
19:49032661:G:C	C56S	0.990
19:49032974:T:G	F82C	0.990
19:49032615:T:A	C41S	0.989
19:49032616:G:C	C41S	0.989

dbSNP variants (sampled 300 via entrez): RS1000447906 (19:49031911 C>A), RS1001724214 (19:49031721 C>G,T), RS1002007268 (19:49030785 A>G), RS1003520882 (19:49032911 G>A,C,T), RS1003734032 (19:49030256 T>C), RS1004088235 (19:49030163 A>G), RS1005514294 (19:49031733 C>G,T), RS1005852474 (19:49031172 C>A,G,T), RS1005905010 (19:49031332 C>G), RS1006801131 (19:49033659 G>A), RS1008419223 (19:49032255 A>C,G,T), RS1008476090 (19:49032371 G>A,C), RS1010371713 (19:49031579 A>G), RS1010466592 (19:49031686 A>C,G,T), RS1010803595 (19:49030769 G>A,C,T)

Disease associations

OMIM: gene MIM:608824 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ethyl-p-hydroxybenzoate	decreases expression	1
beta-lapachone	increases expression	1
norfluoxetine	increases expression	1
CGP 52608	affects binding, increases reaction	1
enniatins	increases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Estradiol	affects cotreatment, increases expression	1
Colforsin	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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