PPA1

protein-coding

inorganic pyrophosphatase 1

Gene summary

The protein encoded by this gene is a member of the inorganic pyrophosphatase (PPase) family. PPases catalyze the hydrolysis of pyrophosphate to inorganic phosphate, which is important for the phosphate metabolism of cells. Studies of a similar protein in bovine suggested a cytoplasmic localization of this enzyme. [provided by RefSeq, Jul 2008]

Previous symbols:

MANE transcript

NM_021129.4

Inheritance

—

ClinVar variants

U:47

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr10:70,202,835-70,233,911

External References & Databases

Ensembl (ENSG00000180817)

Transcript & Mutation Effects

hg38 • Region Span ~31.1 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 PPA1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 35

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021129.4. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar			4
missense			39 clinvar			39
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	47	0	0	47

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 26 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021129.4	RefSeq	NP_066952.1	11	MANE Select
ENST00000373232.8	Ensembl	ENSP00000362329.2	11	MANE Select
ENST00000373230.7	Ensembl	ENSP00000362327.4	7	Standard
ENST00000625364.1	Ensembl	ENSP00000486162.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Oxidative phosphorylation - Homo sapiens (human)
tRNA Aminoacylation
Translation
Metabolism of proteins
Pyrophosphate hydrolysis

Biological Process

tRNA aminoacylation for protein translation
phosphate-containing compound metabolic process
diphosphate metabolic process

Molecular Function

magnesium ion binding
inorganic diphosphatase activity

Cellular Component

cytoplasm
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000373232
Coding exons: 11
Length: 31082
Individuals with no LoFs: 125683
Homozygous LoFs: 0
Heterozygous LoFs: 60
Defined: 125743
p: 0.000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.837	129	159	0.813	0.00000794	1940
Missense (PolyPhen)		42	58.209	0.72154		748
Synonymous	0.541	48	53.0	0.905	0.00000281	491
Loss of Function	1.55	10	16.9	0.592	7.16e-7	225

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00060	0.00045	rare
South Asian	0.00017	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.693

Intolerance Scores

LoFtool: 0.771
RVIS EVS: -0.27
RVIS percentile EVS: 33.97

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.674

Gene Damage Prediction

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