TMPRSS15

protein-coding

transmembrane serine protease 15, the group of Type II transmembrane serine proteases|Scavenger receptor cysteine rich domain containing

Gene summary

This gene encodes an enzyme that converts the pancreatic proenzyme trypsinogen to trypsin, which activates other proenzymes including chymotrypsinogen and procarboxypeptidases. The precursor protein is cleaved into two chains that form a heterodimer linked by a disulfide bond. This protein is a member of the trypsin family of peptidases. Mutations in this gene cause enterokinase deficiency, a malabsorption disorder characterized by diarrhea and failure to thrive. [provided by RefSeq, Jul 2008]

Previous symbols:

PRSS7

MANE transcript

NM_002772.3

Inheritance

ClinVar variants

P:90U:249B:181

Top phenotype

Enterokinase deficiency

gnomAD constraint

pLI —, LoF o/e 0.91

Max pathogenic AF

—

Genomic locus

chr21:18,269,116-18,485,879

External References & Databases

Ensembl (ENSG00000154646)

Transcript & Mutation Effects

hg38 • Region Span ~216.8 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital enteropathy due to enteropeptidase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009173

Submitter: PanelApp Australia

congenital enteropathy due to enteropeptidase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009173

Submitter: Ambry Genetics

congenital enteropathy due to enteropeptidase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009173

Submitter: Labcorp Genetics (formerly Invitae)

congenital enteropathy due to enteropeptidase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009173

Submitter: Orphanet

Clinical Genomic Database (CGD)

Enterokinase deficiencyAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: The condition tends to self-resolve, but early in life, pancreatic enzyme replacement or hydrolyzed formula can be beneficial

Refs: 4180366; 4322674; 1147667; 943355; 6347801; 11719902

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMPRSS15 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 534

not specifiedTotal: 169

Enterokinase deficiencyTotal: 31

TMPRSS15-related disorderTotal: 23

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002772.3. 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	142 clinvar	3 clinvar	147
missense		2 clinvar	244 clinvar	27 clinvar	9 clinvar	282
nonsense	25 clinvar	5 clinvar	2 clinvar			32
start loss						0
frameshift	23 clinvar	10 clinvar				33
splice donor/acceptor (+/-2bp)		25 clinvar	1 clinvar			26
Total	48	42	249	169	12	520

Highest pathogenic variant AF is 0.0013315126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 11 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002772.3	RefSeq	NP_002763.3	25	MANE Select
ENST00000284885.8	Ensembl	ENSP00000284885.3	25	MANE Select
NM_001428056.1	RefSeq	NP_001414985.1	27	Standard
NM_001428057.1	RefSeq	NP_001414986.1	25	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

proteolysis
receptor-mediated endocytosis

Molecular Function

serine-type endopeptidase activity
scavenger receptor activity
protein binding

Cellular Component

brush border
membrane
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000284885
Coding exons: 25
Length: 216765
Individuals with no LoFs: 125287
Homozygous LoFs: 1
Heterozygous LoFs: 459
Defined: 125747
p: 0.00183

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.860	582	526	1.11	0.0000264	6708
Missense (PolyPhen)		203	185.35	1.0952		2391
Synonymous	-0.676	204	192	1.06	0.0000106	1885
Loss of Function	0.613	51	56.0	0.911	0.00000280	687

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00056	0.00055	rare
Latino/Admixed American	0.0028	0.0027	notable
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00082	0.00082	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.0024	0.0023	notable
South Asian	0.0017	0.0015	notable
Other	0.0046	0.0046	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.;
Disease: DISEASE: Enterokinase deficiency (ENTKD) [MIM:226200]: Life- threatening intestinal malabsorption disorder characterized by diarrhea and failure to thrive. {ECO:0000269|PubMed:11719902}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.245

Intolerance Scores

RVIS EVS: 1.92
RVIS percentile EVS: 97.45

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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