GeneBe

APH1B

aph-1 homolog B, gamma-secretase subunit

Basic information

Region (hg38): 15:63276018-63309126

Links

ENSG00000138613 ∙ NCBI:83464 ∙ OMIM:607630 ∙ HGNC:24080 ∙ Uniprot:Q8WW43 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the APH1B gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APH1B 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
8
clinvar
 8
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 0 8 0 0

Variants in APH1B

This is a list of pathogenic ClinVar variants found in the APH1B region.

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

Position Type Phenotype Significance ClinVar
15-63277633-G-A not specified Uncertain significance (Mar 20, 2024)3306531
15-63277666-G-C not specified Uncertain significance (Mar 13, 2023)2495794
15-63277691-T-G not specified Uncertain significance (Nov 03, 2023)3127817
15-63279166-T-C not specified Uncertain significance (Apr 06, 2024)3306537
15-63279186-C-G not specified Uncertain significance (Aug 01, 2022)2347966
15-63279315-T-C not specified Uncertain significance (Dec 20, 2023)3127814
15-63287451-G-A not specified Uncertain significance (Jan 03, 2022)2268835
15-63287475-C-T not specified Uncertain significance (Jan 09, 2024)3127815
15-63302359-G-C not specified Uncertain significance (Mar 25, 2024)3306522
15-63302386-G-A not specified Uncertain significance (Oct 05, 2022)2317174
15-63305735-T-C not specified Uncertain significance (Mar 29, 2022)2355281

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
APH1Bprotein_codingprotein_codingENST00000261879 633109
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
2.84e-110.02231256970511257480.000203
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.1801471411.040.000006931654
Missense in Polyphen7258.6931.2267701
Synonymous-0.3906258.21.060.00000308528
Loss of Function-0.5331512.91.167.93e-7137

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003300.000313
Ashkenazi Jewish0.0004020.000397
East Asian0.0002240.000217
Finnish0.000.00
European (Non-Finnish)0.0002650.000255
Middle Eastern0.0002240.000217
South Asian0.0002080.000196
Other0.0001630.000163

dbNSFP

Source: dbNSFP

Function
FUNCTION: Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (amyloid-beta precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A. {ECO:0000269|PubMed:12297508}.;
Pathway
Alzheimer,s disease - Homo sapiens (human);Notch signaling pathway - Homo sapiens (human);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
0.172

Intolerance Scores

loftool
0.870
rvis_EVS
0.53
rvis_percentile_EVS
80.73

Haploinsufficiency Scores

pHI
0.354
hipred
N
hipred_score
0.492
ghis
0.409

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
S
essential_gene_gene_trap
N
gene_indispensability_pred
N
gene_indispensability_score
0.240

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Aph1b
Phenotype
normal phenotype;

Zebrafish Information Network

Gene name
aph1b
Affected structure
post-vent region
Phenotype tag
abnormal
Phenotype quality
decreased length

Gene ontology

Biological process
Notch signaling pathway;Notch receptor processing;locomotory behavior;protein processing;Notch receptor processing, ligand-dependent;positive regulation of catalytic activity
Cellular component
endoplasmic reticulum;plasma membrane;integral component of plasma membrane;endosome membrane;integral component of membrane;transport vesicle;gamma-secretase complex
Molecular function
endopeptidase activity;protein binding;peptidase activity