SI (sucrase-isomaltase)

Gene

• Entrez ID: 6476
• Gene name: Sucrase-isomaltase
• Gene symbol: SI
• Synonyms (NCBI Gene): -
• Chromosome: 3
• Chromosome location: 3q26.1
• Summary: This gene encodes a sucrase-isomaltase enzyme that is expressed in the intestinal brush border. The encoded protein is synthesized as a precursor protein that is cleaved by pancreatic proteases into two enzymatic subunits sucrase and isomaltase. These two

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs79717168	A>C	Uncertain-significance, pathogenic	Coding sequence variant, missense variant
rs121912611	T>G	Pathogenic	Missense variant, coding sequence variant
rs121912612	T>C	Pathogenic	Missense variant, coding sequence variant
rs121912613	A>G	Pathogenic	Missense variant, coding sequence variant
rs121912614	C>T	Pathogenic	Missense variant, coding sequence variant
rs121912615	A>C,G	Pathogenic-likely-pathogenic	Missense variant, coding sequence variant
rs121912616	C>T	Conflicting-interpretations-of-pathogenicity, likely-pathogenic	Missense variant, coding sequence variant
rs200451408	G>A,C	Pathogenic, likely-pathogenic	Coding sequence variant, missense variant, stop gained
rs267607049	A>G	Pathogenic	Coding sequence variant, missense variant
rs758259365	C>A,T	Pathogenic	Stop gained, missense variant, coding sequence variant
rs776569472	AA>-	Likely-pathogenic, uncertain-significance	Coding sequence variant, frameshift variant
rs779803851	G>A	Pathogenic, uncertain-significance	Stop gained, coding sequence variant
rs780535026	TA>-	Likely-pathogenic	Frameshift variant, coding sequence variant
rs1553775177	A>C	Likely-pathogenic	Splice donor variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030316	hsa-miR-26b-5p	Microarray	19088304
MIRT1348092	hsa-miR-1179	CLIP-seq
MIRT1348093	hsa-miR-3121-3p	CLIP-seq
MIRT1348094	hsa-miR-3158-3p	CLIP-seq
MIRT1348095	hsa-miR-3163	CLIP-seq
MIRT1348096	hsa-miR-323-3p	CLIP-seq
MIRT1348097	hsa-miR-369-3p	CLIP-seq
MIRT1348098	hsa-miR-374a	CLIP-seq
MIRT1348099	hsa-miR-374b	CLIP-seq
MIRT1348100	hsa-miR-4263	CLIP-seq
MIRT1348101	hsa-miR-4282	CLIP-seq
MIRT1348102	hsa-miR-4446-3p	CLIP-seq
MIRT1348103	hsa-miR-4735-5p	CLIP-seq
MIRT1348104	hsa-miR-4753-3p	CLIP-seq
MIRT1348105	hsa-miR-576-5p	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
GATA4	Activation	22539995
PIAS1	Activation	22539995

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0003824	Function	Catalytic activity	IEA
GO:0004553	Function	Hydrolase activity, hydrolyzing O-glycosyl compounds	IEA
GO:0004558	Function	Alpha-1,4-glucosidase activity	IBA
GO:0004574	Function	Oligo-1,6-glucosidase activity	IDA	27480812
GO:0004574	Function	Oligo-1,6-glucosidase activity	IEA
GO:0004575	Function	Sucrose alpha-glucosidase activity	IEA
GO:0004575	Function	Sucrose alpha-glucosidase activity	TAS
GO:0005515	Function	Protein binding	IPI	36968271
GO:0005794	Component	Golgi apparatus	TAS	1717481
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0005903	Component	Brush border	TAS	1717481
GO:0005975	Process	Carbohydrate metabolic process	IEA
GO:0005987	Process	Sucrose catabolic process	IDA	27480812
GO:0016020	Component	Membrane	IEA
GO:0016324	Component	Apical plasma membrane	IEA
GO:0016787	Function	Hydrolase activity	IEA
GO:0016798	Function	Hydrolase activity, acting on glycosyl bonds	IEA
GO:0030246	Function	Carbohydrate binding	IEA
GO:0044245	Process	Polysaccharide digestion	TAS
GO:0046352	Process	Disaccharide catabolic process	IEA
GO:0070062	Component	Extracellular exosome	HDA	23533145
GO:0090599	Function	Alpha-glucosidase activity	IEA

Other IDs

• MIM: 609845
• HGNC: 10856
• e!Ensembl: ENSG00000090402

Protein

• UniProt ID: P14410
• Protein name: Sucrase-isomaltase, intestinal [Cleaved into: Sucrase (EC 3.2.1.48); Isomaltase (EC 3.2.1.10)]
• Protein 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.
• PDB: 3LPO, 3LPP
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00088	Trefoil	63 → 109	Trefoil (P-type) domain	Domain
  PF16863	NtCtMGAM_N	125 → 234	N-terminal barrel of NtMGAM and CtMGAM, maltase-glucoamylase	Domain
  PF01055	Glyco_hydro_31	324 → 797	Glycosyl hydrolases family 31	Family
  PF00088	Trefoil	933 → 977	Trefoil (P-type) domain	Domain
  PF16863	NtCtMGAM_N	994 → 1107	N-terminal barrel of NtMGAM and CtMGAM, maltase-glucoamylase	Domain
  PF13802	Gal_mutarotas_2	1108 → 1175	Galactose mutarotase-like	Domain
  PF01055	Glyco_hydro_31	1195 → 1691	Glycosyl hydrolases family 31	Family

• Tissue specificity: TISSUE SPECIFICITY: Expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells. Expressed at very low levels in the colon. {ECO:0000269|PubMed:1677636}.
• Sequence:

  MARKKFSGLEISLIVLFVIVTIIAIALIVVLATKTPAVDEISDSTSTPATTRVTTNPSDS
  GKCPNVLNDPVNVRINCIPEQFPTEGICAQRGCCWRPWNDSLIPWCFFVDNHGYNVQDMT
  TTSIGVEAKLNRIPSPTLFGNDINSVLFTTQNQTPNRFRFKITDPNNRRYEVPHQYVKEF
  TGPTVSDTLYDVKVAQNPFSIQVIRKSNGKTLFDTSIGPLVYSDQYLQISTRLPSDYIYG
  IGEQVHKRFRHDLSWKTWPIFTRDQLPGDNNNNLYGHQTFFMCIEDTSGKSFGVFLMNSN
  AMEIFIQPTPIVTYRVTGGILDFYILLGDTPEQVVQQYQQLVGLPAMPAYWNLGFQLSRW
  NYKSLDVVKEVVRRNREAGIPFDTQVTDIDYMEDKKDFTYDQVAFNGLPQFVQDLHDHGQ
  KYVIILDPAISIGRRANGTTYATYERGNTQHVWINESDGSTPIIGEVWPGLTVYPDFTNP
  NCIDWWANECSIFHQEVQYDGLWIDMNEVSSFIQGSTKGCNVNKLNYPPFTPDILDKLMY
  SKTICMDAVQNWGKQYDVHSLYGYSMAIATEQAVQKVFPNKRSFILTRSTFAGSGRHAAH
  WLGDNTASWEQMEWSITGMLEFSLFGIPLVGADICGFVAETTEELCRRWMQLGAFYPFSR
  NHNSDGYEHQDPAFFGQNSLLVKSSRQYLTIRYTLLPFLYTLFYKAHVFGETVARPVLHE
  FYEDTNSWIEDTEFLWGPALLITPVLKQGADTVSAYIPDAIWYDYESGAKRPWRKQRVDM
  YLPADKIGLHLRGGYIIPIQEPDVTTTASRKNPLGLIVALGENNTAKGDFFWDDGETKDT
  IQNGNYILYTFSVSNNTLDIVCTHSSYQEGTTLAFQTVKILGLTDSVTEVRVAENNQPMN
  AHSNFTYDASNQVLLIADLKLNLGRNFSVQWNQIFSENERFNCYPDADLATEQKCTQRGC
  VWRTGSSLSKAPECYFPRQDNSYSVNSARYSSMGITADLQLNTANARIKLPSDPISTLRV
  EVKYHKNDMLQFKIYDPQKKRYEVPVPLNIPTTPISTYEDRLYDVEIKENPFGIQIRRRS
  SGRVIWDSWLPGFAFNDQFIQISTRLPSEYIYGFGEVEHTAFKRDLNWNTWGMFTRDQPP
  GYKLNSYGFHPYYMALEEEGNAHGVFLLNSNAMDVTFQPTPALTYRTVGGILDFYMFLGP
  TPEVATKQYHEVIGHPVMPAYWALGFQLCRYGYANTSEVRELYDAMVAANIPYDVQYTDI
  DYMERQLDFTIGEAFQDLPQFVDKIRGEGMRYIIILDPAISGNETKTYPAFERGQQNDVF
  VKWPNTNDICWAKVWPDLPNITIDKTLTEDEAVNASRAHVAFPDFFRTSTAEWWAREIVD
  FYNEKMKFDGLWIDMNEPSSFVNGTTTNQCRNDELNYPPYFPELTKRTDGLHFRTICMEA
  EQILSDGTSVLHYDVHNLYGWSQMKPTHDALQKTTGKRGIVISRSTYPTSGRWGGHWLGD
  NYARWDNMDKSIIGMMEFSLFGMSYTGADICGFFNNSEYHLCTRWMQLGAFYPYSRNHNI
  ANTRRQDPASWNETFAEMSRNILNIRYTLLPYFYTQMHEIHANGGTVIRPLLHEFFDEKP
  TWDIFKQFLWGPAFMVTPVLEPYVQTVNAYVPNARWFDYHTGKDIGVRGQFQTFNASYDT
  INLHVRGGHILPCQEPAQNTFYSRQKHMKLIVAADDNQMAQGSLFWDDGESIDTYERDLY
  LSVQFNLNQTTLTSTILKRGYINKSETRLGSLHVWGKGTTPVNAVTLTYNGNKNSLPFNE
  DTTNMILRIDLTTHNVTLEEPIEINWS

• Sequence length: 1827

Pathways

KEGG:

Galactose metabolism
Starch and sucrose metabolism
Metabolic pathways
Carbohydrate digestion and absorption

Reactome:

Digestion of dietary carbohydrate
Intestinal saccharidase deficiencies

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Congenital sucrose-isomaltase deficiency	Likely pathogenic; Pathogenic	rs200972419	RCV001250214	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
SI-related disorder	Likely pathogenic; Pathogenic	rs774405472, rs201055347, rs781470490, rs2473240506, rs2473317311, rs1435641758, rs2473282291	RCV003401994 RCV003401824 RCV004750308 RCV003414501 RCV003405837 RCV003946963 RCV003976862	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Sucrase-isomaltase deficiency	Likely pathogenic; Pathogenic	rs1185991890, rs2108219188, rs1714177959, rs2108217077, rs772671498, rs1000661675, rs1298467427, rs898055093, rs375113759, rs1294620045, rs754468827, rs2108202378, rs201055347, rs267607049, rs121912612, rs121912613, rs121912614, rs1038499768, rs754961413, rs2473358472, rs781470490, rs769229932, rs751534972, rs751263307, rs1713910885, rs1712611940, rs1714299831, rs2473296292, rs757893762, rs775933206, rs1718661487, rs776569472, rs200451408, rs758259365, rs1553775177, rs1221816681, rs200972419, rs200328403	RCV002476717 RCV001535941 RCV001536069 RCV001785874 RCV005025665 RCV002507698 RCV005032062 RCV005023456 RCV002489908 RCV002468653 RCV005038422 RCV002506888 RCV005038432 RCV000001478 RCV000001479 RCV000001480 RCV000001481 RCV005028147 RCV003989808 RCV005034781 RCV003404134 RCV004017945 RCV005034422 RCV005034447 RCV005034589 RCV003155534 RCV003389590 RCV005036844 RCV005036911 RCV005036924 RCV005030209 RCV000778684 RCV002481579 RCV003129929 RCV000605151 RCV002499337 RCV000778685 RCV001265580	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGENITAL SUCRASE-ISOMALTASE DEFICIENCY	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Benign; Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GENERALIZED ANXIETY DISORDER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations