SERPINE2

protein-coding

serpin family E member 2, the group of Serpin peptidase inhibitors

Gene summary

This gene encodes a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. Thrombin, urokinase, plasmin and trypsin are among the proteases that this family member can inhibit. This gene is a susceptibility gene for chronic obstructive pulmonary disease and for emphysema. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]

Previous symbols:

MANE transcript

NM_001136528.2

Inheritance

—

ClinVar variants

U:48B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.17

Max pathogenic AF

—

Genomic locus

chr2:223,975,045-224,039,318

External References & Databases

Ensembl (ENSG00000135919)

Transcript & Mutation Effects

hg38 • Region Span ~64.3 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 SERPINE2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 45

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001136528.2. 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				1 clinvar		1
missense			47 clinvar	2 clinvar		49
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	48	3	0	51

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 77 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001136528.2	RefSeq	NP_001130000.1	8	MANE Select
ENST00000409304.6	Ensembl	ENSP00000386412.1	8	MANE Select
NM_001136530.1	RefSeq	NP_001130002.1	9	Standard
NM_006216.4	RefSeq	NP_006207.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in epithelium - TarBase
miR-targeted genes in leukocytes - TarBase
miR-targeted genes in lymphocytes - TarBase
Dissolution of Fibrin Clot
Intrinsic Pathway of Fibrin Clot Formation

Biological Process

blood coagulation
negative regulation of cell population proliferation
negative regulation of plasminogen activation
negative regulation of sodium ion transport
negative regulation of endopeptidase activity

Molecular Function

serine-type endopeptidase inhibitor activity
signaling receptor binding
protein binding
glycosaminoglycan binding
heparin binding

Cellular Component

extracellular region
extracellular space
cytosol
platelet alpha granule
extrinsic component of external side of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000447280
Coding exons: 9
Length: 64208
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.59	170	239	0.711	0.0000134	2690
Missense (PolyPhen)		50	89.877	0.55631		1066
Synonymous	-0.390	104	99.1	1.05	0.00000653	807
Loss of Function	3.20	3	17.4	0.172	8.24e-7	210

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000034	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serine protease inhibitor with activity toward thrombin, trypsin, and urokinase. Promotes neurite extension by inhibiting thrombin. Binds heparin.;

Recessive Scores

pRec: 0.639

Intolerance Scores

LoFtool: 0.0962
RVIS EVS: -0.4
RVIS percentile EVS: 26.53

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.802

Gene Damage Prediction

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