ALPL
alkaline phosphatase, biomineralization associated, the group of Alkaline phosphatases
Basic information
Region (hg38): 1:21509397-21578410
Previous symbols: [ "HOPS" ]
Links
Phenotypes
GenCC
Source:
- hypophosphatasia (Definitive), mode of inheritance: AR
- adult hypophosphatasia (Strong), mode of inheritance: AD
- infantile hypophosphatasia (Strong), mode of inheritance: AR
- childhood hypophosphatasia (Definitive), mode of inheritance: AR
- perinatal lethal hypophosphatasia (Supportive), mode of inheritance: AR
- infantile hypophosphatasia (Supportive), mode of inheritance: AR
- childhood hypophosphatasia (Supportive), mode of inheritance: AD
- adult hypophosphatasia (Supportive), mode of inheritance: AD
- odontohypophosphatasia (Supportive), mode of inheritance: AD
- adult hypophosphatasia (Strong), mode of inheritance: AD
- infantile hypophosphatasia (Strong), mode of inheritance: AR
- adult hypophosphatasia (Definitive), mode of inheritance: AD
- childhood hypophosphatasia (Definitive), mode of inheritance: AR
- childhood hypophosphatasia (Definitive), mode of inheritance: AD
- infantile hypophosphatasia (Definitive), mode of inheritance: AR
- hypophosphatasia (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hypophosphatasia, infantile; Hypophosphatasia, childhood; Hypophosphatasia, adult; Odontohypophosphatasia | AD/AR | Endocrine; Neurologic | In some forms, abnormal calcium levels can be treated; Seizures can be treated with vitamin B6; Bisphosphonates and excess vitamin D should be avoided due to potential hypercalcemia leading to renal damage; Enzymatic therapy has shown benefit in individuals with severe forms of hypophosphatasia | Dental; Endocrine; Musculoskeletal; Neurologic | 18110134 ; 13800162; 4288761; 4309618 ; 5013867; 7235780; 7305584; 7072744; 7182980; 3960066; 1409720; 3174660; 8406453; 10332035; 10872988; 11479741; 11999978; 12357339; 17519318; 17213282; 21488855; 20978533; 20301329; 22397652 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (1027 variants)
- Hypophosphatasia (621 variants)
- Adult_hypophosphatasia (315 variants)
- Infantile_hypophosphatasia (286 variants)
- Childhood_hypophosphatasia (221 variants)
- not_specified (82 variants)
- ALPL-related_disorder (65 variants)
- Inborn_genetic_diseases (41 variants)
- Osteogenesis_imperfecta (27 variants)
- Decreased_circulating_alkaline_phosphatase_activity (15 variants)
- Odontohypophosphatasia (6 variants)
- Perinatal_lethal_hypophosphatasia (2 variants)
- See_cases (2 variants)
- Micromelia (2 variants)
- Microcephaly (1 variants)
- Alpha_thalassemia-X-linked_intellectual_disability_syndrome (1 variants)
- Multiple_epiphyseal_dysplasia (1 variants)
- Hypophosphatemia (1 variants)
- Connective_tissue_disorder (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ALPL gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000478.6. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 15 | 279 | 298 | |||
| missense | 46 | 360 | 254 | 668 | ||
| nonsense | 26 | 17 | 45 | |||
| start loss | 3 | 1 | 4 | |||
| frameshift | 62 | 40 | 104 | |||
| splice donor/acceptor (+/-2bp) | 19 | 18 | 40 | |||
| Total | 156 | 439 | 274 | 289 | 1 |
Highest pathogenic variant AF is 0.00141319
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ALPL | protein_coding | protein_coding | ENST00000374840 | 11 | 69048 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.000364 | 0.998 | 125701 | 0 | 47 | 125748 | 0.000187 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.27 | 266 | 331 | 0.804 | 0.0000210 | 3421 |
| Missense in Polyphen | 110 | 161.7 | 0.68028 | 1678 | ||
| Synonymous | -0.717 | 161 | 150 | 1.07 | 0.0000117 | 1053 |
| Loss of Function | 2.71 | 10 | 24.5 | 0.409 | 0.00000133 | 267 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000478 | 0.000478 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.000247 | 0.000246 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: This isozyme may play a role in skeletal mineralization.;
- Disease
- DISEASE: Hypophosphatasia (HOPS) [MIM:146300]: A metabolic bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Four forms are distinguished, depending on the age of onset: perinatal, infantile, childhood and adult type. The perinatal form is the most severe and is almost always fatal. The adult form is mild and characterized by recurrent fractures, osteomalacia, rickets, and loss of teeth. Some cases are asymptomatic, while some patients manifest dental features without skeletal manifestations (odontohypophosphatasia). {ECO:0000269|PubMed:10094560, ECO:0000269|PubMed:10332035, ECO:0000269|PubMed:10679946, ECO:0000269|PubMed:10690885, ECO:0000269|PubMed:10834525, ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:11479741, ECO:0000269|PubMed:11745997, ECO:0000269|PubMed:11760847, ECO:0000269|PubMed:11834095, ECO:0000269|PubMed:11855933, ECO:0000269|PubMed:11999978, ECO:0000269|PubMed:12815606, ECO:0000269|PubMed:12920074, ECO:0000269|PubMed:1409720, ECO:0000269|PubMed:15135428, ECO:0000269|PubMed:15694177, ECO:0000269|PubMed:19500388, ECO:0000269|PubMed:22266140, ECO:0000269|PubMed:23039266, ECO:0000269|PubMed:23688511, ECO:0000269|PubMed:25982064, ECO:0000269|PubMed:3174660, ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8406453, ECO:0000269|PubMed:8954059, ECO:0000269|PubMed:9452105, ECO:0000269|PubMed:9747027, ECO:0000269|PubMed:9781036}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypophosphatasia childhood type (HOPSC) [MIM:241510]: A bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. {ECO:0000269|PubMed:11760847}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Hypophosphatasia infantile type (HOPSI) [MIM:241500]: A severe bone disease characterized by defective skeletal mineralization and biochemically by deficient activity of the tissue non-specific isoenzyme of alkaline phosphatase. Three more or less distinct types of infantile hypophosphatasia can be identified: (1) type 1 with onset in utero or in early postnatal life, craniostenosis, severe skeletal abnormalities, hypercalcemia, and death in the first year or so of life; (2) type 2 with later, more gradual development of symptoms, moderately severe 'rachitic' skeletal changes and premature loss of teeth; (3) type 3 with no symptoms, the condition being determined on routine studies. {ECO:0000269|PubMed:10834525, ECO:0000269|PubMed:11438998, ECO:0000269|PubMed:7833929, ECO:0000269|PubMed:8954059}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Folate biosynthesis - Homo sapiens (human);Thiamine metabolism - Homo sapiens (human);Hypophosphatasia;Vitamin B6 Metabolism;AGE-RAGE pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;NOTCH1 regulation of human endothelial cell calcification;Role of Osx and miRNAs in tooth development;Endochondral Ossification;regulators of bone mineralization;Post-translational modification: synthesis of GPI-anchored proteins;Post-translational protein modification;Metabolism of proteins;TNFalpha
(Consensus)
Recessive Scores
- pRec
- 0.928
Intolerance Scores
- loftool
- 0.0447
- rvis_EVS
- 0.0000761
- rvis_percentile_EVS
- 53.98
Haploinsufficiency Scores
- pHI
- 0.456
- hipred
- Y
- hipred_score
- 0.623
- ghis
- 0.480
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.944
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Alpl
- Phenotype
- muscle phenotype; craniofacial phenotype; homeostasis/metabolism phenotype; cellular phenotype; growth/size/body region phenotype; reproductive system phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype; digestive/alimentary phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- skeletal system development;osteoblast differentiation;endochondral ossification;developmental process involved in reproduction;dephosphorylation;response to lipopolysaccharide;response to vitamin D;response to antibiotic;response to glucocorticoid;cellular response to organic cyclic compound;cementum mineralization
- Cellular component
- extracellular region;plasma membrane;membrane;extracellular matrix;anchored component of membrane;extracellular membrane-bounded organelle;extracellular exosome
- Molecular function
- alkaline phosphatase activity;protein binding;pyrophosphatase activity;metal ion binding