SERPINB8

serpin family B member 8, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 18:63970029-64019779

Previous symbols: [ "PI8" ]

Links

ENSG00000166401 ∙ NCBI:5271 ∙ OMIM:601697 ∙ HGNC:8952 ∙ Uniprot:P50452 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• peeling skin syndrome 5 (Strong), mode of inheritance: AR
• peeling skin syndrome 5 (Moderate), mode of inheritance: AR
• exfoliative ichthyosis (Supportive), mode of inheritance: AR
• peeling skin syndrome 5 (Limited), mode of inheritance: AD
• peeling skin syndrome 5 (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Peeling skin syndrome 5	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	Dermatologic	27476651

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINB8 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINB8 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				7	3	10
missense			33	4	5	42
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			1	1	1	3
non coding					11	11
Total	0	1	34	11	19

Variants in SERPINB8

This is a list of pathogenic ClinVar variants found in the SERPINB8 region.

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

Position	Type	Phenotype	Significance	ClinVar
18-63978310-T-C		Peeling skin syndrome 5	Pathogenic (Sep 13, 2016)
18-63978343-C-G		not specified	Uncertain significance (Feb 14, 2023)
18-63978389-C-T			Benign (Oct 07, 2023)
18-63978394-T-C			Benign (Aug 31, 2023)
18-63978438-A-G		not specified	Uncertain significance (Dec 27, 2023)
18-63979829-T-C		not specified	Uncertain significance (Jun 29, 2022)
18-63979835-G-A		Peeling skin syndrome 5	Benign (Jan 29, 2024)
18-63979886-T-G			Benign (Jan 04, 2024)
18-63979901-AC-A		Peeling skin syndrome 5	Likely pathogenic (-)
18-63979920-G-C		not specified	Uncertain significance (Jul 28, 2021)
18-63979936-C-T			Likely benign (Dec 15, 2022)
18-63980032-C-T			Benign (May 14, 2021)
18-63980245-A-T			Benign (Jun 19, 2021)
18-63981491-C-T			Benign (May 22, 2021)
18-63981603-G-A			Benign (May 22, 2021)
18-63981769-T-A			Uncertain significance (Sep 13, 2022)
18-63981776-T-G		not specified	Uncertain significance (May 24, 2023)
18-63981804-G-A			Likely benign (Jan 16, 2022)
18-63981844-A-G			Uncertain significance (May 29, 2022)
18-63981936-A-G			Benign (May 15, 2021)
18-63983631-G-A		Peeling skin syndrome 5	Benign (Jan 29, 2024)
18-63983689-T-C		not specified	Likely benign (Oct 06, 2022)
18-63983701-A-G		not specified	Uncertain significance (Feb 28, 2024)
18-63983715-C-G			Likely benign (May 15, 2023)
18-63983718-C-T		SERPINB8-related disorder	Likely benign (Apr 26, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINB8	protein_coding	protein_coding	ENST00000397985	6	35120

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
2.78e-9	0.162	125521	0	227	125748	0.000903

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.950	240	202	1.19	0.0000100	2489
Missense in Polyphen		72	62.877	1.1451		837
Synonymous	-0.658	86	78.6	1.09	0.00000456	675
Loss of Function	0.348	14	15.5	0.905	7.70e-7	205

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00244	0.00245
Ashkenazi Jewish	0.0126	0.0127
East Asian	0.000109	0.000109
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000273	0.000273
Middle Eastern	0.000109	0.000109
South Asian	0.000561	0.000555
Other	0.000651	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has an important role in epithelial desmosome-mediated cell-cell adhesion. {ECO:0000269|PubMed:27476651}.
• Disease: DISEASE: Peeling skin syndrome 5 (PSS5) [MIM:617115]: A form of peeling skin syndrome, a genodermatosis characterized by generalized, continuous shedding of the outer layers of the epidermis. Two main PSS subtypes have been suggested. Patients with non-inflammatory PSS (type A) manifest white scaling, with painless and easy removal of the skin, irritation when in contact with water, dust and sand, and no history of erythema, pruritis or atopy. Inflammatory PSS (type B) is associated with generalized erythema, pruritus and atopy. It is an ichthyosiform erythroderma characterized by lifelong patchy peeling of the entire skin with onset at birth or shortly after. Several patients have been reported with high IgE levels. PSS5 patients manifest hyperkeratosis and superficial peeling of areas of the palmar and dorsal faces of hands and feet. Additional variable features include erythema, superficial scaling of forearms and legs and diffuse yellowish hyperkeratotic palmoplantar plaques. PSS5 inheritance is autosomal recessive. {ECO:0000269|PubMed:27476651}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Dissolution of Fibrin Clot;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.488

Intolerance Scores

• loftool: 0.0876
• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.58

Haploinsufficiency Scores

• pHI: 0.118
• hipred: N
• hipred_score: 0.208
• ghis: 0.543

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.822

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Serpinb8

Gene ontology

• Biological process: negative regulation of endopeptidase activity;epithelial cell-cell adhesion
• Cellular component: extracellular space;cytoplasm;cytosol;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: serine-type endopeptidase inhibitor activity;protein binding