APH1A
aph-1 homolog A, gamma-secretase subunit
Basic information
Region (hg38): 1:150265398-150269580
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the APH1A 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 | 0 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 9 | 1 | 0 |
Variants in APH1A
This is a list of pathogenic ClinVar variants found in the APH1A region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 1-150266545-G-C | not specified | Uncertain significance (Nov 07, 2022) | ||
| 1-150267128-G-A | not specified | Uncertain significance (Dec 19, 2022) | ||
| 1-150267749-T-C | not specified | Uncertain significance (May 30, 2023) | ||
| 1-150267790-C-CTGGGG | APH1A-related disorder | Likely benign (Apr 24, 2020) | ||
| 1-150267988-C-T | not specified | Uncertain significance (Dec 09, 2023) | ||
| 1-150268045-G-A | not specified | Uncertain significance (Aug 10, 2021) | ||
| 1-150268060-C-T | not specified | Uncertain significance (Aug 02, 2022) | ||
| 1-150268090-C-T | not specified | Uncertain significance (Jun 16, 2023) | ||
| 1-150268096-C-A | not specified | Uncertain significance (Oct 17, 2023) | ||
| 1-150268745-C-G | not specified | Uncertain significance (Jun 03, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| APH1A | protein_coding | protein_coding | ENST00000369109 | 7 | 4177 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.795 | 0.205 | 123956 | 15 | 821 | 124792 | 0.00336 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.03 | 86 | 158 | 0.545 | 0.00000852 | 1670 |
| Missense in Polyphen | 20 | 59.097 | 0.33843 | 668 | ||
| Synonymous | 0.514 | 59 | 64.2 | 0.918 | 0.00000324 | 584 |
| Loss of Function | 2.97 | 2 | 14.0 | 0.143 | 7.64e-7 | 144 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0527 | 0.0518 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000800 | 0.0000794 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.000295 | 0.000294 |
| Other | 0.000827 | 0.000825 |
dbNSFP
Source:
- Function
- FUNCTION: Non-catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12297508, PubMed:12522139, PubMed:12763021, PubMed:12679784, PubMed:25043039, PubMed:26280335). Required for normal gamma- secretase assembly (PubMed:12522139, PubMed:12471034, PubMed:12763021, PubMed:19369254). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). {ECO:0000269|PubMed:12297508, ECO:0000269|PubMed:12471034, ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12763021, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000305}.;
- Pathway
- Alzheimer,s disease - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);NOTCH-Ncore;Alzheimers Disease;Notch Signaling Pathway;Notch Signaling Pathway;Notch Signaling Pathway;Notch;Disease;Signal Transduction;DroToll-like;Notch;Signaling by NOTCH1;Signaling by NOTCH2;NOTCH3 Activation and Transmission of Signal to the Nucleus;Signaling by NOTCH3;Signaling by NOTCH4;Signaling by NOTCH;A third proteolytic cleavage releases NICD;NRIF signals cell death from the nucleus;NOTCH2 Activation and Transmission of Signal to the Nucleus;Death Receptor Signalling;Regulated proteolysis of p75NTR;p75 NTR receptor-mediated signalling;Notch signaling pathway;Nuclear signaling by ERBB4;Signaling by ERBB4;Constitutive Signaling by NOTCH1 PEST Domain Mutants;Signaling by NOTCH1 PEST Domain Mutants in Cancer;Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants;Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer;Signaling by NOTCH1 in Cancer;Signaling by Receptor Tyrosine Kinases;Diseases of signal transduction;p75(NTR)-mediated signaling;Cell death signalling via NRAGE, NRIF and NADE;Presenilin action in Notch and Wnt signaling;Syndecan-3-mediated signaling events;Activated NOTCH1 Transmits Signal to the Nucleus
(Consensus)
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- loftool
- 0.646
- rvis_EVS
- 0.13
- rvis_percentile_EVS
- 62.74
Haploinsufficiency Scores
- pHI
- 0.0951
- hipred
- Y
- hipred_score
- 0.656
- ghis
- 0.479
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.963
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Aph1a
- Phenotype
- craniofacial phenotype; muscle phenotype; growth/size/body region phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal 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); 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); skeleton phenotype; embryo phenotype;
Gene ontology
- Biological process
- metanephros development;membrane protein ectodomain proteolysis;Notch signaling pathway;Notch receptor processing;protein processing;membrane protein intracellular domain proteolysis;amyloid-beta formation;Notch receptor processing, ligand-dependent;amyloid precursor protein metabolic process;amyloid precursor protein catabolic process;positive regulation of catalytic activity
- Cellular component
- mitochondrion;endoplasmic reticulum;endoplasmic reticulum membrane;Golgi apparatus;plasma membrane;integral component of plasma membrane;endosome membrane;membrane;integral component of membrane;Golgi cisterna membrane;gamma-secretase complex;integral component of presynaptic membrane
- Molecular function
- endopeptidase activity;protein binding