CGB8

Summary

CGB8 (chorionic gonadotropin subunit beta 8, HGNC:16453) is a protein-coding gene on chromosome 19q13.33, encoding Choriogonadotropin subunit beta 3 (P0DN86). Beta subunit of the human chorionic gonadotropin (hCG). hCG is a complex glycoprotein composed of two glycosylated subunits alpha and beta which are non-covalently associated.

This gene is a member of the glycoprotein hormone beta chain family and encodes the beta 8 subunit of chorionic gonadotropin (CG). Glycoprotein hormones are heterodimers consisting of a common alpha subunit and an unique beta subunit which confers biological specificity. CG is produced by the trophoblastic cells of the placenta and stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy. The beta subunit of CG is encoded by 6 genes which are arranged in tandem and inverted pairs on chromosome 19q13.3 and contiguous with the luteinizing hormone beta subunit gene.

Source: NCBI Gene 94115 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 55 total
• MANE Select transcript: NM_033183

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16453
Approved symbol	CGB8
Name	chorionic gonadotropin subunit beta 8
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000213030
Ensembl biotype	protein_coding
OMIM	608827
Entrez	94115

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000448456, ENST00000933082

RefSeq mRNA: 1 — MANE Select: NM_033183 NM_033183

CCDS: CCDS12753

Canonical transcript exons

ENST00000448456 — 3 exons

Exon	Start	End
ENSE00002502852	49048205	49048372
ENSE00002534829	49047638	49047969
ENSE00002799764	49048725	49049111

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 81.71.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
placenta	UBERON:0001987	81.71	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.76	gold quality
pituitary gland	UBERON:0000007	45.67	gold quality
skeletal muscle tissue	UBERON:0001134	38.90	gold quality
adenohypophysis	UBERON:0002196	38.19	gold quality
sural nerve	UBERON:0015488	37.43	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
muscle tissue	UBERON:0002385	37.04	silver quality
right uterine tube	UBERON:0001302	36.53	silver quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
bone marrow	UBERON:0002371	32.79	gold quality
duodenum	UBERON:0002114	32.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
smooth muscle tissue	UBERON:0001135	31.34	gold quality
prefrontal cortex	UBERON:0000451	30.34	silver quality
adrenal tissue	UBERON:0018303	30.29	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	29.75	gold quality
body of pancreas	UBERON:0001150	29.31	gold quality
vermiform appendix	UBERON:0001154	29.14	gold quality
skin of leg	UBERON:0001511	29.03	gold quality
pancreas	UBERON:0001264	29.00	gold quality
muscle of leg	UBERON:0001383	28.71	gold quality
tonsil	UBERON:0002372	28.66	gold quality
zone of skin	UBERON:0000014	28.62	gold quality
gastrocnemius	UBERON:0001388	28.06	gold quality
skin of abdomen	UBERON:0001416	27.86	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-7407	yes	31721.10
E-HCAD-24	yes	18347.85
E-MTAB-10018	yes	2586.04
E-HCAD-23	yes	1208.05
E-MTAB-8221	yes	105.36
E-HCAD-5	yes	29.23
E-MTAB-8060	no	37643.41
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

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), CGB1 (ENSG00000267631)

Protein

Protein identifiers

Choriogonadotropin subunit beta 3 — P0DN86 (reviewed: P0DN86)

Alternative names: Choriogonadotropin subunit beta, Chorionic gonadotropin chain beta

All UniProt accessions (2): A0A0F7RQP8, P0DN86

UniProt curated annotations — full annotation on UniProt →

Function. Beta subunit of the human chorionic gonadotropin (hCG). hCG is a complex glycoprotein composed of two glycosylated subunits alpha and beta which are non-covalently associated. The alpha subunit is identical to those in the pituitary gonadotropin hormones (LH, FSH and TSH). The beta subunits are distinct in each of the hormones and confer receptor and biological specificity. Has an essential role in pregnancy and maternal adaptation. Stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy.

Subunit / interactions. Heterodimer of a common alpha chain identical in LH, FSH, TSH and HCG and a unique beta chain distinct in each of the hormones.

Subcellular location. Secreted.

Tissue specificity. High expression in the placenta throughout pregnancy.

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?
P0DN86-1	1	yes
P0DN86-2	2

RefSeq proteins (1): NP_149439* (*=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 (37 total): sequence variant 9, disulfide bond 6, strand 6, glycosylation site 6, sequence conflict 4, signal peptide 1, chain 1, splice variant 1, region of interest 1, compositionally biased region 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
1HCN	X-RAY DIFFRACTION	2.6
9RHU	ELECTRON MICROSCOPY	2.65
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0DN86-F1	79.10	0.47

Antibody-complex structures (SAbDab): 2 — 1QFW, 7FIG

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): 29–77, 43–92, 46–130, 54–108, 58–110, 113–120

Glycosylation sites (6): 33, 50, 141, 147, 152, 158

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-209822	Glycoprotein hormones
R-HSA-8866910	TFAP2 (AP-2) family regulates transcription of growth factors and their receptors

MSigDB gene sets: 15 (showing top): BENPORATH_ES_WITH_H3K27ME3, LU_EZH2_TARGETS_UP, EGR_Q6, REACTOME_PEPTIDE_HORMONE_METABOLISM, REACTOME_TRANSCRIPTIONAL_REGULATION_BY_THE_AP_2_TFAP2_FAMILY_OF_TRANSCRIPTION_FACTORS, REACTOME_TFAP2_AP_2_FAMILY_REGULATES_TRANSCRIPTION_OF_GROWTH_FACTORS_AND_THEIR_RECEPTORS, ZFP3_TARGET_GENES, ZNF92_TARGET_GENES, chr19q13, REACTOME_RNA_POLYMERASE_II_TRANSCRIPTION, TATAAA_TATA_01, REACTOME_PEPTIDE_HORMONE_BIOSYNTHESIS, BENPORATH_EED_TARGETS, BENPORATH_PRC2_TARGETS, BENPORATH_SUZ12_TARGETS

GO Biological Process (6): apoptotic process (GO:0006915), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), cell-cell signaling (GO:0007267), female gamete generation (GO:0007292), hormone-mediated signaling pathway (GO:0009755)

GO Molecular Function (3): hormone activity (GO:0005179), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), pituitary gonadotropin complex (GO:0061696)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide hormone biosynthesis	1
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell communication	2
signaling	2
signal transduction	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cellular process	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
gamete generation	1
cellular response to hormone stimulus	1
receptor ligand activity	1
protein binding	1
binding	1
intracellular anatomical structure	1
extracellular protein-containing complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CGA	CGB5	psi-mi:“MI:0407”(direct interaction)	0.590
CGA	CGB5	psi-mi:“MI:0915”(physical association)	0.590
CGB5	SMCP	psi-mi:“MI:0915”(physical association)	0.560
CGB5	GPHA2	psi-mi:“MI:0915”(physical association)	0.370
CGB5	CFTR	psi-mi:“MI:0915”(physical association)	0.370
CGB5	IGSF3	psi-mi:“MI:0914”(association)	0.350
CGB5	DNAJC5	psi-mi:“MI:2364”(proximity)	0.270
CGB5	SMCP	psi-mi:“MI:0915”(physical association)	0.000

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

258 predictions. Top by Δscore:

Variant	Effect	Δscore
19:49048200:CTCA:C	donor_loss	1.0000
19:49048201:TCACC:T	donor_loss	1.0000
19:49048203:A:AC	donor_gain	1.0000
19:49048203:A:C	donor_loss	1.0000
19:49048204:C:CA	donor_loss	1.0000
19:49048204:C:CC	donor_gain	1.0000
19:49048369:GCCCC:G	acceptor_loss	1.0000
19:49048371:CC:C	acceptor_gain	1.0000
19:49048371:CCCT:C	acceptor_loss	1.0000
19:49048372:CC:C	acceptor_gain	1.0000
19:49048372:CCT:C	acceptor_loss	1.0000
19:49048373:C:T	acceptor_gain	1.0000
19:49048374:T:G	acceptor_loss	1.0000
19:49048203:AC:A	donor_gain	0.9900
19:49048204:CC:C	donor_gain	0.9900
19:49048204:CCATG:C	donor_gain	0.9900
19:49048369:GCCC:G	acceptor_gain	0.9900
19:49048370:CCC:C	acceptor_gain	0.9900
19:49048370:CCCC:C	acceptor_gain	0.9900
19:49048371:CCC:C	acceptor_gain	0.9900
19:49048373:C:CC	acceptor_gain	0.9900
19:49047978:CG:C	acceptor_gain	0.9800
19:49047979:G:C	acceptor_gain	0.9800
19:49048204:CCA:C	donor_gain	0.9800
19:49048204:CCAT:C	donor_gain	0.9800
19:49048368:AGCCC:A	acceptor_gain	0.9800
19:49047977:CCG:C	acceptor_gain	0.9700
19:49048201:TCA:T	donor_gain	0.9700
19:49048202:CAC:C	donor_gain	0.9700
19:49048203:A:AT	donor_gain	0.9700

AlphaMissense

1048 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:49047923:C:G	C77S	0.997
19:49047924:A:T	C77S	0.997
19:49048222:C:A	G56C	0.997
19:49047923:C:T	C77Y	0.996
19:49048227:C:G	C54S	0.996
19:49048227:C:T	C54Y	0.996
19:49048228:A:T	C54S	0.996
19:49048226:A:C	C54W	0.995
19:49047830:C:T	C108Y	0.994
19:49047922:G:C	C77W	0.994
19:49047923:C:A	C77F	0.994
19:49048221:C:A	G56V	0.994
19:49047815:C:G	C113S	0.993
19:49047816:A:T	C113S	0.993
19:49047830:C:G	C108S	0.993
19:49047831:A:T	C108S	0.993
19:49047878:C:G	C92S	0.993
19:49047879:A:T	C92S	0.993
19:49047924:A:G	C77R	0.993
19:49048215:C:G	C58S	0.993
19:49048215:C:T	C58Y	0.993
19:49048216:A:T	C58S	0.993
19:49048228:A:G	C54R	0.993
19:49048302:C:G	C29S	0.993
19:49048303:A:T	C29S	0.993
19:49047794:C:G	C120S	0.992
19:49047795:A:T	C120S	0.992
19:49047829:A:C	C108W	0.992
19:49048214:G:C	C58W	0.992
19:49047824:C:G	C110S	0.991

dbSNP variants (sampled 300 via entrez): RS1000098020 (19:49049947 A>C), RS1000806615 (19:49050890 G>C,T), RS1001221375 (19:49049618 CCT>C), RS1001287613 (19:49050122 C>T), RS1002989083 (19:49050749 A>T), RS1003219076 (19:49047584 A>G), RS1003375832 (19:49050435 C>T), RS1003451845 (19:49050856 C>G), RS1003616800 (19:49047454 C>G), RS1003631413 (19:49050591 G>A,C,T), RS1003731474 (19:49050355 G>A), RS1003879512 (19:49049576 C>T), RS1005636592 (19:49049643 A>C), RS1006022593 (19:49049170 G>A,T), RS1006390613 (19:49050739 A>C)

Disease associations

OMIM: gene MIM:608827 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011369_27	Iron status biomarkers (ferritin levels)	4.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004459	ferritin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression	2
ethyl-p-hydroxybenzoate	decreases expression	1
beta-lapachone	increases expression	1
zinc chromate	decreases expression, increases abundance	1
chromium hexavalent ion	decreases expression, increases abundance	1
jinfukang	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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