APBB1

amyloid beta precursor protein binding family B member 1

Basic information

Region (hg38): 11:6395125-6419414

Previous symbols: [ "RIR" ]

Links

ENSG00000166313 ∙ NCBI:322 ∙ OMIM:602709 ∙ HGNC:581 ∙ Uniprot:O00213 ∙ 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 APBB1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the APBB1 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				3	4	7
missense			29	5	1	35
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	29	8	5

Variants in APBB1

This is a list of pathogenic ClinVar variants found in the APBB1 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-6395560-T-C		not specified	Uncertain significance (Sep 20, 2023)
11-6395583-G-A		not specified	Uncertain significance (Mar 18, 2024)
11-6395585-C-A		not specified	Uncertain significance (Feb 28, 2024)
11-6395677-C-T		not specified	Uncertain significance (Apr 05, 2023)
11-6395698-G-A		not specified	Uncertain significance (Jul 13, 2022)
11-6395823-G-A		not specified	Uncertain significance (Dec 14, 2023)
11-6395833-C-T		not specified	Uncertain significance (Apr 26, 2024)
11-6395869-C-T		not specified	Uncertain significance (Jan 19, 2024)
11-6395932-G-A		not specified	Uncertain significance (Dec 27, 2023)
11-6396146-C-A		not specified	Uncertain significance (Jan 02, 2024)
11-6396197-C-T		not specified	Uncertain significance (Jun 22, 2021)
11-6401007-G-T		not specified	Uncertain significance (Oct 29, 2021)
11-6401396-C-G		not specified	Uncertain significance (Apr 08, 2024)
11-6401404-C-T		not specified	Uncertain significance (Oct 17, 2023)
11-6401413-C-T		not specified	Uncertain significance (Jan 03, 2024)
11-6401416-C-T		not specified	Uncertain significance (Sep 20, 2023)
11-6401630-G-A		not specified	Uncertain significance (Feb 17, 2024)
11-6401637-G-A			Benign (Apr 06, 2018)
11-6402101-C-T		not specified	Uncertain significance (Mar 15, 2024)
11-6402113-G-A		not specified	Uncertain significance (Apr 24, 2023)
11-6402145-G-C		not specified	Uncertain significance (Jul 15, 2021)
11-6402189-C-T		not specified	Likely benign (May 30, 2023)
11-6402596-T-C		APBB1-related disorder	Likely benign (Mar 31, 2022)
11-6402643-T-C		APBB1-related disorder	Likely benign (Apr 28, 2022)
11-6402655-A-G		not specified	Uncertain significance (Aug 19, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
APBB1	protein_coding	protein_coding	ENST00000299402	13	24290

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.968	0.0319	125741	0	7	125748	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.56	331	421	0.786	0.0000258	4561
Missense in Polyphen		76	131.17	0.5794		1343
Synonymous	0.122	171	173	0.988	0.0000107	1448
Loss of Function	4.49	5	32.7	0.153	0.00000159	362

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000119	0.000119
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.000168	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription coregulator that can have both coactivator and corepressor functions. Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro- apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its transcription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s). {ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:18922798, ECO:0000269|PubMed:19234442, ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:25342469}.
• Pathway: Alzheimer,s disease - Homo sapiens (human);Alzheimers Disease;DNA Repair;DNA Double-Strand Break Repair;Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks;DNA Double Strand Break Response;Validated nuclear estrogen receptor alpha network (Consensus)

Recessive Scores

• pRec: 0.360

Intolerance Scores

• loftool: 0.121
• rvis_EVS: -0.55
• rvis_percentile_EVS: 19.93

Haploinsufficiency Scores

• pHI: 0.210
• hipred: Y
• hipred_score: 0.775
• ghis: 0.574

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.894

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Apbb1
• Phenotype: cellular phenotype; growth/size/body region phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;double-strand break repair;regulation of transcription, DNA-templated;apoptotic process;cellular response to DNA damage stimulus;cell cycle arrest;signal transduction;axonogenesis;response to iron ion;positive regulation of neuron projection development;negative regulation of cell growth;positive regulation of apoptotic process;histone H4 acetylation;positive regulation of DNA repair;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;positive regulation of protein secretion;negative regulation of thymidylate synthase biosynthetic process
• Cellular component: nucleus;nucleoplasm;cytoplasm;plasma membrane;nuclear speck;lamellipodium;growth cone;protein-containing complex;presynaptic membrane;neuronal cell body;dendritic spine;main axon;synapse;postsynaptic membrane;perinuclear region of cytoplasm;growth cone lamellipodium;growth cone filopodium
• Molecular function: amyloid-beta binding;chromatin binding;protein binding;transcription factor binding;histone binding;protein-containing complex binding;tau protein binding;proline-rich region binding