GeneBe

SI

protein-coding

sucrase-isomaltase, the group of Glycoside hydrolase family 31

Gene 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 subunits heterodimerize to form the sucrose-isomaltase complex. This complex is essential for the digestion of dietary carbohydrates including starch, sucrose and isomaltose. Mutations in this gene are the cause of congenital sucrase-isomaltase deficiency.[provided by RefSeq, Apr 2010]

MANE transcript

NM_001041.4

Inheritance

AR, SD

ClinVar variants

P:178U:727B:366

Top phenotype

Sucrase-isomaltase deficiency, congenital

gnomAD constraint

pLI —, LoF o/e 0.88

Max pathogenic AF

—

Genomic locus

chr3:164,978,898-165,078,496

External References & Databases

Ensembl (ENSG00000090402)NCBI Gene (6476)OMIM (609845)HGNC:10856GenCCUniProt (P14410)AlphaFoldClinVar (SI)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~99.6 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

congenital sucrase-isomaltase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009114

Submitter: Labcorp Genetics (formerly Invitae)

congenital sucrase-isomaltase deficiencySTRONG

Inheritance Pattern: SD

Disease ID:MONDO:0009114

Submitter: PanelApp Australia

congenital sucrase-isomaltase deficiencySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0009114

Submitter: Orphanet

congenital sucrase-isomaltase deficiencySTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0009114

Submitter: Laboratory for Molecular Medicine

This gene-disease relationship has undergone rapid assessment. Classifications are based on preliminary review of gene-disease validity during analysis of genomic sequencing results.

Clinical Genomic Database (CGD)

Sucrase-isomaltase deficiency, congenitalAR

Manifestation: Gastrointestinal

Intervention: Gastrointestinal

Rationale: Sucrose and other carbohydrate ingestion results in osmotic diarrhea, and dietary/medical therapy (eg, sucrose-reduced diet, treatment with sacrosidase) can be effective

Refs: 5848222; 6082247; 925457; 3553946; 3807985; 3403721; 1717481; 8648532; 8609217; 8648527; 9932843; 10445568; 10903344; 11340066; 12014995; 14724820; 16329100; 18043509; 19680155; 23103650; 23103652; 23103658Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SI variants in ClinVar

9 Conditions Cataloged
not providedTotal: 1355
Sucrase-isomaltase deficiencyTotal: 490
Inborn genetic diseasesTotal: 237
not specifiedTotal: 89
SI-related disorderTotal: 56
SI-related disordersTotal: 9
Congenital sucrose-isomaltase deficiencyTotal: 1
Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001041.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
16
clinvar
307
clinvar
6
clinvar
 329
missense
6
clinvar
10
clinvar
702
clinvar
52
clinvar
1
clinvar
 771
nonsense
30
clinvar
29
clinvar
2
clinvar
 61
start loss
1
clinvar
 1
frameshift
30
clinvar
27
clinvar
4
clinvar
 61
splice donor/acceptor (+/-2bp)
1
clinvar
45
clinvar
2
clinvar
 48
Total6711172735971271

Highest pathogenic variant AF is 0.0026619514

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001041.4RefSeqNP_001032.247MANE Select
ENST00000264382.8EnsemblENSP00000264382.347MANE Select
ENST00000476593.1EnsemblENSP00000419450.12Standard
XM_011513078.3RefSeqXP_011511380.147Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • carbohydrate metabolic process
  • polysaccharide digestion

Molecular Function

  • alpha-1,4-glucosidase activity
  • oligo-1,6-glucosidase activity
  • sucrose alpha-glucosidase activity
  • carbohydrate binding

Cellular Component

  • Golgi apparatus
  • plasma membrane
  • brush border
  • integral component of membrane
  • apical plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000264382
Coding exons
47
Length
99598
Individuals with no LoFs
125417
Homozygous LoFs
0
Heterozygous LoFs
330
Defined
125747
p
0.00131
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense-1.0810679721.100.000049712024
Missense (PolyPhen)316328.220.962773998
Synonymous-2.293733211.160.00001663308
Loss of Function1.18991120.8800.000005441344

Population LoF Frequency

PopulationCAFp-valueStatus
African0.00100.00092notable
Latino/Admixed American0.00130.0013notable
Ashkenazi Jewish00.0absent
East Asian0.000490.00049rare
Finnish0.000600.00060rare
European (Non-Finnish)0.00170.0017notable
South Asian0.00180.0018notable
Other0.000820.00081rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.172

Intolerance Scores

LoFtool
0.0899
RVIS EVS
0.67
RVIS percentile EVS
84.62

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.586

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumHigh
CancerMediumMediumMedium
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