UNC13B

Summary

UNC13B (unc-13 homolog B, HGNC:12566) is a protein-coding gene on chromosome 9p13.3, encoding Protein unc-13 homolog B (O14795). Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway.

This gene is expressed in the kidney cortical epithelial cells and is upregulated by hyperglycemia. The encoded protein shares a high level of similarity to the rat homolog, and contains 3 C2 domains and a diacylglycerol-binding C1 domain. Hyperglycemia increases the levels of diacylglycerol, which has been shown to induce apoptosis in cells transfected with this gene and thus contribute to the renal cell complications of hyperglycemia. Studies in other species also indicate a role for this protein in the priming step of synaptic vesicle exocytosis.

Source: NCBI Gene 10497 — RefSeq curated summary.

At a glance

• Gene–disease (curated): epilepsy (Limited, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 226 total
• MANE Select transcript: NM_001371189

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12566
Approved symbol	UNC13B
Name	unc-13 homolog B
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	hmunc13, Unc13h2, Munc13-2
Ensembl gene	ENSG00000198722
Ensembl biotype	protein_coding
OMIM	605836
Entrez	10497

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 19 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000378495, ENST00000396787, ENST00000481299, ENST00000485086, ENST00000617908, ENST00000619578, ENST00000634487, ENST00000635942, ENST00000636694, ENST00000637271, ENST00000893382, ENST00000893383, ENST00000893384, ENST00000893385, ENST00000893386, ENST00000893387, ENST00000893388, ENST00000893389, ENST00000926708, ENST00000926709, ENST00000960050, ENST00000960051

RefSeq mRNA: 10 — MANE Select: NM_001371189 NM_001330653, NM_001371186, NM_001371187, NM_001371188, NM_001371189, NM_001387551, NM_001387553, NM_001387554, NM_001387555, NM_006377

CCDS: CCDS6579, CCDS83361, CCDS94404, CCDS94405

Canonical transcript exons

ENST00000635942 — 40 exons

Exon	Start	End
ENSE00001601970	35397167	35397310
ENSE00001604130	35390629	35390714
ENSE00001606211	35399161	35399284
ENSE00001630741	35400296	35400443
ENSE00001637880	35396476	35396602
ENSE00001647802	35382357	35382507
ENSE00001671723	35381556	35381719
ENSE00001681649	35378295	35378436
ENSE00001686073	35377468	35377695
ENSE00001686544	35399392	35399448
ENSE00001691463	35399649	35399729
ENSE00001698775	35384246	35384314
ENSE00001700709	35403167	35403259
ENSE00001712544	35381100	35381215
ENSE00001716271	35385724	35385813
ENSE00001732787	35403440	35403599
ENSE00001747930	35386165	35386293
ENSE00001764783	35389846	35389973
ENSE00001779184	35375127	35375201
ENSE00001784178	35380470	35380639
ENSE00001786745	35370318	35370396
ENSE00001799823	35376028	35376247
ENSE00002288367	35403748	35405335
ENSE00002719065	35162009	35162305
ENSE00003458834	35236469	35236586
ENSE00003485032	35228015	35228044
ENSE00003494008	35396841	35396937
ENSE00003529139	35398882	35399034
ENSE00003537615	35237703	35237826
ENSE00003557749	35398554	35398642
ENSE00003589037	35398211	35398288
ENSE00003661933	35397635	35397712
ENSE00003669762	35231120	35231219
ENSE00003711555	35310467	35310781
ENSE00003716525	35313899	35313989
ENSE00003726831	35295696	35295930
ENSE00003728345	35243291	35243364
ENSE00003732064	35366947	35366993
ENSE00003749875	35258993	35259050
ENSE00003795905	35300166	35308412

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 94.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 15.1145 / max 309.7271, expressed in 1669 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96569	10.9151	1619
96568	3.0940	1395
96578	0.7271	245
96577	0.1877	103
96579	0.1701	78
96570	0.0119	4
96571	0.0087	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lung	UBERON:0002167	94.75	gold quality
pancreatic ductal cell	CL:0002079	94.15	gold quality
lower lobe of lung	UBERON:0008949	93.53	gold quality
pigmented layer of retina	UBERON:0001782	93.32	gold quality
sperm	CL:0000019	92.93	gold quality
lung	UBERON:0002048	92.52	gold quality
upper lobe of lung	UBERON:0008948	92.46	gold quality
upper lobe of left lung	UBERON:0008952	92.31	gold quality
male germ cell	CL:0000015	92.25	gold quality
palpebral conjunctiva	UBERON:0001812	92.03	gold quality
seminal vesicle	UBERON:0000998	90.96	gold quality
epithelium of esophagus	UBERON:0001976	90.95	gold quality
middle temporal gyrus	UBERON:0002771	90.95	gold quality
esophagus squamous epithelium	UBERON:0006920	90.81	gold quality
triceps brachii	UBERON:0001509	90.53	gold quality
vastus lateralis	UBERON:0001379	90.49	gold quality
ileal mucosa	UBERON:0000331	90.48	gold quality
amniotic fluid	UBERON:0000173	90.33	gold quality
cardia of stomach	UBERON:0001162	90.32	gold quality
rectum	UBERON:0001052	90.27	gold quality
quadriceps femoris	UBERON:0001377	90.22	gold quality
choroid plexus epithelium	UBERON:0003911	90.16	gold quality
muscle of leg	UBERON:0001383	89.78	gold quality
parotid gland	UBERON:0001831	89.77	gold quality
nasal cavity epithelium	UBERON:0005384	89.62	gold quality
islet of Langerhans	UBERON:0000006	89.61	gold quality
muscle organ	UBERON:0001630	89.61	gold quality
gastrocnemius	UBERON:0001388	89.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.56	gold quality
epithelium of bronchus	UBERON:0002031	89.45	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting UNC13B, 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-6873-3P	100.00	71.42	2626
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-5197-5P	99.64	69.08	1494
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-4273	99.45	67.93	1206
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-548V	99.29	69.47	1157
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-320A-5P	98.88	66.75	1248
HSA-MIR-6840-3P	98.68	65.95	1923

Literature-anchored findings (GeneRIF, showing 13)

• Munc13-1 regulates insulin exocytosis (PMID:12871971)
• Data suggest that diacylglycerol-activated hmunc13 serves as an effector of Rab34, mediating lysosome-Golgi trafficking. (PMID:16138900)
• Data identified a polymorphism in the UNC13B gene associated with nephropathy. UNC13B mediates apopotosis in glomerular cells in the presence of hyperglycemia, an event occurring early in the development of nephropathy. (PMID:18633107)
• In the bound state, the hydrophobic anchor residue of the calmodulin (CaM)-binding motif in Munc13 contacts two distinct methionine residues in the carboxyl-terminal domain of CaM. (PMID:19492809)
• mechanistic basis for high glucose-induced protein secretion is through interaction of munc13 and rab34, indicating a potentially critical role for this newly described pathway in the pathogenesis of DN. (PMID:19641095)
• The 1-5-8-26 CaM binding motif discovered in Munc13-1 cannot be induced in the classical CaM target skMLCK, indicating unique features of the Munc13 CaM binding motif. (PMID:24854537)
• A rare missense variation (V1525M) in UNC13B was identified by WES in the multiplex family; this variation was present in five of six affected individuals, but not in eight unaffected individuals or one individual of unknown disease status. Resequencing UNC13B coding regions identified five rare missense variations (T103M, M813T, P1349T, I1362T, and V1525M). (PMID:26990377)
• Assisted by NSF/alpha-SNAP, syntaxin-1 escapes tomosyn arrest and assembles into the Munc18-1/syntaxin-1 complex. Munc13-1 then catalyzes the transit of syntaxin-1 from the Munc18-1/syntaxin-1 complex to the SNARE complex (PMID:29485200)
• Abnormal splicing mutation in UNC13B was identified in the patient with bipolar disorder. (PMID:30117296)
• There were no significant differences in the distribution of allele or genotype frequencies in the five UNC13B SNP markers (rs13293564, rs17360668, rs10114937, rs661712, and rs2281999) between the Diabetic Kidney Disease group and control group of patients with type 2 diabetes mellitus . (PMID:31713534)
• TRPC6 exocytosis by targeting to the C1 domain of Munc13-2. (PMID:32134975)
• UNC13B variants associated with partial epilepsy with favourable outcome. (PMID:33876820)
• Munc13 structural transitions and oligomers that may choreograph successive stages in vesicle priming for neurotransmitter release. (PMID:35135883)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	UNC13B	ENSDARG00000099113
mus_musculus	Unc13b	ENSMUSG00000028456
rattus_norvegicus	Unc13b	ENSRNOG00000008237

Paralogs (2): UNC13A (ENSG00000130477), UNC13C (ENSG00000137766)

Protein

Protein identifiers

Protein unc-13 homolog B — O14795 (reviewed: O14795)

Alternative names: Munc13-2

All UniProt accessions (7): O14795, A0A0U1RRB5, A0A0U1RRL2, A0A1B0GUS7, A0A1B0GVW8, B1AM27, I6L9J0

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-depending refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in a subset of excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. In collaboration with UNC13A, facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release.

Subunit / interactions. Interacts with RIMS1.

Subcellular location. Cytoplasm. Membrane. Cell membrane. Synapse.

Tissue specificity. Expressed in kidney cortical epithelial cells and brain.

Domain organisation. The C2 domains are not involved in calcium-dependent phospholipid binding.

Similarity. Belongs to the unc-13 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O14795-1	1	yes
O14795-2	2

RefSeq proteins (10): NP_001317582, NP_001358115, NP_001358116, NP_001358117, NP_001358118, NP_001374480, NP_001374482, NP_001374483, NP_001374484, NP_006368 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR002219	PKC_DAG/PE	Domain
IPR010439	MUN_dom	Domain
IPR014770	Munc13_1	Domain
IPR014772	Munc13_dom-2	Domain
IPR027080	Unc-13	Family
IPR035892	C2_domain_sf	Homologous_superfamily
IPR037302	Unc-13_C2B	Domain
IPR046349	C1-like_sf	Homologous_superfamily

Pfam: PF00130, PF00168, PF06292

UniProt features (34 total): binding site 8, compositionally biased region 5, domain 4, modified residue 4, sequence conflict 4, sequence variant 3, region of interest 2, chain 1, splice variant 1, zinc finger region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14795-F1	75.85	0.40

Functional residue map

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

Ligand- & substrate-binding residues (8): 616; 616; 622; 668; 668; 670; 670; 687

Post-translational modifications (4): 16, 176, 295, 367

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-181429	Serotonin Neurotransmitter Release Cycle
R-HSA-181430	Norepinephrine Neurotransmitter Release Cycle
R-HSA-210500	Glutamate Neurotransmitter Release Cycle
R-HSA-212676	Dopamine Neurotransmitter Release Cycle
R-HSA-264642	Acetylcholine Neurotransmitter Release Cycle

MSigDB gene sets: 236 (showing top): GOBP_SINGLE_FERTILIZATION, MODULE_416, GOBP_VESICLE_LOCALIZATION, GCANCTGNY_MYOD_Q6, MODULE_64, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_VESICLE_MEDIATED_TRANSPORT, GOMF_GTPASE_BINDING, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, CAGCTG_AP4_Q5, GOBP_CELL_CELL_SIGNALING

GO Biological Process (13): chemical synaptic transmission (GO:0007268), positive regulation of synaptic vesicle priming (GO:0010808), obsolete synaptic vesicle docking (GO:0016081), synaptic vesicle priming (GO:0016082), synaptic transmission, glutamatergic (GO:0035249), positive regulation of apoptotic process (GO:0043065), positive regulation of protein secretion (GO:0050714), acrosomal vesicle exocytosis (GO:0060478), dense core granule priming (GO:0061789), cellular response to glucose stimulus (GO:0071333), positive regulation of inhibitory postsynaptic potential (GO:0097151), neuronal dense core vesicle exocytosis (GO:0099011), exocytosis (GO:0006887)

GO Molecular Function (10): calcium ion binding (GO:0005509), calmodulin binding (GO:0005516), phospholipid binding (GO:0005543), zinc ion binding (GO:0008270), syntaxin-1 binding (GO:0017075), diacylglycerol binding (GO:0019992), GTP-dependent protein binding (GO:0030742), small GTPase binding (GO:0031267), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (11): Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), synaptic vesicle membrane (GO:0030672), neuromuscular junction (GO:0031594), presynaptic membrane (GO:0042734), terminal bouton (GO:0043195), presynaptic active zone (GO:0048786), cytoplasm (GO:0005737), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Neurotransmitter release cycle	5

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
presynapse	3
protein-containing complex assembly	2
exocytic process	2
dense core granule exocytosis	2
protein binding	2
lipid binding	2
cytoplasm	2
anterograde trans-synaptic signaling	1
regulation of synaptic vesicle priming	1
synaptic vesicle priming	1
positive regulation of protein-containing complex assembly	1
synaptic vesicle exocytosis	1
chemical synaptic transmission	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
protein secretion	1
regulation of protein secretion	1
positive regulation of protein transport	1
positive regulation of secretion by cell	1
acrosome reaction	1
calcium-ion regulated exocytosis	1
intracellular glucose homeostasis	1
response to glucose	1
cellular response to hexose stimulus	1
positive regulation of nervous system process	1
inhibitory postsynaptic potential	1
modulation of inhibitory postsynaptic potential	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
metal ion binding	1
transition metal ion binding	1
syntaxin binding	1
GTPase binding	1
binding	1
cation binding	1
endomembrane system	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
UNC13B	ERC1	Q8IUD2	993
UNC13B	RIMS1	Q86UR5	987
UNC13B	STXBP1	P61764	970
UNC13B	CALM1	P02593	966
UNC13B	CALML3	P27482	964
UNC13B	CALML5	Q9NZT1	964
UNC13B	CALML6	Q8TD86	962
UNC13B	CALML4	Q96GE6	962
UNC13B	PPFIA3	O75145	920
UNC13B	SNAP25	P13795	912
UNC13B	SYT1	P21579	887
UNC13B	VAMP2	P19065	886
UNC13B	STX1A	Q16623	863
UNC13B	PPFIA1	Q13136	858
UNC13B	RAB3A	P20336	857

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
DIRAS2	UNC13B	psi-mi:“MI:0914”(association)	0.530
DIRAS1	UNC13B	psi-mi:“MI:0914”(association)	0.500
DIRAS1	UNC13B	psi-mi:“MI:0915”(physical association)	0.500
NS1		psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
NS1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
ECH1	A2ML1	psi-mi:“MI:0914”(association)	0.350
CCDC40	PSMD9	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
CALM1	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM2	MYO1C	psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CTCFL	TARS3	psi-mi:“MI:0914”(association)	0.350
COQ3	TARS3	psi-mi:“MI:0914”(association)	0.350
DOC2B	POTEF	psi-mi:“MI:0914”(association)	0.350
CALML3	MYO1C	psi-mi:“MI:0914”(association)	0.350
CCDC71	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CCDC40	TRAF5	psi-mi:“MI:0914”(association)	0.350
C2CD6	ACACB	psi-mi:“MI:0914”(association)	0.350
ZNF418	ZNF195	psi-mi:“MI:0914”(association)	0.350
DNAJC22	UNC13B	psi-mi:“MI:0914”(association)	0.350
GARS1	UNC13B	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CEP72	UNC13B	psi-mi:“MI:0914”(association)	0.350
FBXO11	ABLIM1	psi-mi:“MI:0914”(association)	0.350
GLB1	UNC13B	psi-mi:“MI:0914”(association)	0.350
EXOC1	UNC13B	psi-mi:“MI:0915”(physical association)	0.000
UNC13B	hslO	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (67): UNC13B (Biochemical Activity), STX1A (Two-hybrid), UNC13B (Affinity Capture-Western), UNC13B (Affinity Capture-MS), UNC13B (Affinity Capture-MS), UNC13B (Affinity Capture-MS), UNC13B (Affinity Capture-MS), UNC13B (Affinity Capture-MS), UNC13B (Reconstituted Complex), UNC13B (Affinity Capture-RNA), STX1B (Two-hybrid), UNC13B (Two-hybrid), SPTBN2 (Two-hybrid), RIMS1 (Two-hybrid), RIMS1 (Reconstituted Complex)

ESM2 similar proteins: A0A4X1TB62, A4VCH4, G3V7Q0, O14795, O35841, O43237, O70585, P23116, P48553, Q0P5J8, Q14152, Q15542, Q1JU68, Q3TLI0, Q3UHE1, Q4R5P6, Q5R660, Q5R7S4, Q5R7U7, Q5RE09, Q5RE70, Q5VSL9, Q5XI83, Q658Y4, Q68E01, Q6IQ26, Q6PAL8, Q6PDL0, Q6TEP1, Q6WKZ8, Q7SYD9, Q7TPD0, Q8BIK4, Q8BWQ6, Q8C079, Q8C092, Q8C9H6, Q8CBY8, Q8IWV8, Q8K400

Diamond homologs: A0JJX5, A1CQG2, A1ZBD6, A2QQ28, A3KGK3, A4IFJ5, A6QQP7, A8KBH6, B1WAZ6, B8N7E5, G0S9J5, O14065, O14795, O43581, O75131, O75923, O94812, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P0C869, P0C871, P10102, P10829, P13677, P17252, P20444, P21521, P27715, P29101, P41823, P41885, P46097, P46935, P49147, P63318

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
UNC13B	“up-regulates activity”	SNARE_complex	“transcriptional regulation”
RIMS2	“up-regulates activity”	UNC13B	relocalization
RIMS3	“up-regulates activity”	UNC13B	relocalization
RIMS1	“up-regulates activity”	UNC13B	relocalization
UNC13B	up-regulates	Synaptic_vesicle_exocytosis

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	185
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

8596 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35168496:T:G	acceptor_gain	1.0000
9:35203771:G:T	donor_gain	1.0000
9:35231116:A:AG	acceptor_gain	1.0000
9:35231116:AAAG:A	acceptor_loss	1.0000
9:35231117:A:G	acceptor_gain	1.0000
9:35231118:A:AG	acceptor_gain	1.0000
9:35231119:G:GC	acceptor_loss	1.0000
9:35231119:G:GG	acceptor_gain	1.0000
9:35231119:GATA:G	acceptor_gain	1.0000
9:35231119:GATAA:G	acceptor_gain	1.0000
9:35231217:GTT:G	donor_gain	1.0000
9:35231220:G:GG	donor_gain	1.0000
9:35236467:A:AG	acceptor_gain	1.0000
9:35236468:G:GA	acceptor_gain	1.0000
9:35236468:GT:G	acceptor_gain	1.0000
9:35236468:GTGA:G	acceptor_gain	1.0000
9:35237702:GGAA:G	acceptor_gain	1.0000
9:35243284:A:AG	acceptor_gain	1.0000
9:35243284:AT:A	acceptor_gain	1.0000
9:35243285:T:G	acceptor_gain	1.0000
9:35243285:T:TA	acceptor_gain	1.0000
9:35243287:GTAGA:G	acceptor_loss	1.0000
9:35243289:A:C	acceptor_loss	1.0000
9:35243290:G:GT	acceptor_loss	1.0000
9:35243290:GAT:G	acceptor_gain	1.0000
9:35243361:TGAG:T	donor_loss	1.0000
9:35243363:AGG:A	donor_loss	1.0000
9:35243364:GG:G	donor_loss	1.0000
9:35243365:G:A	donor_loss	1.0000
9:35243366:T:G	donor_loss	1.0000

AlphaMissense

28831 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35382422:T:C	L825P	1.000
9:35382488:T:C	F847S	1.000
9:35384277:T:C	L864P	1.000
9:35384289:T:C	L868P	1.000
9:35384301:T:C	L872P	1.000
9:35385785:T:C	L897P	1.000
9:35385790:A:C	S899R	1.000
9:35385792:C:A	S899R	1.000
9:35385792:C:G	S899R	1.000
9:35385799:T:C	F902L	1.000
9:35385801:C:A	F902L	1.000
9:35385801:C:G	F902L	1.000
9:35231144:T:C	L26P	0.999
9:35236542:G:T	G76W	0.999
9:35376053:T:C	L465P	0.999
9:35376130:T:C	C491R	0.999
9:35376131:G:A	C491Y	0.999
9:35376132:C:G	C491W	0.999
9:35376154:T:A	W499R	0.999
9:35376154:T:C	W499R	0.999
9:35376181:T:C	C508R	0.999
9:35376183:C:G	C508W	0.999
9:35376214:T:C	C519R	0.999
9:35377552:G:C	R558P	0.999
9:35377558:G:C	R560P	0.999
9:35378313:T:C	L612P	0.999
9:35378417:T:A	W647R	0.999
9:35378417:T:C	W647R	0.999
9:35380510:T:A	W667R	0.999
9:35380510:T:C	W667R	0.999

dbSNP variants (sampled 300 via entrez): RS1000006488 (9:35218253 T>C), RS1000020977 (9:35218179 G>A), RS1000021676 (9:35362746 G>A), RS1000028947 (9:35266539 T>G), RS1000050046 (9:35285887 A>G), RS1000050471 (9:35276277 G>A), RS1000059994 (9:35266926 C>A,T), RS1000078361 (9:35173607 A>G), RS1000095127 (9:35381832 A>G), RS1000097612 (9:35165395 G>A,C), RS1000107765 (9:35311770 G>T), RS1000115621 (9:35334758 C>A,T), RS1000132661 (9:35172937 C>A,T), RS1000147656 (9:35286191 A>G), RS1000164900 (9:35317906 T>A)

Disease associations

OMIM: gene MIM:605836 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
epilepsy	Limited	Autosomal dominant

Mondo (1): epilepsy (MONDO:0005027)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001189_2	Parkinson’s disease	3.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004827	Epilepsy	C10.228.140.490

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
dicrotophos	increases expression	1
sodium arsenite	increases reaction, affects binding	1
perfluorooctanoic acid	increases expression	1
aflatoxin B2	decreases methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	affects expression	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	affects expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

300 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