CGB1

Summary

CGB1 (chorionic gonadotropin subunit beta 1, HGNC:16721) is a protein-coding gene on chromosome 19q13.33, encoding Choriogonadotropin subunit beta variant 1 (A6NKQ9).

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 CGB1 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 155 aa protein, translated from a different frame, is about the same size, and shares 98% identity with other CGB subunits.

Source: NCBI Gene 114335 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_033377

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16721
Approved symbol	CGB1
Name	chorionic gonadotropin subunit beta 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000267631
Ensembl biotype	protein_coding
OMIM	608823
Entrez	114335

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000301407, ENST00000601167

RefSeq mRNA: 2 — MANE Select: NM_033377 NM_001382421, NM_033377

CCDS: CCDS12751

Canonical transcript exons

ENST00000301407 — 3 exons

Exon	Start	End
ENSE00001682722	49036703	49036895
ENSE00002438035	49035569	49035900
ENSE00003516532	49036136	49036303

Expression profiles

Bgee: expression breadth broad, 68 present calls, max score 86.95.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.95	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.35	gold quality
body of pancreas	UBERON:0001150	51.96	gold quality
hindlimb stylopod muscle	UBERON:0004252	49.76	gold quality
duodenum	UBERON:0002114	48.73	gold quality
granulocyte	CL:0000094	47.51	silver quality
stromal cell of endometrium	CL:0002255	45.54	gold quality
pancreas	UBERON:0001264	44.45	gold quality
right uterine tube	UBERON:0001302	44.24	silver quality
fundus of stomach	UBERON:0001160	43.93	gold quality
mucosa of transverse colon	UBERON:0004991	40.15	silver quality
pituitary gland	UBERON:0000007	39.80	gold quality
descending thoracic aorta	UBERON:0002345	38.67	silver quality
body of stomach	UBERON:0001161	38.19	gold quality
skeletal muscle tissue	UBERON:0001134	38.03	gold quality
left adrenal gland cortex	UBERON:0035825	37.81	gold quality
stomach	UBERON:0000945	37.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	37.22	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
cortex of kidney	UBERON:0001225	36.40	gold quality
adenohypophysis	UBERON:0002196	36.22	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
left adrenal gland	UBERON:0001234	36.16	gold quality
adrenal tissue	UBERON:0018303	36.09	gold quality
right lung	UBERON:0002167	36.03	silver quality
metanephros cortex	UBERON:0010533	35.97	silver quality
mucosa of stomach	UBERON:0001199	35.90	silver quality
smooth muscle tissue	UBERON:0001135	35.64	silver quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	595.70
E-HCAD-24	yes	128.54
E-HCAD-5	yes	29.23
E-MTAB-8060	no	1132.82
E-ANND-3	no	0.33

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• 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)
• these data provide new insight into the roles and mechanisms of b-hCG in regulating Epithelial ovarian cancer (EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention. (PMID:30582718)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Gpb5	FBGN0063368

Paralogs (9): CGB2 (ENSG00000104818), LHB (ENSG00000104826), CGB3 (ENSG00000104827), FSHB (ENSG00000131808), TSHB (ENSG00000134200), GPHB5 (ENSG00000179600), CGB5 (ENSG00000189052), CGB7 (ENSG00000196337), CGB8 (ENSG00000213030)

Protein

Protein identifiers

Choriogonadotropin subunit beta variant 1 — A6NKQ9 (reviewed: A6NKQ9)

All UniProt accessions (2): A6NKQ9, K7ELM3

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.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NKQ9-1	1	yes
A6NKQ9-2	2

RefSeq proteins (2): NP_001369350, NP_203695* (*=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 (15 total): disulfide bond 6, splice variant 2, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NKQ9-F1	74.53	0.32

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): 88–140, 143–150, 59–107, 73–122, 76–160, 84–138

Glycosylation sites (2): 63, 80

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): CCTGTGA_MIR513, GOMF_SIGNALING_RECEPTOR_BINDING, GOMF_HORMONE_ACTIVITY, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, TAFAZZIN_TARGET_GENES, TERT_TARGET_GENES, BDP1_TARGET_GENES, CC2D1A_TARGET_GENES, GOMF_MOLECULAR_FUNCTION_ACTIVATOR_ACTIVITY, chr19q13

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

0 interactions, top by confidence (×1000):

IntAct

4 interactions, top by confidence:

A	B	Type	Score
CGB1	ZNRF2	psi-mi:“MI:0915”(physical association)	0.400
CGB1	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CGB2	CGB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): CGB1 (Affinity Capture-MS), CGB1 (Affinity Capture-MS), ZNRF2 (Affinity Capture-MS), CGB1 (Negative Genetic), CGB1 (Negative Genetic), CGB1 (Negative Genetic)

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

428 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49036132:TCACC:T	donor_loss	1.0000
19:49036133:CACCA:C	donor_loss	1.0000
19:49036134:A:AC	donor_gain	1.0000
19:49036134:ACCAT:A	donor_loss	1.0000
19:49036135:C:CC	donor_gain	1.0000
19:49035674:T:TA	donor_gain	0.9900
19:49036134:AC:A	donor_gain	0.9900
19:49036135:CC:C	donor_gain	0.9900
19:49036135:CCATG:C	donor_gain	0.9900
19:49036302:CT:C	acceptor_gain	0.9900
19:49036304:C:CC	acceptor_gain	0.9900
19:49035714:TGGG:T	donor_gain	0.9800
19:49035909:CG:C	acceptor_gain	0.9800
19:49035910:G:C	acceptor_gain	0.9800
19:49036300:GCCT:G	acceptor_gain	0.9800
19:49036300:GCCTC:G	acceptor_loss	0.9800
19:49036301:CCTC:C	acceptor_gain	0.9800
19:49036302:CTCTG:C	acceptor_loss	0.9800
19:49036303:TCTG:T	acceptor_loss	0.9800
19:49036304:C:T	acceptor_loss	0.9800
19:49036305:T:A	acceptor_loss	0.9800
19:49036535:A:AC	donor_gain	0.9700
19:49036536:C:CC	donor_gain	0.9700
19:49035691:A:AC	donor_gain	0.9600
19:49035908:CCG:C	acceptor_gain	0.9600
19:49035909:C:T	acceptor_gain	0.9600
19:49036135:CCA:C	donor_gain	0.9600
19:49036135:CCAT:C	donor_gain	0.9600
19:49036299:AGCCT:A	acceptor_gain	0.9600
19:49035912:G:C	acceptor_gain	0.9500

AlphaMissense

980 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000388115 (19:49038170 T>C), RS1000442863 (19:49038348 A>C), RS1002736778 (19:49036378 C>T), RS1002813143 (19:49036922 A>C), RS1003198893 (19:49036485 AC>A), RS1004259953 (19:49038611 C>A,T), RS1004580892 (19:49037598 CCG>C), RS1004590910 (19:49037860 C>A,G), RS1006251902 (19:49037034 G>A,C,T), RS1006262953 (19:49037077 G>A,C,T), RS1006593052 (19:49036667 C>G), RS1006650939 (19:49036829 C>A,G), RS1007445205 (19:49038637 C>A,T), RS1008654367 (19:49035407 C>T), RS1009046089 (19:49035210 G>C)

Disease associations

OMIM: gene MIM:608823 | 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

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases secretion, increases methylation, decreases reaction, increases expression	2
beta-lapachone	increases expression	1
27-hydroxycholesterol	decreases expression, decreases reaction	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases expression, decreases reaction	1
CGP 52608	affects binding, increases reaction	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
abrine	increases expression	1
5-amino-2-methylsulfanyl-4-(3-(2-morpholin-4-ylacetylamino)phenyl)thieno(2,3-d)pyrimidine-6-carboxylic acid tert-butylamide	affects binding	1
Resveratrol	affects cotreatment, decreases expression	1
Pioglitazone	increases expression	1
Benzo(a)pyrene	increases methylation	1
Colforsin	increases expression, increases secretion, decreases reaction	1
Niclosamide	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Asbestos, Serpentine	increases expression	1
beta-Naphthoflavone	decreases expression	1

Clinical trials (associated diseases)

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