SERPINA6

serpin family A member 6, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 14:94304248-94323389

Previous symbols: [ "CBG" ]

Links

ENSG00000170099 ∙ NCBI:866 ∙ OMIM:122500 ∙ HGNC:1540 ∙ Uniprot:P08185 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• corticosteroid-binding globulin deficiency (Supportive), mode of inheritance: Semidominant
• corticosteroid-binding globulin deficiency (Strong), mode of inheritance: AR
• corticosteroid-binding globulin deficiency (Moderate), mode of inheritance: AD
• corticosteroid-binding globulin deficiency (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Corticosteroid-binding globulin deficiency	AD/AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Endocrine	7061486; 8212073; 10634411; 11502797; 17245537; 20610591; 22013108; 22337907; 22948765

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINA6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINA6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1	5	6
missense			21			21
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding						0
Total	0	0	21	1	5

Variants in SERPINA6

This is a list of pathogenic ClinVar variants found in the SERPINA6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-94304457-C-G			Uncertain significance (Dec 09, 2022)
14-94304471-C-T		Corticosteroid-binding globulin deficiency • SERPINA6-related disorder	Conflicting classifications of pathogenicity (Feb 26, 2022)
14-94304490-G-C		SERPINA6-related disorder	Likely benign (Jun 25, 2019)
14-94304498-T-G		Inborn genetic diseases	Uncertain significance (Oct 30, 2023)
14-94304500-A-C		Inborn genetic diseases	Uncertain significance (Jul 17, 2024)
14-94304525-T-C		Inborn genetic diseases	Likely benign (May 01, 2024)
14-94304599-A-G		Inborn genetic diseases	Uncertain significance (Feb 17, 2024)
14-94306092-G-A		SERPINA6-related disorder	Benign (Dec 07, 2023)
14-94306093-T-C		Inborn genetic diseases	Uncertain significance (Dec 07, 2021)
14-94306106-G-A		Inborn genetic diseases	Uncertain significance (Aug 28, 2023)
14-94306167-G-A		SERPINA6-related disorder	Benign (Nov 12, 2019)
14-94306210-T-A		Inborn genetic diseases	Uncertain significance (Sep 09, 2024)
14-94306224-C-T		SERPINA6-related disorder	Likely benign (Mar 02, 2019)
14-94309759-C-A		Inborn genetic diseases	Uncertain significance (Oct 08, 2024)
14-94309771-G-C		Inborn genetic diseases	Uncertain significance (May 07, 2024)
14-94309773-C-G			Uncertain significance (Aug 17, 2022)
14-94309791-T-A		Inborn genetic diseases	Uncertain significance (Jan 09, 2024)
14-94309801-C-T		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
14-94309816-C-T		SERPINA6-related disorder	Benign (Sep 30, 2019)
14-94309818-G-A		Inborn genetic diseases	Uncertain significance (Sep 03, 2024)
14-94309848-C-T		Inborn genetic diseases	Uncertain significance (Dec 03, 2024)
14-94309882-C-T		SERPINA6-related disorder	Benign (Nov 12, 2019)
14-94309892-A-G		Inborn genetic diseases	Uncertain significance (Oct 07, 2024)
14-94309899-T-C		Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
14-94309907-C-T		Inborn genetic diseases	Uncertain significance (Nov 27, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINA6	protein_coding	protein_coding	ENST00000341584	4	19147

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
8.34e-7	0.312	125720	0	26	125746	0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.662	244	217	1.13	0.0000124	2685
Missense in Polyphen		59	58.942	1.001		830
Synonymous	-0.647	97	89.2	1.09	0.00000537	800
Loss of Function	0.367	10	11.3	0.882	4.99e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000702	0.000702
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000704	0.0000703
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species. {ECO:0000269|PubMed:18513745}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:10634411, ECO:0000269|PubMed:1504007, ECO:0000269|PubMed:17245537, ECO:0000269|PubMed:8212073}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glucocorticoid Pathway (Peripheral Tissue), Pharmacodynamics (Consensus)

Recessive Scores

• pRec: 0.212

Intolerance Scores

• loftool: 0.173
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.51

Haploinsufficiency Scores

• pHI: 0.245
• hipred: N
• hipred_score: 0.123
• ghis: 0.426

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.160

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Serpina6
• Phenotype: homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Gene ontology

• Biological process: glucocorticoid metabolic process;negative regulation of endopeptidase activity
• Cellular component: extracellular space;extracellular exosome
• Molecular function: serine-type endopeptidase inhibitor activity;steroid binding