SERPINB7

protein-coding

serpin family B member 7, the group of Serpin peptidase inhibitors

Gene summary

This gene encodes a member of a family of proteins which function as protease inhibitors. Expression of this gene is upregulated in IgA nephropathy and mutations have been found to cause palmoplantar keratoderma, Nagashima type. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

MANE transcript

NM_003784.4

Inheritance

ClinVar variants

P:16U:75B:13

Top phenotype

Palmoplantar keratoderma, Nagashima type

gnomAD constraint

pLI —, LoF o/e 0.84

Max pathogenic AF

—

Genomic locus

chr18:63,752,935-63,805,376

External References & Databases

Ensembl (ENSG00000166396)

Transcript & Mutation Effects

hg38 • Region Span ~52.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

palmoplantar keratoderma, Nagashima typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014272

Submitter: Genomics England PanelApp

palmoplantar keratoderma, Nagashima typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014272

Submitter: Labcorp Genetics (formerly Invitae)

palmoplantar keratoderma, Nagashima typeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014272

Submitter: Orphanet

palmoplantar keratoderma, Nagashima typeDEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014272

Submitter: G2P

palmoplantar keratoderma, Nagashima typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014272

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Palmoplantar keratoderma, Nagashima typeAR

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: 24207119; 24773080

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SERPINB7 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 61

not providedTotal: 42

Palmoplantar keratoderma, Nagashima typeTotal: 11

SERPINB7-related disorderTotal: 11

Palmoplantar keratodermasTotal: 1

not specifiedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003784.4. 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				8 clinvar	1 clinvar	9
missense	1 clinvar	1 clinvar	73 clinvar	3 clinvar	1 clinvar	79
nonsense	3 clinvar					3
start loss						0
frameshift	4 clinvar	4 clinvar				8
splice donor/acceptor (+/-2bp)	2 clinvar	1 clinvar	2 clinvar			5
Total	10	6	75	11	2	104

Highest pathogenic variant AF is 0.00030538422

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003784.4	RefSeq	NP_003775.1	7	MANE Select
ENST00000398019.7	Ensembl	ENSP00000381101.2	7	MANE Select
NM_001040147.3	RefSeq	NP_001035237.1	7	Standard
NM_001261830.2	RefSeq	NP_001248759.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of endopeptidase activity
positive regulation of transforming growth factor beta1 production
positive regulation of collagen biosynthetic process
positive regulation of glomerular mesangial cell proliferation
positive regulation of platelet-derived growth factor production

Molecular Function

serine-type endopeptidase inhibitor activity

Cellular Component

extracellular space
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000398019
Coding exons: 7
Length: 52436
Individuals with no LoFs: 125497
Homozygous LoFs: 0
Heterozygous LoFs: 250
Defined: 125747
p: 0.000995

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.532	225	204	1.10	0.0000104	2515
Missense (PolyPhen)		78	72.055	1.0825		914
Synonymous	-0.248	82	79.2	1.04	0.00000443	707
Loss of Function	0.613	14	16.7	0.838	8.69e-7	208

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.011	0.011	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00036	0.00036	rare
South Asian	0.00035	0.00033	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Might function as an inhibitor of Lys-specific proteases. Might influence the maturation of megakaryocytes via its action as a serpin.;

Recessive Scores

pRec: 0.145

Intolerance Scores

LoFtool: 0.276
RVIS EVS: -0.36
RVIS percentile EVS: 29.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.450

Gene Damage Prediction

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