BEST2

Summary

BEST2 (bestrophin 2, HGNC:17107) is a protein-coding gene on chromosome 19p13.13, encoding Bestrophin-2a (Q8NFU1). Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+).

This gene is a member of the bestrophin gene family of anion channels. Bestrophin genes share a similar gene structure with highly conserved exon-intron boundaries, but with distinct 3’ ends. Bestrophins are transmembrane proteins that contain a homologous region rich in aromatic residues, including an invariant arg-phe-pro motif. Mutation in one of the family members (bestrophin 1) is associated with vitelliform macular dystrophy. The bestrophin 2 gene is mainly expressed in the retinal pigment epithelium and colon.

Source: NCBI Gene 54831 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 91 total — 3 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_017682

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17107
Approved symbol	BEST2
Name	bestrophin 2
Location	19p13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20132
Ensembl gene	ENSG00000039987
Ensembl biotype	protein_coding
OMIM	607335
Entrez	54831

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000042931, ENST00000549706, ENST00000552539, ENST00000553030, ENST00000863399, ENST00000863400, ENST00000863401, ENST00000946152

RefSeq mRNA: 1 — MANE Select: NM_017682 NM_017682

CCDS: CCDS42506

Canonical transcript exons

ENST00000553030 — 10 exons

Exon	Start	End
ENSE00000355210	12756141	12756295
ENSE00000681675	12755379	12755456
ENSE00000681682	12754877	12755031
ENSE00000681688	12754552	12754785
ENSE00000836335	12753260	12753354
ENSE00000836336	12755615	12755767
ENSE00000836337	12755855	12755935
ENSE00002335931	12757651	12758458
ENSE00002350430	12751791	12751839
ENSE00002412942	12752542	12752744

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 89.30.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0799 / max 22.0667, expressed in 33 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174012	0.0663	30
174011	0.0137	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	89.30	gold quality
transverse colon	UBERON:0001157	84.30	gold quality
mucosa of sigmoid colon	UBERON:0004993	78.02	gold quality
rectum	UBERON:0001052	77.69	gold quality
colonic mucosa	UBERON:0000317	77.19	gold quality
skin of abdomen	UBERON:0001416	76.77	gold quality
ileal mucosa	UBERON:0000331	76.42	gold quality
skin of leg	UBERON:0001511	75.51	gold quality
small intestine Peyer’s patch	UBERON:0003454	74.60	gold quality
zone of skin	UBERON:0000014	71.38	gold quality
large intestine	UBERON:0000059	70.27	gold quality
colon	UBERON:0001155	69.95	gold quality
intestine	UBERON:0000160	68.98	gold quality
small intestine	UBERON:0002108	66.97	gold quality
upper leg skin	UBERON:0004262	63.24	gold quality
tongue squamous epithelium	UBERON:0006919	62.03	gold quality
pancreatic ductal cell	CL:0002079	60.75	silver quality
colonic epithelium	UBERON:0000397	58.58	gold quality
lower esophagus mucosa	UBERON:0035834	56.88	gold quality
putamen	UBERON:0001874	55.80	gold quality
cranial nerve II	UBERON:0000941	55.69	silver quality
amygdala	UBERON:0001876	55.14	gold quality
caudate nucleus	UBERON:0001873	54.94	gold quality
nucleus accumbens	UBERON:0001882	54.80	gold quality
skin of hip	UBERON:0001554	54.79	silver quality
monocyte	CL:0000576	53.12	gold quality
mononuclear cell	CL:0000842	53.08	gold quality
leukocyte	CL:0000738	52.99	gold quality
tonsil	UBERON:0002372	52.91	gold quality
gastrocnemius	UBERON:0001388	52.85	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-125970	yes	21.25
E-GEOD-124858	no	3.42
E-ANND-3	no	2.67

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

20 targeting BEST2, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-549A-3P	99.54	68.17	825
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6837-3P	98.42	66.71	1149
HSA-MIR-4704-3P	98.28	69.33	1300
HSA-MIR-5196-3P	97.57	65.98	979
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-6131	97.22	66.72	960
HSA-MIR-4793-5P	96.88	65.90	872
HSA-MIR-339-5P	96.73	66.01	820
HSA-MIR-151A-5P	95.79	68.73	162
HSA-MIR-151B	95.79	68.73	162

Literature-anchored findings (GeneRIF, showing 8)

• identified three novel VMD2-related human genes demonstrating a high degree of conservation in their respective RFP-TM domains [VMD2L1, VMD2L2, VMD2L3] (PMID:12032738)
• Results provide evidence that the bestrophins are expressed in pancreatic duct cells and, more specifically, that hBest1 plays a role in the calcium activated chloride channels found in these cells. (PMID:19237432)
• we examine data obtained from tissue-type and animal models and discuss the current state of bestrophin research, what roles Best2 may play in ocular epithelia and electrophysiology, how perturbation of these functions may result in disease. [REVIEW] (PMID:19398034)
• These data suggest that Best2 may play a functional role in the regulation of aqueous flow and drainage in humans. (PMID:20157619)
• Bestrophin-2 mediates bicarbonate transport by goblet cells in mouse colon (PMID:20407206)
• A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration. (PMID:22360420)
• BEST2 and BEST4 could be added to the lineage-specific genes of humans intestinal epithelial cells (PMID:24223998)
• Low expression of bestrophin-2 is associated with poor prognosis in colon cancer. (PMID:34902511)

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
danio_rerio	best2	ENSDARG00000079163
mus_musculus	Best2	ENSMUSG00000052819
rattus_norvegicus	Best2	ENSRNOG00000003737
drosophila_melanogaster	Best4	FBGN0036491
drosophila_melanogaster	Best3	FBGN0036492
drosophila_melanogaster	Best1	FBGN0040238
caenorhabditis_elegans		WBGENE00007203
caenorhabditis_elegans		WBGENE00007204
caenorhabditis_elegans		WBGENE00007404
caenorhabditis_elegans		WBGENE00007808
caenorhabditis_elegans	best-8	WBGENE00007988
caenorhabditis_elegans	best-10	WBGENE00008185
caenorhabditis_elegans	best-11	WBGENE00008186
caenorhabditis_elegans		WBGENE00008821
caenorhabditis_elegans		WBGENE00013520
caenorhabditis_elegans	best-25	WBGENE00014102
caenorhabditis_elegans	best-26	WBGENE00014103
caenorhabditis_elegans		WBGENE00015628
caenorhabditis_elegans		WBGENE00020046
caenorhabditis_elegans		WBGENE00021368
caenorhabditis_elegans		WBGENE00022797
caenorhabditis_elegans		WBGENE00206487
caenorhabditis_elegans		WBGENE00220250

Paralogs (3): BEST3 (ENSG00000127325), BEST4 (ENSG00000142959), BEST1 (ENSG00000167995)

Protein

Protein identifiers

Bestrophin-2a — Q8NFU1 (reviewed: Q8NFU1)

Alternative names: Vitelliform macular dystrophy 2-like protein 1

All UniProt accessions (2): Q8NFU1, H0YIH1

UniProt curated annotations — full annotation on UniProt →

Function. Ligand-gated anion channel that allows the movement of anions across cell membranes when activated by calcium (Ca2+). Transports a large specter of anions, namely mediates the movement of chloride, L-glutamate and iodide. Calcium-binding triggers the dilation of the aperture, but calcium-dependent gating is only effective when the size of the passing anion is bigger than the closed aperture. Mediates the calcium-activated hydrogencarbonate movement and participates in colonic hydrogencarbonate secretion concomitant with mucin secretion. In non-pigmented epithelium (NPE), mediates the efflux of intracellular L-glutamate; binding of intracellular L-glutamate activates and open both the neck and the aperture of the channel, leading to L-glutamate exit promoting chloride influx movement from the extracellular side in trans. Also exhibits a directional permeability for intracellular glutamine, in a similar manner as for L-glutamate.

Subunit / interactions. Pentamer. Interacts with GLUL; this interaction tethers a fraction of GLUL to the membrane, causing a decrease of cytosolic glutamine synthase (GS) activity and inhibits the chloride channel activity of BEST2 by affecting the gating at the aperture in the absence of intracellular glutamate.

Subcellular location. Cell membrane. Basolateral cell membrane.

Tissue specificity. Mainly confined to the retinal pigment epithelium. Expressed in colon.

Activity regulation. Chloride channel activity is allosterically inhibited by GLUL/glutamine synthase (GS) which affects the gating at the aperture in the absence of intracellular glutamate. Inhibitory effect of GLUL is relieved upon increasing of L-glutamate intracellular level.

Domain organisation. The C-terminal auto-inhibitory segment (AS) modulates the open/closed conformation of the channel and determines paralog specificity among bestrophins. In a closed conformation, the C-terminal auto-inhibitory segment constricts the channel concentrically by wrapping around the channel periphery in an inter-protomer manner.

Similarity. Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.

RefSeq proteins (1): NP_060152* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000615	Bestrophin	Family
IPR021134	Bestrophin-like	Family

Pfam: PF01062

Catalyzed reactions (Rhea), 5 shown:

• hydrogencarbonate(in) = hydrogencarbonate(out) (RHEA:28695)
• chloride(in) = chloride(out) (RHEA:29823)
• iodide(out) = iodide(in) (RHEA:66324)
• L-glutamate(out) = L-glutamate(in) (RHEA:66336)
• L-glutamine(out) = L-glutamine(in) (RHEA:73419)

UniProt features (45 total): helix 18, topological domain 5, binding site 5, transmembrane region 4, turn 4, compositionally biased region 2, mutagenesis site 2, strand 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
8D1E	ELECTRON MICROSCOPY	1.78
8D1F	ELECTRON MICROSCOPY	1.82
8D1H	ELECTRON MICROSCOPY	1.94
8D1G	ELECTRON MICROSCOPY	2.07
9DYK	ELECTRON MICROSCOPY	2.27
9DYJ	ELECTRON MICROSCOPY	2.31
9DYN	ELECTRON MICROSCOPY	2.44
9DYO	ELECTRON MICROSCOPY	2.57
9DYI	ELECTRON MICROSCOPY	3.03
9DYH	ELECTRON MICROSCOPY	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFU1-F1	82.03	0.71

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 (5): 10 (in other chain); 293; 296; 301; 304

Mutagenesis-validated functional residues (2):

Position	Phenotype
299	does not affect expression level. does not affect interaction with glul. does not affect tethering of glul to the membra
304	does not affect expression level. does not affect interaction with glul. does not affect tethering of glul to the membra

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2672351	Stimuli-sensing channels
R-HSA-382551	Transport of small molecules
R-HSA-983712	Ion channel transport

MSigDB gene sets: 89 (showing top): RNGTGGGC_UNKNOWN, GOBP_MEMBRANE_DEPOLARIZATION, GOBP_SENSORY_PERCEPTION_OF_CHEMICAL_STIMULUS, GOBP_INORGANIC_ANION_TRANSPORT, CAGCTG_AP4_Q5, HATADA_METHYLATED_IN_LUNG_CANCER_DN, GOBP_MONOATOMIC_CATION_TRANSPORT, GOBP_CHLORIDE_TRANSPORT, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_BICARBONATE_TRANSPORT, GOBP_SENSORY_PERCEPTION, P300_01, HAND1E47_01, GOBP_TRANSMEMBRANE_TRANSPORT, GOBP_REGULATION_OF_MEMBRANE_POTENTIAL

GO Biological Process (8): sensory perception of smell (GO:0007608), membrane depolarization (GO:0051899), chloride transmembrane transport (GO:1902476), monoatomic ion transport (GO:0006811), chloride transport (GO:0006821), bicarbonate transport (GO:0015701), monoatomic ion transmembrane transport (GO:0034220), monoatomic cation transmembrane transport (GO:0098655)

GO Molecular Function (8): intracellularly ligand-gated monoatomic ion channel activity (GO:0005217), chloride channel activity (GO:0005254), metal ion binding (GO:0046872), ligand-gated monoatomic cation channel activity (GO:0099094), ligand-gated monoatomic anion channel activity (GO:0099095), bicarbonate channel activity (GO:0160133), protein binding (GO:0005515), channel activity (GO:0015267)

GO Cellular Component (5): plasma membrane (GO:0005886), cilium (GO:0005929), basolateral plasma membrane (GO:0016323), chloride channel complex (GO:0034707), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Ion channel transport	1
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ligand-gated monoatomic ion channel activity	3
transport	2
monoatomic anion channel activity	2
sensory perception of chemical stimulus	1
regulation of membrane potential	1
chloride transport	1
monoatomic anion transmembrane transport	1
monoatomic anion transport	1
inorganic anion transport	1
monoatomic ion transport	1
transmembrane transport	1
monoatomic cation transport	1
monoatomic ion transmembrane transport	1
chloride transmembrane transporter activity	1
cation binding	1
monoatomic cation channel activity	1
bicarbonate transmembrane transporter activity	1
channel activity	1
binding	1
passive transmembrane transporter activity	1
membrane	1
cell periphery	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
basal plasma membrane	1
plasma membrane region	1
monoatomic ion channel complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BEST2	CNGA2	Q16280	721
BEST2	CLCA1	A8K7I4	589
BEST2	CLCA4	Q14CN2	589
BEST2	CLCA2	Q9UQC9	589
BEST2	ANO1	Q5XXA6	531
BEST2	ZNF764	Q96H86	504
BEST2	TFF3	Q07654	480
BEST2	RTBDN	Q9BSG5	472
BEST2	ANO2	Q9NQ90	460
BEST2	GPR153	Q6NV75	445
BEST2	LRRC8B	Q6P9F7	442
BEST2	RPE65	Q16518	437
BEST2	SLC12A2	P55011	394
BEST2	EYS	Q5T1H1	378
BEST2	LRRC8A	Q8IWT6	377

IntAct

49 interactions, top by confidence:

A	B	Type	Score
MALL	BEST2	psi-mi:“MI:0915”(physical association)	0.560
BEST2	UNC93B1	psi-mi:“MI:0915”(physical association)	0.560
CYB561	BEST2	psi-mi:“MI:0915”(physical association)	0.560
GPR25	BEST2	psi-mi:“MI:0915”(physical association)	0.560
BEST2	TMEM60	psi-mi:“MI:0915”(physical association)	0.560
PNLIPRP1	BEST2	psi-mi:“MI:0915”(physical association)	0.560
COMT	BEST2	psi-mi:“MI:0915”(physical association)	0.560
BEST2	RFT1	psi-mi:“MI:0915”(physical association)	0.560
UPK1B	BEST2	psi-mi:“MI:0915”(physical association)	0.560
FXYD3	BEST2	psi-mi:“MI:0915”(physical association)	0.560
EFNA5	BEST2	psi-mi:“MI:0915”(physical association)	0.560
MFSD5	BEST2	psi-mi:“MI:0915”(physical association)	0.560
CLDN10	BEST2	psi-mi:“MI:0915”(physical association)	0.560
BEST2	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
SLC66A2	BEST2	psi-mi:“MI:0915”(physical association)	0.560
TMEM128	BEST2	psi-mi:“MI:0915”(physical association)	0.560
UNC93B1	BEST2	psi-mi:“MI:0915”(physical association)	0.000
CYB561	BEST2	psi-mi:“MI:0915”(physical association)	0.000
GPR25	BEST2	psi-mi:“MI:0915”(physical association)	0.000
TMEM60	BEST2	psi-mi:“MI:0915”(physical association)	0.000
COMT	BEST2	psi-mi:“MI:0915”(physical association)	0.000
RFT1	BEST2	psi-mi:“MI:0915”(physical association)	0.000
CLDN10	BEST2	psi-mi:“MI:0915”(physical association)	0.000
DNAJC30	BEST2	psi-mi:“MI:0915”(physical association)	0.000
SLC66A2	BEST2	psi-mi:“MI:0915”(physical association)	0.000
TMEM128	BEST2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): BEST2 (Two-hybrid), FXYD3 (Two-hybrid), COMT (Two-hybrid), UNC93B1 (Two-hybrid), UPK1B (Two-hybrid), PQLC1 (Two-hybrid), TMEM128 (Two-hybrid), CLDN10 (Two-hybrid), TMEM60 (Two-hybrid), MALL (Two-hybrid), RFT1 (Two-hybrid), GPR25 (Two-hybrid), DNAJC30 (Two-hybrid), MFSD5 (Two-hybrid), EFNA5 (Two-hybrid)

ESM2 similar proteins: A2YD22, E1BF86, O18304, O22757, O42412, O43306, O45363, O45435, O49873, O76090, O76819, O80452, O88870, P30804, P34319, P34577, P34672, P48768, P51639, P54960, P93766, Q01341, Q03343, Q0DC45, Q13488, Q17528, Q17529, Q17851, Q19978, Q21973, Q22566, Q23369, Q5JN63, Q6H1V1, Q6IWH7, Q6UY87, Q6YVM4, Q851L8, Q8BGM5, Q8K596

Diamond homologs: E1BF86, O18304, O45435, O76090, O88870, P34319, P34577, P34672, Q17528, Q17529, Q17851, Q19978, Q21973, Q22566, Q23369, Q6H1V1, Q6UY87, Q8BGM5, Q8N1M1, Q8NFU0, Q8NFU1, Q8WMR7, Q94175, O18303, O45363

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	79
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
3248501	NC_000019.9:g.(?12651855)(13373667_?)del	Pathogenic
395272	GRCh37/hg19 19p13.2(chr19:12204632-13497073)x1	Pathogenic
685830	GRCh37/hg19 19p13.2(chr19:12354642-13424014)x1	Pathogenic
2684885	GRCh37/hg19 19p13.2(chr19:12281048-13573342)x3	Likely pathogenic

SpliceAI

1500 predictions. Top by Δscore:

Variant	Effect	Δscore
19:12752535:C:G	acceptor_gain	1.0000
19:12752725:GCGC:G	donor_gain	1.0000
19:12753320:G:GG	donor_gain	1.0000
19:12754547:TGCA:T	acceptor_loss	1.0000
19:12754548:GCAG:G	acceptor_loss	1.0000
19:12754549:CAGG:C	acceptor_loss	1.0000
19:12754550:A:AG	acceptor_gain	1.0000
19:12754550:AG:A	acceptor_gain	1.0000
19:12754551:G:GA	acceptor_gain	1.0000
19:12754551:GG:G	acceptor_gain	1.0000
19:12754551:GGC:G	acceptor_gain	1.0000
19:12754551:GGCT:G	acceptor_gain	1.0000
19:12754551:GGCTT:G	acceptor_gain	1.0000
19:12754781:GGCTG:G	donor_gain	1.0000
19:12754782:GCTG:G	donor_gain	1.0000
19:12754782:GCTGG:G	donor_gain	1.0000
19:12754784:TG:T	donor_gain	1.0000
19:12754785:GG:G	donor_gain	1.0000
19:12754785:GGT:G	donor_loss	1.0000
19:12754786:G:C	donor_loss	1.0000
19:12754786:G:GG	donor_gain	1.0000
19:12754787:T:A	donor_loss	1.0000
19:12754875:A:AG	acceptor_gain	1.0000
19:12754875:AG:A	acceptor_gain	1.0000
19:12754875:AGG:A	acceptor_gain	1.0000
19:12754876:G:A	acceptor_gain	1.0000
19:12754876:G:GT	acceptor_gain	1.0000
19:12754876:GGG:G	acceptor_gain	1.0000
19:12754876:GGGT:G	acceptor_gain	1.0000
19:12755046:G:GT	donor_gain	1.0000

AlphaMissense

3301 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:12754681:G:C	R126P	1.000
19:12754554:T:C	F84L	0.999
19:12754556:T:A	F84L	0.999
19:12754556:T:G	F84L	0.999
19:12754678:G:C	R125P	0.999
19:12754680:C:A	R126S	0.999
19:12754687:T:C	L128P	0.999
19:12754692:C:A	R130S	0.999
19:12754693:G:C	R130P	0.999
19:12754705:T:C	L134P	0.999
19:12754734:A:C	S144R	0.999
19:12754736:C:A	S144R	0.999
19:12754736:C:G	S144R	0.999
19:12754755:T:C	F151L	0.999
19:12754756:T:C	F151S	0.999
19:12754757:C:A	F151L	0.999
19:12754757:C:G	F151L	0.999
19:12754898:G:C	R168P	0.999
19:12754939:T:A	W182R	0.999
19:12754939:T:C	W182R	0.999
19:12754946:C:A	P184H	0.999
19:12754946:C:G	P184R	0.999
19:12754954:T:A	W187R	0.999
19:12754954:T:C	W187R	0.999
19:12754967:T:C	L191P	0.999
19:12754978:G:C	A195P	0.999
19:12755440:C:A	P233H	0.999
19:12755440:C:G	P233R	0.999
19:12755883:G:A	G299E	0.999
19:12754579:G:C	R92P	0.998

dbSNP variants (sampled 300 via entrez): RS1000625487 (19:12749850 C>A), RS1000699938 (19:12754406 G>A), RS1000804567 (19:12755250 C>A,T), RS1001243055 (19:12752078 G>A), RS1002123241 (19:12753707 C>T), RS1002298001 (19:12751162 C>T), RS1002337576 (19:12756605 A>G), RS1002881978 (19:12756795 A>G), RS1003591550 (19:12756869 C>A,T), RS1004194140 (19:12751877 G>T), RS1004832185 (19:12757658 AAAG>A), RS1005199562 (19:12750628 A>G), RS1005244110 (19:12751616 G>A), RS1005591832 (19:12757515 C>T), RS1006325690 (19:12756442 T>C)

Disease associations

OMIM: gene MIM:607335 | disease phenotypes: MIM:108500, MIM:617106

GenCC curated gene-disease

Mondo (2): episodic ataxia type 2 (MONDO:0007163), developmental and epileptic encephalopathy, 42 (MONDO:0014917)

Orphanet (1): Familial paroxysmal ataxia (Orphanet:97)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C535506	Episodic Ataxia, Type 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

17 total (human), top 17 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07221292	PHASE3	NOT_YET_RECRUITING	Pivotal Study of N-acetyl-L-leucine for CACNA1A
NCT01543750	PHASE2	WITHDRAWN	4-Aminopyridine in Episodic Ataxia Type 2