APBB2

protein-coding

amyloid beta precursor protein binding family B member 2

Gene summary

The protein encoded by this gene interacts with the cytoplasmic domains of amyloid beta (A4) precursor protein and amyloid beta (A4) precursor-like protein 2. This protein contains two phosphotyrosine binding (PTB) domains, which are thought to function in signal transduction. Polymorphisms in this gene have been associated with Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

MANE transcript

NM_004307.2

Inheritance

—

ClinVar variants

U:120B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr4:40,810,027-41,216,714

External References & Databases

Ensembl (ENSG00000163697)

Transcript & Mutation Effects

hg38 • Region Span ~406.7 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 APBB2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 108

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004307.2. 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			5 clinvar			5
missense			111 clinvar	2 clinvar		113
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	120	2	0	122

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 102 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004307.2	RefSeq	NP_004298.1	14	MANE Select
ENST00000508593.6	Ensembl	ENSP00000427211.1	14	MANE Select
NM_001166050.2	RefSeq	NP_001159522.1	14	Standard
NM_001166051.2	RefSeq	NP_001159523.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

neuron migration
regulation of transcription, DNA-templated
cell cycle arrest
axon guidance
extracellular matrix organization

Molecular Function

amyloid-beta binding
protein binding
transcription factor binding

Cellular Component

nucleus
cytoplasm
membrane
lamellipodium
growth cone

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000508593
Coding exons: 14
Length: 406688
Individuals with no LoFs: 124772
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 124801
p: 0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.12	320	446	0.717	0.0000262	5000
Missense (PolyPhen)		119	203.05	0.58607		2207
Synonymous	0.187	176	179	0.982	0.0000118	1487
Loss of Function	4.26	10	38.5	0.260	0.00000229	406

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00013	0.00013	rare
Latino/Admixed American	0.000091	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000093	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May modulate the internalization of amyloid-beta precursor protein.;

Recessive Scores

pRec: 0.237

Intolerance Scores

LoFtool: 0.741
RVIS EVS: -0.37
RVIS percentile EVS: 28.16

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.921

Gene Damage Prediction

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