PRSS1

serine protease 1, the group of Serine proteases

Basic information

Region (hg38): 7:142749468-142753072

Previous symbols: [ "TRY1" ]

Links

ENSG00000204983 ∙ NCBI:5644 ∙ OMIM:276000 ∙ HGNC:9475 ∙ Uniprot:P07477 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary chronic pancreatitis (Supportive), mode of inheritance: AD
• hereditary chronic pancreatitis (Definitive), mode of inheritance: AD
• hereditary chronic pancreatitis (Definitive), mode of inheritance: AD
• hereditary chronic pancreatitis (Definitive), mode of inheritance: AD
• malignant pancreatic neoplasm (Moderate), mode of inheritance: AD
• hereditary chronic pancreatitis (Strong), mode of inheritance: AD
• hereditary chronic pancreatitis (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pancreatitis, hereditary	AD	Gastrointestinal; Oncologic	To decrease attacks, dietary measures (eg, low-fat diet), hydration, and antioxidants, with avoidance of precipitants, such as alcohol and tobacco can beneficial; Medical management (including with pancreatic enzyme replacement) may be benefiical; Individuals may be at increased risk for manifestations such as pancreatic cancer, and awareness may allow prompt detection and treatment	Gastrointestinal; Oncologic	6023921; 8841182; 9322498; 9557894; 10204851; 18184119; 18755888; 22088471; 22094894; 22379635; 23503650; 23864476; 24236450; 24242859; 24624459

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PRSS1 gene.

• Hereditary_pancreatitis (791 variants)
• not_specified (85 variants)
• not_provided (35 variants)
• PRSS1-related_disorder (4 variants)
• Trypsinogen_deficiency (2 variants)
• Vitamin_D-dependent_rickets_type_II_with_alopecia (1 variants)
• Myoepithelial_tumor (1 variants)
• Hereditary_cancer-predisposing_syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PRSS1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000002769.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		3	195	2	201
missense	5	9	465	27	3	509
nonsense	1		8			9
start loss			4			4
frameshift			7			7
splice donor/acceptor (+/-2bp)			7	1	1	9
Total	7	9	494	223	6

Highest pathogenic variant AF is 0.000142705

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PRSS1	protein_coding	protein_coding	ENST00000311737	5	3605

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.14e-11	0.0145	125642	1	105	125748	0.000422

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.01	194	130	1.50	0.00000764	1561
Missense in Polyphen		55	37.875	1.4522		499
Synonymous	-3.10	78	50.1	1.56	0.00000307	460
Loss of Function	-0.941	14	10.7	1.31	6.38e-7	112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00159	0.00152
Ashkenazi Jewish	0.000900	0.000695
East Asian	0.000274	0.000272
Finnish	0.000344	0.000323
European (Non-Finnish)	0.000442	0.000413
Middle Eastern	0.000274	0.000272
South Asian	0.000312	0.000294
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Has activity against the synthetic substrates Boc-Phe- Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val- Pro-Arg-Mec. The single-chain form is more active than the two- chain form against all of these substrates. {ECO:0000269|PubMed:7945238}.
• Disease: DISEASE: Pancreatitis, hereditary (PCTT) [MIM:167800]: A disease characterized by pancreas inflammation, permanent destruction of the pancreatic parenchyma, maldigestion, and severe abdominal pain attacks. {ECO:0000269|PubMed:10204851, ECO:0000269|PubMed:10381903, ECO:0000269|PubMed:10930381, ECO:0000269|PubMed:11073545, ECO:0000269|PubMed:11788572, ECO:0000269|PubMed:11866271, ECO:0000269|PubMed:14695529, ECO:0000269|PubMed:15776435, ECO:0000269|PubMed:8841182, ECO:0000269|PubMed:9322498, ECO:0000269|PubMed:9633818}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Influenza A - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Pancreatic secretion - Homo sapiens (human);Neuroactive ligand-receptor interaction - Homo sapiens (human);Extracellular matrix organization;Cobalamin (Cbl, vitamin B12) transport and metabolism;Metabolism;Metabolism of water-soluble vitamins and cofactors;Activation of Matrix Metalloproteinases;Metabolism of vitamins and cofactors;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.781

Intolerance Scores

• loftool: 0.125
• rvis_EVS: -0.12
• rvis_percentile_EVS: 44.89

Haploinsufficiency Scores

• pHI: 0.478
• hipred: N
• hipred_score: 0.203
• ghis: 0.439

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.370

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Try10

Gene ontology

• Biological process: proteolysis;digestion;cobalamin metabolic process;extracellular matrix disassembly
• Cellular component: extracellular region;extracellular space;collagen-containing extracellular matrix;blood microparticle
• Molecular function: serine-type endopeptidase activity;serine-type peptidase activity;metal ion binding