KPTN
Basic information
Region (hg38): 19:47475149-47484265
Links
Phenotypes
GenCC
Source:
- macrocephaly-developmental delay syndrome (Supportive), mode of inheritance: AR
- macrocephaly-developmental delay syndrome (Strong), mode of inheritance: AR
Clinical Genomic Database
Source:
Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
---|---|---|---|---|---|
Intellectual developmental disorder, autosomal recessive 41 | 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 | Craniofacial; Neurologic | 24239382 |
ClinVar
This is a list of variants' phenotypes submitted to
- Macrocephaly-developmental delay syndrome (109 variants)
- not provided (32 variants)
- Inborn genetic diseases (28 variants)
- not specified (13 variants)
- KPTN-related condition (3 variants)
- Intellectual disability (1 variants)
- See cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KPTN 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 | 23 | 30 | ||||
missense | 60 | 65 | ||||
nonsense | 3 | |||||
start loss | 0 | |||||
frameshift | 8 | |||||
inframe indel | 1 | |||||
splice donor/acceptor (+/-2bp) | 3 | |||||
splice region ? | 6 | 7 | 1 | 14 | ||
non coding ? | 18 | |||||
Total | 8 | 6 | 65 | 35 | 14 |
Highest pathogenic variant AF is 0.000105
Variants in KPTN
This is a list of pathogenic ClinVar variants found in the KPTN region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
Position | Type | Phenotype | Significance | ClinVar |
---|---|---|---|---|
19-47475414-G-A | Benign (May 04, 2021) | |||
19-47475422-G-A | Macrocephaly-developmental delay syndrome | Likely benign (Sep 06, 2022) | ||
19-47475435-G-T | Macrocephaly-developmental delay syndrome | Uncertain significance (Mar 06, 2020) | ||
19-47475451-C-T | Inborn genetic diseases | Uncertain significance (May 31, 2023) | ||
19-47475454-C-T | Inborn genetic diseases | Likely benign (Jun 03, 2022) | ||
19-47475459-T-C | not specified • Macrocephaly-developmental delay syndrome | Uncertain significance (Nov 08, 2022) | ||
19-47475464-C-T | Macrocephaly-developmental delay syndrome | Likely benign (Jul 12, 2022) | ||
19-47475477-C-T | Macrocephaly-developmental delay syndrome • Inborn genetic diseases | Uncertain significance (Sep 13, 2023) | ||
19-47475482-C-T | Macrocephaly-developmental delay syndrome | Benign (Jan 31, 2024) | ||
19-47475484-T-C | Macrocephaly-developmental delay syndrome | Uncertain significance (Jun 13, 2022) | ||
19-47475493-C-T | Macrocephaly-developmental delay syndrome | Uncertain significance (Feb 08, 2020) | ||
19-47475502-G-A | Macrocephaly-developmental delay syndrome | Conflicting classifications of pathogenicity (Aug 11, 2019) | ||
19-47475538-GGCTGTGCTGTGGGGAACAAGAGAATGAGGGGGATGGAGCTGAGGAAGA-G | Inborn genetic diseases | Uncertain significance (Nov 03, 2021) | ||
19-47475545-C-T | Macrocephaly-developmental delay syndrome | Pathogenic (May 04, 2022) | ||
19-47476524-G-A | Likely benign (Dec 15, 2017) | |||
19-47476546-C-T | not specified • Inborn genetic diseases | Uncertain significance (Nov 03, 2022) | ||
19-47476545-A-ACGCCCTTCAGGGAGACCACGGCAAGCTCCTGCAGCCCATC | Macrocephaly-developmental delay syndrome | Uncertain significance (Aug 30, 2022) | ||
19-47476547-G-A | Macrocephaly-developmental delay syndrome | Uncertain significance (Feb 08, 2022) | ||
19-47476601-G-A | Macrocephaly-developmental delay syndrome | Likely benign (Sep 04, 2022) | ||
19-47476635-C-T | Inborn genetic diseases | Uncertain significance (Aug 02, 2021) | ||
19-47476636-G-A | Inborn genetic diseases | Uncertain significance (May 03, 2023) | ||
19-47476643-C-G | Likely benign (Sep 19, 2018) | |||
19-47476658-G-A | Macrocephaly-developmental delay syndrome • KPTN-related disorder | Benign (Jan 13, 2024) | ||
19-47476679-C-G | Macrocephaly-developmental delay syndrome | Likely benign (Feb 17, 2020) | ||
19-47476679-C-T | not specified • Macrocephaly-developmental delay syndrome | Likely benign (Apr 01, 2024) |
GnomAD
Source:
Gene | Type | Bio Type | Transcript | Coding Exons | Length |
---|---|---|---|---|---|
KPTN | protein_coding | protein_coding | ENST00000338134 | 12 | 9125 |
pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
---|---|---|---|---|---|---|
0.0000113 | 0.989 | 124726 | 0 | 84 | 124810 | 0.000337 |
Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
---|---|---|---|---|---|---|
Missense | 1.45 | 200 | 266 | 0.751 | 0.0000154 | 2776 |
Missense in Polyphen | 68 | 90.477 | 0.75157 | 1016 | ||
Synonymous | 0.829 | 106 | 117 | 0.903 | 0.00000703 | 902 |
Loss of Function | 2.28 | 12 | 24.0 | 0.499 | 0.00000122 | 248 |
LoF frequencies by population
Ethnicity | Sum of pLOFs | p |
---|---|---|
African & African-American | 0.000571 | 0.000555 |
Ashkenazi Jewish | 0.00 | 0.00 |
East Asian | 0.000308 | 0.000278 |
Finnish | 0.0000928 | 0.0000928 |
European (Non-Finnish) | 0.000522 | 0.000521 |
Middle Eastern | 0.000308 | 0.000278 |
South Asian | 0.0000981 | 0.0000980 |
Other | 0.000330 | 0.000330 |
dbNSFP
Source:
- Function
- FUNCTION: As part of the KICSTOR complex functions in the amino acid-sensing branch of the TORC1 signaling pathway. Recruits, in an amino acid-independent manner, the GATOR1 complex to the lysosomal membranes and allows its interaction with GATOR2 and the RAG GTPases. Functions upstream of the RAG GTPases and is required to negatively regulate mTORC1 signaling in absence of amino acids. In absence of the KICSTOR complex mTORC1 is constitutively localized to the lysosome and activated. The KICSTOR complex is also probably involved in the regulation of mTORC1 by glucose. {ECO:0000269|PubMed:28199306}.;
- Disease
- DISEASE: Mental retardation, autosomal recessive 41 (MRT41) [MIM:615637]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT41 most consistent features are global developmental delay, macrocephaly with frontal bossing, high levels of anxiety, and some features suggestive of a pervasive developmental disorder. Less common features include fifth finger clinodactyly, recurrent pneumonia, and hepatosplenomegaly. {ECO:0000269|PubMed:24239382}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- loftool
- 0.441
- rvis_EVS
- -0.47
- rvis_percentile_EVS
- 23.43
Haploinsufficiency Scores
- pHI
- 0.193
- hipred
- N
- hipred_score
- 0.378
- ghis
- 0.555
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.966
Gene Damage Prediction
All | Recessive | Dominant | |
---|---|---|---|
Mendelian | Medium | Medium | Medium |
Primary Immunodeficiency | Medium | Medium | Medium |
Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Kptn
- Phenotype
- immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype;
Gene ontology
- Biological process
- actin filament organization;cellular response to amino acid starvation;cellular response to glucose starvation;protein localization to lysosome;negative regulation of TORC1 signaling
- Cellular component
- lysosomal membrane;lamellipodium;filamentous actin;stereocilium;postsynaptic actin cytoskeleton;KICSTOR complex
- Molecular function
- actin filament binding