SERPINA6

Summary

SERPINA6 (serpin family A member 6, HGNC:1540) is a protein-coding gene on chromosome 14q32.13, encoding Corticosteroid-binding globulin (P08185). Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.

This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events.

Source: NCBI Gene 866 — RefSeq curated summary.

At a glance

• Gene–disease (curated): corticosteroid-binding globulin deficiency (Strong, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 95 total — 1 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 0 (q < 0.05)
• Phenotypes (HPO): 13
• ChEMBL bioactivity: 16 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.01 (unconstrained)
• MANE Select transcript: NM_001756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1540
Approved symbol	SERPINA6
Name	serpin family A member 6
Location	14q32.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170099
Ensembl biotype	protein_coding
OMIM	122500
Entrez	866

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 13 protein_coding, 1 nonsense_mediated_decay

MANE Select: ENST00000341584

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2

ENST00000341584, ENST00000555056, ENST00000557225, ENST00000874317, ENST00000874318, ENST00000874319, ENST00000874320, ENST00000874321, ENST00000990125, ENST00000990126, ENST00000990127, ENST00000990128, ENST00001101098, ENST00001140047

RefSeq mRNA: 1 — MANE Select: NM_001756 NM_001756

CCDS: CCDS9924

Canonical transcript exons

ENST00000341584 — 5 exons

Exon	Start	End
ENSE00001011206	94304248	94304603
ENSE00001384926	94314036	94314667
ENSE00002502468	94323267	94323336
ENSE00003654268	94306071	94306218
ENSE00003662159	94309736	94310006

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 98.74.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.9234 / max 1824.3789, expressed in 90 samples.

Highest expression (Bgee): liver, lobe of liver, gall bladder, islet of Langerhans, pancreas.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SERPINA6 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

6 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Ovary	eqtl	4.9e-06	+0.58	14:94323158:C:G
Cells EBV-transformed lymphocytes	eqtl	7.3e-05	+0.44	14:94328865:C:T
Pancreas	eqtl	8.1e-05	-0.28	14:94372765:A:G
Colon Transverse	eqtl	7.1e-04	+0.14	14:94364111:A:T
Lung	eqtl	8.4e-04	+0.22	14:94337956:A:C
Testis	eqtl	1.4e-03	+0.30	14:94324006:T:C

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
144688	3.6524	80
207347	0.1296	24
207348	0.1102	22
207349	0.0312	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	98.74	gold quality
right lobe of liver	UBERON:0001114	98.70	gold quality
gall bladder	UBERON:0002110	94.27	gold quality
islet of Langerhans	UBERON:0000006	83.96	gold quality
pancreas	UBERON:0001264	82.04	gold quality
body of pancreas	UBERON:0001150	81.78	gold quality
right uterine tube	UBERON:0001302	80.17	gold quality
adult mammalian kidney	UBERON:0000082	79.20	gold quality
kidney	UBERON:0002113	74.51	gold quality
metanephros cortex	UBERON:0010533	74.26	gold quality
cortex of kidney	UBERON:0001225	69.98	gold quality
fallopian tube	UBERON:0003889	68.21	gold quality
rectum	UBERON:0001052	66.66	gold quality
endocervix	UBERON:0000458	63.90	gold quality
mucosa of transverse colon	UBERON:0004991	61.46	gold quality
transverse colon	UBERON:0001157	59.22	gold quality
colonic epithelium	UBERON:0000397	57.45	gold quality
uterine cervix	UBERON:0000002	57.02	gold quality
ectocervix	UBERON:0012249	52.85	gold quality
endometrium	UBERON:0001295	51.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	50.22	gold quality
duodenum	UBERON:0002114	48.11	gold quality
colon	UBERON:0001155	46.26	gold quality
placenta	UBERON:0001987	46.21	gold quality
left uterine tube	UBERON:0001303	45.81	gold quality
adrenal tissue	UBERON:0018303	45.37	gold quality
vagina	UBERON:0000996	43.61	gold quality
bone marrow cell	CL:0002092	43.53	gold quality
intestine	UBERON:0000160	43.10	gold quality
fundus of stomach	UBERON:0001160	40.40	gold quality
ovary	UBERON:0000992	40.21	gold quality
hindlimb stylopod muscle	UBERON:0004252	40.02	silver quality
lower esophagus mucosa	UBERON:0035834	39.77	gold quality
left ovary	UBERON:0002119	39.71	gold quality
thoracic mammary gland	UBERON:0005200	38.12	gold quality
right lung	UBERON:0002167	37.53	silver quality
stomach	UBERON:0000945	37.16	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
blood	UBERON:0000178	36.41	gold quality
right coronary artery	UBERON:0001625	35.98	gold quality
bone marrow	UBERON:0002371	35.51	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
body of stomach	UBERON:0001161	35.45	silver quality
right ovary	UBERON:0002118	35.41	gold quality
muscle tissue	UBERON:0002385	35.06	gold quality
smooth muscle tissue	UBERON:0001135	33.88	gold quality
myometrium	UBERON:0001296	33.59	gold quality
vermiform appendix	UBERON:0001154	33.55	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
small intestine	UBERON:0002108	32.74	gold quality
mucosa of stomach	UBERON:0001199	32.68	gold quality
tonsil	UBERON:0002372	32.28	gold quality
small intestine Peyer’s patch	UBERON:0003454	32.24	gold quality
multicellular organism	UBERON:0000468	31.92	gold quality
lung	UBERON:0002048	31.48	gold quality
muscle layer of sigmoid colon	UBERON:0035805	31.47	gold quality
lymph node	UBERON:0000029	31.34	gold quality
body of uterus	UBERON:0009853	30.99	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.28	gold quality
right adrenal gland	UBERON:0001233	30.13	silver quality
right atrium auricular region	UBERON:0006631	30.07	gold quality
adrenal gland	UBERON:0002369	29.90	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
skin of abdomen	UBERON:0001416	29.28	gold quality
monocyte	CL:0000576	29.11	gold quality
leukocyte	CL:0000738	28.97	gold quality
upper lobe of left lung	UBERON:0008952	28.93	gold quality
heart	UBERON:0000948	28.70	gold quality
thoracic aorta	UBERON:0001515	28.34	gold quality
spleen	UBERON:0002106	27.38	gold quality
ascending aorta	UBERON:0001496	27.32	gold quality
zone of skin	UBERON:0000014	27.27	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	26.68	silver quality
heart left ventricle	UBERON:0002084	26.40	gold quality
subcutaneous adipose tissue	UBERON:0002190	25.88	gold quality
prostate gland	UBERON:0002367	25.88	gold quality
right hemisphere of cerebellum	UBERON:0014890	25.32	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
cerebral cortex	UBERON:0000956	24.54	gold quality
right adrenal gland cortex	UBERON:0035827	24.54	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality
pituitary gland	UBERON:0000007	23.77	gold quality
brain	UBERON:0000955	23.51	silver quality
cerebellum	UBERON:0002037	23.21	gold quality
calcaneal tendon	UBERON:0003701	23.08	gold quality
cerebellar cortex	UBERON:0002129	23.05	gold quality
cerebellar hemisphere	UBERON:0002245	22.96	gold quality
tibial nerve	UBERON:0001323	22.92	gold quality
right frontal lobe	UBERON:0002810	22.51	gold quality
anterior cingulate cortex	UBERON:0009835	22.06	gold quality
caudate nucleus	UBERON:0001873	21.80	gold quality
adenohypophysis	UBERON:0002196	21.66	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	21.52	gold quality
temporal lobe	UBERON:0001871	21.20	gold quality
amygdala	UBERON:0001876	21.03	gold quality
Brodmann (1909) area 9	UBERON:0013540	20.98	gold quality
right lobe of thyroid gland	UBERON:0001119	20.92	gold quality
nucleus accumbens	UBERON:0001882	20.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-98	yes	761.64
E-ANND-3	yes	4.70

HPA expression

RNA tissue specificity: Tissue enriched

48 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Liver	tissue	725.8	not detected
Kidney	tissue	40.6	not detected
Gallbladder	tissue	33.0	not detected
Pancreas	tissue	16.4	not detected
Fallopian tube	tissue	11.9	not detected
Breast	tissue	8.0	not detected
Colon	tissue	3.3	not detected
Cervix	tissue	1.7	not detected
Rectum	tissue	1.5	not detected
Hippocampal formation	tissue	1.2
Cerebellum	tissue	0.9	not detected
Spinal cord	tissue	0.8
Prefrontal cortex	tissue	0.6
Cerebral cortex	tissue	0.6	not detected
Putamen	tissue	0.6
Endometrium 1	tissue	0.5	not detected
Basal ganglia	tissue	0.5	not detected
Entorhinal cortex	tissue	0.5
Retrosplenial cortex	tissue	0.5
Insular cortex	tissue	0.5
Motor cortex	tissue	0.4
Amygdala	tissue	0.4
Thalamus	tissue	0.4
Superior colliculi	tissue	0.4
Retrosplenial and cingulate cortex	tissue	0.4
Septum	tissue	0.4
Somatosensory cortex	tissue	0.4
Temporal cortex	tissue	0.4
Occipital cortex	tissue	0.4
Vagina	tissue	0.3	not detected
Midbrain	tissue	0.3
Medulla oblongata	tissue	0.3
Substantia nigra	tissue	0.3
Corpus callosum	tissue	0.3
Ventral forebrain	tissue	0.3
Olfactory bulb	tissue	0.3
Pons	tissue	0.2
Hypothalamus	tissue	0.2
Thymus	tissue	0.2
Periaqueductal gray	tissue	0.2
Testis	tissue	0.1	high
Stomach 1	tissue	0.1	not detected
Ovary	tissue	0.1	not detected
Smooth muscle	tissue	0.1	not detected
Lung	tissue	0.1	not detected
Duodenum	tissue	0.1	not detected
Locus coeruleus	tissue	0.1
Hippocampus	tissue	0.1	not detected

Brain sub-regions (HPA Brain Atlas): detected in 55; highest nTPM — Ventral hippocampus (1.2), Dorsal hippocampus (1.0), Ventral spinal cord (0.8), Dorsal spinal cord (0.7), Subiculum (0.5).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXM1, HNF1A, HNF1B, NR3C1, ONECUT1

miRNA regulators (miRDB)

Targeting SERPINA6 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

16 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-432-5P	98.00	68.13	989
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-514A-5P	96.94	65.49	801
HSA-MIR-134-3P	96.83	66.22	1001

Functional genomics

gnomAD constraint: pLI 1.85e-05, LOEUF 1.01, missense Z 0.919 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000341584 — one region, missense o/e 0.94.

Literature-anchored findings (GeneRIF, showing 40)

• findings support the hypothesis that the corticosteroid binding globulin level is an interesting indicator for both insulin resistance and low grade inflammation (PMID:12364459)
• CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. (PMID:12554596)
• human Fallopian tube cells actively express and secrete a CBG-like progesterone-binding protein, which might play a role in the in vivo modulation of human sperm acrosome reaction (PMID:14871264)
• Homozygosity for the serine allele of the CBG gene may predispose to chronic fatigue syndrome, perhaps due to an effect on hypothalamic-pituitary-adrenal axis function related to altered CBG-cortisol transport function or immune-cortisol interactions. (PMID:15554358)
• Circulating adiponectin, CBG concentration, and fasting cortisol were significantly interrelated in healthy subjects. A significant sexual dimorphism exists in this association. (PMID:15877287)
• We concluded that CBG gene polymorphisms might modulate the influence of the HPA axis on the fat mass distribution in obese women. (PMID:16222046)
• To the best of our knowledge, this case represents the first de novo mutation reported for corticosteroid-binding globulin deficiency, implicating a pathogenic role of variants of SERPINA6 in some cases of muscle fatigue. (PMID:17245537)
• A mechanism for the effect of CBG mutations on fatigue is not readily apparent because free cortisol levels are normal. (PMID:17547679)
• The crystal structures of cleaved human CBG (cCBG) at 1.8-A resolution and its complex with cortisol at 2.3-A resolution, is reported. (PMID:18513745)
• several substitutions (E334A, V336R, G340S, and T342P) increased the steroid binding affinities of human CBG even before elastase cleavage (PMID:19011238)
• Results describe the expression of corticosteroid-binding globulin (CBG) in the low-grade malignant human astrocytoma cell line 1321N1. (PMID:19172388)
• Effect of mutations of SERPINA6 on cortisol-binding, and thermal and protease sensitivity are reported. (PMID:20226861)
• SHBG, CBG and total cortisol and free plasma cortisol were measured and to investigate whether or not these analytes correlated with the degree of insulin resistance and the presence of the metabolic syndrome. (PMID:20354921)
• Plasma cortisol responses attenuated more rapidly in the able-bodied men, compared to spinal cord-injured subjects, due to significant rise in circulating corticosteroid-binding globulin. (PMID:20839151)
• Allosteric modulation of hormone release from thyroxine and corticosteroid-binding globulins. (PMID:21325280)
• N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal neuraminic acid residues. (PMID:21558494)
• Data show thatin chronic hepatitis C patients, IL28B polymorphism was associated with serum levels of corticosteroid binding globulin, a major transporter of cortisol. (PMID:21750736)
• CBG influences the endocrine and neurobehavioral response to stress, including the development of pain/fatigue syndromes (PMID:21795453)
• We found that polymorphisms in SLC6A4, TPH2, and SERPINA6 appear to be maternal factors increasing the risk of having a child with facial clefts. (PMID:22072571)
• investigation of physicochemical, electronic, and structural requirements for selective and effective binding of steroids (many are endogenous steroid metabolites) to CBG and SHBG active/ligand-binding sites (PMID:22242800)
• genetic association studies in Chinese populations: Data suggest that SERPINA6 with SNP (A51V) is poorly produced/secreted; plasma corticosteroid-binding globulin levels in heterozygous subjects for this variant are 50% lower than in normal subjects. (PMID:22337907)
• The influence of glucocorticoid receptor and corticosteroid-binding globulin gene polymorphisms in obesity and/or cortisol action in prepubertal obese children. (PMID:22576823)
• three polymorphisms, -26 C/G, -54 C/T, and -144 G/C located close to the putative hepatic nuclear factor (HNF) 1 binding elements, altered the transactivation effect of HNF1beta (PMID:22932886)
• Atomic interactions observed between progesterone and CBG explain the lower affinity of progesterone in comparison to corticosteroids. (PMID:23300763)
• CBG is coexpressed with hypothalamic neuropeptides.CBG may be involved in control of systemic and central stress response. (PMID:24246737)
• genetic variation in the SERPINA6 gene may be associated with altered CBG levels during adolescence. (PMID:24691024)
• Exome chip and 1000 Genomes imputation analysis of this locus in the CROATIA-Korcula cohort identified missense mutations in SERPINA6 and SERPINA1 that did not account for the effects of common variants (PMID:25010111)
• SERPINA6-rs1998056 regulated by FOXA/ERalpha might be associated with female HCC risk (PMID:25198130)
• Human cardiomyocytes express mineralocorticoid receptors, but are mostly free of nuclear glucocorticoid receptors. CBG is expressed in myocardium and in Purkinje fibers. CBG in heart is colocalized with mineralocorticoid receptor. (PMID:25251318)
• 8 naturally occurring CBG mutants with abnormalities in cortisol-binding affinity, cortisol-binding capacity, production/secretion, sensitivity to proteolytic cleavage of the reactive center loop, or recognition by monoclonal antibodies used for ELISAs were identified (PMID:25322275)
• the results suggest that DEX repression of Corticosteroid-binding globulin involves tethering of the glucocorticoid receptor to C/EBPb. (PMID:25335188)
• The study investigate the half-life of intact and elastase cleaved CBG in the rabbit. The half-lives of intact and cleaved human CBG are 10 h and identical. (PMID:25636722)
• Data indicate there was no significant circadian variation in serum cortisol-binding globulin (CBG) concentration in any of the 4 groups. (PMID:26603673)
• The results suggest reduced CBG cleavage in central obesity, possibly contributing to the characteristic inflammatory phenotype of the central obesity and metabolic syndrome. (PMID:27300474)
• In conclusion, site-specific CBG N-glycosylation regulates the bioavailability of cortisol in inflamed environments by fine-tuning the RCL proteolysis by endogenous and exogenous elastases. (PMID:27339896)
• Corticosteroid-binding globulin cleavage may be pathogen-dependent in bloodstream infection (PMID:27887960)
• Data suggest that some individuals with adrenal insufficiency due to SERPINA6 mutations present with hypotension or nonspecific symptoms such as fatigue, nausea, or chronic pain, but symptomatology varies widely, even between family members with identical mutations. [REVIEW] (PMID:29194043)
• N-glycans at other sites also appear to protect CBG from neutrophil elastase or chymotrypsin. (PMID:29273683)
• We generated weighted polygenic risk score (PRS) based on 6 genome-wide significant SNPs (rs11621961, rs11629171, rs7161521, rs2749527, rs3762132, rs4900229). salivary cortisol increased in the high PRS group. It remained unchanged in low PRS group. These results were mainly driven by minor alleles of rs7161521 (SERPINA6) and rs4900229 (SERPINA1). (PMID:29679879)
• Low circulating haCBG concentrations are associated with mortality in septic shock (PMID:30160799)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Serpina6	ENSMUSG00000060807
rattus_norvegicus	Serpina6	ENSRNOG00000009438

Paralogs (36): SERPINB1 (ENSG00000021355), SERPINB3 (ENSG00000057149), SERPIND1 (ENSG00000099937), SERPINA4 (ENSG00000100665), SERPINE1 (ENSG00000106366), SERPINI2 (ENSG00000114204), SERPINC1 (ENSG00000117601), SERPINA7 (ENSG00000123561), SERPINB6 (ENSG00000124570), SERPINF1 (ENSG00000132386), AGT (ENSG00000135744), SERPINE2 (ENSG00000135919), SERPINA10 (ENSG00000140093), SERPING1 (ENSG00000149131), SERPINH1 (ENSG00000149257), SERPINI1 (ENSG00000163536), SERPINA12 (ENSG00000165953), SERPINB7 (ENSG00000166396), SERPINB8 (ENSG00000166401), SERPINB12 (ENSG00000166634), SERPINF2 (ENSG00000167711), SERPINA9 (ENSG00000170054), SERPINB9 (ENSG00000170542), SERPINA11 (ENSG00000186910), SERPINA5 (ENSG00000188488), SERPINA3 (ENSG00000196136), SERPINA1 (ENSG00000197249), SERPINB2 (ENSG00000197632), SERPINB13 (ENSG00000197641), SERPINB11 (ENSG00000206072), SERPINB4 (ENSG00000206073), SERPINB5 (ENSG00000206075), HMSD (ENSG00000221887), SERPINB10 (ENSG00000242550), SERPINE3 (ENSG00000253309), SERPINA2 (ENSG00000258597)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88278) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal circulating corticosterone level	2
decreased locomotor activity	1
behavioral despair	1
increased adrenocorticotropin level	1
abnormal cytokine level	1
increased susceptibility to endotoxin shock	1
impaired behavioral response to cocaine	1
abnormal circulating cytokine level	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pan troglodytes	P61640	99.8%	Diamond
Bos taurus	A2I7N0	99.5%	Diamond
Pongo abelii	Q5RCR2	98.4%	Diamond
Tamias sibiricus	O54759	98.1%	Diamond
Papio anubis	P01010	97.0%	Diamond
Chlorocebus aethiops	O00394	96.7%	Diamond
Ovis aries	P50450	96.1%	Diamond
Bombyx mori	P22922	94.7%	Diamond
Cavia porcellus	P22324	94.0%	Diamond
Sus scrofa	Q9TT35	89.8%	Diamond
Mus saxicola	Q63969	87.1%	Diamond
Oryctolagus cuniculus	P47776	86.3%	Diamond
Saimiri sciureus	P50451	86.2%	Diamond
Mus caroli	P26595	86.1%	Diamond
Ictidomys tridecemlineatus	O54761	81.1%	Diamond
Callosciurus caniceps	O54763	80.8%	Diamond
Ursus arctos	B2D1U1	76.5%	Diamond
Mesocricetus auratus	P97277	76.3%	Diamond
Meriones unguiculatus	Q64118	76.3%	Diamond
Apodemus sylvaticus	Q60396	75.5%	Diamond
Equus caballus	P38029	74.1%	Diamond
Methanosarcina acetivorans C2A	Q8TMP0	67.6%	Diamond
Didelphis virginiana	Q03044	59.8%	Diamond
Ixodes ricinus	A0A0K8RJV9	56.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SERPINA2	protein-coding	390502
SERPINA10	protein-coding	51156
SERPINA1	protein-coding	5265
SERPINA11	protein-coding	256394
PPP4R4	protein-coding	57718
IFI27L2	protein-coding	83982

Protein

Protein identifiers

Corticosteroid-binding globulin — P08185 (reviewed: P08185)

Alternative names: Serpin A6, Transcortin

All UniProt accessions (3): P08185, G3V350, G3V4V7

UniProt curated annotations — full annotation on UniProt →

Function. Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.

Subcellular location. Secreted.

Tissue specificity. Plasma; synthesized in liver. Has also been identified in a number of glycocorticoid responsive cells.

Post-translational modifications. N-glycosylated; binds 5 oligosaccharide chains. Glycosylation in position Asn-260 is needed for steroid binding.

Disease relevance. Corticosteroid-binding globulin deficiency (CBG deficiency) [MIM:611489] Extremely rare hereditary disorder characterized by reduced corticosteroid-binding capacity with normal or low plasma corticosteroid-binding globulin concentration, and normal or low basal cortisol levels associated with hypo/hypertension and muscle fatigue. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Proteolytic cleavage leads to an important conformation change. This reduces the affinity for steroids.

Similarity. Belongs to the serpin family.

RefSeq proteins (1): NP_001747* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000215	Serpin_fam	Family
IPR023795	Serpin_CS	Conserved_site
IPR023796	Serpin_dom	Domain
IPR036186	Serpin_sf	Homologous_superfamily
IPR042178	Serpin_sf_1	Homologous_superfamily
IPR042185	Serpin_sf_2	Homologous_superfamily

Pfam: PF00079

UniProt features (52 total): strand 18, helix 13, glycosylation site 6, turn 5, binding site 4, sequence variant 3, signal peptide 1, chain 1, site 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
4C41	Corticosteroid-binding globulin with engineered disulphide bridge between residues 100 …	X-RAY DIFFRACTION	1.8
2VDX	Crystal Structure of the reactive loop Cleaved Corticosteroid Binding Globulin	X-RAY DIFFRACTION	1.84
2VDY	Crystal structure of the reactive loop cleaved Corticosteroid Binding Globulin complexed …	X-RAY DIFFRACTION	2.3
4BB2	Crystal structure of cleaved corticosteroid-binding globulin in complex with progesterone	X-RAY DIFFRACTION	2.48
4C49	Reactive loop cleaved human CBG in complex with cortisol	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P08185-F1	86.77	0.74

Human Protein Atlas

Protein class: Predicted secreted proteins, Plasma proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH approved

Functional residue map

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

Catalytic / active sites (1)

Position	Role
250	conserved cysteine within steroid binding domain

Ligand- & substrate-binding residues (4)

Position	Role
254	cortisol
286	cortisol
390	cortisol
393	cortisol

Glycosylation sites (6)

Type	Positions
N-linked (glcnac…) asparagine	260, 330, 369, 31, 96, 176

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-194002	Glucocorticoid biosynthesis	curated
R-HSA-9757110	Prednisone ADME	curated
R-HSA-9748784	Drug ADME	—
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-196071	Metabolism of steroid hormones	—
R-HSA-8957322	Metabolism of steroids	—

MSigDB gene sets: 141 (showing top): MODULE_52, GRUETZMANN_PANCREATIC_CANCER_DN, GOBP_GLUCOCORTICOID_METABOLIC_PROCESS, GNF2_HPN, HNF1_Q6, MODULE_404, LEE_LIVER_CANCER_CIPROFIBRATE_DN, STOSSI_RESPONSE_TO_ESTRADIOL, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, SMID_BREAST_CANCER_LUMINAL_B_UP, HSIAO_LIVER_SPECIFIC_GENES, GOBP_STEROID_BIOSYNTHETIC_PROCESS, GOBP_GLUCOCORTICOID_BIOSYNTHETIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GNF2_HPX

GO Biological Process (1): glucocorticoid biosynthetic process (GO:0006704)

GO Molecular Function (4): serine-type endopeptidase inhibitor activity (GO:0004867), steroid binding (GO:0005496), molecular carrier activity (GO:0140104), lipid binding (GO:0008289)

GO Cellular Component (2): extracellular region (GO:0005576), extracellular exosome (GO:0070062)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of steroid hormones	1
Drug ADME	1
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

9 GO namespaces:

Category	Terms
binding	2
glucocorticoid metabolic process	1
steroid hormone biosynthetic process	1
serine-type endopeptidase activity	1
endopeptidase inhibitor activity	1
lipid binding	1
molecular_function	1
cellular anatomical structure	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 3 of 8 annotations. The rest are phylogenetic / computational / electronic (IEA).

3 experimentally-supported GO terms:

GO term	NS	Evidence
extracellular exosome	CC	high-throughput assay
molecular carrier activity	MF	experiment
steroid binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 906 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SERPINA6	SHBG	P04278	908
SERPINA6	ALB	P02768	723
SERPINA6	POMC	P01189	717
SERPINA6	HSD11B2	P80365	653
SERPINA6	NR2F1	P10589	639
SERPINA6	CRH	P06850	591
SERPINA6	HSD11B1	P28845	582
SERPINA6	PPP1R1C	Q8WVI7	552
SERPINA6	NR3C1	P04150	551
SERPINA6	GPR55	Q9Y2T6	547
SERPINA6	KLK1	P06870	522
SERPINA6	KLK2	P20151	512
SERPINA6	NR3C2	P08235	505
SERPINA6	MC2R	Q01718	486
SERPINA6	ELANE	P08246	474

IntAct

Human interaction partners of SERPINA6 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
COCH	association	0.530	2
METRN	physical association	0.400	1

BioGRID (21 interactions; top human partners by supporting records): COCH (Affinity Capture-MS; 3 records), DHFRL1 (Affinity Capture-MS; 3 records), PAM (Affinity Capture-MS; 3 records), SERPINF1 (Affinity Capture-MS; 2 records), C16orf72 (Positive Genetic), COL4A2 (Affinity Capture-MS), FN1 (Affinity Capture-MS), HLA-DPB1 (Affinity Capture-MS), IPO5 (Affinity Capture-MS), KLK10 (Affinity Capture-MS), METRN (Affinity Capture-MS), P3H4 (Affinity Capture-MS), UBE2U (Affinity Capture-MS), WRB (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for SERPINA6: 95 ClinVar records (2 pathogenic / likely pathogenic); 6 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	70
Likely benign	14
Benign	5

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
16976	NM_001756.4(SERPINA6):c.32G>A (p.Trp11Ter)	Pathogenic	no assertion criteria provided	1
1077111	NM_001756.4(SERPINA6):c.164_165del (p.Val55fs)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore SERPINA6’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 34 predictions of 435):

Position(s)	Effect	Δscore	Sites
14:94306069–94306070	donor_loss	1.0000	5
14:94304604–94304605	acceptor_loss	0.9900	6
14:94306219–94306220	acceptor_loss	0.9900	6
14:94309734–94309735	donor_loss	0.9900	2
14:94310007–94310008	acceptor_loss	0.9900	6
14:94304607	acceptor_gain	0.9800
14:94306225	acceptor_gain	0.9800
14:94309734–94309735	donor_loss	0.9800	2
14:94323265–94323266	donor_loss	0.9800	4
14:94304611	acceptor_gain	0.9700

AlphaMissense

340 missense substitutions predicted likely pathogenic (of 2,690 scored), across 128 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F221	7	0.905	0.979
F383	7	0.861	0.974
F211	7	0.857	0.958
F397	7	0.773	0.888
D389	7	0.678	0.824
D245	7	0.668	0.721
W288	6	0.921	0.975
P302	6	0.876	0.927
W207	6	0.860	0.946
F109	6	0.826	0.931
M234	6	0.807	0.884
N62	6	0.775	0.925
C250	6	0.760	0.946
F46	5	0.862	0.914
F132	5	0.852	0.914
F143	5	0.850	0.936
F95	5	0.841	0.914
F379	5	0.831	0.922
P268	5	0.773	0.859
M233	5	0.712	0.769

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Liver Hepatocellular Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.00066

Disease associations

OMIM: gene MIM:122500 | disease phenotypes: MIM:611489

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
corticosteroid-binding globulin deficiency	Strong	Autosomal recessive	5

Mondo (1): corticosteroid-binding globulin deficiency (MONDO:0012675)

Orphanet (1): Corticosteroid-binding globulin deficiency (Orphanet:199247)

HPO phenotypes

13 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000822	Hypertension
HP:0001903	Anemia
HP:0002615	Hypotension
HP:0002900	Hypokalemia
HP:0003581	Adult onset
HP:0003750	Increased muscle fatiguability
HP:0008163	Decreased circulating cortisol level
HP:0012364	Decreased urinary potassium
HP:0012378	Fatigue
HP:0025406	Asthenia
HP:6000243	Decreased circulating corticosteroid-binding globulin concentration

GWAS associations

6 associations:

Study	Trait	p-value
GCST010243_94	Apolipoprotein B levels	4e-13
GCST010245_23	LDL cholesterol levels	4e-12
GCST90011898_123	Alanine aminotransferase levels	5e-12
GCST007615_19	C-reactive protein levels	1e-9
GCST001585_36	Breast size	8e-7
GCST002932_29	Manganese levels	6e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004458	C-reactive protein measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2421 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,121,353 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

16 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL135	ESTRADIOL	4	124,045
CHEMBL193482	ESTRIOL	4	21,447
CHEMBL1405	ESTRONE	4	36,940
CHEMBL389621	HYDROCORTISONE	4	209,845
CHEMBL1091	HYDROCORTISONE ACETATE	4	45,281
CHEMBL90593	PRASTERONE	4	23,701
CHEMBL131	PREDNISOLONE	4	142,034
CHEMBL103	PROGESTERONE	4	163,382
CHEMBL386630	TESTOSTERONE	4	131,189
CHEMBL110739	CORTICOSTERONE	3	28,608
CHEMBL1499	CORTISONE	3	79,712
CHEMBL757	NANDROLONE	3	9,614
CHEMBL273453	ALDOSTERONE	2	50,963
CHEMBL253144	CORTODOXONE	2	11,009
CHEMBL27769	STANOLONE	2	34,484
CHEMBL253363	PREGNENOLONE	1	9,099

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

22 measured of 27 human assays (30 total across all organisms); most potent 22 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
DHT	EC50	0.05 nM
[3H]Aldosterone	EC50	1.3 nM
(1S,2R,10S,11S,14S,15S)-14-(2-hydroxyacetyl)-2,15-dimethyltetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one	KI	1.4 nM
11-Deoxycortisol	KI	13 nM
Delalutin	KI	18 nM
CHEMBL432825	KI	20 nM
CHEBI:17609	KI	28 nM
CHEMBL433198	KI	76 nM
folliculin	IC50	109 nM
CORTISONE	KI	129 nM
CHEBI:34188	KI	151 nM
4-pregnene-3,11,20-trione	KI	166 nM
3alpha-hydroxy-5beta-androstan-17-one	IC50	182 nM
(3beta,17beta)-androst-5-ene-3,17-diol	IC50	230 nM
Androst-4-en-3,17-dione, 2	IC50	489 nM
CHEBI:763	KI	562 nM
(17beta)-17-hydroxyestr-4-en-3-one	KI	724 nM
11beta,17,21-trihydroxy-2alpha-methyl-9alphafluoro-4-pregnene-3,20-dione	KI	1580 nM
PREGNENOLONE	KI	5890 nM
HYDROXYPREGNENOLONE	KI	10000 nM
ANDROSTANEDIOL	KI	10000 nM
ESTRIOL	IC50	20100 nM

ChEMBL bioactivities

31 potent at pChembl≥5 of 31 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.88	Ki	13.18	nM	CORTICOSTERONE
7.88	Ki	13.18	nM	HYDROCORTISONE
7.88	Ki	13.18	nM	CORTODOXONE
7.74	Ki	18.2	nM	HYDROXYPROGESTERONE
7.69	Ki	20.42	nM	CHEMBL432825
7.65	Ki	22.39	nM	DESOXYCORTICOSTERONE
7.55	Ki	28.18	nM	HYDROCORTISONE ACETATE
7.51	Ki	30.9	nM	PREDNISOLONE
7.38	Ki	41.69	nM	PROGESTERONE
7.20	Ki	63.1	nM	CORTICOSTERONE
7.12	Ki	75.86	nM	CHEMBL433198
6.89	Ki	128.8	nM	CORTISONE
6.82	Ki	151.4	nM	CHEMBL284109
6.78	Ki	166	nM	CHEMBL284253
6.72	Ki	190.6	nM	TESTOSTERONE
6.28	Ki	524.8	nM	ALDOSTERONE
6.25	Ki	562.3	nM	CHEMBL2311120
6.14	Ki	724.4	nM	NANDROLONE
5.92	Ki	1202	nM	STANOLONE
5.80	Ki	1585	nM	CHEMBL93948
5.76	Ki	1738	nM	ANDROSTENEDIONE
5.61	Ki	2455	nM	ANDROSTERONE
5.23	Ki	5888	nM	PREGNENOLONE
5.23	Ki	5888	nM	ETIOCHOLANOLONE
5.00	Ki	1e+04	nM	ANDROSTENEDIOL
5.00	Ki	1e+04	nM	ESTRONE
5.00	Ki	1e+04	nM	ESTRIOL
5.00	Ki	1e+04	nM	HYDROXYPREGNENOLONE
5.00	Ki	1e+04	nM	PRASTERONE
5.00	Ki	1e+04	nM	ANDROSTANEDIOL
5.00	Ki	1e+04	nM	ESTRADIOL

PubChem BioAssay actives

31 with measured affinity, of 274 total; 30 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(8R,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0132	uM
(8S,9S,10R,11S,13S,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0132	uM
hydrocortisone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0132	uM
hydroxyprogesterone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0182	uM
(8S,9S,10R,13S,14S,17R)-17-hydroxy-17-(2-hydroxyacetyl)-2,10,13-trimethyl-1,2,6,7,8,9,12,14,15,16-decahydrocyclopenta[a]phenanthrene-3,11-dione	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0204	uM
desoxycortone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0224	uM
Hydrocortisone Acetate	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0282	uM
Prednisolone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0309	uM
Progesterone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0417	uM
(6S)-17-acetyl-6,10,13-trimethyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.0759	uM
Cortisone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.1288	uM
(8R,9S,10R,13S,14S,17S)-17-acetyl-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.1514	uM
(8S,9S,10R,13S,14S,17S)-17-acetyl-10,13-dimethyl-2,6,7,8,9,12,14,15,16,17-decahydro-1H-cyclopenta[a]phenanthrene-3,11-dione	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.1660	uM
Testosterone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.1905	uM
(8S,9S,10R,11S,13R,14S,17S)-11-hydroxy-17-(2-hydroxyacetyl)-10-methyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-13-carbaldehyde	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.5248	uM
(8R,9S,10R,13S,14S,16R,17S)-17-acetyl-16,17-dihydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.5623	uM
(8R,9S,10R,13S,14S,17S)-17-hydroxy-13-methyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	0.7244	uM
(5S,8R,9S,10S,13S,14S,17S)-17-hydroxy-10,13-dimethyl-1,2,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydrocyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	1.2023	uM
(2R,8S,9R,10S,11S,13S,14S,17R)-9-fluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-2,10,13-trimethyl-1,2,6,7,8,11,12,14,15,16-decahydrocyclopenta[a]phenanthren-3-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	1.5849	uM
(8R,9S,10R,13S,14S)-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	1.7378	uM
(3R,5S,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	2.4547	uM
(3R,5R,8R,9S,10S,13S,14S)-3-hydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-one	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	5.8884	uM
1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]ethanone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	5.8884	uM
1-[(3R,5R,8R,9S,10S,13S,14S,17R)-3,17-dihydroxy-10,13-dimethyl-1,2,3,4,5,6,7,8,9,11,12,14,15,16-tetradecahydrocyclopenta[a]phenanthren-17-yl]ethanone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
(3S,8R,9S,10R,13S,14S,17S)-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
(3S,5S,8R,9S,10S,13S,14S,17S)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-3,17-diol	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
Estriol	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
Estradiol	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
Estrone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM
prasterone	51055: Binding affinity to human CBG receptor (corticosteroid-binding globulins)	ki	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases methylation, affects methylation	4
Cyclosporine	decreases expression	4
Aflatoxin B1	affects expression, decreases expression, decreases methylation, increases expression	4
Dexamethasone	affects cotreatment, affects binding, increases activity, decreases expression, increases expression	3
bisphenol A	affects expression, decreases methylation	2
Acetaminophen	decreases expression	2
Ethinyl Estradiol	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
withaferin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
norgestimate	affects cotreatment, increases expression	1
sodium arsenite	decreases expression	1
periodate-oxidized adenosine	affects expression	1
drospirenone	increases expression, affects cotreatment	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
2,3-dimethoxy-1,4-naphthoquinone	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
Ortho Evra	increases expression	1
theaflavin-3,3’-digallate	affects expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Air Pollutants	decreases expression	1
Cadmium	decreases expression	1
Caffeine	decreases expression	1
Copper	affects binding	1
Dimethylnitrosamine	decreases expression	1
Estradiol	increases expression, increases reaction	1
Glucocorticoids	increases transport	1

ChEMBL screening assays

14 unique, capped per target: 14 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL665988	Binding	In silico binding affinity to human corticosteriod binding globulin	Validation of EGSITE2, a mixed integer program for deducing objective site models for experimental binding data. — *J Med Chem*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SERPINA6 across ~30M SureChEMBL compounds — explore on Sugi Predict.