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): 133 total — 2 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001163

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: 4 — 3 protein_coding, 1 retained_intron

ENST00000265381, ENST00000470082, ENST00000628769, ENST00000699288

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.

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

138 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA3, SP3

miRNA regulators (miRDB)

194 targeting APBA1, 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-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

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

5 orthologs

Organism	Symbol	Gene ID
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)

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): Q02410, A0A0D9SFA9, A0A8V8TPS8

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 (67 total): strand 19, modified residue 15, helix 8, 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.

PDB	Method	Resolution (Å)
1AQC	X-RAY DIFFRACTION	2.3
1X11	X-RAY DIFFRACTION	2.5
1U37	SOLUTION NMR
1U38	SOLUTION NMR
1U39	SOLUTION NMR
1U3B	SOLUTION NMR
1X45	SOLUTION NMR
1Y7N	SOLUTION NMR

Predicted structure (AlphaFold)

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

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): 78, 242, 246, 248, 263, 280, 285, 305, 313, 367, 370, 401, 403, 408, 568

Mutagenesis-validated functional residues (1):

Position	Phenotype
608	diminishes interaction with app.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-6794361	Neurexins and neuroligins
R-HSA-9609736	Assembly and cell surface presentation of NMDA receptors
R-HSA-112310	Neurotransmitter release cycle
R-HSA-112314	Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315	Transmission across Chemical Synapses
R-HSA-112316	Neuronal System
R-HSA-442755	Activation of NMDA receptors and postsynaptic events
R-HSA-6794362	Protein-protein interactions at 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 (15): in utero embryonic development (GO:0001701), intracellular protein transport (GO:0006886), cell adhesion (GO:0007155), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), locomotory behavior (GO:0007626), axo-dendritic transport (GO:0008088), regulation of gene expression (GO:0010468), glutamate secretion (GO:0014047), gamma-aminobutyric acid secretion (GO:0014051), multicellular organism growth (GO:0035264), protein-containing complex assembly (GO:0065003), presynaptic modulation of chemical synaptic transmission (GO:0099171), protein transport (GO:0015031), establishment of localization in cell (GO:0051649)

GO Molecular Function (2): amyloid-beta binding (GO:0001540), 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), 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), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

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

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	3
intracellular protein localization	2
presynapse	2
intracellular membrane-bounded organelle	2
synapse	2
chordate embryonic development	1
protein transport	1
intracellular transport	1
cellular process	1
anterograde trans-synaptic signaling	1
system development	1
behavior	1
transport along microtubule	1
neuron projection	1
gene expression	1
regulation of macromolecule biosynthetic process	1
dicarboxylic acid transport	1
acidic amino acid transport	1
secretion by cell	1
nitrogen compound transport	1
gamma-aminobutyric acid transport	1
acid secretion	1
multicellular organismal process	1
developmental growth	1
cellular component assembly	1
protein-containing complex organization	1
modulation of chemical synaptic transmission	1
transport	1
establishment of protein localization	1
establishment of localization	1
cellular localization	1
peptide binding	1
binding	1
intracellular anatomical structure	1
endomembrane system	1
membrane	1
cell periphery	1
exocytic vesicle	1
dendrite	1

Protein interactions and networks

STRING

1304 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APBA1	CASK	O14936	982
APBA1	LIN7A	O14910	981
APBA1	KIF17	Q9P2E2	956
APBA1	STXBP1	P61764	940
APBA1	APP	P05067	914
APBA1	LIN7C	Q9NUP9	902
APBA1	CASKIN1	Q8WXD9	827
APBA1	APBB1	O00213	809
APBA1	NRXN1	Q9ULB1	807
APBA1	APBB2	Q92870	803
APBA1	LIN7B	Q9HAP6	747
APBA1	APLP1	P51693	717
APBA1	CNTNAP3	Q9BZ76	707
APBA1	NCR3	O14931	704
APBA1	GRIN2B	Q13224	700

IntAct

873 interactions, top by confidence:

A	B	Type	Score
APBA1	APP	psi-mi:“MI:0915”(physical association)	0.730
APP	APBA1	psi-mi:“MI:0915”(physical association)	0.730
PSEN1	APBA1	psi-mi:“MI:0915”(physical association)	0.700
PSEN1	APP	psi-mi:“MI:0914”(association)	0.700
APBA2	APP	psi-mi:“MI:0914”(association)	0.690
E6	TAX1BP3	psi-mi:“MI:0914”(association)	0.650
E	APBA1	psi-mi:“MI:0915”(physical association)	0.610
E	APBA1	psi-mi:“MI:0407”(direct interaction)	0.610
APBA1	LIN7A	psi-mi:“MI:0914”(association)	0.590
APBA1	PKP4	psi-mi:“MI:0407”(direct interaction)	0.590
APBA1	APBA1	psi-mi:“MI:0407”(direct interaction)	0.590
ARHGEF26	APBA1	psi-mi:“MI:0407”(direct interaction)	0.590
RPS6KA3	APBA1	psi-mi:“MI:0407”(direct interaction)	0.590
PRKD2	APBA1	psi-mi:“MI:0407”(direct interaction)	0.590
APBA2	HERC2	psi-mi:“MI:0914”(association)	0.530
LIN7C	ABLIM1	psi-mi:“MI:0914”(association)	0.530
LIN7B	CASK	psi-mi:“MI:0914”(association)	0.530
APBA1	E6	psi-mi:“MI:0407”(direct interaction)	0.520
E6	APBA1	psi-mi:“MI:0407”(direct interaction)	0.520
E6	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
NRXN3	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA1	PTEN	psi-mi:“MI:0407”(direct interaction)	0.440
APBA1	HTRA1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA1	MMP24	psi-mi:“MI:0407”(direct interaction)	0.440
GAS2L2	APBA1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA1	PARD3B	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (128): STXBP1 (Reconstituted Complex), APBA1 (Affinity Capture-MS), APBA1 (Affinity Capture-Western), APBA1 (Reconstituted Complex), Cask (Reconstituted Complex), APBA1 (Affinity Capture-MS), APBA1 (Affinity Capture-MS), APBA1 (Affinity Capture-MS), APBA1 (Affinity Capture-MS), APBA1 (Affinity Capture-Western), APBA1 (Affinity Capture-Western), APBA1 (Affinity Capture-Western), APBA1 (Affinity Capture-Western), APBA1 (Two-hybrid), APBA1 (Two-hybrid)

ESM2 similar proteins: A1YFY6, A2T6X9, A6H7I8, B2RUJ5, F1M5F3, F1N2W9, O35430, O35431, O95487, O95628, O95644, P0C6S7, P14316, P17863, P22681, P22682, P23798, P23906, P35227, P81133, P98084, Q02410, Q0IHY4, Q13469, Q14190, Q14432, Q1L994, Q3UR85, Q52L14, Q5CD77, Q5RD33, Q60591, Q61045, Q61079, Q66JB6, Q69ZT9, Q6NRE7, Q6QB00, Q8BIZ1, Q8BT14

Diamond homologs: B2RUJ5, O17583, O19132, O35430, O35431, O55164, O70248, O88382, O88888, O96018, P29475, P98084, Q02410, Q29498, Q4KLN0, Q5RD33, Q86UL8, Q8VBX6, Q99767, Q9WVQ1, O88952, Q0P5F3, Q5F425, Q5RAA5, Q792I0, Q9NUP9, A0A0A2J1Z6, A0A100IM63, A0A140LI67, A0A2U1KZS6, A0A2U1LIM9, A1JJS2, A7MJ63, A8G9X6, B1B557, C5YJG8, G5ECY0, O15018, O19114, O34453

SIGNOR signaling

5 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

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 158 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
Tight junction interactions	8	26.8×	1e-07
Neurexins and neuroligins	10	17.9×	1e-07
Assembly and cell surface presentation of NMDA receptors	7	16.1×	4e-05
Protein-protein interactions at synapses	5	12.1×	7e-03
Neurotransmitter receptors and postsynaptic signal transmission	7	6.4×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
calcium-independent cell-cell adhesion	6	34.1×	1e-05
bicellular tight junction assembly	8	18.8×	1e-05
synapse organization	6	11.9×	2e-03
cell-cell adhesion	9	6.5×	2e-03
chemical synaptic transmission	11	6.0×	7e-04
cell adhesion	18	4.8×	2e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	112
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
59106	GRCh38/hg38 9q21.11-21.12(chr9:68426796-69606104)x1	Pathogenic
685659	GRCh37/hg19 9q21.11-21.31(chr9:70974661-81829792)x1	Pathogenic
148455	GRCh38/hg38 9q21.11-21.12(chr9:68420349-70939579)x1	Likely pathogenic

SpliceAI

3059 predictions. Top by Δscore:

Variant	Effect	Δscore
9:69440992:TTA:T	donor_loss	1.0000
9:69440993:TA:T	donor_loss	1.0000
9:69440994:A:AC	donor_gain	1.0000
9:69440994:ACAA:A	donor_loss	1.0000
9:69440995:C:CC	donor_gain	1.0000
9:69440995:C:T	donor_loss	1.0000
9:69440995:CA:C	donor_gain	1.0000
9:69440995:CAAT:C	donor_gain	1.0000
9:69440995:CAATT:C	donor_gain	1.0000
9:69449797:C:CC	acceptor_gain	1.0000
9:69449798:T:G	acceptor_loss	1.0000
9:69452121:CAT:C	donor_gain	1.0000
9:69456241:CCTTA:C	donor_loss	1.0000
9:69456242:CTTAC:C	donor_loss	1.0000
9:69456244:TACAT:T	donor_loss	1.0000
9:69456245:A:AC	donor_gain	1.0000
9:69456245:ACAT:A	donor_gain	1.0000
9:69456245:ACATC:A	donor_gain	1.0000
9:69456246:C:CC	donor_gain	1.0000
9:69456246:CA:C	donor_gain	1.0000
9:69456246:CAT:C	donor_gain	1.0000
9:69456246:CATC:C	donor_gain	1.0000
9:69456246:CATCC:C	donor_gain	1.0000
9:69456248:T:TA	donor_gain	1.0000
9:69456249:C:A	donor_gain	1.0000
9:69456258:CGAAG:C	donor_gain	1.0000
9:69456285:G:GA	donor_gain	1.0000
9:69456296:T:TA	donor_gain	1.0000
9:69456428:GTCTC:G	acceptor_gain	1.0000
9:69456430:CTC:C	acceptor_gain	1.0000

AlphaMissense

5539 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:69431358:A:G	L828P	1.000
9:69431358:A:T	L828Q	1.000
9:69431361:A:G	L827P	1.000
9:69431364:C:A	R826M	1.000
9:69431368:A:C	Y825D	1.000
9:69431368:A:G	Y825H	1.000
9:69431376:G:T	A822D	1.000
9:69431379:G:T	P821Q	1.000
9:69431382:A:G	M820T	1.000
9:69431391:A:C	M817R	1.000
9:69431391:A:T	M817K	1.000
9:69432555:A:G	L808P	1.000
9:69432555:A:T	L808H	1.000
9:69432564:A:T	V805D	1.000
9:69432585:G:T	A798D	1.000
9:69432591:A:T	V796D	1.000
9:69432593:G:C	S795R	1.000
9:69432593:G:T	S795R	1.000
9:69432595:T:G	S795R	1.000
9:69432606:A:T	I791N	1.000
9:69432612:A:C	I789S	1.000
9:69432612:A:T	I789N	1.000
9:69432615:A:C	I788S	1.000
9:69432615:A:G	I788T	1.000
9:69432615:A:T	I788N	1.000
9:69432618:C:G	R787P	1.000
9:69432621:T:C	H786R	1.000
9:69432624:C:A	G785V	1.000
9:69432624:C:T	G785E	1.000
9:69432625:C:A	G785W	1.000

dbSNP variants (sampled 300 via entrez): RS1000000803 (9:69560876 C>A), RS1000001413 (9:69449294 G>A), RS1000037226 (9:69462961 T>C), RS1000054551 (9:69457945 C>T), RS1000062017 (9:69486853 T>A,C), RS1000069997 (9:69561197 C>T), RS1000078463 (9:69651665 G>A), RS1000103543 (9:69558084 A>G), RS1000116642 (9:69560375 G>T), RS1000132075 (9:69656906 C>T), RS1000143426 (9:69605828 T>C), RS1000150901 (9:69482627 A>G), RS1000157027 (9:69599003 G>A), RS1000171425 (9:69512837 T>C), RS1000207743 (9:69607201 ACT>A)

Disease associations

OMIM: gene MIM:602414 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004364_16	Intelligence	6.000000e-08
GCST004364_34	Intelligence	4.000000e-08
GCST004862_88	Itch intensity from mosquito bite adjusted by bite size	9.000000e-06
GCST005141_65	Cognitive ability (MTAG)	1.000000e-10
GCST005142_66	Cognitive ability	4.000000e-07
GCST005316_55	Intelligence (MTAG)	2.000000e-10
GCST005316_56	Intelligence (MTAG)	1.000000e-08
GCST007044_20	Extremely high intelligence	2.000000e-09
GCST008595_134	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	1.000000e-11
GCST010002_320	Refractive error	3.000000e-39

EFO canonical traits (4, from GWAS)

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

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 93,106 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL449317	HESPERIDIN	3	18,753

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

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	affects cotreatment, decreases expression	1
titanium dioxide	decreases methylation	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	affects cotreatment, decreases expression	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)

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