SPINK1

serine peptidase inhibitor Kazal type 1, the group of Serine peptidase inhibitors, Kazal type

Basic information

Region (hg38): 5:147824571-147831671

Links

ENSG00000164266 ∙ NCBI:6690 ∙ OMIM:167790 ∙ HGNC:11244 ∙ Uniprot:P00995 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hereditary chronic pancreatitis (No Known Disease Relationship), mode of inheritance: Unknown
• tropical pancreatitis (Strong), mode of inheritance: AD
• hereditary chronic pancreatitis (Strong), mode of inheritance: AD
• hereditary chronic pancreatitis (Supportive), 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	Dietary measures (eg, low-fat diet with frequent feeding), hydration, and antioxidants, with avoidance of precipitants such as alcohol and tobacco, can beneficial in order to ameliorate episodes of pancreatitis; Individuals may be at high risk of pancreatic cancer, and awareness may allow early diagnosis and treatment	Gastrointestinal; Oncologic	2813331; 10691414; 10835640; 11938439; 12011155; 16492714; 17274009; 18184119; 18755888; 20543535; 20664488; 21610753; 20676769; 21415673; 21375584; 20977904; 22228370; 24624459

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPINK1 gene.

• Hereditary pancreatitis (148 variants)
• not specified (37 variants)
• not provided (35 variants)
• Tropical pancreatitis (3 variants)
• SPINK1-related condition (2 variants)
• Hereditary pancreatitis;Tropical pancreatitis (2 variants)
• Pancreatitis, chronic, susceptibility to (1 variants)
• Diabetes mellitus (1 variants)
• Chronic pancreatitis (1 variants)
• Pancreatitis (1 variants)
• Finnish congenital nephrotic syndrome (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPINK1 gene is commonly pathogenic or not.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				27		27
missense			62	6		68
nonsense	2		1			3
start loss			1			1
frameshift	1	1				2
inframe indel		1	1			2
splice donor/acceptor (+/-2bp)	1	2				3
splice region			5	3		8
non coding			10	18	3	31
Total	4	4	75	51	3

Highest pathogenic variant AF is 0.0000197

Variants in SPINK1

This is a list of pathogenic ClinVar variants found in the SPINK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-147824583-GA-G		Hereditary pancreatitis	Uncertain significance (Jun 14, 2016)
5-147824596-AT-A		not specified	Uncertain significance (Aug 18, 2023)
5-147824610-A-G		Hereditary pancreatitis	Likely benign (Apr 27, 2017)
5-147824613-G-A		Hereditary pancreatitis	Uncertain significance (Jan 12, 2018)
5-147824622-GCCTCGCGGTGACCTGATGGGATTTCAAAA-G		not specified	Uncertain significance (Aug 18, 2023)
5-147824627-G-A		Hereditary pancreatitis	Benign (Jan 12, 2018)
5-147824629-G-A		Hereditary pancreatitis	Benign/Likely benign (Apr 20, 2020)
5-147824634-C-A		Hereditary pancreatitis	Conflicting classifications of pathogenicity (Sep 09, 2019)
5-147824662-C-T		Hereditary pancreatitis	Likely benign (Jun 24, 2022)
5-147824664-G-T		Hereditary pancreatitis	Uncertain significance (Nov 29, 2016)
5-147824665-C-T		Hereditary pancreatitis	Uncertain significance (Apr 03, 2023)
5-147824666-A-C		Hereditary pancreatitis	Uncertain significance (Jun 28, 2022)
5-147824669-G-A		Hereditary pancreatitis	Uncertain significance (Jun 20, 2022)
5-147824670-C-A		Hereditary pancreatitis	Likely benign (Dec 21, 2023)
5-147824670-C-G		Hereditary pancreatitis	Likely benign (Oct 22, 2019)
5-147824670-C-T		not specified • Hereditary pancreatitis	Benign/Likely benign (Jan 27, 2024)
5-147824672-C-G		Hereditary pancreatitis	Uncertain significance (Aug 30, 2022)
5-147824674-G-C		Hereditary pancreatitis	Uncertain significance (Oct 23, 2017)
5-147824675-A-C		Hereditary pancreatitis	Uncertain significance (Feb 11, 2024)
5-147824677-T-A		not specified • Hereditary pancreatitis	Uncertain significance (Nov 22, 2023)
5-147824679-T-C		Hereditary pancreatitis	Likely benign (May 24, 2021)
5-147824680-T-C		Hereditary pancreatitis	Likely benign (Oct 15, 2022)
5-147824683-A-G		Hereditary pancreatitis	Uncertain significance (Sep 29, 2023)
5-147824684-T-A		not specified • Hereditary pancreatitis	Uncertain significance (Jan 13, 2022)
5-147824685-G-A		not specified • Hereditary pancreatitis	Likely benign (Oct 20, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPINK1	protein_coding	protein_coding	ENST00000296695	4	7219

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.315	0.621	125456	0	82	125538	0.000327

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.123	45	42.7	1.05	0.00000216	501
Missense in Polyphen		13	14.521	0.89527		164
Synonymous	-0.773	18	14.3	1.26	6.11e-7	146
Loss of Function	1.43	1	4.14	0.241	1.73e-7	54

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000870	0.0000870
Ashkenazi Jewish	0.00	0.00
East Asian	0.00335	0.00334
Finnish	0.00	0.00
European (Non-Finnish)	0.000124	0.000123
Middle Eastern	0.00335	0.00334
South Asian	0.0000660	0.0000653
Other	0.000329	0.000327

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease inhibitor which exhibits anti-trypsin activity (PubMed:7142173). In the pancreas, protects against trypsin-catalyzed premature activation of zymogens (By similarity). {ECO:0000250|UniProtKB:P09036, ECO:0000269|PubMed:7142173}.
• 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:10691414, ECO:0000269|PubMed:10835640, ECO:0000269|PubMed:12974284, ECO:0000269|PubMed:18617776, ECO:0000269|PubMed:19888199}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Tropical calcific pancreatitis (TCP) [MIM:608189]: Idiopathic, juvenile, nonalcoholic form of chronic pancreatitis widely prevalent in several tropical countries. It can be associated with fibrocalculous pancreatic diabetes (FCPD) depending on both environmental and genetic factors. TCP differs from alcoholic pancreatitis by a much younger age of onset, pancreatic calcification, a high incidence of insulin dependent but ketosis resistant diabetes mellitus, and an exceptionally high incidence of pancreatic cancer. {ECO:0000269|PubMed:12011155, ECO:0000269|PubMed:12187509}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• Pathway: Androgen Receptor Network in Prostate Cancer (Consensus)

Recessive Scores

• pRec: 0.179

Intolerance Scores

• loftool: 0.542
• rvis_EVS: 0.81
• rvis_percentile_EVS: 87.82

Haploinsufficiency Scores

• pHI: 0.384
• hipred: N
• hipred_score: 0.146

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.547

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spink1
• Phenotype: homeostasis/metabolism phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); endocrine/exocrine gland phenotype; immune system phenotype; digestive/alimentary phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: negative regulation of nitric oxide mediated signal transduction;sperm capacitation;negative regulation of peptidyl-tyrosine phosphorylation;regulation of acrosome reaction;negative regulation of calcium ion import;negative regulation of serine-type endopeptidase activity;regulation of store-operated calcium entry
• Cellular component: extracellular exosome
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity;protein binding