TPSG1

protein-coding

tryptase gamma 1, the group of Serine proteases

Gene summary

Tryptases comprise a family of trypsin-like serine proteases, the peptidase family S1. Tryptases are enzymatically active only as heparin-stabilized tetramers, and they are resistant to all known endogenous proteinase inhibitors. Several tryptase genes are clustered on chromosome 16p13.3. There is uncertainty regarding the number of genes in this cluster. Currently four functional genes - alpha I, beta I, beta II and gamma I - have been identified. And beta I has an allelic variant named alpha II, beta II has an allelic variant beta III, also gamma I has an allelic variant gamma II. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha-tryptases predominant. This gene differs from other members of the tryptase gene family in that it has C-terminal hydrophobic domain, which may serve as a membrane anchor. Tryptases have been implicated as mediators in the pathogenesis of asthma and other allergic and inflammatory disorders. [provided by RefSeq, Jul 2008]

MANE transcript

NM_012467.4

Inheritance

—

ClinVar variants

U:79B:15

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.85

Max pathogenic AF

—

Genomic locus

chr16:1,221,651-1,225,793

External References & Databases

Ensembl (ENSG00000116176)

Transcript & Mutation Effects

hg38 • Region Span ~4.1 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 TPSG1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 82

not providedTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_012467.4. 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			2 clinvar	3 clinvar	1 clinvar	6
missense			75 clinvar	9 clinvar	1 clinvar	85
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	79	13	2	94

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_012467.4	RefSeq	NP_036599.4	6	MANE Select
ENST00000234798.5	Ensembl	ENSP00000234798.4	6	MANE Select
ENST00000711428.1	Ensembl	ENSP00000518745.1	2	Standard
ENST00000711428.2	Ensembl	ENSP00000518745.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity
serine-type peptidase activity

Cellular Component

extracellular space
integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000234798
Coding exons: 6
Length: 3607
Individuals with no LoFs: 125562
Homozygous LoFs: 0
Heterozygous LoFs: 82
Defined: 125644
p: 0.000326

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.45	300	202	1.48	0.0000138	1962
Missense (PolyPhen)		100	64.063	1.561		671
Synonymous	-3.45	137	94.4	1.45	0.00000659	730
Loss of Function	-2.39	17	9.19	1.85	3.92e-7	109

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.00068	0.00067	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00022	0.00022	rare
Finnish	0.000053	0.000046	rare
European (Non-Finnish)	0.00020	0.00018	rare
South Asian	0.00046	0.00046	rare
Other	0.00036	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.315

Intolerance Scores

LoFtool: 0.128
RVIS EVS: 1.2
RVIS percentile EVS: 93.01

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.138

Gene Damage Prediction

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