PPT1
Basic information
Region (hg38): 1:40072710-40097260
Previous symbols: [ "PPT" ]
Links
Phenotypes
GenCC
Source:
- 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:
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
- Neuronal ceroid lipofuscinosis 1 (45 variants)
- not provided (7 variants)
- Neuronal ceroid lipofuscinosis (2 variants)
- Inborn genetic diseases (2 variants)
- PPT1-related disorder (1 variants)
- Retinitis pigmentosa (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 | 125 | 127 | ||||
missense | 24 | 147 | 179 | |||
nonsense | 11 | 13 | 24 | |||
start loss | 5 | |||||
frameshift | 20 | 30 | 50 | |||
inframe indel | 3 | |||||
splice donor/acceptor (+/-2bp) | 18 | 25 | ||||
splice region | 1 | 10 | 44 | 2 | 57 | |
non coding | 35 | 94 | 36 | 167 | ||
Total | 45 | 91 | 186 | 219 | 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:
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:
- 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