APBA2

Summary

APBA2 (amyloid beta precursor protein binding family A member 2, HGNC:579) is a protein-coding gene on chromosome 15q13.1, encoding Amyloid-beta A4 precursor protein-binding family A member 2 (Q99767). Putative function in synaptic vesicle exocytosis by binding to STXBP1, 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 321 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 292 total — 61 pathogenic, 3 likely-pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_001353788

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:579
Approved symbol	APBA2
Name	amyloid beta precursor protein binding family A member 2
Location	15q13.1
Locus type	gene with protein product
Status	Approved
Aliases	D15S1518E, LIN-10, MGC:14091, HsT16821
Ensembl gene	ENSG00000034053
Ensembl biotype	protein_coding
OMIM	602712
Entrez	321

Gene structure

Transcript identifiers

Ensembl transcripts: 79 — 77 protein_coding, 2 retained_intron

ENST00000382938, ENST00000411764, ENST00000558206, ENST00000558259, ENST00000558330, ENST00000558358, ENST00000558402, ENST00000558804, ENST00000559709, ENST00000559814, ENST00000560283, ENST00000561069, ENST00000683413, ENST00000852543, ENST00000852544, ENST00000852545, ENST00000852546, ENST00000852547, ENST00000852548, ENST00000852549, ENST00000852550, ENST00000852551, ENST00000852552, ENST00000852553, ENST00000852554, ENST00000852555, ENST00000852556, ENST00000852557, ENST00000852558, ENST00000852559, ENST00000852560, ENST00000852561, ENST00000852562, ENST00000852563, ENST00000852564, ENST00000852565, ENST00000852566, ENST00000852567, ENST00000852568, ENST00000852569, ENST00000852570, ENST00000852571, ENST00000852572, ENST00000852573, ENST00000852574, ENST00000852575, ENST00000852576, ENST00000852577, ENST00000852578, ENST00000852579, ENST00000852580, ENST00000852581, ENST00000852582, ENST00000852583, ENST00000923484, ENST00000923485, ENST00000923486, ENST00000923487, ENST00000923488, ENST00000923489, ENST00000923490, ENST00000923491, ENST00000923492, ENST00000923493, ENST00000923494, ENST00000923495, ENST00000941649, ENST00000941650, ENST00000941651, ENST00000941652, ENST00000941653, ENST00000941654, ENST00000941655, ENST00000941656, ENST00000941657, ENST00000941658, ENST00000941659, ENST00000941660, ENST00000941661

RefSeq mRNA: 13 — MANE Select: NM_001353788 NM_001130414, NM_001353788, NM_001353789, NM_001353790, NM_001353791, NM_001353792, NM_001353793, NM_001353794, NM_001353795, NM_001353796, NM_001353797, NM_001379685, NM_005503

CCDS: CCDS10022, CCDS45197

Canonical transcript exons

ENST00000620457 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 97.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.3387 / max 139.4882, expressed in 1257 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
145614	5.1789	1043
145610	2.5631	990
145611	0.4800	235
145612	0.1978	95
145627	0.1700	59
145616	0.1327	49
145618	0.1177	59
145613	0.1110	52
145624	0.1085	48
145626	0.0957	53

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	97.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.14	gold quality
cerebellum	UBERON:0002037	97.12	gold quality
cerebellar cortex	UBERON:0002129	97.11	gold quality
cerebellar hemisphere	UBERON:0002245	97.10	gold quality
primary visual cortex	UBERON:0002436	96.91	gold quality
prefrontal cortex	UBERON:0000451	96.64	gold quality
frontal cortex	UBERON:0001870	96.62	gold quality
right frontal lobe	UBERON:0002810	96.51	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.31	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	96.23	gold quality
cerebral cortex	UBERON:0000956	96.12	gold quality
anterior cingulate cortex	UBERON:0009835	95.52	gold quality
Ammon’s horn	UBERON:0001954	95.44	gold quality
ganglionic eminence	UBERON:0004023	94.99	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.75	gold quality
cortical plate	UBERON:0005343	94.61	gold quality
temporal lobe	UBERON:0001871	94.08	gold quality
amygdala	UBERON:0001876	94.01	gold quality
substantia nigra	UBERON:0002038	93.83	gold quality
hypothalamus	UBERON:0001898	93.53	gold quality
brain	UBERON:0000955	93.21	gold quality
corpus callosum	UBERON:0002336	92.47	gold quality
nucleus accumbens	UBERON:0001882	91.61	gold quality
putamen	UBERON:0001874	91.13	gold quality
caudate nucleus	UBERON:0001873	91.04	gold quality
granulocyte	CL:0000094	90.91	gold quality
ventricular zone	UBERON:0003053	90.88	gold quality
blood	UBERON:0000178	85.41	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.57	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.51
E-MTAB-6058	no	16.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting APBA2, 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-3646	100.00	73.56	5283
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6507-3P	99.35	67.32	1059
HSA-MIR-5693	99.24	66.67	1106
HSA-MIR-6815-3P	99.13	68.98	1530
HSA-MIR-4705	99.10	69.10	1091
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-4763-5P	98.75	63.89	854
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-890	97.47	68.67	982
HSA-MIR-6799-3P	97.35	65.60	1302
HSA-MIR-3173-5P	97.35	65.82	1282
HSA-MIR-4529-5P	96.74	65.77	569
HSA-MIR-1293	96.16	64.69	916
HSA-MIR-6514-5P	95.07	66.02	655
HSA-MIR-6821-5P	89.96	64.05	42

Literature-anchored findings (GeneRIF, showing 17)

• The APBA2 gene has been found to map to a more telomeric location in chromosome 15q13 than previously found, and is partially duplicated within the broader region located approximately 5 Mb distal to the intact locus. (PMID:12720574)
• hXB51 isoforms regulate Abeta generation differently, either enhancing it by modifying the association of X11L with APP or suppressing it in an X11L-independent manner (PMID:12780348)
• This protein, which is a member of the mammalian LIN-10 protein family and a possible regulator of Abeta production, elevated APP and APLP2 phosphorylation (PMID:14970211)
• X11alpha and X11beta have roles in beta-amyloid precursor protein processing (PMID:15699037)
• Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia. (PMID:17989066)
• Phosphorylation of amino acids Ser236 and Ser238 in the X11L regulatory region are critical for increasing association of X11L and amyloid beta-protein precursor and are conserved in X11, a neuronal X11 family protein, but not in non-neuronal X11L2. (PMID:19222704)
• X11beta-mediated reduction in cerebral Abeta is associated with cognition and long-term potentiation in Alzheimer’s disease APPswe transgenic mice. (PMID:19744962)
• APBA2 were genes activated in early endometrial endometrioid carcinoma (stages I-II). (PMID:20015385)
• Interaction of transcriptional coactivators with Mint1 or Mint2 prevents nuclear localization and transactivation of the transduction network mediated by amyloid precursor protein. (PMID:20016085)
• The co-occurrence of two nonsynonymous mutations in both affected siblings in a single family, each transmitted from a different unaffected parent, suggest a role for APBA2 mutations in rare individuals with ASD. (PMID:20029827)
• Amyloid beta A4 precursor protein-binding family A member 2 contains a potent neuronal promoter whose activity may be regulated by DNA methylation and glucocorticoid receptor [alpha], paired box protein 5. (PMID:22222501)
• a significant difference was shown for APBA2 gene expression of peripheral lymphocytes between Chinese Han Tourette syndrome (TS) group and healthy controls idicating the APBA2 gene is a promising peripheral blood biomarker that discriminates between patients with TS and healthy subjects (PMID:23076970)
• Aberrant MINT2 methylation in body fluids may predict peritoneal micrometastasis for gastric cancer (GC) patients, which is a potential poor prognostic factor in GC. (PMID:24385013)
• 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)
• These results support the hypothesis that APBA2 gene expression in different areas of Alzheimer’s patient’s brains. (PMID:28164769)
• A rare autism-associated MINT2/APBA2 mutation disrupts neurexin trafficking and synaptic function. (PMID:30988517)
• Using exome sequencing and QTL analysis, study identified seven genome-wide significant loci accounting for approximately one-third of total variance and two-thirds of genetic variance in exploratory locomotion (EL), a behavioral phenotype correlated with vulnerability to addiction, and found convergent evidence for a role of APBA2 in humans. (PMID:31182603)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	apba2b	ENSDARG00000060639
danio_rerio	apba2a	ENSDARG00000063314
mus_musculus	Apba2	ENSMUSG00000030519
rattus_norvegicus	Apba2	ENSRNOG00000016358
drosophila_melanogaster	X11Lbeta	FBGN0052677
caenorhabditis_elegans	lin-10	WBGENE00002999

Paralogs (4): APBA3 (ENSG00000011132), APBA1 (ENSG00000107282), SDCBP2 (ENSG00000125775), SDCBP (ENSG00000137575)

Protein

Protein identifiers

Amyloid-beta A4 precursor protein-binding family A member 2 — Q99767 (reviewed: Q99767)

Alternative names: Adapter protein X11beta, Neuron-specific X11L protein, Neuronal Munc18-1-interacting protein 2

All UniProt accessions (5): Q99767, H0YL28, H0YMS0, H0YNE8, H0YNG7

UniProt curated annotations — full annotation on UniProt →

Function. Putative function in synaptic vesicle exocytosis by binding to STXBP1, 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.

Subunit / interactions. Part of a multimeric complex containing STXBP1 and syntaxin-1. Binds to the cytoplasmic domain of amyloid-beta protein, and to the nuclear factor NF-kappa-B/p65 via its PDZ domain. Interacts with the N-terminal domain of NECAB3.

Tissue specificity. Brain.

Domain organisation. Composed of an N-terminal domain that binds STXBP1, 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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99767-1	1	yes
Q99767-2	2

RefSeq proteins (13): NP_001123886, NP_001340717, NP_001340718, NP_001340719, NP_001340720, NP_001340721, NP_001340722, NP_001340723, NP_001340724, NP_001340725, NP_001340726, NP_001366614, NP_005494 (=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 (24 total): sequence conflict 7, compositionally biased region 5, region of interest 4, domain 3, modified residue 2, chain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99767-F1	59.74	0.17

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 (2): 11, 208

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins
R-HSA-112316	Neuronal System
R-HSA-6794362	Protein-protein interactions at synapses

MSigDB gene sets: 158 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_BEHAVIOR, GOBP_GROWTH, chr15q13, TGACCTY_ERR1_Q2, KANNAN_TP53_TARGETS_DN, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING, MODULE_66, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_MULTICELLULAR_ORGANISM_GROWTH, MODULE_213, GOBP_SYNAPTIC_SIGNALING, MA_MYELOID_DIFFERENTIATION_DN

GO Biological Process (8): in utero embryonic development (GO:0001701), chemical synaptic transmission (GO:0007268), nervous system development (GO:0007399), locomotory behavior (GO:0007626), regulation of gene expression (GO:0010468), protein transport (GO:0015031), multicellular organism growth (GO:0035264), 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 (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), dendritic spine (GO:0043197), Schaffer collateral - CA1 synapse (GO:0098685), presynapse (GO:0098793)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Protein-protein interactions at synapses	1
Neuronal System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
synapse	2
chordate embryonic development	1
anterograde trans-synaptic signaling	1
system development	1
behavior	1
gene expression	1
regulation of macromolecule biosynthetic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
multicellular organismal process	1
developmental growth	1
modulation of chemical synaptic transmission	1
presynapse	1
peptide binding	1
protein binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1
dendrite	1
neuron spine	1
postsynapse	1

Protein interactions and networks

STRING

1238 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
APBA2	APP	P05067	988
APBA2	NECAB3	Q96P71	880
APBA2	TAMALIN	Q7Z6J2	840
APBA2	STXBP1	P61764	827
APBA2	APBB2	Q92870	824
APBA2	APBB1	O00213	785
APBA2	NSMCE3	Q96MG7	743
APBA2	CLSTN1	O94985	709
APBA2	MLH1	P40692	665
APBA2	XPNPEP2	O43895	649
APBA2	KIF17	Q9P2E2	647
APBA2	NRXN1	Q9ULB1	608
APBA2	PEX5L	Q8IYB4	603
APBA2	MAGI2	Q86UL8	599
APBA2	APLP2	Q06481	589

IntAct

882 interactions, top by confidence:

A	B	Type	Score
SEC23B	SEC24D	psi-mi:“MI:0914”(association)	0.920
APBA2	APP	psi-mi:“MI:0407”(direct interaction)	0.690
APBA2	APP	psi-mi:“MI:0914”(association)	0.690
APBA2	CLSTN1	psi-mi:“MI:0407”(direct interaction)	0.610
APBA2	APBA2	psi-mi:“MI:0407”(direct interaction)	0.610
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
APBA2	HERC2	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
IFNLR1	JAK1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	PRORP	psi-mi:“MI:0914”(association)	0.530
APBA2	PSEN1	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	CCS	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	CACNA1B	psi-mi:“MI:0407”(direct interaction)	0.440
CREBBP	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	C	psi-mi:“MI:0407”(direct interaction)	0.440
E6	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	E	psi-mi:“MI:0407”(direct interaction)	0.440
PTEN	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
APBA2	RPS6KA1	psi-mi:“MI:0407”(direct interaction)	0.440
RPS6KA1	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440
E	APBA2	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (73): STXBP1 (Reconstituted Complex), APBA1 (Affinity Capture-MS), USP20 (Affinity Capture-MS), IQSEC2 (Affinity Capture-MS), APBA2 (Affinity Capture-MS), APBA2 (Affinity Capture-MS), TJAP1 (Affinity Capture-MS), IQSEC1 (Affinity Capture-MS), AAGAB (Affinity Capture-MS), APBA2 (Affinity Capture-MS), BTRC (Affinity Capture-MS), USP33 (Affinity Capture-MS), PLD1 (Affinity Capture-MS), FBXW11 (Affinity Capture-MS), DMWD (Affinity Capture-MS)

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, Q5F488, Q5TCQ9, Q9EQJ9, Q9JK71, A1A5G4, P97879, Q2KIB6, Q925T6, Q96JH8, Q9Y3R0, A1L1I3, A5PMU4, D3ZAR1, O08919

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
APBA2	“up-regulates activity”	STXBP1	binding
APBA2	“up-regulates activity”	NRXN1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 118 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
RHOQ GTPase cycle	6	14.5×	6e-04
Neurexins and neuroligins	5	13.1×	3e-03
RHO GTPase cycle	11	8.8×	2e-05
RHOA GTPase cycle	8	8.0×	9e-04
CDC42 GTPase cycle	8	7.7×	1e-03
Signaling by Rho GTPases	11	5.0×	1e-03
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	11	4.9×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	61
Likely pathogenic	3
Uncertain significance	152
Likely benign	39
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
146447	GRCh38/hg38 15q11.2-13.1(chr15:23319714-30361733)x4	Pathogenic
146449	GRCh38/hg38 15q11.2-13.1(chr15:23319714-30073921)x4	Pathogenic
146726	GRCh38/hg38 15q11.2-13.2(chr15:23319714-30073876)x4	Pathogenic
147837	GRCh38/hg38 15q11.1-13.2(chr15:20480943-30217181)x3	Pathogenic
148504	GRCh38/hg38 15q11.2-13.2(chr15:23319714-30361733)x4	Pathogenic
148557	GRCh38/hg38 15q11.2-13.1(chr15:23319714-30073921)x4	Pathogenic
148883	GRCh38/hg38 15q13.1-13.2(chr15:28694893-30785630)x3	Pathogenic
149258	GRCh38/hg38 15q11.2-13.1(chr15:23319714-32384654)x1	Pathogenic
150213	GRCh38/hg38 15q11.2-13.1(chr15:23319714-31175232)x3	Pathogenic
150590	GRCh38/hg38 15q13.1-13.3(chr15:28744504-32222779)x1	Pathogenic
151938	GRCh38/hg38 15q11.1-13.3(chr15:19840581-32621939)x4	Pathogenic
154724	GRCh38/hg38 15q11.2-13.2(chr15:23319714-30527306)x4	Pathogenic
155159	GRCh38/hg38 15q11.2-13.2(chr15:23328044-30023809)x1	Pathogenic
155312	GRCh38/hg38 15q11.2-13.2(chr15:23328044-30094350)x4	Pathogenic
155586	GRCh38/hg38 15q11.2-13.3(chr15:23328044-32151843)x3	Pathogenic
160989	GRCh38/hg38 15q11.2-13.1(chr15:23319714-30361733)x3	Pathogenic
1684563	GRCh37/hg19 15q13.1-13.3(chr15:28780392-32784132)x1	Pathogenic
1703231	Single allele	Pathogenic
1703671	GRCh37/hg19 15q11.2-13.2(chr15:23285775-30386399)	Pathogenic
1703689	Single allele	Pathogenic
1707424	GRCh37/hg19 15q11.2-13.3(chr15:30370019-30374368)	Pathogenic
1808704	GRCh37/hg19 15q13.1-13.3(chr15:28540415-32446830)x1	Pathogenic
253412	GRCh37/hg19 15q11.2-13.3(chr15:25583931-32418279)x3	Pathogenic
253558	GRCh37/hg19 15q11.1-13.3(chr15:20190548-32917857)x4	Pathogenic
2574688	GRCh37/hg19 15q11.2-13.2(chr15:22770421-30386398)	Pathogenic
2671594	Single allele	Pathogenic
2684749	GRCh37/hg19 15q11.2-13.3(chr15:22770422-32915593)x3	Pathogenic
3062003	GRCh38/hg38 15q11.2-13.3(chr15:22612582-32116118)	Pathogenic
3062004	GRCh38/hg38 15q11.2-13.1(chr15:22612582-29993699)	Pathogenic
3063348	GRCh37/hg19 15q11.2-13.3(chr15:22770421-32446830)x3	Pathogenic

SpliceAI

5484 predictions. Top by Δscore:

Variant	Effect	Δscore
15:28921634:TTACA:T	acceptor_loss	1.0000
15:28921635:TACAG:T	acceptor_loss	1.0000
15:28921636:ACAGT:A	acceptor_loss	1.0000
15:28921637:C:G	acceptor_gain	1.0000
15:28921637:CAGTC:C	acceptor_loss	1.0000
15:28921638:A:AG	acceptor_gain	1.0000
15:28921638:A:T	acceptor_loss	1.0000
15:28921639:G:GA	acceptor_gain	1.0000
15:28921639:GT:G	acceptor_gain	1.0000
15:28921639:GTC:G	acceptor_gain	1.0000
15:28921639:GTCT:G	acceptor_gain	1.0000
15:28921639:GTCTC:G	acceptor_gain	1.0000
15:28921748:GA:G	donor_gain	1.0000
15:28921750:G:GG	donor_gain	1.0000
15:28995740:T:TA	acceptor_gain	1.0000
15:29076041:A:AG	acceptor_gain	1.0000
15:29076042:T:G	acceptor_gain	1.0000
15:29093216:TCA:T	donor_gain	1.0000
15:29098485:CTTA:C	acceptor_loss	1.0000
15:29098488:A:AC	acceptor_loss	1.0000
15:29098488:A:AG	acceptor_gain	1.0000
15:29098489:G:GG	acceptor_gain	1.0000
15:29098489:GA:G	acceptor_gain	1.0000
15:29098574:CAG:C	donor_loss	1.0000
15:29098575:AGG:A	donor_loss	1.0000
15:29098576:GGTA:G	donor_loss	1.0000
15:29098578:T:A	donor_loss	1.0000
15:29101593:C:CA	acceptor_gain	1.0000
15:29101597:A:AC	acceptor_loss	1.0000
15:29101597:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000008636 (15:28950115 C>G,T), RS1000017548 (15:29058066 A>G), RS1000032692 (15:29059210 TTGA>T), RS1000059140 (15:29046793 A>T), RS1000062986 (15:29091065 G>A), RS1000071571 (15:29035884 A>G), RS1000072655 (15:29052927 A>G), RS1000079742 (15:29057499 T>A,C), RS1000114872 (15:29065027 G>A), RS1000116943 (15:28967591 A>G), RS1000120385 (15:28987756 T>A,C,G), RS1000138363 (15:29096882 G>C,T), RS1000174800 (15:29023319 G>A,T), RS1000180703 (15:29052481 T>G), RS1000183956 (15:29116085 TAG>T)

Disease associations

OMIM: gene MIM:602712 | disease phenotypes: MIM:608636, MIM:105830, MIM:614846, MIM:309800, MIM:209850, MIM:181500, MIM:176270, MIM:614429

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Limited	Autosomal dominant

Mondo (11): 15q11q13 microduplication syndrome (MONDO:0012081), Angelman syndrome (MONDO:0007113), distal tetrasomy 15q (MONDO:0013918), primary ovarian failure (MONDO:0005387), syndromic microphthalmia (MONDO:0016073), autism (MONDO:0005260), schizophrenia (MONDO:0005090), Prader-Willi syndrome (MONDO:0008300), esophageal atresia (MONDO:0001044), ventricular septal defect (MONDO:0002070), epilepsy (MONDO:0005027)

Orphanet (9): 15q11q13 microduplication syndrome (Orphanet:238446), Angelman syndrome (Orphanet:72), 15q overgrowth syndrome (Orphanet:314585), Distal triplication 15q syndrome (Orphanet:314588), Syndromic microphthalmia-anophthalmia-coloboma (Orphanet:202948), Prader-Willi syndrome (Orphanet:739), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Ventricular septal defect (Orphanet:1480)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000717	Autism
HP:0100753	Schizophrenia
HP:0002032	Esophageal atresia
HP:0001629	Ventricular septal defect

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001531_5	Temperament	2.000000e-06
GCST002156_2	Response to mTOR inhibitor (rapamycin)	6.000000e-06
GCST008516_1	Skin pigmentation (conditioned on rs1426654 and rs35397)	5.000000e-07
GCST008516_6	Skin pigmentation (conditioned on rs1426654 and rs35397)	5.000000e-10
GCST012256_23	SAPHO syndrome	5.000000e-07
GCST012419_5	Longevity (100 years and older)	1.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004825	temperament and character inventory
EFO:0005417	response to mTOR inhibitor

MeSH disease descriptors (8)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
D001321	Autistic Disorder	F03.625.164.113.500
D004827	Epilepsy	C10.228.140.490
D004933	Esophageal Atresia	C06.198.330; C06.405.117.260; C16.131.314.330
D006345	Heart Septal Defects, Ventricular	C14.240.400.560.540; C14.280.400.560.540; C16.131.240.400.560.540
D011218	Prader-Willi Syndrome	C10.597.606.360.690; C16.131.077.730; C16.131.260.700; C16.320.180.700; C16.320.447.500; C18.654.726.750.500.740
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C531619	Happy puppet syndrome (formerly) (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Aflatoxin B1	increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
butyraldehyde	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
nickel sulfate	increases expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Vorinostat	decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases expression, decreases reaction	1
Calcitriol	decreases expression	1
Copper	affects binding, decreases expression	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Fluorouracil	affects response to substance	1
Lead	affects splicing	1
Phthalic Acids	increases methylation	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7K5	Ubigene A-549 APBA2 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004637	PHASE4	COMPLETED	Double-Blind, Placebo-Controlled Trial of Vitamin E as Add-on Therapy for Children With Epilepsy
NCT00043914	PHASE4	COMPLETED	Measurement Of Serum Levels Of Two Antiepileptic Drugs During Conversion In Patients With Epilepsy
NCT00132223	PHASE4	UNKNOWN	Effects on the Diagnostic Accuracy of Magnetic Imaging Angiographies of the Supra-Aortic Vessels by Three Different Magnetic Resonance Contrast Agents in Patients
NCT00133081	PHASE4	UNKNOWN	Study to Improve the Treatment of Epilepsy (SITE)
NCT00137709	PHASE4	UNKNOWN	Hormone Profiles in Adults With Newly Diagnosed Epilepsy
NCT00154076	PHASE4	COMPLETED	A Multicenter Comparative Trial of Zonisamide and Topiramate as Initial Monotherapy in Untreated Epilepsies
NCT00165828	PHASE4	TERMINATED	Efficacy and Safety of an add-on Treatment With Zonisamide in Adults With Focal Epileptic Seizures With or Without Secondary Generalization
NCT00181116	PHASE4	COMPLETED	Levetiracetam for Benign Rolandic Epilepsy
NCT00207935	PHASE4	COMPLETED	Use of Sustained Release Antiepileptic Medication (Depakote® ER) for Pediatric Epilepsy in a Mental Retardation/Developmental Disorder Population
NCT00215592	PHASE4	COMPLETED	Open Label, Zonegran (Zonisamide) In Partial Onset Seizures
NCT00266604	PHASE4	COMPLETED	A Study to Evaluate the Dosing, Effectiveness and Safety of Topiramate for the Treatment of Epilepsy
NCT00288639	PHASE4	COMPLETED	Lyrica (Pregabalin) Administered as an Add-on Therapy for Partial Seizures (LEADER).
NCT00312676	PHASE4	UNKNOWN	Compare Tolerability of an Overnight Switch to Gradual Switch Between Two Different Forms of Depakote
NCT00323947	PHASE4	COMPLETED	Methylphenidate for Treating Attention Deficit Hyperactivity Disorder in Children With Both ADHD and Epilepsy
NCT00385411	PHASE4	COMPLETED	Study of Valproate in Young Patients Suffering From Epilepsy
NCT00522418	PHASE4	TERMINATED	Study Comparing Best Medical Practice With or Without VNS Therapy in Pharmacoresistant Partial Epilepsy Patients
NCT00537940	PHASE4	COMPLETED	Comparative Study Of Pregabalin And Gabapentin As Adjunctive Therapy In Subjects With Partial Seizures
NCT00552526	PHASE4	UNKNOWN	Ketogenic Diet vs.Antiepileptic Drug Treatment in Drug Resistant Epilepsy
NCT00564915	PHASE4	COMPLETED	RCT of the Efficacy of the Ketogenic Diet in the Treatment of Epilepsy
NCT00571155	PHASE4	COMPLETED	Trial of Levetiracetam in Patients With Primary Brain Tumors and Symptomatic Seizures Who Undergo Surgery
NCT00572195	PHASE4	COMPLETED	RNS® System LTT Study
NCT00610532	PHASE4	TERMINATED	Evaluating the Transporter Protein Inhibitor Probenecid In Patients With Epilepsy
NCT00630357	PHASE4	COMPLETED	Trial to Evaluate the Safety and Efficacy of Keppra After Conversion to Mono-therapy in Subjects With Partial Epilepsy
NCT00630630	PHASE4	COMPLETED	Study on Safety and Efficacy of Levetiracetam in the Adjunctive Treatment of Female Subjects With C1 Catamenial Epilepsy
NCT00630968	PHASE4	COMPLETED	S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00631150	PHASE4	COMPLETED	A Phase IV-Pharmacovigilance Study of Keppra Greece - S.K.A.T.E.: Safety of Keppra as Adjunctive Therapy in Epilepsy
NCT00659958	PHASE4	COMPLETED	ZAGAL Study: Evaluating Effectiveness and Tolerability of Zonisamide as Adjunctive Therapy in Patients With Partial Onset Seizures Treated With Two Antiepileptic Drugs
NCT00713622	PHASE4	COMPLETED	Comparing The Effect On Cognition Of Adjunctive Therapy With Zonisamide Versus Sodium Valproate
NCT00807989	PHASE4	COMPLETED	The Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00832884	PHASE4	COMPLETED	The Safety of Intravenous Lacosamide
NCT00869622	PHASE4	COMPLETED	Antiepileptic Drugs and Osteoporotic Prevention Trial
NCT00896987	PHASE4	COMPLETED	Lamotrigine Cognitive Function Study in Adult Untreated Epilepsies
NCT00952081	PHASE4	COMPLETED	A Pilot Study to Evaluate Efficacy and Safety of Clevidipine in Neurosurgical Patients
NCT01118455	PHASE4	TERMINATED	Trial to Assess Vagus Nerve Stimulation Therapy vs. Anti-Epileptic Drug (AED) Treatment in Children With Refractory Seizures
NCT01127165	PHASE4	COMPLETED	Low and High Dose Zonisamide in Children as Monotherapy
NCT01127256	PHASE4	COMPLETED	Comparative Study of Zonisamide and Carbamazepine as an Initial Monotherapy: Efficacy and Safety Evaluation
NCT01140867	PHASE4	COMPLETED	Open-label, Multi-center Trial of Zonisamide as Adjunctive Therapy in Patients With Uncontrolled Partial Epilepsy
NCT01175954	PHASE4	COMPLETED	Cognitive and Behavioral Effects of Lacosamide
NCT01229735	PHASE4	COMPLETED	Levetiracetam Versus Topiramate as Adjunctive Therapy to Evaluate Efficacy and Safety in Subjects With Refractory Partial Onset Seizures
NCT01244724	PHASE4	TERMINATED	Lexapro for Major Depression in Patients With Epilepsy