Information on ALPI
Basic details
Alt. symbols: IAP
Approved name: alkaline phosphatase, intestinal
Alt. names: intestinal alkaline phosphatase
Location: 2q37.1: 232456125 - 232460753 (+)
Gene type: protein_coding, 2 transcripts.
Scores: LoFtool: 0.248000 | pLI: 0.00000000 | LOEUF: 1.486
Normal function
Most mammals harbor 4 different alkaline phosphatase isozymes: placental, germ cell, intestinal and tissue non-specific (liver/bone/kidney). ALPI encodes the intestinal form and is mainly expressed in the small intestinal brush border, from which it is released into the lumen within vesicles that transport the active enzyme to distal intestinal sites where it can dephosphorylate microbiota?derived LPS and thereby considerably reduce its TLR4 agonist activity (PMID: 29567797).
Dysfunction and disease
Parlato et al. (2018) identified biallelic ALPI variants in 2 pediatric patients with inflammatory bowel disease (IBD), one of very early onset (~age 2) and one of later onset (~age 15) (PMID: 29567797). The former (P1) had severe gastrointestinal (GI) disease without significant extra-GI manifestations, while the latter (P2) initially presented with joint symptoms that improved with IBD management. Both showed evidence of autoantibody production, but P2 also had hypergammaglobulinemia and eleva ted inflammatory markers. Both were found to be compound heterozygous for parentally-inherited variants in the catalytic domain – A97T and A350V in the case of P1 and A360V and Q439X in the case of P2. Via in vitro studies in HEK293 cells, the authors showed that these variants either impaired the stability or catalytic activity of ALPI. They also found that ALPI expression was markedly reduced in patients’ small intestinal biopsies, and its activity was undetectable in their stool samples. In keeping with its proposed role in reducing LPS-dependent intestinal immune activation, the ALPI mutants were also unable to inhibit LPS activity as indicated by in vitro IL-8 induction. [Load More]
[Reviewed by Andrés Caballero-Oteyza on 2021-10-20 09:09:37]
Associated conditions
| Acronym | Condition's_name | MOI | Mode_of_action |
OMIM_ID | No.cases |
|---|---|---|---|---|---|
IBD33 |
Inflammatory bowel disease 33 | AR |
- | 0 (0 fams) |
Please mind that full curation (inclusion of all published patients) of this gene has not started yet. Please contact us if you want to volunteer.
Transcripts of ALPI
| Name | ENSEMBL_ID | LRG_ID | CCDS_ID | MANE | Transcript.type | Exons | Canonical | CDS_length | REFSEQ_ID |
|---|---|---|---|---|---|---|---|---|---|
| 201 | ENST00000295463.4 | CCDS2492 | Select | protein_coding | 11 | Yes | 3241 | NM_001631 |
Published variants
Found 0 variants
| Var.name | Exon/Intron | cDNA_pos. | CDS_change | Prot.change | Var.type | Var.class. | Patients |
|---|
Please mind that full curation (inclusion of all published variants) of this gene has not started yet. Please contact us if you want to volunteer.
Diagnostic pitfalls & paradigms
Considerations to take into account when analyzing this gene
| Year | Paradigm ⓘ | PMID | Notes |
|---|---|---|---|
| - | Regions of Homology | - | |
| - | Cryptic splicing | - | Unreported or not recorded in our DB. |
| - | Uniparental disomy | - | Unreported or not recorded in our DB. |
| - | Mosaicism | - | Unreported or not recorded in our DB. |
| - | Incomplete penetrance | - | Unreported or not recorded in our DB. |
| - | Di-/oligo-genic inheritance | - | Unreported or not recorded in our DB. |
| - | Somatic reversion | - | Unreported or not recorded in our DB. |
References linked to variants in ALPI
| ID | Year | Title | Journal | PMID | Variants |
|---|