ALPP

protein-coding

alkaline phosphatase, placental, the group of Alkaline phosphatases

Gene summary

The protein encoded by this gene is an alkaline phosphatase, a metalloenzyme that catalyzes the hydrolysis of phosphoric acid monoesters. It belongs to a multigene family composed of four alkaline phosphatase isoenzymes. The enzyme functions as a homodimer and has a catalytic site containing one magnesium and two zinc ions, which are required for its enzymatic function. One of the main sources of this enzyme is the liver, and thus, it's one of several indicators of liver injury in different clinical conditions. In pregnant women, this protein is primarily expressed in placental and endometrial tissue, however, strong ectopic expression has been detected in ovarian adenocarcinoma, serous cystadenocarcinoma, and other ovarian cancer cells. [provided by RefSeq, Aug 2020]

MANE transcript

NM_001632.5

Inheritance

—

ClinVar variants

U:119B:13

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.9

Max pathogenic AF

—

Genomic locus

chr2:232,378,724-232,382,889

External References & Databases

Ensembl (ENSG00000163283)

Transcript & Mutation Effects

hg38 • Region Span ~4.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to ALPP variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 119

not providedTotal: 9

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001632.5. 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 clinvar	1 clinvar	4 clinvar	6
missense			114 clinvar	6 clinvar	2 clinvar	122
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	119	7	6	132

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 2 of 2 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001632.5	RefSeq	NP_001623.3	11	MANE Select
ENST00000392027.3	Ensembl	ENSP00000375881.2	11	MANE Select

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)
Vesicle-mediated transport
Membrane Trafficking
Intra-Golgi traffic

Biological Process

dephosphorylation

Molecular Function

magnesium ion binding
alkaline phosphatase activity
protein binding
zinc ion binding

Cellular Component

plasma membrane
cell surface
integral component of membrane
anchored component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000392027
Coding exons: 11
Length: 4356
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 90
Defined: 125746
p: 0.000358

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.448	364	341	1.07	0.0000229	3364
Missense (PolyPhen)		148	135.89	1.0891		1398
Synonymous	1.26	137	157	0.872	0.0000120	1117
Loss of Function	0.452	21	23.4	0.899	0.00000141	226

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.00038	0.00038	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0010	0.0010	notable
Finnish	0	0.0	absent
European (Non-Finnish)	0.00023	0.00023	rare
South Asian	0.00026	0.00026	rare
Other	0.00099	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.137

Intolerance Scores

LoFtool: 0.174
RVIS EVS: 1.36
RVIS percentile EVS: 94.44

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.996

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium