APBA1

Summary

APBA1 (amyloid beta precursor protein binding family A member 1, HGNC:578) is a protein-coding gene on chromosome 9q21.12, encoding Amyloid-beta A4 precursor protein-binding family A member 1 (Q02410). Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery.

The protein encoded by this gene is a member of the X11 protein family. It is a neuronal adapter protein that interacts with the Alzheimer’s disease amyloid precursor protein (APP). It stabilizes APP and inhibits production of proteolytic APP fragments including the A beta peptide that is deposited in the brains of Alzheimer’s disease patients. This gene product is believed to be involved in signal transduction processes. It is also regarded as a putative vesicular trafficking protein in the brain that can form a complex with the potential to couple synaptic vesicle exocytosis to neuronal cell adhesion.

Source: NCBI Gene 320 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 134 total — 3 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 25 tissues, sQTL in 0 (q < 0.05)
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.98 (unconstrained)
• MANE Select transcript: NM_001163
• Notable: 134 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:578
Approved symbol	APBA1
Name	amyloid beta precursor protein binding family A member 1
Location	9q21.12
Locus type	gene with protein product
Status	Approved
Aliases	D9S411E, X11
Ensembl gene	ENSG00000107282
Ensembl biotype	protein_coding
OMIM	602414
Entrez	320

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

MANE Select: ENST00000265381

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000265381, ENST00000470082, ENST00000628769, ENST00000699288, ENST00001135179

RefSeq mRNA: 1 — MANE Select: NM_001163 NM_001163

CCDS: CCDS6630

Canonical transcript exons

ENST00000265381 — 13 exons

Exon	Start	End
ENSE00000917481	69456247	69456432
ENSE00000982740	69467823	69467968
ENSE00000982742	69452122	69452301
ENSE00000982743	69449584	69449796
ENSE00000982744	69440996	69441115
ENSE00000982745	69432536	69432676
ENSE00001015445	69458156	69458188
ENSE00001089892	69471656	69471695
ENSE00001089894	69516011	69517279
ENSE00001089895	69476048	69476143
ENSE00001228144	69672153	69672371
ENSE00001228156	69427532	69431398
ENSE00003683323	69457053	69457139

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 92.64.

FANTOM5 (CAGE): breadth broad, TPM avg 2.3566 / max 63.1991, expressed in 730 samples.

Highest expression (Bgee): superior frontal gyrus, prefrontal cortex, frontal cortex, frontal lobe, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

APBA1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 25 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 25 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Mucosa	eqtl	1.2e-16	+0.34	9:69737687:T:C
Heart Left Ventricle	eqtl	6.4e-11	+0.51	9:69501059:C:T
Thyroid	eqtl	6.8e-09	-0.46	9:69485202:G:A
Cells Cultured fibroblasts	eqtl	2.7e-08	+0.17	9:69917151:C:T
Prostate	eqtl	5.0e-07	-0.43	9:69650451:C:T
Artery Coronary	eqtl	3.0e-06	+4.34	9:68734537:G:T
Nerve Tibial	eqtl	7.0e-05	-0.13	9:69499663:G:GT
Skin Not Sun Exposed Suprapubic	eqtl	8.2e-05	-0.67	9:69789681:A:G
Esophagus Muscularis	eqtl	5.3e-04	-0.14	9:69674733:A:G
Testis	eqtl	1.7e-03	-0.40	9:69404264:A:G
Brain Cerebellum	eqtl	1.7e-03	+0.22	9:69463950:G:A
Minor Salivary Gland	eqtl	2.3e-03	-0.20	9:69645393:G:C
Whole Blood	eqtl	4.0e-03	-0.35	9:69415086:T:C
Skin Sun Exposed Lower leg	eqtl	7.4e-03	+0.32	9:69569875:C:T
Artery Aorta	eqtl	8.3e-03	+0.21	9:69469092:C:T
Muscle Skeletal	eqtl	1.3e-02	-0.10	9:68990750:A:G
Brain Frontal Cortex BA9	eqtl	1.3e-02	+0.65	9:69574682:G:A
Stomach	eqtl	1.6e-02	+0.14	9:69605583:C:T
Brain Putamen basal ganglia	eqtl	1.6e-02	+0.60	9:70481315:T:G
Pancreas	eqtl	1.7e-02	+0.28	9:69719122:C:T

FANTOM5 promoters

4 alternative TSS:

Promoter ID	TPM avg	Samples expressed
100820	1.4613	573
100819	0.4036	169
100821	0.3294	114
100818	0.1623	76

Top tissues by expression

showing 100 of 138 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	92.64	gold quality
prefrontal cortex	UBERON:0000451	91.57	gold quality
frontal cortex	UBERON:0001870	91.51	gold quality
frontal lobe	UBERON:0016525	91.51	gold quality
right frontal lobe	UBERON:0002810	91.33	gold quality
cortical plate	UBERON:0005343	90.88	gold quality
temporal lobe	UBERON:0001871	90.46	gold quality
amygdala	UBERON:0001876	90.41	gold quality
cerebral cortex	UBERON:0000956	90.39	gold quality
anterior cingulate cortex	UBERON:0009835	90.35	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.33	gold quality
hypothalamus	UBERON:0001898	90.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.77	gold quality
nucleus accumbens	UBERON:0001882	89.38	gold quality
primary visual cortex	UBERON:0002436	88.82	gold quality
Ammon’s horn	UBERON:0001954	88.66	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.57	gold quality
cerebellum	UBERON:0002037	88.29	gold quality
cerebellar cortex	UBERON:0002129	88.25	gold quality
cerebellar hemisphere	UBERON:0002245	88.23	gold quality
substantia nigra	UBERON:0002038	88.16	gold quality
brain	UBERON:0000955	88.03	gold quality
putamen	UBERON:0001874	87.24	gold quality
caudate nucleus	UBERON:0001873	87.04	gold quality
corpus callosum	UBERON:0002336	83.69	gold quality
stromal cell of endometrium	CL:0002255	82.78	gold quality
liver	UBERON:0002107	80.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.15	gold quality
right lobe of liver	UBERON:0001114	79.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.46	gold quality
embryo	UBERON:0000922	78.19	gold quality
ganglionic eminence	UBERON:0004023	78.19	gold quality
sural nerve	UBERON:0015488	76.66	gold quality
rectum	UBERON:0001052	74.95	gold quality
ventricular zone	UBERON:0003053	74.64	gold quality
ovary	UBERON:0000992	73.72	gold quality
pituitary gland	UBERON:0000007	73.70	gold quality
left ovary	UBERON:0002119	73.69	gold quality
adenohypophysis	UBERON:0002196	73.55	gold quality
popliteal artery	UBERON:0002250	73.33	gold quality
tibial artery	UBERON:0007610	73.33	gold quality
tibial nerve	UBERON:0001323	73.24	gold quality
right ovary	UBERON:0002118	73.08	gold quality
islet of Langerhans	UBERON:0000006	72.98	gold quality
descending thoracic aorta	UBERON:0002345	72.31	gold quality
myometrium	UBERON:0001296	72.12	gold quality
placenta	UBERON:0001987	71.87	gold quality
thoracic aorta	UBERON:0001515	71.77	gold quality
body of uterus	UBERON:0009853	71.66	gold quality
ascending aorta	UBERON:0001496	71.53	gold quality
right coronary artery	UBERON:0001625	71.46	gold quality
ectocervix	UBERON:0012249	71.30	gold quality
zone of skin	UBERON:0000014	71.07	gold quality
skin of abdomen	UBERON:0001416	71.03	gold quality
skin of leg	UBERON:0001511	70.99	gold quality
skeletal muscle tissue	UBERON:0001134	70.89	gold quality
left coronary artery	UBERON:0001626	70.60	gold quality
smooth muscle tissue	UBERON:0001135	70.39	gold quality
material anatomical entity	UBERON:0000465	70.27	gold quality
multicellular organism	UBERON:0000468	70.27	gold quality
gall bladder	UBERON:0002110	70.16	gold quality
right atrium auricular region	UBERON:0006631	70.16	gold quality
muscle tissue	UBERON:0002385	70.14	gold quality
urinary bladder	UBERON:0001255	70.03	gold quality
uterine cervix	UBERON:0000002	70.02	gold quality
vagina	UBERON:0000996	69.77	gold quality
muscle layer of sigmoid colon	UBERON:0035805	69.64	gold quality
subcutaneous adipose tissue	UBERON:0002190	69.47	gold quality
mammary gland	UBERON:0001911	69.28	gold quality
thoracic mammary gland	UBERON:0005200	69.28	gold quality
spleen	UBERON:0002106	69.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	69.05	gold quality
calcaneal tendon	UBERON:0003701	68.91	gold quality
adipose tissue	UBERON:0001013	68.74	gold quality
mucosa of stomach	UBERON:0001199	68.54	gold quality
heart	UBERON:0000948	68.51	gold quality
colon	UBERON:0001155	68.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	68.43	gold quality
endometrium	UBERON:0001295	68.23	gold quality
transverse colon	UBERON:0001157	68.02	gold quality
fundus of stomach	UBERON:0001160	67.97	gold quality
endocervix	UBERON:0000458	67.83	gold quality
omental fat pad	UBERON:0010414	67.74	gold quality
left uterine tube	UBERON:0001303	67.68	gold quality
lower esophagus mucosa	UBERON:0035834	67.45	gold quality
skeletal muscle organ	UBERON:0014892	67.42	gold quality
metanephros cortex	UBERON:0010533	67.32	gold quality
muscle of leg	UBERON:0001383	67.29	gold quality
lower esophagus	UBERON:0013473	67.22	gold quality
lower esophagus muscularis layer	UBERON:0035833	67.21	gold quality
intestine	UBERON:0000160	67.04	gold quality
pancreas	UBERON:0001264	66.98	gold quality
heart left ventricle	UBERON:0002084	66.71	gold quality
tonsil	UBERON:0002372	66.38	gold quality
adult mammalian kidney	UBERON:0000082	66.34	gold quality
fallopian tube	UBERON:0003889	66.30	gold quality
colonic epithelium	UBERON:0000397	66.12	silver quality
gastrocnemius	UBERON:0001388	66.01	gold quality
esophagus	UBERON:0001043	65.96	gold quality
saliva-secreting gland	UBERON:0001044	65.73	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 75 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM
Locus coeruleus	tissue	114.0
Postcentral gyrus	tissue	106.9
Hippocampus	tissue	91.2
Frontal cortex	tissue	67.0
Nucleus accumbens	tissue	67.0
Cerebral cortex	tissue	62.5
Motor cortex	tissue	62.5
Prefrontal cortex	tissue	61.1
Substantia nigra	tissue	60.8
Midbrain	tissue	59.7
Thalamus	tissue	58.4
Somatosensory cortex	tissue	56.9
Pons	tissue	56.7
Hippocampal formation	tissue	55.1
Retrosplenial cortex	tissue	54.2
Retrosplenial and cingulate cortex	tissue	54.1
Occipital cortex	tissue	52.8
Insular cortex	tissue	52.6
Temporal cortex	tissue	51.6
Entorhinal cortex	tissue	49.3
Superior colliculi	tissue	47.6
Amygdala	tissue	44.8
Hypothalamus	tissue	36.9
Caudate putamen	tissue	34.2
Septum	tissue	33.6
Ventral forebrain	tissue	33.3
Basal ganglia	tissue	32.4
Medulla oblongata	tissue	31.9
Periaqueductal gray	tissue	31.7
Cerebellum	tissue	31.1
Olfactory bulb	tissue	30.8
Putamen	tissue	29.3
Corpus callosum	tissue	22.7
Spinal cord	tissue	21.5
Parathyroid gland	tissue	12.8
Choroid plexus	tissue	11.4
Retina	tissue	9.9
Liver	tissue	8.4
Pituitary gland	tissue	5.8
Spleen	tissue	4.9
Skin 1	tissue	4.6
Ovary	tissue	4.4
Salivary gland	tissue	4.4
Rectum	tissue	4.1
Breast	tissue	3.7
Vagina	tissue	3.3
Colon	tissue	3.2
Endometrium 1	tissue	3.1
Cervix	tissue	3.0
Testis	tissue	2.9
Skeletal muscle	tissue	2.9
Esophagus	tissue	2.6
Placenta	tissue	2.6
Gallbladder	tissue	2.6
Heart muscle	tissue	2.5
Adrenal gland	tissue	2.5
Adipose tissue	tissue	2.3
Smooth muscle	tissue	2.1
Tongue	tissue	2.0
Seminal vesicle	tissue	1.9

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Perirhinal gyrus (109.9), Olfactory area (109.2), Nucleus raphe magnus (105.9), Stria terminalis, bed nucleus (103.1), Corticomedial amygdala (102.7).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, SP3

miRNA regulators (miRDB)

Targeting APBA1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 194 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4673	100.00	66.64	1490
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882

Functional genomics

gnomAD constraint: pLI 1.15e-13, LOEUF 0.978, missense Z 0.405 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000265381 splits into 6 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
9:69,431,330–69,431,394	17 / 30.3	0.56	no
9:69,431,395–69,449,589	119 / 124.8	0.95	no
9:69,449,590–69,456,255	97 / 166.8	0.58	no
9:69,456,256–69,457,063	103 / 91.9	1.12	no
9:69,457,064–69,471,688	76 / 122.2	0.62	no
9:69,471,689–69,517,210	678 / 647.1	1.05	no

Literature-anchored findings (GeneRIF, showing 19)

• Munc18a acts through direct and indirect interactions with X11 proteins and powerfully regulates APP metabolism and Abeta secretion. (PMID:12016213)
• Coexpression of X11alpha with amyloid protein precursor retarded its maturation, prolonged its half-life, and inhibited amyloid protein precursor, Abeta40, and Abeta42 secretion. (PMID:12849748)
• human X11alpha inhibits Abeta production and deposition in vivo in the brain in transgenic mice harboring a familial Alzheimer’s disease mutant APP that produces increased levels of Abeta. (PMID:12970358)
• Involvement of X11L in the phosphorylation of APP family proteins in cellular stress and suggest that X11L protein may be . (PMID:14970211)
• X11alpha and X11beta have roles in beta-amyloid precursor protein processing (PMID:15699037)
• Mediates exocytosis and decreases beta-amyloid peptide formation in Alzheimer disease. (PMID:16413130)
• Data show that neuronal munc18-1-interacting protein 1 is an inclusion body component in neuronal intranuclear inclusion disease identified by anti-SUMO-1-immunocapture. (PMID:18836734)
• ApoEr2 regulates cell movement, and both X11alpha and Reelin enhance this effect. (PMID:19720620)
• A novel consensus sequence for interaction with the PDZ-1 and PDZ-2 domains of amyloid precursor protein (APP)-interacting proteins Mint1, Mint2, and Mint3 is reported, with multiple novel interactors for these proteins. (PMID:20016085)
• Methylation of MINT1 was significantly more prevalent in UC-CRC cases compared with controls. (PMID:20160714)
• Our findings show a new function for X11alpha that may impact on Alzheimer’s disease pathogenesis. (PMID:20531236)
• Transcriptional co-activators Taz and Yap mediate signaling via the amyloid beta protein precursor paralogues APLP1 and APLP2 through interactions with Mint1 and Mint3. (PMID:21178287)
• Study identified the conserved binding site for the peptide on the CASK calmodulin kinase domain. A related EPIWVMRQ peptide from Mint1 was also discovered to be sufficient for binding. (PMID:21763699)
• an autoinhibitory mechanism in Mint1 is important for regulating APP processing and may provide novel therapies for Alzheimer’s disease (PMID:22355143)
• Mint1 826 bridges APP to the small GTPase (PMID:23737971)
• Mints are necessary for activity-induced APP and PS1 trafficking and provide insight into the cellular fate of APP in endocytic pathways essential for Abeta production. (PMID:24742670)
• Mint1 causes amyloid precursor protein accumulation in the trans-Golgi network. (PMID:26865271)
• Status of Gene Methylation and Polymorphism in Different Courses of Ulcerative Colitis and Their Comparison with Sporadic Colorectal Cancer. (PMID:32793962)
• RNA sequencing and functional studies of patient-derived cells reveal that neurexin-1 and regulators of this pathway are associated with poor outcomes in Ewing sarcoma. (PMID:34403115)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	apba1b	ENSDARG00000074328
danio_rerio	apba1a	ENSDARG00000103848
mus_musculus	Apba1	ENSMUSG00000024897
rattus_norvegicus	Apba1	ENSRNOG00000014928
drosophila_melanogaster	X11Lbeta	FBGN0052677
caenorhabditis_elegans	lin-10	WBGENE00002999

Paralogs (4): APBA3 (ENSG00000011132), APBA2 (ENSG00000034053), SDCBP2 (ENSG00000125775), SDCBP (ENSG00000137575)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1860297) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 6 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body size	1
ataxia	1
abnormal dopamine level	1
abnormal inhibitory postsynaptic currents	1
abnormal behavior	1
impaired behavioral response to addictive substance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5RD33	97.5%	Diamond
Oryctolagus cuniculus	O19132	94.1%	Diamond
Ovis aries	Q29498	91.9%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
CFAP95	protein-coding	138255
PTAR1	protein-coding	375743
CFAP95-DT	ncRNA	494558
ENTREP1	protein-coding	9413
BANCR	ncRNA	100885775
TJP2	protein-coding	9414

Protein

Protein identifiers

Amyloid-beta A4 precursor protein-binding family A member 1 — Q02410 (reviewed: Q02410)

Alternative names: Adapter protein X11alpha, Neuron-specific X11 protein, Neuronal Munc18-1-interacting protein 1

All UniProt accessions (3): A0A0D9SFA9, A0A8V8TPS8, Q02410

UniProt curated annotations — full annotation on UniProt →

Function. Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta. Component of the LIN-10-LIN-2-LIN-7 complex, which associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules.

Subunit / interactions. Part of a multimeric complex containing STXBP1 and STX1A. Interacts with STXBP1. Also part of the brain-specific heterotrimeric complex LIN-10/X11-alpha, LIN-2/CASK, and LIN7. Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules. Within the complex, interacts (via PDZ domain) with the motor protein KIF17; the interaction is direct and is required for association of KIF17 with the cargo that is to be transported. Both isoform 1 and isoform 2 bind to the cytoplasmic domain of amyloid protein (APP). Interacts (via PDZ 1 and 2 domains) with FSPB. Isoform 2, but not isoform 1, interacts (via its truncated PID domain) with active, GTP-bound RAB6A and RAB6B.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus Golgi apparatus.

Tissue specificity. Brain and spinal cord. Isoform 2 is expressed in testis and brain, but not detected in lung, liver or spleen.

Domain organisation. Composed of an N-terminal domain that binds Munc18-1 and LIN-2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the amyloid-beta precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane. The autoinhibitory helix linker occludes the APP binding site. The PID domain, truncated by 11 amino acids, as observed in isoform 2, but not full-length, mediates the interaction with RAB6A and RAB6B.

Miscellaneous. This isoform interacts with RAB6 GTPases.

Isoforms (2)

UniProt ID	Names	Canonical?
Q02410-1	1	yes
Q02410-2	2, Mint1_826

RefSeq proteins (1): NP_001154* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001478	PDZ	Domain
IPR006020	PTB/PI_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR036034	PDZ_sf	Homologous_superfamily
IPR051230	APP-Binding	Family

Pfam: PF00595, PF00640

UniProt features (68 total): strand 19, modified residue 15, helix 9, sequence conflict 6, region of interest 6, compositionally biased region 4, domain 3, turn 2, chain 1, splice variant 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
1AQC	X11 PTB DOMAIN-10MER PEPTIDE COMPLEX	X-RAY DIFFRACTION	2.3
1X11	X11 PTB DOMAIN	X-RAY DIFFRACTION	2.5
1U37	Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed …	SOLUTION NMR
1U38	Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed …	SOLUTION NMR
1U39	Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed …	SOLUTION NMR
1U3B	Auto-inhibition Mechanism of X11s/Mints Family Scaffold Proteins Revealed by the Closed …	SOLUTION NMR
1X45	Solution structure of the first PDZ domain of amyloid beta A4 precursor protein-binding …	SOLUTION NMR
1Y7N	Solution structure of the second PDZ domain of the human neuronal adaptor X11alpha	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q02410-F1	58.85	0.12

Human Protein Atlas

Protein class: Transporters, Accessory Factors Involved in Transport, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (15)

Type	Positions
Phosphoserine	78, 242, 246, 248, 263, 280, 285, 313, 367, 401, 403, 408, 568
Phosphothreonine	305, 370

Mutagenesis-validated functional residues (1)

Position	Phenotype
608	diminishes interaction with app.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 9; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

9 pathways:

ID	Pathway	Evidence
R-HSA-212676	Dopamine Neurotransmitter Release Cycle	curated
R-HSA-442755	Activation of NMDA receptors and postsynaptic events	—
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors	electronic
R-HSA-6794361	Neurexins and neuroligins	electronic
R-HSA-112316	Neuronal System	—
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission	—
R-HSA-112310	Neurotransmitter release cycle	—
R-HSA-6794362	Protein-protein interactions at synapses	—
R-HSA-112315	Transmission across Chemical Synapses	—

MSigDB gene sets: 219 (showing top): RNGTGGGC_UNKNOWN, CREL_01, RRAGTTGT_UNKNOWN, GOBP_GLUTAMATE_SECRETION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_ACID_SECRETION, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXO_DENDRITIC_TRANSPORT, MODULE_274, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, GOBP_GROWTH, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GGGTGGRR_PAX4_03

GO Biological Process (8): intracellular protein transport (GO:0006886), cell adhesion (GO:0007155), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), axo-dendritic transport (GO:0008088), protein transport (GO:0015031), protein-containing complex assembly (GO:0065003), presynaptic modulation of chemical synaptic transmission (GO:0099171)

GO Molecular Function (3): amyloid-beta binding (GO:0001540), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), membrane (GO:0016020), dendritic spine (GO:0043197), perinuclear region of cytoplasm (GO:0048471), presynaptic active zone membrane (GO:0048787), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978)

Reactome top-level categories

6 top-level categories:

Category	Pathways
Transmission across Chemical Synapses	2
Neuronal System	2
Neurotransmitter release cycle	1
Protein-protein interactions at synapses	1
Activation of NMDA receptors and postsynaptic events	1
Neurotransmitter receptors and postsynaptic signal transmission	1

GO top-level categories

33 GO namespaces:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular protein localization	2
presynapse	2
intracellular membrane-bounded organelle	2
synapse	2
protein transport	1
intracellular transport	1
cellular process	1
anterograde trans-synaptic signaling	1
system development	1
animal gross anatomical part developmental process	1
transport along microtubule	1
neuron projection	1
transport	1
establishment of protein localization	1
cellular component assembly	1
protein-containing complex organization	1
modulation of chemical synaptic transmission	1
peptide binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1
cell periphery	1
exocytic vesicle	1
dendrite	1
neuron spine	1
postsynapse	1
presynaptic membrane	1
presynaptic active zone	1
synaptic membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 2 of 23 annotations. The rest are phylogenetic / computational / electronic (IEA).

2 experimentally-supported GO terms:

GO term	NS	Evidence
Golgi apparatus	CC	direct assay
identical protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 946 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APBA1	LIN7A	O14910	889
APBA1	CASK	O14936	866
APBA1	KIF17	Q9P2E2	851
APBA1	CASKIN1	Q8WXD9	828
APBA1	APBB2	Q92870	818
APBA1	APBB1	O00213	799
APBA1	STXBP1	P61764	766
APBA1	LIN7B	Q9HAP6	760
APBA1	LIN7C	Q9NUP9	734
APBA1	NRXN1	Q9ULB1	729
APBA1	CNTNAP4	Q9C0A0	725
APBA1	CASKIN2	Q8WXE0	719
APBA1	CNTNAP3	Q9BZ76	718
APBA1	GRIN2B	Q13224	714
APBA1	APP	P05067	695

IntAct

Human interaction partners of APBA1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 482 partners by confidence:

Partner	Interaction type	MIscore	Records
APBA2	direct interaction	0.760	2
LIN7C	direct interaction	0.760	1
APP	physical association	0.730	5
PSEN1	physical association	0.700	3
CASK	direct interaction	0.700	2
E	physical association	0.610	5
DLG1	direct interaction	0.590	3
DLG4	direct interaction	0.590	3
ARHGEF26	direct interaction	0.590	2
LIN7A	association	0.590	2
PKP4	direct interaction	0.590	2
PRKD2	direct interaction	0.590	2
RPS6KA3	direct interaction	0.590	2
NET1	direct interaction	0.590	1
RSRC2	direct interaction	0.590	1
E6	direct interaction	0.520	20
GRIP1	direct interaction	0.440	7
PATJ	direct interaction	0.440	7
LNX1	direct interaction	0.440	5
PDZK1	direct interaction	0.440	5
RPS6KA1	direct interaction	0.440	5
GRIP2	direct interaction	0.440	4
LNX2	direct interaction	0.440	4
MAGI2	direct interaction	0.440	4
NRXN3	direct interaction	0.440	4
PDLIM4	direct interaction	0.440	4
DLG3	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
FRMPD4	direct interaction	0.440	3
NHERF2	direct interaction	0.440	3

BioGRID (132 interactions; top human partners by supporting records): APP (Affinity Capture-Western; 11 records), CCS (Affinity Capture-MS; 5 records), LIN7C (Affinity Capture-MS; 5 records), LRP8 (Affinity Capture-Western; 4 records), LIN7B (Affinity Capture-Western; 3 records), STXBP1 (Reconstituted Complex; 3 records), APBA2 (Affinity Capture-MS; 2 records), CASK (Affinity Capture-MS; 2 records), DLG1 (Affinity Capture-Western; 2 records), KCNJ12 (Affinity Capture-MS; 2 records), TJAP1 (Affinity Capture-MS; 2 records), ABLIM1 (Affinity Capture-MS), ACOX1 (Affinity Capture-MS), AP3M1 (Affinity Capture-MS), ARF3 (Two-hybrid)

SIGNOR signaling

5 signaling interactions:

A	Effect	B	Mechanism
APBA1	up-regulates	Exocytosis
APBA1	“form complex”	“CASK-Mint1-Veli complex”	binding
APBA1	“up-regulates activity”	STXBP1	binding
APBA1	“up-regulates activity”	NRXN1	binding
APBA1	“up-regulates activity”	CASK	binding

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
LIN2-LIN7-SAP97-MINT1 complex	4	CASK, DLG1, LIN7A, APBA1
CASK-LIN7C-APBA1 complex	3	APBA1, CASK, LIN7C

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 482 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Unblocking of NMDA receptors, glutamate binding and activation	11	17.7×	8e-10
Long-term potentiation	12	16.9×	3e-10
Tight junction interactions	15	16.4×	1e-12
Negative regulation of NMDA receptor-mediated neuronal transmission	10	16.1×	2e-08
Ras activation upon Ca2+ influx through NMDA receptor	8	13.5×	5e-06
Synaptic adhesion-like molecules	8	12.9×	7e-06
Assembly and cell surface presentation of NMDA receptors	15	11.3×	4e-10
Trafficking of AMPA receptors	7	11.3×	9e-05

GO biological processes:

GO term	Partners	Fold	FDR
calcium-independent cell-cell adhesion	12	21.3×	3e-11
glutamate receptor signaling pathway	9	18.6×	1e-07
establishment or maintenance of epithelial cell apical/basal polarity	12	15.4×	2e-09
positive regulation of synaptic transmission, glutamatergic	10	13.8×	3e-07
protein localization to synapse	8	13.5×	1e-05
regulation of postsynaptic membrane neurotransmitter receptor levels	12	13.1×	2e-08
bicellular tight junction assembly	17	12.4×	1e-11
sodium-independent organic anion transport	5	12.4×	2e-03

Disease & clinical

Genetic variants

Variant evidence for APBA1: 134 ClinVar records (4 pathogenic / likely pathogenic); 10 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	112
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (4)

Showing all 4 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59106	GRCh38/hg38 9q21.11-21.12(chr9:68426796-69606104)x1	Pathogenic	criteria provided, single submitter	1
4851080	GRCh37/hg19 9q21.11-21.12(chr9:71762494-72325050)x1	Pathogenic	criteria provided, single submitter	1
685659	GRCh37/hg19 9q21.11-21.31(chr9:70974661-81829792)x1	Pathogenic	no assertion criteria provided	1
148455	GRCh38/hg38 9q21.11-21.12(chr9:68420349-70939579)x1	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore APBA1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 1,522):

Position(s)	Effect	Δscore	Sites
9:69440994–69440995	donor_loss	1.0000	5
9:69449797–69449798	acceptor_loss	1.0000	6
9:69456245–69456246	donor_loss	1.0000	5
9:69456249	donor_gain	1.0000
9:69456433–69456434	acceptor_loss	1.0000	6
9:69456441	acceptor_gain	1.0000
9:69457051–69457052	donor_loss	1.0000	4
9:69467821–69467822	donor_loss	1.0000	5
9:69467969–69467970	acceptor_loss	1.0000	4
9:69518846	donor_gain	1.0000

AlphaMissense

2,817 missense substitutions predicted likely pathogenic (of 5,539 scored), across 532 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M558	9	0.996	1.000
M483	9	0.992	1.000
M820	9	0.986	1.000
M587	9	0.969	0.999
M707	9	0.945	0.998
M817	9	0.925	1.000
M772	9	0.904	0.997
M538	9	0.902	0.996
M381	9	0.879	0.991
D550	8	1.000	1.000
F461	8	0.999	1.000
D518	8	0.999	1.000
F592	8	0.999	1.000
F608	8	0.999	1.000
H786	8	0.999	1.000
F761	8	0.998	1.000
D596	8	0.997	1.000
F520	8	0.996	1.000
D454	8	0.995	0.999
H801	8	0.995	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	0.000656
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000918

Disease associations

OMIM: gene MIM:602414 | disease phenotypes:

GWAS associations

10 associations:

Study	Trait	p-value
GCST010002_297	Refractive error	3e-39
GCST008595_144	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1e-11
GCST005141_40	Cognitive ability (MTAG)	1e-10
GCST005316_355	Intelligence (MTAG)	2e-10
GCST007044_20	Extremely high intelligence	2e-9
GCST005316_356	Intelligence (MTAG)	1e-8
GCST004364_9	Intelligence	4e-8
GCST004364_13	Intelligence	6e-8
GCST005142_34	Cognitive ability	4e-7
GCST004862_138	Itch intensity from mosquito bite adjusted by bite size	9e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2097170 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,781 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL193	NIFEDIPINE	4	74,779
CHEMBL449317	HESPERIDIN	3	19,002

PharmGKB: 1 entry (CPIC guideline: no)

ChEMBL bioactivities

295 potent at pChembl≥5 of 582 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.67	IC50	212	nM	CHEMBL1375867
6.66	IC50	221	nM	CHEMBL1346321
6.65	IC50	225	nM	CHEMBL1302524
6.58	IC50	260	nM	CHEMBL1529201
6.56	IC50	278	nM	CHEMBL1600114
6.48	IC50	331	nM	CHEMBL131037
6.29	IC50	507	nM	CHEMBL1374242
6.28	IC50	521	nM	CHEMBL1447467
6.23	IC50	586	nM	CHEMBL1447467
6.13	IC50	749	nM	CHEMBL1440962
6.13	IC50	738	nM	CHEMBL3197242
6.13	IC50	745	nM	CHEMBL1526855
6.06	IC50	871	nM	CHEMBL1338442
5.98	IC50	1040	nM	CHEMBL1546396
5.96	IC50	1090	nM	CHEMBL1386349
5.95	IC50	1120	nM	NIFEDIPINE
5.95	IC50	1130	nM	CHEMBL1561089
5.94	IC50	1150	nM	CHEMBL1412731
5.90	IC50	1270	nM	CHEMBL1468575
5.89	IC50	1280	nM	CHEMBL1340587
5.86	IC50	1390	nM	CHEMBL1383746
5.85	IC50	1420	nM	CHEMBL1966746
5.85	IC50	1400	nM	CHEMBL1600114
5.82	IC50	1500	nM	CHEMBL1528890
5.82	IC50	1530	nM	CHEMBL1367314
5.82	IC50	1530	nM	CHEMBL1427185
5.80	IC50	1590	nM	CHEMBL1501151
5.78	IC50	1680	nM	CHEMBL1364395
5.78	IC50	1660	nM	CHEMBL1582771
5.74	IC50	1840	nM	CHEMBL1464280
5.71	IC50	1940	nM	CHEMBL1530272
5.71	IC50	1970	nM	CHEMBL1387248
5.71	IC50	1930	nM	CHEMBL1486729
5.70	IC50	2000	nM	CHEMBL1601009
5.70	IC50	1980	nM	CHEMBL1342736
5.69	IC50	2050	nM	CHEMBL1451059
5.68	IC50	2100	nM	CHEMBL1469916
5.67	IC50	2160	nM	CHEMBL1338442
5.67	IC50	2150	nM	CHEMBL1399979
5.66	IC50	2190	nM	CHEMBL1548870
5.64	IC50	2280	nM	CHEMBL1310699
5.64	IC50	2300	nM	CHEMBL3194601
5.63	IC50	2330	nM	CHEMBL3198930
5.62	IC50	2380	nM	CHEMBL1387961
5.62	IC50	2420	nM	CHEMBL1334484
5.61	IC50	2450	nM	CHEMBL1383746
5.61	IC50	2460	nM	CHEMBL1519298
5.61	IC50	2480	nM	CHEMBL1600114
5.59	IC50	2590	nM	CHEMBL1402286
5.58	IC50	2600	nM	CHEMBL1334484

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects methylation, decreases expression	4
trichostatin A	decreases expression, increases expression	2
sodium arsenite	affects cotreatment, decreases expression	2
Nickel	decreases expression	2
Valproic Acid	affects expression, decreases expression, decreases methylation	2
Aflatoxin B1	decreases methylation	2
FR900359	increases phosphorylation	1
methyleugenol	decreases expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression, affects cotreatment	1
titanium dioxide	decreases methylation	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	decreases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	affects methylation	1
diallyl trisulfide	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lead	affects expression	1
Methapyrilene	increases methylation	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	decreases expression	1

ChEMBL screening assays

4 unique, capped per target: 2 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614128	Binding	PUBCHEM_BIOASSAY: Homogeneous Time-Resolved Fluorescence Resonance Energy Transfer (HTRF) Assay. Confirmatory Screen for inhibitors of association between Mint1-PDZ domains and N-type Ca2+ channel carboxyl-terminal peptide (NC peptide). (Cl	PubChem BioAssay data set
CHEMBL1738583	Functional	PUBCHEM_BIOASSAY: SAR analysis of small molecule inhibitors of Mint-PDZ and N-type Ca2+ channel carboxyl-terminal peptide association using HTRF - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID2073, AI	PubChem BioAssay data set

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for APBA1 across ~30M SureChEMBL compounds — explore on Sugi Predict.