PPT2

protein-coding

palmitoyl-protein thioesterase 2

Gene summary

This gene encodes a member of the palmitoyl-protein thioesterase family. The encoded glycosylated lysosomal protein has palmitoyl-CoA hydrolase activity in vitro, but does not hydrolyze palmitate from cysteine residues in proteins. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream EGFL8 (EGF-like-domain, multiple 8) gene. [provided by RefSeq, Feb 2011]

MANE transcript

NM_005155.7

Inheritance

—

ClinVar variants

U:31B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.39

Max pathogenic AF

—

Genomic locus

chr6:32,153,441-32,163,678

External References & Databases

Ensembl (ENSG00000221988)

Transcript & Mutation Effects

hg38 • Region Span ~10.2 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 PPT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 32

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_005155.7. 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			30 clinvar	2 clinvar		32
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	31	2	0	33

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_005155.7	RefSeq	NP_005146.4	8	MANE Select
ENST00000324816.11	Ensembl	ENSP00000320528.6	8	MANE Select
NM_001204103.2	RefSeq	NP_001191032.1	8	Standard
NM_138717.3	RefSeq	NP_619731.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Fatty acid elongation - Homo sapiens (human)
Metabolism of lipids
Fatty acyl-CoA biosynthesis
Metabolism

Biological Process

fatty-acyl-CoA biosynthetic process
macromolecule depalmitoylation

Molecular Function

palmitoyl-(protein) hydrolase activity
thiolester hydrolase activity
palmitoyl hydrolase activity

Cellular Component

lysosome
lysosomal lumen
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000361568
Coding exons: 9
Length: 12794
Individuals with no LoFs: 125735
Homozygous LoFs: 0
Heterozygous LoFs: 13
Defined: 125748
p: 0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.05	108	187	0.578	0.0000102	2000
Missense (PolyPhen)		29	62.269	0.46572		687
Synonymous	1.96	55	76.9	0.715	0.00000404	621
Loss of Function	2.41	7	18.0	0.388	8.99e-7	183

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000066	0.000062	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000054	0.000053	rare
South Asian	0.000099	0.000098	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. Has the highest S- thioesterase activity for the acyl groups palmitic and myristic acid followed by other short- and long-chain acyl substrates. However, because of structural constraints, is unable to remove palmitate from peptides or proteins. {ECO:0000269|PubMed:10417332, ECO:0000269|PubMed:12855696, ECO:0000269|PubMed:9341199}.;

Intolerance Scores

LoFtool: 0.106
RVIS EVS: 0.26
RVIS percentile EVS: 70.06

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.862

Gene Damage Prediction

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