SERPINB4

protein-coding

serpin family B member 4, the group of Serpin peptidase inhibitors

Gene summary

The protein encoded by this gene is a member of the serpin family of serine protease inhibitors. The encoded protein is highly expressed in many tumor cells and can inactivate granzyme M, an enzyme that kills tumor cells. This protein, along with serpin B3, can be processed into smaller fragments that aggregate to form an autoantigen in psoriasis, probably by causing chronic inflammation. [provided by RefSeq, Jan 2017]

Previous symbols:

SCCA2

MANE transcript

NM_002974.4

Inheritance

—

ClinVar variants

U:73B:9

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 1.41

Max pathogenic AF

—

Genomic locus

chr18:63,637,259-63,644,256

External References & Databases

Ensembl (ENSG00000206073)

Transcript & Mutation Effects

hg38 • Region Span ~7.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SERPINB4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 79

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002974.4. 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						0
missense			72 clinvar	9 clinvar		81
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	73	9	0	82

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002974.4	RefSeq	NP_002965.1	7	MANE Select
ENST00000341074.10	Ensembl	ENSP00000343445.5	7	MANE Select
NM_175041.2	RefSeq	NP_778206.1	7	Standard
ENST00000413673.5	Ensembl	ENSP00000398645.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Amoebiasis - Homo sapiens (human)

Biological Process

negative regulation of peptidase activity
negative regulation of endopeptidase activity
regulation of proteolysis
protection from natural killer cell mediated cytotoxicity

Molecular Function

protease binding
serine-type endopeptidase inhibitor activity
enzyme binding

Cellular Component

extracellular space
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000341074
Coding exons: 7
Length: 7040
Individuals with no LoFs: 125324
Homozygous LoFs: 0
Heterozygous LoFs: 385
Defined: 125709
p: 0.00153

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.87	279	204	1.37	0.00000994	2604
Missense (PolyPhen)		86	67.139	1.2809		913
Synonymous	-3.14	115	79.4	1.45	0.00000447	685
Loss of Function	-1.46	21	14.9	1.41	6.95e-7	182

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0027	0.0026	notable
Latino/Admixed American	0.0040	0.0040	notable
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.0015	0.0015	notable
South Asian	0.00027	0.00026	rare
Other	0.0021	0.0021	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May act as a protease inhibitor to modulate the host immune response against tumor cells.;

Recessive Scores

pRec: 0.117

Intolerance Scores

LoFtool: 0.235
RVIS EVS: -0.33
RVIS percentile EVS: 30.7

Essentials

Essential (CRISPR): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.534

Gene Damage Prediction

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