PTCD3

protein-coding

pentatricopeptide repeat domain 3, the group of Small nucleolar RNA protein coding host genes|Pentatricopeptide repeat containing

Gene summary

Enables rRNA binding activity and ribosomal small subunit binding activity. Involved in mitochondrial translation. Located in mitochondrial matrix. Implicated in combined oxidative phosphorylation deficiency 51. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_017952.6

Inheritance

ClinVar variants

P:17U:130B:15

Top phenotype

Combined oxidative phosphorylation deficiency 51

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr2:86,106,223-86,142,157

External References & Databases

Ensembl (ENSG00000132300)

Transcript & Mutation Effects

hg38 • Region Span ~35.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Leigh syndromeLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0009723

Submitter: ClinGen

The relationship between PTCD3 and Leigh syndrome spectrum was evaluated using the ClinGen Clinical Validity Framework as of June 9, 2019. PTCD3 was first reported in relation to autosomal recessive Leigh syndrome spectrum in 2019 (Borna et al., PMID 30607703). There are no variants in this gene listed in ClinVar. Evidence supporting this gene-disease relationship includes case-level data (PMID 30607703) to reach a case-level evidence score of 2.5 points. This gene-disease association is further supported by the function of the gene product and expression studies, reaching an experimental score of 2 points. The mechanism for disease is impaired mitochondrial translation. In summary, PTCD3 currently has a limited association with autosomal recessive Leigh syndrome spectrum. This classification was approved by the NICHD U24 ClinGen Mitochondrial Disease Gene Curation Expert Panel on June 10, 2019 (SOP Version 6).

combined oxidative phosphorylation deficiency 51STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033631

Submitter: PanelApp Australia

combined oxidative phosphorylation deficiency 51MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0033631

Submitter: Ambry Genetics

combined oxidative phosphorylation deficiency 51STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0033631

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Combined oxidative phosphorylation deficiency 51AR

Manifestation: Audiologic/Otolaryngologic; Biochemical; Neurologic; Ophthalmologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 30607703; 30706245

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTCD3 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 108

Combined oxidative phosphorylation deficiency 51Total: 19

not providedTotal: 16

PTCD3-related disorderTotal: 8

not specifiedTotal: 6

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017952.6. 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			5 clinvar	4 clinvar	1 clinvar	10
missense		1 clinvar	114 clinvar	9 clinvar	1 clinvar	125
nonsense		5 clinvar	1 clinvar			6
start loss						0
frameshift	2 clinvar	3 clinvar	1 clinvar			6
splice donor/acceptor (+/-2bp)	2 clinvar	4 clinvar	9 clinvar			15
Total	4	13	130	13	2	162

Highest pathogenic variant AF is 0.00008510649

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 70 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017952.6	RefSeq	NP_060422.4	24	MANE Select
ENST00000254630.12	Ensembl	ENSP00000254630.7	24	MANE Select
ENST00000409326.6	Ensembl	ENSP00000386963.2	3	Standard
ENST00000409783.6	Ensembl	ENSP00000386922.3	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Mitochondrial translation initiation
Translation
Metabolism of proteins
Mitochondrial translation elongation
Mitochondrial translation termination

Biological Process

regulation of translation
mitochondrial translation
mitochondrial translational elongation
mitochondrial translational termination

Molecular Function

RNA binding
protein binding
rRNA binding
ribosomal small subunit binding

Cellular Component

nucleoplasm
mitochondrion
mitochondrial inner membrane
cytosol
ribosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000254630
Coding exons: 24
Length: 35976
Individuals with no LoFs: 125644
Homozygous LoFs: 0
Heterozygous LoFs: 104
Defined: 125748
p: 0.000414

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.480	394	368	1.07	0.0000181	4559
Missense (PolyPhen)		81	85.775	0.94433		1134
Synonymous	-0.714	138	128	1.08	0.00000646	1229
Loss of Function	1.10	38	46.1	0.825	0.00000238	551

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00064	0.00064	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00038	0.00038	rare
Finnish	0.00018	0.00018	rare
European (Non-Finnish)	0.00047	0.00047	rare
South Asian	0.00017	0.00016	rare
Other	0.00083	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mitochondrial RNA-binding protein that has a role in mitochondrial translation. {ECO:0000269|PubMed:19427859}.;

Recessive Scores

pRec: 0.0835

Intolerance Scores

LoFtool: 0.941
RVIS EVS: -0.57
RVIS percentile EVS: 19.01

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.884

Gene Damage Prediction

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