PPT1

palmitoyl-protein thioesterase 1, the group of Depalmitoylases

Basic information

Region (hg38): 1:40072710-40097260

Previous symbols: [ "PPT" ]

Links

ENSG00000131238

∙ NCBI:5538 ∙ OMIM:600722 ∙ HGNC:9325 ∙ Uniprot:P50897 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neuronal ceroid lipofuscinosis 1 (Definitive), mode of inheritance: AR
neuronal ceroid lipofuscinosis 1 (Definitive), mode of inheritance: AR
neuronal ceroid lipofuscinosis 1 (Strong), mode of inheritance: AR
neuronal ceroid lipofuscinosis 1 (Supportive), mode of inheritance: AR
neuronal ceroid lipofuscinosis 1 (Strong), mode of inheritance: AR
neuronal ceroid lipofuscinosis 1 (Definitive), mode of inheritance: AR
neuronal ceroid lipofuscinosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 1	AR	General	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	Biochemical; Neurologic; Ophthalmologic	5706364; 4121459; 4698309; 6890163; 7637805; 9664077; 9425237; 9535296; 11506414; 15965709; 17261688; 21235444; 21990111

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PPT1 gene.

Neuronal_ceroid_lipofuscinosis_1 (617 variants)
not_provided (109 variants)
Inborn_genetic_diseases (60 variants)
not_specified (45 variants)
Neuronal_ceroid_lipofuscinosis (20 variants)
PPT1-related_disorder (8 variants)
Intellectual_disability (2 variants)
Retinitis_pigmentosa (2 variants)
See_cases (1 variants)
Central_core_myopathy (1 variants)
Abnormality_of_the_nervous_system (1 variants)
Neuronal_Ceroid-Lipofuscinosis,_Recessive (1 variants)
Spastic_ataxia (1 variants)
Neurodevelopmental_disorder_with_dysmorphic_facies_and_distal_limb_anomalies (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PPT1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000310.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			7 clinvar	141 clinvar		148
missense	11 clinvar	40 clinvar	167 clinvar	2 clinvar	2 clinvar	222
nonsense	15 clinvar	15 clinvar				30
start loss	2	3				5
frameshift	28 clinvar	27 clinvar				55
splice donor/acceptor (+/-2bp)	14 clinvar	21 clinvar				35
Total	70	106	174	143	2

Highest pathogenic variant AF is 0.000453566

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PPT1	protein_coding	protein_coding	ENST00000433473	9	24997

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000486	0.968	125645	0	103	125748	0.000410

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0339	163	164	0.993	0.00000885	2006
Missense in Polyphen		51	61.262	0.83249		817
Synonymous	-1.10	74	62.9	1.18	0.00000343	582
Loss of Function	1.94	10	19.2	0.521	9.90e-7	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000275	0.000275
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000819	0.000818
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000653	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

Function: FUNCTION: Removes thioester-linked fatty acyl groups such as palmitate from modified cysteine residues in proteins or peptides during lysosomal degradation. Prefers acyl chain lengths of 14 to 18 carbons (PubMed:8816748). {ECO:0000269|PubMed:8816748}.;
Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 1 (CLN1) [MIM:256730]: A form of neuronal ceroid lipofuscinosis with variable age at onset. Infantile, late-infantile, juvenile, and adult onset have been reported. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The lipopigment pattern seen most often in CLN1 is referred to as granular osmiophilic deposits (GROD). {ECO:0000269|PubMed:11506414, ECO:0000269|PubMed:19201763, ECO:0000269|PubMed:19941651, ECO:0000269|PubMed:21990111, ECO:0000269|PubMed:7637805, ECO:0000269|PubMed:9425237, ECO:0000269|PubMed:9664077}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Lysosome - Homo sapiens (human);Fatty acid elongation - Homo sapiens (human);Long-chain-3-hydroxyacyl-coa dehydrogenase deficiency (LCHAD);Fatty Acid Elongation In Mitochondria;Metabolism of lipids;Fatty acyl-CoA biosynthesis;Metabolism;Fatty acid metabolism (Consensus)

Recessive Scores

pRec: 0.583

Intolerance Scores

loftool: 0.204
rvis_EVS: -0.16
rvis_percentile_EVS: 41.91

Haploinsufficiency Scores

pHI: 0.339
hipred: N
hipred_score: 0.253
ghis: 0.537

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.965

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Ppt1
Phenotype: growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; pigmentation phenotype; hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); renal/urinary system phenotype; skeleton phenotype;

Gene ontology

Biological process: protein depalmitoylation;receptor-mediated endocytosis;pinocytosis;lysosomal lumen acidification;neurotransmitter secretion;nervous system development;brain development;visual perception;grooming behavior;associative learning;adult locomotory behavior;protein transport;lipid catabolic process;sphingolipid catabolic process;protein catabolic process;negative regulation of cell growth;membrane raft organization;regulation of phospholipase A2 activity;negative regulation of apoptotic process;negative regulation of neuron apoptotic process;cellular protein catabolic process;fatty-acyl-CoA biosynthetic process;positive regulation of receptor-mediated endocytosis;positive regulation of pinocytosis;neuron development;regulation of synapse structure or activity;response to stimulus;cofactor transport;cofactor metabolic process
Cellular component: extracellular region;nucleus;lysosome;Golgi apparatus;cytosol;synaptic vesicle;membrane;axon;dendrite;neuronal cell body;lysosomal lumen;membrane raft;extracellular exosome
Molecular function: protein binding;palmitoyl-(protein) hydrolase activity;palmitoyl-CoA hydrolase activity