TMPRSS9

protein-coding

transmembrane serine protease 9, the group of Type II transmembrane serine proteases

Gene summary

The protein encoded by this gene is a membrane-bound type II serine polyprotease that is cleaved to release three different proteases. Two of the proteases are active and can be inhibited by serine protease inhibitors, and one is thought to be catalytically inactive. This gene enhances the invasive capability of pancreatic cancer cells and may be involved in cancer progression. [provided by RefSeq, Jul 2016]

MANE transcript

NM_001395513.1

Inheritance

ClinVar variants

P:2U:259B:39

Top phenotype

Global developmental delay

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr19:2,360,238-2,426,261

External References & Databases

Ensembl (ENSG00000178297)

Transcript & Mutation Effects

hg38 • Region Span ~66.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0700092

Submitter: PanelApp Australia

complex neurodevelopmental disorderLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0100038

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMPRSS9 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 273

not providedTotal: 18

Global developmental delayTotal: 2

TMPRSS9-related neurodevelopmental disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001395513.1. 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	5 clinvar	2 clinvar	9
missense			250 clinvar	29 clinvar	3 clinvar	282
nonsense		1 clinvar	1 clinvar			2
start loss						0
frameshift		1 clinvar	1 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	2	259	34	5	300

Highest pathogenic variant AF is 0.0000049563223

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 13 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001395513.1	RefSeq	NP_001382442.1	18	MANE Select
ENST00000696167.1	Ensembl	ENSP00000512457.1	18	MANE Select
NM_001385642.1	RefSeq	NP_001372571.1	12	Standard
NM_182973.3	RefSeq	NP_892018.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis

Molecular Function

serine-type endopeptidase activity

Cellular Component

integral component of plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000332578
Coding exons: 17
Length: 36469
Individuals with no LoFs: 125321
Homozygous LoFs: 2
Heterozygous LoFs: 425
Defined: 125748
p: 0.00170

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.22	744	656	1.13	0.0000431	6647
Missense (PolyPhen)		285	256.14	1.1127		2596
Synonymous	-1.79	336	297	1.13	0.0000213	2279
Loss of Function	1.73	33	45.6	0.723	0.00000247	479

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00091	0.00086	rare
Latino/Admixed American	0.0011	0.0010	notable
Ashkenazi Jewish	0.00031	0.00030	rare
East Asian	0.0010	0.0010	notable
Finnish	0.00071	0.00065	rare
European (Non-Finnish)	0.0026	0.0024	notable
South Asian	0.0020	0.0019	notable
Other	0.0010	0.00098	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serase-1 and serase-2 are serine proteases that hydrolyze the peptides N-t-Boc-Gln-Ala-Arg-AMC and N-t-Boc-Gln- Gly-Arg-AMC. In contrast, N-t-Boc-Ala-Phe-Lys-AMC and N-t-Boc-Ala- Pro-Ala-AMC are not significantly hydrolyzed.;

Intolerance Scores

LoFtool: 0.0742
RVIS EVS: 1.65
RVIS percentile EVS: 96.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.188

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High