SERPINB8

protein-coding

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

Gene summary

The protein encoded by this gene is a member of the ov-serpin family of serine protease inhibitors. The encoded protein is produced by platelets and can bind to and inhibit the function of furin, a serine protease involved in platelet functions. In addition, this protein has been found to enhance the mechanical stability of cell-cell adhesion in the skin, and defects in this gene have been associated with an autosomal-recessive form of exfoliative ichthyosis. [provided by RefSeq, Jan 2017]

Previous symbols:

MANE transcript

NM_002640.4

Inheritance

AD, AR

ClinVar variants

P:5U:58B:20

Top phenotype

Peeling skin syndrome 5

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr18:63,970,029-64,019,779

External References & Databases

Ensembl (ENSG00000166401)

Transcript & Mutation Effects

hg38 • Region Span ~49.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

peeling skin syndrome 5LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014923

Submitter: Ambry Genetics

peeling skin syndrome 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014923

Submitter: Genomics England PanelApp

peeling skin syndrome 5LIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0014923

Submitter: Labcorp Genetics (formerly Invitae)

peeling skin syndrome 5LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0014923

Submitter: G2P

peeling skin syndrome 5STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014923

Submitter: PanelApp Australia

exfoliative ichthyosisSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0017339

Submitter: Orphanet

Clinical Genomic Database (CGD)

Peeling skin syndrome 5AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Refs: 27476651

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SERPINB8 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 37

SERPINB8-related disorderTotal: 10

Peeling skin syndrome 5Total: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002640.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				10 clinvar	1 clinvar	11
missense			55 clinvar	6 clinvar	3 clinvar	64
nonsense		2 clinvar	1 clinvar			3
start loss	1 clinvar					1
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	1	4	58	16	4	83

Highest pathogenic variant AF is 0.0004516253

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002640.4	RefSeq	NP_002631.3	6	MANE Select
ENST00000397985.7	Ensembl	ENSP00000381072.2	6	MANE Select
NM_001031848.2	RefSeq	NP_001027018.1	6	Standard
NM_001276490.2	RefSeq	NP_001263419.1	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Dissolution of Fibrin Clot
Hemostasis

Biological Process

negative regulation of endopeptidase activity
epithelial cell-cell adhesion

Molecular Function

serine-type endopeptidase inhibitor activity
protein binding

Cellular Component

extracellular space
cytoplasm
cytosol
collagen-containing extracellular matrix
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000397985
Coding exons: 6
Length: 35120
Individuals with no LoFs: 125521
Homozygous LoFs: 0
Heterozygous LoFs: 227
Defined: 125748
p: 0.000903

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.950	240	202	1.19	0.0000100	2489
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0022	0.0022	notable
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0.013	0.013	notable
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.00056	0.00056	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.488

Intolerance Scores

LoFtool: 0.0876
RVIS EVS: 0.35
RVIS percentile EVS: 74.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.822

Gene Damage Prediction

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