SPINT2

serine peptidase inhibitor, Kunitz type 2

Basic information

Region (hg38): 19:38244035-38292615

Links

ENSG00000167642 ∙ NCBI:10653 ∙ OMIM:605124 ∙ HGNC:11247 ∙ Uniprot:O43291 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital secretory sodium diarrhea 3 (Strong), mode of inheritance: AR
• congenital secretory sodium diarrhea 3 (Moderate), mode of inheritance: AR
• congenital secretory sodium diarrhea 3 (Strong), mode of inheritance: AR
• syndromic congenital sodium diarrhea (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies	AD	Gastrointestinal	Due to fecal sodium loss, individuals may present with severe (potentially lethal) secretory diarrhea and related electrolyte/metabolic derangements, including hyponatremic metabolic acidosis, and recognition may allow appropriate medical management, which includes parenteral nutrition (weaning from parenteral nutrition, with oral sodium citrate supplementation, is possible in childhood	Craniofacial; Dermatologic; Gastrointestinal; Hematologic; Musculoskeletal; Ophthalmologic	11113072; 17786112; 19185281; 20009592

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SPINT2 gene.

• not_provided (147 variants)
• Inborn_genetic_diseases (25 variants)
• Congenital_secretory_sodium_diarrhea_3 (15 variants)
• SPINT2-related_disorder (7 variants)
• Congenital_sodium_diarrhea (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SPINT2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000021102.4. 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				45	3	48
missense	2	3	51	5	2	63
nonsense	1					1
start loss	3					3
frameshift	1	1	2			4
splice donor/acceptor (+/-2bp)	3	3	1			7
Total	10	7	54	50	5

Highest pathogenic variant AF is 0.00019660403

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SPINT2	protein_coding	protein_coding	ENST00000301244	7	48580

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000751	0.931	125726	0	22	125748	0.0000875

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.997	118	153	0.773	0.00000960	1631
Missense in Polyphen		25	36.717	0.68088		436
Synonymous	0.477	60	64.9	0.925	0.00000400	517
Loss of Function	1.61	7	13.4	0.523	6.84e-7	145

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000905	0.0000905
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000149	0.000149
Middle Eastern	0.000109	0.000109
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Inhibitor of HGF activator. Also inhibits plasmin, plasma and tissue kallikrein, and factor XIa.
• Disease: DISEASE: Diarrhea 3, secretory sodium, congenital, with or without other congenital anomalies (DIAR3) [MIM:270420]: A disease characterized by life-threatening secretory diarrhea, severe metabolic acidosis and hyponatremia. Hyponatremia is secondary to extraordinarily high fecal sodium loss, with low or normal excretion of urinary sodium, in the absence of infectious, autoimmune and endocrine causes. {ECO:0000269|PubMed:19185281}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Signal Transduction;MET Receptor Activation;Signaling by MET;Signaling by MST1;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.335

Intolerance Scores

• loftool: 0.664
• rvis_EVS: 0.44
• rvis_percentile_EVS: 77.7

Haploinsufficiency Scores

• pHI: 0.100
• hipred: N
• hipred_score: 0.210
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Spint2
• Phenotype: limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); embryo 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: neural tube closure;establishment or maintenance of cell polarity;negative regulation of endopeptidase activity;negative regulation of cell-cell adhesion;epithelial cell morphogenesis involved in placental branching;basement membrane organization;cellular response to BMP stimulus;negative regulation of cell motility;negative regulation of neural precursor cell proliferation
• Cellular component: extracellular region;cytoplasm;plasma membrane;integral component of membrane
• Molecular function: endopeptidase inhibitor activity;serine-type endopeptidase inhibitor activity