PDE12

protein-coding

phosphodiesterase 12

Gene summary

Enables poly(A)-specific ribonuclease activity. Involved in several processes, including cellular response to interferon-alpha; innate immune response; and mRNA catabolic process. Located in mitochondrial matrix. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_177966.7

Inheritance

ClinVar variants

U:73B:2

Top phenotype

mitochondrial disease

gnomAD constraint

pLI —, LoF o/e 0.3

Max pathogenic AF

—

Genomic locus

chr3:57,556,274-57,656,480

External References & Databases

Ensembl (ENSG00000174840)

Transcript & Mutation Effects

hg38 • Region Span ~100.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

mitochondrial diseaseSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: PanelApp Australia

mitochondrial diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0044970

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PDE12 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 72

PDE12-related conditionTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_177966.7. 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
missense			73 clinvar	1 clinvar		74
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	73	2	0	75

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 15 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_177966.7	RefSeq	NP_808881.3	3	MANE Select
ENST00000311180.9	Ensembl	ENSP00000309142.7	3	MANE Select
NM_001322176.2	RefSeq	NP_001309105.1	3	Standard
NM_001322177.2	RefSeq	NP_001309106.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Phosphodiesterases in neuronal function

Biological Process

nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay
mitochondrial mRNA catabolic process
mRNA processing
cellular response to interferon-alpha
regulation of mitochondrial mRNA stability

Molecular Function

3'-5'-exoribonuclease activity
exonuclease activity
poly(A)-specific ribonuclease activity
oligoribonucleotidase activity
metal ion binding

Cellular Component

mitochondrial matrix
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000311180
Coding exons: 3
Length: 10569
Individuals with no LoFs: 125722
Homozygous LoFs: 0
Heterozygous LoFs: 26
Defined: 125748
p: 0.000103

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.40	268	340	0.787	0.0000159	3947
Missense (PolyPhen)		51	71.491	0.71338		837
Synonymous	0.818	130	142	0.913	0.00000696	1268
Loss of Function	2.87	6	19.8	0.303	9.02e-7	240

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00013	0.00013	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Enzyme that cleaves 2',5'-phosphodiester bond linking adenosines of the 5'-triphosphorylated oligoadenylates, triphosphorylated oligoadenylates referred as 2-5A modulates the 2-5A system. This enzyme degraded triphosphorylated 2-5A to produce AMP and ATP. Also cleaves 3',5'-phosphodiester bond of oligoadenylates. Plays a role as a negative regulator of the The 2-5A system that is one of the major pathways for antiviral and antitumor functions induced by interferons (IFNs). Suppression of this enzyme induces reduction of viral replication in Hela cells, thus counteracting the antiviral pathway probably by inhibiting the 2-5A system. {ECO:0000269|PubMed:15231837, ECO:0000269|PubMed:21245038, ECO:0000269|PubMed:21666256, ECO:0000269|PubMed:22285541}.;

Recessive Scores

pRec: 0.109

Intolerance Scores

LoFtool: 0.403
RVIS EVS: -0.18
RVIS percentile EVS: 40.36

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.850

Gene Damage Prediction

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