PPT1

palmitoyl-protein thioesterase 1, the group of Depalmitoylases

Basic information

Region (hg38): 1:40072709-40097260

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 (535 variants)
• not provided (124 variants)
• not specified (42 variants)
• Inborn genetic diseases (41 variants)
• Neuronal ceroid lipofuscinosis (18 variants)
• Neuronal Ceroid-Lipofuscinosis, Recessive (7 variants)
• PPT1-related condition (3 variants)
• Retinitis pigmentosa (2 variants)
• Intellectual disability (2 variants)
• Global developmental delay (1 variants)
• Intellectual disability;Seizure (1 variants)
• Central core myopathy (1 variants)
• Spastic ataxia (1 variants)
• Abnormality of the nervous system (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	106		108
missense	5	21	141		3	170
nonsense	9	12	1			22
start loss	2	3				5
frameshift	15	28				43
inframe indel		1	2			3
splice donor/acceptor (+/-2bp)	7	15				22
splice region			10	36	2	48
non coding		1	35	72	36	144
Total	38	81	181	178	39

Highest pathogenic variant AF is 0.000598

Variants in PPT1

This is a list of pathogenic ClinVar variants found in the PPT1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-40072760-T-TC		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
1-40072766-C-G		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40072769-ACTT-A		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
1-40072786-C-T		Neuronal ceroid lipofuscinosis 1	Benign (Jan 13, 2018)
1-40072907-A-G		Neuronal ceroid lipofuscinosis 1	Likely benign (Jan 12, 2018)
1-40072973-C-T		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40072999-C-T		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 13, 2018)
1-40073000-G-A		Neuronal ceroid lipofuscinosis 1	Likely benign (Jan 13, 2018)
1-40073042-G-A		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 13, 2018)
1-40073063-C-G		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
1-40073070-A-G		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073092-T-C		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073147-T-C		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 13, 2018)
1-40073151-G-A		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073160-G-A		Neuronal ceroid lipofuscinosis 1	Likely benign (Jan 12, 2018)
1-40073183-A-G		Neuronal ceroid lipofuscinosis 1	Benign (Jan 13, 2018)
1-40073249-G-A		Neuronal Ceroid-Lipofuscinosis, Recessive	Uncertain significance (Jun 14, 2016)
1-40073250-T-C		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073259-G-A		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073280-T-A		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 13, 2018)
1-40073334-T-G		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073352-A-G		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)
1-40073353-T-G		Neuronal ceroid lipofuscinosis 1	Conflicting classifications of pathogenicity (Aug 27, 2021)
1-40073360-C-T		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 13, 2018)
1-40073382-G-T		Neuronal ceroid lipofuscinosis 1	Uncertain significance (Jan 12, 2018)

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