APBB3

Summary

APBB3 (amyloid beta precursor protein binding family B member 3, HGNC:20708) is a protein-coding gene on chromosome 5q31.3, encoding Amyloid-beta A4 precursor protein-binding family B member 3 (O95704). May modulate the internalization of amyloid-beta precursor protein.

The protein encoded by this gene is a member of the APBB protein family. It is found in the cytoplasm and binds to the intracellular domain of the Alzheimer’s disease beta-amyloid precursor protein (APP) as well as to other APP-like proteins. It is thought that the protein encoded by this gene may modulate the internalization of APP. Multiple transcript variants encoding several different isoforms have been found for this gene.

Source: NCBI Gene 10307 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 91 total
• MANE Select transcript: NM_133173

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20708
Approved symbol	APBB3
Name	amyloid beta precursor protein binding family B member 3
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FE65L2
Ensembl gene	ENSG00000113108
Ensembl biotype	protein_coding
OMIM	602711
Entrez	10307

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 11 retained_intron, 8 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000354402, ENST00000356738, ENST00000357560, ENST00000358580, ENST00000412920, ENST00000467078, ENST00000503850, ENST00000503979, ENST00000504872, ENST00000505617, ENST00000506165, ENST00000506289, ENST00000506958, ENST00000509914, ENST00000510241, ENST00000511201, ENST00000511459, ENST00000511463, ENST00000511896, ENST00000513507, ENST00000515056, ENST00000890595, ENST00000954981

RefSeq mRNA: 4 — MANE Select: NM_133173 NM_006051, NM_133172, NM_133173, NM_133174

CCDS: CCDS4227, CCDS4228, CCDS4229, CCDS47279

Canonical transcript exons

ENST00000357560 — 13 exons

Exon	Start	End
ENSE00001812697	140564197	140564598
ENSE00002469166	140561844	140561849
ENSE00003461709	140562353	140562499
ENSE00003469630	140562663	140562723
ENSE00003475617	140561018	140561101
ENSE00003485001	140563752	140563915
ENSE00003515406	140562100	140562227
ENSE00003608460	140563594	140563670
ENSE00003613898	140561587	140561701
ENSE00003618336	140560639	140560754
ENSE00003674070	140560313	140560504
ENSE00003679400	140561365	140561449
ENSE00003913168	140558268	140558821

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.01.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4299 / max 531.0456, expressed in 1732 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
63798	5.6106	1493
63800	4.0407	1253
63801	0.5266	285
63799	0.2521	105

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.01	gold quality
left ovary	UBERON:0002119	96.95	gold quality
right ovary	UBERON:0002118	96.66	gold quality
cerebellar hemisphere	UBERON:0002245	96.56	gold quality
cerebellar cortex	UBERON:0002129	96.53	gold quality
right adrenal gland	UBERON:0001233	96.52	gold quality
cerebellum	UBERON:0002037	96.51	gold quality
right testis	UBERON:0004534	96.35	gold quality
right adrenal gland cortex	UBERON:0035827	96.30	gold quality
left adrenal gland cortex	UBERON:0035825	96.26	gold quality
left testis	UBERON:0004533	96.15	gold quality
ovary	UBERON:0000992	96.11	gold quality
right lobe of thyroid gland	UBERON:0001119	96.10	gold quality
left adrenal gland	UBERON:0001234	96.01	gold quality
pituitary gland	UBERON:0000007	95.90	gold quality
left lobe of thyroid gland	UBERON:0001120	95.62	gold quality
thyroid gland	UBERON:0002046	95.47	gold quality
tibial nerve	UBERON:0001323	95.24	gold quality
testis	UBERON:0000473	95.23	gold quality
adenohypophysis	UBERON:0002196	95.14	gold quality
minor salivary gland	UBERON:0001830	94.96	gold quality
saliva-secreting gland	UBERON:0001044	94.94	gold quality
adrenal gland	UBERON:0002369	94.85	gold quality
right uterine tube	UBERON:0001302	94.76	gold quality
endocervix	UBERON:0000458	94.37	gold quality
right frontal lobe	UBERON:0002810	94.09	gold quality
left uterine tube	UBERON:0001303	94.07	gold quality
body of uterus	UBERON:0009853	93.89	gold quality
gall bladder	UBERON:0002110	93.57	gold quality
fundus of stomach	UBERON:0001160	93.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
TYMS	Repression

Upstream regulators (CollecTRI, top): MYCN

miRNA regulators (miRDB)

30 targeting APBB3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-142-5P	99.48	70.92	2416
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-6814-5P	99.03	66.68	1273
HSA-MIR-6830-5P	99.01	68.73	1884
HSA-MIR-1245B-5P	98.88	66.55	576
HSA-MIR-3142	98.88	66.09	529
HSA-MIR-12120	98.05	68.44	1768
HSA-MIR-4438	97.96	63.70	947
HSA-MIR-1295B-3P	96.68	66.11	276
HSA-MIR-711	96.60	65.75	528
HSA-MIR-553	94.01	65.93	158
HSA-MIR-4732-5P	90.07	64.77	412

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	apbb3	ENSDARG00000053771
mus_musculus	Apbb3	ENSMUSG00000117679
rattus_norvegicus	Apbb3	ENSRNOG00000017849
caenorhabditis_elegans		WBGENE00001410

Paralogs (2): APBB2 (ENSG00000163697), APBB1 (ENSG00000166313)

Protein

Protein identifiers

Amyloid-beta A4 precursor protein-binding family B member 3 — O95704 (reviewed: O95704)

Alternative names: Protein Fe65-like 2

All UniProt accessions (4): D6RBA1, D6RJB2, E7EX91, O95704

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Interacts with APP (via intracellular domain). Interacts with APLP1 and APLP2 (via intracellular domain).

Subcellular location. Cytoplasm. Nucleus Nucleus Nucleus.

Tissue specificity. Expressed in various tissues, highest expression in brain.

Miscellaneous. Increased expression upon apoptotic stimuli.

Isoforms (6)

UniProt ID	Names	Canonical?
O95704-1	II	yes
O95704-2	I
O95704-3	III
O95704-4	IV
O95704-5	I-214
O95704-6	I-245

RefSeq proteins (4): NP_006042, NP_573418, NP_573419, NP_573420 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036020	WW_dom_sf	Homologous_superfamily
IPR039576	APBB1/2/3	Family

Pfam: PF00397, PF00640

UniProt features (27 total): strand 11, splice variant 7, domain 3, helix 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
2DYQ	X-RAY DIFFRACTION	3.1
2YSC	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95704-F1	64.76	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 151 (showing top): GCM_GSPT1, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, CAGCTG_AP4_Q5, CAIRO_HEPATOBLASTOMA_CLASSES_DN, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_SECRETION, GGCAGTG_MIR3243P, DOUGLAS_BMI1_TARGETS_DN, ACTTTAT_MIR1425P, GOBP_POSITIVE_REGULATION_OF_TRANSPORT, GOMF_SIGNALING_RECEPTOR_BINDING, GOBP_REGULATION_OF_TRANSPORT, GOBP_POSITIVE_REGULATION_OF_ESTABLISHMENT_OF_PROTEIN_LOCALIZATION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_SECRETION, GCM_RBM8A

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), positive regulation of protein secretion (GO:0050714)

GO Molecular Function (4): amyloid-beta binding (GO:0001540), low-density lipoprotein particle receptor binding (GO:0050750), molecular adaptor activity (GO:0060090), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), actin cytoskeleton (GO:0015629), membrane (GO:0016020), nuclear body (GO:0016604)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
peptide binding	1
lipoprotein particle receptor binding	1
molecular_function	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
cytoskeleton	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1605 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APBB3	APP	P05067	922
APBB3	MAPK8IP1	Q9UQF2	505
APBB3	APBA3	O96018	463
APBB3	APBB1	O00213	459
APBB3	APLP2	Q06481	459
APBB3	NUMB	P49757	455
APBB3	NUMBL	Q9Y6R0	453
APBB3	APBB2	Q92870	452
APBB3	APLP1	P51693	446
APBB3	PTBP1	P26599	437
APBB3	G5EA03	G5EA03	378
APBB3	APPBP2	Q92624	377
APBB3	PKP4	Q99569	369
APBB3	AP4M1	O00189	358
APBB3	SMAD4	Q13485	345

IntAct

22 interactions, top by confidence:

A	B	Type	Score
APBB3	APP	psi-mi:“MI:0915”(physical association)	0.850
PIK3R1	APBB3	psi-mi:“MI:0915”(physical association)	0.560
APLP2	APBB3	psi-mi:“MI:0915”(physical association)	0.550
APBB3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
DAPP1	APBB3	psi-mi:“MI:0915”(physical association)	0.510
APBB3	DAPP1	psi-mi:“MI:0915”(physical association)	0.510
PDPK1	APBB3	psi-mi:“MI:0915”(physical association)	0.490
APBB3	PDPK1	psi-mi:“MI:0915”(physical association)	0.490
APBB3	EGFR	psi-mi:“MI:0407”(direct interaction)	0.440
APBB3	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
APP	APBB3	psi-mi:“MI:0915”(physical association)	0.000
RAB4A	APBB3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (51): APBB3 (Affinity Capture-RNA), PDPK1 (Two-hybrid), APBB3 (Two-hybrid), APBB3 (Affinity Capture-Luminescence), RHOBTB1 (Affinity Capture-MS), RHOBTB2 (Affinity Capture-MS), APLP1 (Affinity Capture-MS), APLP2 (Affinity Capture-MS), APP (Affinity Capture-MS), COPS2 (Affinity Capture-MS), COPS7B (Affinity Capture-MS), COPS3 (Affinity Capture-MS), COPS7A (Affinity Capture-MS), COPS5 (Affinity Capture-MS), UBB (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI67, B5KFD7, D4A7V9, M0R4F8, O08774, O35827, O43187, O70167, O70173, O88866, O88900, O95398, O95704, P0C5Y8, Q0P5I2, Q13322, Q14449, Q4QQS0, Q5BIW4, Q5ICW4, Q5JV73, Q5PQS0, Q5R810, Q60760, Q68DX3, Q6IFT4, Q6IRN0, Q6P4K6, Q6REY9, Q6S5L8, Q6TXD4, Q7TSI1, Q80TQ5, Q80VA5, Q8BW88, Q8CFA1, Q8IWE5, Q8R1C9, Q8R2S1, Q8VCC8

Diamond homologs: O00213, O35827, O95704, P46933, Q8R1C9, Q92870, Q9BKZ9, Q9DBR4, Q9QXJ1, E9Q5F9, Q9BYW2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

91 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2128 predictions. Top by Δscore:

Variant	Effect	Δscore
5:140561102:C:CC	acceptor_gain	1.0000
5:140561359:CCATA:C	donor_loss	1.0000
5:140561360:CATAC:C	donor_loss	1.0000
5:140561361:ATACC:A	donor_loss	1.0000
5:140562348:CTCA:C	donor_loss	1.0000
5:140562351:A:AC	donor_gain	1.0000
5:140562351:A:T	donor_loss	1.0000
5:140562352:C:CC	donor_gain	1.0000
5:140562352:CCTCA:C	donor_gain	1.0000
5:140562495:AAGCA:A	acceptor_gain	1.0000
5:140562496:AGCA:A	acceptor_gain	1.0000
5:140562498:CA:C	acceptor_gain	1.0000
5:140562500:C:CC	acceptor_gain	1.0000
5:140562504:C:CT	acceptor_gain	1.0000
5:140562505:A:T	acceptor_gain	1.0000
5:140562507:G:C	acceptor_gain	1.0000
5:140562507:G:GC	acceptor_gain	1.0000
5:140562508:T:C	acceptor_gain	1.0000
5:140562508:T:TC	acceptor_gain	1.0000
5:140562666:AGCC:A	donor_gain	1.0000
5:140564151:T:TA	donor_gain	1.0000
5:140564155:C:A	donor_gain	1.0000
5:140560442:A:T	acceptor_gain	0.9900
5:140560634:GGTA:G	donor_loss	0.9900
5:140560636:TACC:T	donor_loss	0.9900
5:140560637:A:C	donor_loss	0.9900
5:140560638:C:CA	donor_loss	0.9900
5:140560781:CCAG:C	acceptor_gain	0.9900
5:140560782:CAG:C	acceptor_gain	0.9900
5:140561020:ATGG:A	donor_gain	0.9900

AlphaMissense

3177 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:140560445:A:C	F364L	0.998
5:140560445:A:T	F364L	0.998
5:140560447:A:G	F364L	0.998
5:140563829:A:C	Y46D	0.998
5:140563862:A:G	W35R	0.998
5:140563862:A:T	W35R	0.998
5:140563832:A:C	Y45D	0.997
5:140563860:C:A	W35C	0.997
5:140563860:C:G	W35C	0.997
5:140561032:A:T	V301D	0.996
5:140562489:A:T	V121D	0.996
5:140560413:C:T	G375D	0.995
5:140561645:A:G	F230S	0.995
5:140558815:A:C	Y411D	0.994
5:140560382:G:C	F385L	0.994
5:140560382:G:T	F385L	0.994
5:140560384:A:G	F385L	0.994
5:140561695:G:C	F213L	0.994
5:140561695:G:T	F213L	0.994
5:140561696:A:G	F213S	0.994
5:140561697:A:G	F213L	0.994
5:140560368:A:G	F390S	0.993
5:140561693:G:T	A214D	0.993
5:140562125:A:G	W201R	0.993
5:140562125:A:T	W201R	0.993
5:140562423:A:T	V143D	0.993
5:140560410:A:G	L376P	0.992
5:140562184:A:G	L181P	0.992
5:140561696:A:C	F213C	0.990
5:140562205:A:G	L174P	0.990

dbSNP variants (sampled 300 via entrez): RS1000183069 (5:140565698 T>C), RS1000786513 (5:140564451 T>C), RS1000935895 (5:140558375 G>A), RS1001071782 (5:140564687 C>T), RS1002250498 (5:140558440 T>G), RS1002382269 (5:140558017 C>T), RS1002905015 (5:140564054 C>A), RS1003258643 (5:140559733 C>T), RS1003498866 (5:140565459 G>T), RS1003773896 (5:140565824 G>A), RS1004746086 (5:140562339 C>A,T), RS1005182139 (5:140565634 T>C), RS1005193166 (5:140558893 G>A), RS1005412262 (5:140559235 C>T), RS1005709594 (5:140565258 A>G)

Disease associations

OMIM: gene MIM:602711 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010146_22	Serum immune biomarker levels	7.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004872	inflammatory biomarker measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects cotreatment, increases abundance, increases expression, affects expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Ozone	affects cotreatment, increases expression, increases abundance, affects expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	increases expression, decreases expression, affects cotreatment, increases abundance	2
moringin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
sodium arsenate	decreases expression, increases abundance	1
trichostatin A	affects expression	1
cupric chloride	decreases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Copper	affects binding, increases expression	1
Diazinon	increases methylation	1
Disulfiram	affects binding, increases expression	1
Gasoline	affects cotreatment, increases abundance, increases expression, decreases expression	1
Polycyclic Aromatic Hydrocarbons	increases abundance, increases expression, decreases expression, affects cotreatment	1
Sarin	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.