PDF

protein-coding

peptide deformylase, mitochondrial

Gene summary

Protein synthesis proceeds after formylation of methionine by methionyl-tRNA formyl transferase (FMT) and transfer of the charged initiator f-met tRNA to the ribosome. In eubacteria and eukaryotic organelles the product of this gene, peptide deformylase (PDF), removes the formyl group from the initiating methionine of nascent peptides. In eubacteria, deformylation of nascent peptides is required for subsequent cleavage of initiating methionines by methionine aminopeptidase. The discovery that a natural inhibitor of PDF, actinonin, acts as an antimicrobial agent in some bacteria has spurred intensive research into the design of bacterial-specific PDF inhibitors. In human cells, only mitochondrial proteins have N-formylation of initiating methionines. Protein inhibitors of PDF or siRNAs of PDF block the growth of cancer cell lines but have no effect on normal cell growth. In humans, PDF function may therefore be restricted to rapidly growing cells. [provided by RefSeq, Nov 2008]

MANE transcript

NM_022341.2

Inheritance

—

ClinVar variants

U:63B:5

Top phenotype

COG8-congenital disorder of glycosylation

gnomAD constraint

pLI —, LoF o/e 1.33

Max pathogenic AF

—

Genomic locus

chr16:69,326,913-69,330,588

External References & Databases

Ensembl (ENSG00000258429)

Transcript & Mutation Effects

hg38 • Region Span ~3.7 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 PDF variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 63

not providedTotal: 4

COG8-congenital disorder of glycosylationTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022341.2. 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				2 clinvar	1 clinvar	3
missense			61 clinvar	1 clinvar	1 clinvar	63
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	63	3	2	68

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 6 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022341.2	RefSeq	NP_071736.1	2	MANE Select
ENST00000288022.2	Ensembl	ENSP00000288022.1	2	MANE Select
ENST00001073636.1	Ensembl	ENSP00000743442.1	2	Standard
ENST00001125246.1	Ensembl	ENSP00000795051.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

translation
positive regulation of cell population proliferation
peptidyl-methionine modification
N-terminal protein amino acid modification
co-translational protein modification

Molecular Function

peptide deformylase activity
metal ion binding

Cellular Component

mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000288022
Coding exons: 2
Length: 1975
Individuals with no LoFs: 123444
Homozygous LoFs: 0
Heterozygous LoFs: 12
Defined: 123456
p: 0.0000486

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.19	123	91.1	1.35	0.00000461	1479
Missense (PolyPhen)		34	31.898	1.0659		455
Synonymous	-3.46	69	40.8	1.69	0.00000231	521
Loss of Function	-0.695	7	5.28	1.33	2.30e-7	63

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.000030	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000055	0.000054	rare
South Asian	0.00010	0.000099	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Removes the formyl group from the N-terminal Met of newly synthesized proteins. {ECO:0000250}.;

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.114

Gene Damage Prediction

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