APBB1

protein-coding

amyloid beta precursor protein binding family B member 1

Gene summary

The protein encoded by this gene is a member of the Fe65 protein family. It is an adaptor protein localized in the nucleus. It interacts with the Alzheimer's disease amyloid precursor protein (APP), transcription factor CP2/LSF/LBP1 and the low-density lipoprotein receptor-related protein. APP functions as a cytosolic anchoring site that can prevent the gene product's nuclear translocation. This encoded protein could play an important role in the pathogenesis of Alzheimer's disease. It is thought to regulate transcription. Also it is observed to block cell cycle progression by downregulating thymidylate synthase expression. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Mar 2012]

Previous symbols:

MANE transcript

NM_001164.5

Inheritance

—

ClinVar variants

U:89B:14

Top phenotype

APBB1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.15

Max pathogenic AF

—

Genomic locus

chr11:6,395,125-6,419,414

External References & Databases

Ensembl (ENSG00000166313)

Transcript & Mutation Effects

hg38 • Region Span ~24.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to APBB1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 83

not providedTotal: 9

APBB1-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001164.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	3 clinvar	4 clinvar	10
missense			81 clinvar	6 clinvar	1 clinvar	88
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	89	9	5	103

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 68 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001164.5	RefSeq	NP_001155.1	14	MANE Select
ENST00000609360.6	Ensembl	ENSP00000477213.1	14	MANE Select
NM_001257319.3	RefSeq	NP_001244248.1	14	Standard
NM_001257320.2	RefSeq	NP_001244249.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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

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

Molecular Function

amyloid-beta binding
chromatin binding
protein binding
transcription factor binding
histone binding

Cellular Component

nucleus
nucleoplasm
cytoplasm
plasma membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000299402
Coding exons: 13
Length: 24290
Individuals with no LoFs: 125741
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125748
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.56	331	421	0.786	0.0000258	4561
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000062	0.000062	rare
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

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}.;

Recessive Scores

pRec: 0.360

Intolerance Scores

LoFtool: 0.121
RVIS EVS: -0.55
RVIS percentile EVS: 19.93

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.894

Gene Damage Prediction

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