ALPI
protein-codingalkaline phosphatase, intestinal, the group of Alkaline phosphatases
Gene summary
There are at least four distinct but related alkaline phosphatases: intestinal, placental, placental-like, and liver/bone/kidney (tissue non-specific). The intestinal alkaline phosphatase gene encodes a digestive brush-border enzyme. This enzyme is a component of the gut mucosal defense system and is thought to function in the detoxification of lipopolysaccharide, and in the prevention of bacterial translocation in the gut. [provided by RefSeq, Dec 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~4.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0005265
Submitter: PanelApp Australia
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ALPI variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001631.5. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 40 | 1 | 42 | ||
| missense | 89 | 9 | 5 | 103 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 1 | 91 | 49 | 6 | 147 |
Highest pathogenic variant AF is 0.00009812531
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001622.2 | 11 | MANE Select | |
| Ensembl | ENSP00000295463.3 | 11 | MANE Select | |
| Ensembl | ENSP00000413068.1 | 1 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| alpi.1 | Danio rerio | Structure: alkaline phosphatase activity Quality: decreased occurrence abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Folate biosynthesis - Homo sapiens (human)
- Thiamine metabolism - Homo sapiens (human)
- Vitamin D Receptor Pathway
- Metabolism of lipids
- Post-translational modification: synthesis of GPI-anchored proteins
Biological Process
- phosphatidic acid biosynthetic process
- digestion
- dephosphorylation
Molecular Function
- magnesium ion binding
- protease binding
- alkaline phosphatase activity
- protein binding
- zinc ion binding
Cellular Component
- extracellular region
- plasma membrane
- anchored component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000295463
- Coding exons
- 11
- Length
- 3910
- Individuals with no LoFs
- 125505
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 239
- Defined
- 125744
- p
- 0.000951
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.403 | 327 | 348 | 0.939 | 0.0000227 | 3375 |
| Missense (PolyPhen) | 95 | 113.93 | 0.83383 | 1062 | ||
| Synonymous | 0.519 | 156 | 164 | 0.949 | 0.0000124 | 1097 |
| Loss of Function | -0.326 | 26 | 24.3 | 1.07 | 0.00000131 | 241 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00056 | 0.00055 | rare |
| Latino/Admixed American | 0.00043 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.0010 | 0.0010 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00034 | 0.00033 | rare |
| South Asian | 0.0051 | 0.0051 | notable |
| Other | 0.00034 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
Recessive Scores
- pRec
- 0.910
Intolerance Scores
- LoFtool
- 0.248
- RVIS EVS
- -0.39
- RVIS percentile EVS
- 27.03
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.991
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |