SI

sucrase-isomaltase, the group of Glycoside hydrolase family 31

Basic information

Region (hg38): 3:164978897-165078496

Links

ENSG00000090402 ∙ NCBI:6476 ∙ OMIM:609845 ∙ HGNC:10856 ∙ Uniprot:P14410 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital sucrase-isomaltase deficiency (Strong), mode of inheritance: AR
• congenital sucrase-isomaltase deficiency (Strong), mode of inheritance: AR
• congenital sucrase-isomaltase deficiency (Strong), mode of inheritance: AR
• congenital sucrase-isomaltase deficiency (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Sucrase-isomaltase deficiency, congenital	AR	Gastrointestinal	Sucrose and other carbohydrate ingestion results in osmotic diarrhea, and dietary/medical therapy (eg, sucrose-reduced diet, treatment with sacrosidase) can be effective	Gastrointestinal	5848222; 6082247; 925457; 3553946; 3807985; 3403721; 1717481; 8648532; 8609217; 8648527; 9932843; 10445568; 10903344; 11340066; 12014995; 14724820; 16329100; 18043509; 19680155; 23103650; 23103652; 23103658

ClinVar

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

• not provided (944 variants)
• Sucrase-isomaltase deficiency (279 variants)
• Inborn genetic diseases (63 variants)
• not specified (11 variants)
• SI-related condition (9 variants)
• Congenital sucrose-isomaltase deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SI 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			8	149	7	164
missense		2	429	22	6	459
nonsense	20	6				26
start loss			1			1
frameshift	23	1	2			26
inframe indel			5	1		6
splice donor/acceptor (+/-2bp)		23				23
splice region			34	40	6	80
non coding			18	146	17	181
Total	43	32	463	318	30

Highest pathogenic variant AF is 0.000164

Variants in SI

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

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

Position	Type	Phenotype	Significance	ClinVar
3-164978936-C-T		Sucrase-isomaltase deficiency	Benign (Jan 13, 2018)
3-164979047-TA-T		Sucrase-isomaltase deficiency	Likely benign (Jun 14, 2016)
3-164979133-A-G		Sucrase-isomaltase deficiency	Uncertain significance (Jan 13, 2018)
3-164979145-T-G		Sucrase-isomaltase deficiency	Uncertain significance (Jan 12, 2018)
3-164979164-C-A		Sucrase-isomaltase deficiency	Benign (Apr 27, 2017)
3-164979211-T-C		Sucrase-isomaltase deficiency	Uncertain significance (Jan 13, 2018)
3-164979241-G-A		Sucrase-isomaltase deficiency	Uncertain significance (Jan 13, 2018)
3-164979294-A-G		Sucrase-isomaltase deficiency	Benign (Jan 12, 2018)
3-164979365-T-C			Likely benign (Nov 04, 2022)
3-164979380-T-G			Likely benign (May 31, 2022)
3-164979382-T-C			Uncertain significance (Jun 13, 2022)
3-164979385-G-A			Uncertain significance (Aug 16, 2022)
3-164979386-T-A		Inborn genetic diseases	Uncertain significance (May 09, 2023)
3-164979400-C-T			Uncertain significance (Mar 12, 2022)
3-164979400-CAT-C			Uncertain significance (Jul 29, 2022)
3-164979418-C-T			Uncertain significance (Aug 25, 2021)
3-164979423-C-T		SI-related disorder	Likely benign (Dec 25, 2023)
3-164979444-A-G			Likely benign (Apr 06, 2023)
3-164982223-T-C			Likely benign (Aug 17, 2023)
3-164982233-C-T			Likely benign (Dec 28, 2023)
3-164982234-A-G			Likely benign (Nov 28, 2023)
3-164982253-G-C		Sucrase-isomaltase deficiency	Benign (Jan 29, 2024)
3-164982255-G-A		Sucrase-isomaltase deficiency	Conflicting classifications of pathogenicity (Jan 31, 2024)
3-164982265-A-C		Sucrase-isomaltase deficiency • Inborn genetic diseases	Uncertain significance (Dec 14, 2023)
3-164982273-C-A			Likely benign (Jul 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SI	protein_coding	protein_coding	ENST00000264382	47	99598

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
3.94e-60	3.03e-7	125417	0	330	125747	0.00131

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-1.08	1067	972	1.10	0.0000497	12024
Missense in Polyphen		316	328.22	0.96277		3998
Synonymous	-2.29	373	321	1.16	0.0000166	3308
Loss of Function	1.18	99	112	0.880	0.00000544	1344

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00229	0.00220
Ashkenazi Jewish	0.00	0.00
East Asian	0.000493	0.000489
Finnish	0.000602	0.000601
European (Non-Finnish)	0.00169	0.00166
Middle Eastern	0.000493	0.000489
South Asian	0.00185	0.00180
Other	0.000818	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides. {ECO:0000269|PubMed:20356844}.
• Disease: DISEASE: Congenital sucrase-isomaltase deficiency (CSID) [MIM:222900]: Autosomal recessive intestinal disorder that is clinically characterized by fermentative diarrhea, abdominal pain, and cramps upon ingestion of sugar. The symptoms are the consequence of absent or drastically reduced enzymatic activities of sucrase and isomaltase. The prevalence of CSID is 0.02 % in individuals of European descent and appears to be much higher in Greenland, Alaskan, and Canadian native people. CSID arises due to post-translational perturbations in the intracellular transport, polarized sorting, aberrant processing, and defective function of SI. {ECO:0000269|PubMed:10903344, ECO:0000269|PubMed:11340066, ECO:0000269|PubMed:14724820, ECO:0000269|PubMed:16329100, ECO:0000269|PubMed:8609217}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Starch and sucrose metabolism - Homo sapiens (human);Carbohydrate digestion and absorption - Homo sapiens (human);Galactose metabolism - Homo sapiens (human);Glycogen synthetase deficiency;Glycogenosis, Type III. Cori disease, Debrancher glycogenosis;Mucopolysaccharidosis VI. Sly syndrome;Sucrase-isomaltase deficiency;Glycogenosis, Type IV. Amylopectinosis, Anderson disease;Glycogenosis, Type VI. Hers disease;Starch and Sucrose Metabolism;Digestion of dietary carbohydrate;Digestion;Digestion and absorption;sucrose degradation (Consensus)

Recessive Scores

• pRec: 0.172

Intolerance Scores

• loftool: 0.0899
• rvis_EVS: 0.67
• rvis_percentile_EVS: 84.62

Haploinsufficiency Scores

• pHI: 0.0721
• hipred: N
• hipred_score: 0.422

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.586

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Sis

Gene ontology

• Biological process: carbohydrate metabolic process;polysaccharide digestion
• Cellular component: Golgi apparatus;plasma membrane;brush border;integral component of membrane;apical plasma membrane;extracellular exosome
• Molecular function: alpha-1,4-glucosidase activity;oligo-1,6-glucosidase activity;sucrose alpha-glucosidase activity;carbohydrate binding