PTCD1

protein-coding

pentatricopeptide repeat domain 1, the group of Pentatricopeptide repeat containing

Gene summary

This gene encodes a mitochondrial protein that binds leucine tRNAs and other mitochondrial RNAs and plays a role in the regulation of translation. Increased expression of this gene results in decreased mitochondrial leucine tRNA levels. Naturally occurring read-through transcription exists between upstream ATP5J2 (ATP synthase, H+ transporting, mitochondrial Fo complex, subunit F2) and this gene. [provided by RefSeq, Aug 2015]

MANE transcript

NM_015545.4

Inheritance

ClinVar variants

U:69B:20

Top phenotype

Kabuki syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr7:99,416,739-99,466,163

External References & Databases

Ensembl (ENSG00000106246)

Transcript & Mutation Effects

hg38 • Region Span ~49.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

cardiomyopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0004994

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTCD1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 77

not providedTotal: 12

Kabuki syndrome 1Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_015545.4. 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				1 clinvar	4 clinvar	5
missense			68 clinvar	13 clinvar	2 clinvar	83
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	69	14	6	89

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_015545.4	RefSeq	NP_056360.2	7	MANE Select
ENST00000292478.9	Ensembl	ENSP00000292478.5	7	MANE Select
ENST00000419981.1	Ensembl	ENSP00000401600.1	1	Standard
ENST00000430029.1	Ensembl	ENSP00000408059.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

tRNA 3'-end processing

Molecular Function

tRNA binding
RNA binding

Cellular Component

mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000555673
Coding exons: 9
Length: 49426
Individuals with no LoFs: 125651
Homozygous LoFs: 0
Heterozygous LoFs: 97
Defined: 125748
p: 0.000386

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.560	466	433	1.08	0.0000283	4845
Missense (PolyPhen)		138	136.56	1.0106		1560
Synonymous	-2.09	234	197	1.19	0.0000139	1556
Loss of Function	0.924	24	29.4	0.816	0.00000162	332

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00026	0.00026	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00060	0.00060	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00033	0.00033	rare
South Asian	0.00098	0.00098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Mitochondrial protein implicated in negative regulation of leucine tRNA levels, as well as negative regulation of mitochondria-encoded proteins and COX activity. Affects also the 3'-processing of mitochondrial tRNAs. {ECO:0000269|PubMed:21857155}.;

Recessive Scores

pRec: 0.110

Intolerance Scores

RVIS EVS: 0.48
RVIS percentile EVS: 78.87

Essentials

Essential (CRISPR): E
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.971