VSNL1

Summary

VSNL1 (visinin like 1, HGNC:12722) is a protein-coding gene on chromosome 2p24.2, encoding Visinin-like protein 1 (P62760). Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.

This gene is a member of the visinin/recoverin subfamily of neuronal calcium sensor proteins. The encoded protein is strongly expressed in granule cells of the cerebellum where it associates with membranes in a calcium-dependent manner and modulates intracellular signaling pathways of the central nervous system by directly or indirectly regulating the activity of adenylyl cyclase. Alternatively spliced transcript variants have been observed, but their full-length nature has not been determined.

Source: NCBI Gene 7447 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 10 total — 1 pathogenic
• MANE Select transcript: NM_003385

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12722
Approved symbol	VSNL1
Name	visinin like 1
Location	2p24.2
Locus type	gene with protein product
Status	Approved
Aliases	VILIP, HPCAL3, HUVISL1, HLP3, VILIP-1
Ensembl gene	ENSG00000163032
Ensembl biotype	protein_coding
OMIM	600817
Entrez	7447

Gene structure

Transcript identifiers

Ensembl transcripts: 51 — 50 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000295156, ENST00000404666, ENST00000406397, ENST00000451533, ENST00000457525, ENST00000483921, ENST00000894184, ENST00000894185, ENST00000894186, ENST00000894187, ENST00000894188, ENST00000894189, ENST00000894190, ENST00000894191, ENST00000894192, ENST00000894193, ENST00000894194, ENST00000894195, ENST00000894196, ENST00000894197, ENST00000894198, ENST00000913168, ENST00000913169, ENST00000913170, ENST00000913171, ENST00000913172, ENST00000913173, ENST00000913174, ENST00000913175, ENST00000913176, ENST00000913177, ENST00000913178, ENST00000913179, ENST00000913180, ENST00000913181, ENST00000913182, ENST00000913183, ENST00000913184, ENST00000913185, ENST00000913186, ENST00000913187, ENST00000913188, ENST00000913189, ENST00000947071, ENST00000947072, ENST00000947073, ENST00000947074, ENST00000947075, ENST00000947076, ENST00000947077, ENST00000947078

RefSeq mRNA: 5 — MANE Select: NM_003385 NM_001366803, NM_001366804, NM_001366805, NM_001366806, NM_003385

CCDS: CCDS1689

Canonical transcript exons

ENST00000295156 — 4 exons

Exon	Start	End
ENSE00001166427	17592070	17592236
ENSE00001556697	17655197	17657018
ENSE00001597114	17540696	17540918
ENSE00001758065	17649410	17649625

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 99.97.

FANTOM5 (CAGE): breadth broad, TPM avg 57.6840 / max 19104.6606, expressed in 658 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
19053	52.8214	617
19054	1.3800	172
19052	1.1588	122
202104	0.9712	172
19051	0.4239	169
19064	0.2975	72
19059	0.1958	57
19063	0.1421	40
19062	0.1033	37
19060	0.0876	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
middle temporal gyrus	UBERON:0002771	99.97	gold quality
Brodmann (1909) area 23	UBERON:0013554	99.95	gold quality
orbitofrontal cortex	UBERON:0004167	99.92	gold quality
pons	UBERON:0000988	99.90	gold quality
superior frontal gyrus	UBERON:0002661	99.89	gold quality
endothelial cell	CL:0000115	99.85	gold quality
Brodmann (1909) area 10	UBERON:0013541	99.85	gold quality
Brodmann (1909) area 46	UBERON:0006483	99.81	gold quality
occipital lobe	UBERON:0002021	99.78	gold quality
primary visual cortex	UBERON:0002436	99.76	gold quality
frontal pole	UBERON:0002795	99.72	gold quality
lateral nuclear group of thalamus	UBERON:0002736	99.71	gold quality
parietal lobe	UBERON:0001872	99.60	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	99.58	gold quality
postcentral gyrus	UBERON:0002581	99.55	gold quality
CA1 field of hippocampus	UBERON:0003881	99.47	gold quality
cerebellum	UBERON:0002037	99.45	gold quality
cerebellar hemisphere	UBERON:0002245	99.45	gold quality
cerebellar cortex	UBERON:0002129	99.43	gold quality
Brodmann (1909) area 9	UBERON:0013540	99.43	gold quality
frontal cortex	UBERON:0001870	99.41	gold quality
frontal lobe	UBERON:0016525	99.41	gold quality
prefrontal cortex	UBERON:0000451	99.38	gold quality
superior vestibular nucleus	UBERON:0007227	99.34	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.33	gold quality
right frontal lobe	UBERON:0002810	99.32	gold quality
entorhinal cortex	UBERON:0002728	99.18	gold quality
paraflocculus	UBERON:0005351	99.00	gold quality
neocortex	UBERON:0001950	98.96	gold quality
cingulate cortex	UBERON:0003027	98.86	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-HCAD-25	yes	3915.42
E-HCAD-5	yes	499.14
E-CURD-114	yes	71.32
E-HCAD-35	yes	52.12
E-ANND-3	yes	18.97
E-HCAD-30	no	2190.68
E-GEOD-109979	no	244.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NRF1

miRNA regulators (miRDB)

128 targeting VSNL1, 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-3163	100.00	77.23	8605
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-8068	99.98	73.85	2376
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-607	99.97	73.62	5593
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163

Literature-anchored findings (GeneRIF, showing 40)

• ACSL4 can substitute the functions of dAcsl(l(2)44DEa in organismal viability, lipid storage and the neural wiring in visual center. (PMID:19617635)
• this study demonstrated that dAcsl regulates axonal transport of synaptic vesicles and is required for synaptic development and function. (PMID:21307243)
• propose that Acsl plays a role in embryonic segmentation by shifting the anteroposterior boundaries of gap genes Kni and Hb (PMID:21385576)
• our results reveal a novel mechanism whereby dAcsl facilitates Rab11-dependent receptor recycling and provide insights into the pathogenesis of ACSL4-related mental retardation (PMID:24553921)
• Acsl inhibits neuromuscular junction growth. (PMID:27656110)
• novel insights into a critical and previously unappreciated role of Acsl in neurogenesis (PMID:30594466)
• VILIP-1 modulates cGMP-accumulation in transfected neural cells and cerebellar granule neurons (PMID:11579136)
• VILIP-1 is associated with amyloid plaques and extracellular tangles in Alzheimer disease and promotes cell death and tau phosphorylation in vitro (PMID:11592857)
• A shift in the cellular expression of visinin-like protein 1 has been found in the hipppocampi of schizophrenics, since fewer pyramidal neurons but more interneurons show immunoreactivity. (PMID:11930147)
• reversibility and stimulus-dependent occurrence of a calcium-myristoyl switch of VILIP-1 in living neurons, enabling them to activate specific targets localized in distinct membrane compartments (PMID:12196554)
• EF-hand motifs in visinin-like protein 1 (PMID:12200122)
• VILIP-1 modulates the surface expression and agonist sensitivity of the alpha 4beta 2 nicotinic acetylcholine receptor (PMID:12202488)
• VILIP-1 expression is associated with group I mGlu receptor-mediated plasticity in the dentate gyrus in vivo (PMID:12681369)
• The interaction of human VILIP1 and VILIP3 with divalent cations was explored using circular dichroism and fluorescence measurement. (PMID:16703469)
• VILIP-1 is expressed in pancreatic beta-cells. Increased VILIP-1 enhanced insulin secretion in a cAMP-associated manner. Down-regulation of VILIP-1 was accompanied by decreased cAMP accumulation but increased insulin gene transcription (PMID:16731532)
• Distinct roles of proliferative and invasive phenotypes contributing to neuroblastoma progression which demonstrates that VSNL-1 is important in neuroblastoma metastasis. (PMID:17615261)
• VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors (PMID:18301774)
• VILIP-1 and its interaction partner nicotinic receptor alpha4beta2 co-localize in morphologically identified human hippocampal interneurons, the number of which is pathologically up-regulated in schizophrenic brains. (PMID:18691652)
• VILIP1 constitutively binds to P2X2 receptors and displays enhanced interactions in an activation- and calcium-dependent manner owing to exposure of its binding segment in P2X2 receptors (PMID:18922787)
• This protein has been found differentially expressed in the temporal lobe from patients with schizophrenia. (PMID:19034380)
• Results report that overexpression of VILIP-1 enhances ACh responsiveness, whereas siRNA against VILIP-1 reduces alpha4beta2 nAChR currents of hippocampal neurons. (PMID:19063970)
• Data may imply the functional contribution of disulfide dimer to the interaction of VILIP-1 with its physiological target(s). (PMID:19065602)
• Deletion and site-directed mutagenesis combined with in silico transcription factor binding analysis of VSNL1 promoter identified nuclear respiratory factor (NRF)-1/alpha-PAL as a major player in regulating VSNL1 minimal promoter activity. (PMID:19674972)
• Results show that VILIP-1 regulates the cell surface localization of natriuretic peptide receptor B. (PMID:20079378)
• VILIP-1 forms a dimer in solution independent of Ca(2+) and myristoylation. The dimerization site is composed of residues in EF4 and the loop region between EF3 and EF4, confirmed by mutagenesis. (PMID:21169352)
• Data suggest that CSF VILIP-1 and VILIP-1/Abeta42 offer diagnostic utility for early AD, and can predict future cognitive impairment in cognitively normal individuals similarly to tau and tau/Abeta42, respectively. (PMID:21823155)
• SNPs upstream of SLC2A9 and within VSNL1 showed strongest evidence for association with AD + P when compared with controls. (PMID:22005930)
• Patients with high VSNL-1 expression had significantly poorer prognosis than those with low expression in stage III disease (PMID:22052372)
• VSNL1 may play a role in the pathophysiology of aldosterone-producing adenomas harboring mutations in the potassium channel KCNJ5 via its antiapoptotic function in response to calcium cytotoxicity and its effect on aldosterone production. (PMID:22331379)
• The findings suggest that CSF VILIP-1 and VILIP-1/Abeta42 predict rates of global cognitive decline similarly to tau and tau/Abeta42, and may be useful CSF surrogates for neurodegeneration in early Alzheimer disease. (PMID:22357717)
• VSNL1 single-nucleotide polymorphisms and pathological changes in VILIP-1 protein expression, possibly occurring during brain development, may contribute to the morphological and functional deficits observed in schizophrenia. (PMID:22832524)
• The results showed that the CSF VILIP-1 level had significantly increased in Alzheimer disease patients compared with both normal controls and Lewy body dementia patients. (PMID:23800322)
• The results suggest that both serum and cerebrospinal fluid levels of VILIP-1 may be one of predictive markers of acute encephalopathy with biphasic seizures. (PMID:24075506)
• We show for the first time that the C-terminus of VILIP-1, containing Cys187, might represent a novel redox-sensitive motif and that VILIP-1 dimerization and aggregation are hallmarks of amyotrophic lateral sclerosis (PMID:24742816)
• Results show that in the presence of calcium, N-myristoylation significantly increases the kinetic rate of VILIP adsorption to the membrane. (PMID:25019684)
• Underexpression of VSNL1 is associated with glioblastoma multiforme. (PMID:26683098)
• These findings suggest a unique role for cerebrospinal fluid Vilip-1 as a biomarker of entorhinal cortex neuron loss in Alzheimer disease (PMID:26769253)
• These data indicate that VILIP-1 alone or in combination with other AD CSF biomarkers represent a valuable marker for the early diagnosis of AD, recognition of MCI patients at higher risk to develop dementia, and in differentiating AD from LBD. (PMID:26836160)
• The BDNF level showed a significant ability to discriminate stroke and control patients but did not predict mortality. The VILIP-1 level showed insignificant ability to discriminate stroke patients and again did not predict mortality. (PMID:30826210)
• Transcriptional profiling of medulloblastoma with extensive nodularity (MBEN) reveals two clinically relevant tumor subsets with VSNL1 as potent prognostic marker. (PMID:31781912)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	vsnl1a	ENSDARG00000023228
danio_rerio	vsnl1b	ENSDARG00000044053
mus_musculus	Vsnl1	ENSMUSG00000054459
rattus_norvegicus	Vsnl1	ENSRNOG00000005345
drosophila_melanogaster	CG7646	FBGN0036926
drosophila_melanogaster	CG5890	FBGN0039380
caenorhabditis_elegans	ncs-2	WBGENE00003564
caenorhabditis_elegans		WBGENE00015867

Paralogs (14): CLXN (ENSG00000034239), GUCA1A (ENSG00000048545), NCALD (ENSG00000104490), NCS1 (ENSG00000107130), RCVRN (ENSG00000109047), GUCA1B (ENSG00000112599), KCNIP3 (ENSG00000115041), HPCAL1 (ENSG00000115756), HPCAL4 (ENSG00000116983), KCNIP2 (ENSG00000120049), HPCA (ENSG00000121905), GUCA1C (ENSG00000138472), KCNIP1 (ENSG00000182132), KCNIP4 (ENSG00000185774)

Protein

Protein identifiers

Visinin-like protein 1 — P62760 (reviewed: P62760)

Alternative names: Hippocalcin-like protein 3

All UniProt accessions (3): E7ER47, E9PE24, P62760

UniProt curated annotations — full annotation on UniProt →

Function. Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.

Tissue specificity. Brain and retina. Neuron-specific in the central and peripheral nervous system. Increased in the cerebrospinal fluid of Alzheimer disease patients (at protein level).

Miscellaneous. Probably binds three calcium ions.

Similarity. Belongs to the recoverin family.

RefSeq proteins (5): NP_001353732, NP_001353733, NP_001353734, NP_001353735, NP_003376* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR028846	Recoverin	Family

Pfam: PF00036, PF13499

UniProt features (28 total): binding site 15, domain 4, sequence conflict 4, sequence variant 2, initiator methionine 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P62760-F1	86.68	0.63

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 (15): 84; 109; 111; 113; 115; 120; 159; 161; 163; 165; 170; 73 …

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 269 (showing top): ACTACCT_MIR196A_MIR196B, TGCGCANK_UNKNOWN, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, JAEGER_METASTASIS_DN, GOBP_INSULIN_SECRETION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_EXOCYTOSIS, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_NEGATIVE_REGULATION_OF_PEPTIDE_SECRETION, GOBP_HORMONE_TRANSPORT, TGACCTY_ERR1_Q2, GOBP_VESICLE_MEDIATED_TRANSPORT, CHX10_01

GO Biological Process (4): regulation of signal transduction (GO:0009966), positive regulation of insulin secretion involved in cellular response to glucose stimulus (GO:0035774), positive regulation of exocytosis (GO:0045921), negative regulation of insulin secretion (GO:0046676)

GO Molecular Function (3): calcium ion binding (GO:0005509), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (2): cytosol (GO:0005829), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
positive regulation of insulin secretion	1
insulin secretion involved in cellular response to glucose stimulus	1
regulation of insulin secretion involved in cellular response to glucose stimulus	1
exocytosis	1
regulation of exocytosis	1
positive regulation of secretion by cell	1
insulin secretion	1
negative regulation of protein secretion	1
regulation of insulin secretion	1
negative regulation of peptide hormone secretion	1
metal ion binding	1
binding	1
cation binding	1
cytoplasm	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

88 interactions, top by confidence:

A	B	Type	Score
DTX2	VSNL1	psi-mi:“MI:0915”(physical association)	0.780
FAM131C	VSNL1	psi-mi:“MI:0915”(physical association)	0.780
VSNL1	DTX2	psi-mi:“MI:0915”(physical association)	0.780
VSNL1	FAM131C	psi-mi:“MI:0915”(physical association)	0.780
ATXN1	VSNL1	psi-mi:“MI:0915”(physical association)	0.670
VSNL1	TEX13B	psi-mi:“MI:0915”(physical association)	0.560
ENDOD1	VSNL1	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	LITAF	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	SPRED2	psi-mi:“MI:0915”(physical association)	0.560
SPRY3	VSNL1	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	SPRED1	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	COL10A1	psi-mi:“MI:0915”(physical association)	0.560
TFF1	VSNL1	psi-mi:“MI:0915”(physical association)	0.560
VSNL1	SRL	psi-mi:“MI:0915”(physical association)	0.560
	VSNL1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (48): DTX2 (Two-hybrid), FAM131C (Two-hybrid), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), DTX2 (Two-hybrid), FAM131C (Two-hybrid), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS), VSNL1 (Affinity Capture-MS)

ESM2 similar proteins: A9JTH1, B3DLU1, B3VSB7, B5FZ84, P29104, P29105, P35332, P36608, P37235, P37236, P42324, P42325, P61601, P61602, P62166, P62167, P62168, P62748, P62749, P62758, P62759, P62760, P62761, P62762, P62763, P62764, P84074, P84075, P84076, Q06AT0, Q06AT1, Q09711, Q16982, Q28IM6, Q4PL64, Q4R4N4, Q4R5F7, Q5PQN0, Q5R632, Q5R6S5

Diamond homologs: A9JTH1, B3DLU1, B3VSB7, B5FZ84, O73761, O73762, O73763, O95843, P21457, P22728, P25296, P29104, P29105, P31227, P34057, P35243, P35332, P36608, P36609, P37235, P37236, P42322, P42324, P42325, P43080, P43081, P46065, P51177, P61601, P61602, P62166, P62167, P62168, P62748, P62749, P62758, P62759, P62760, P62761, P62762

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	7
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4820251	GRCh37/hg19 2p24.3-24.2(chr2:12770188-18905174)x3	Pathogenic

SpliceAI

1023 predictions. Top by Δscore:

Variant	Effect	Δscore
2:17592068:A:AG	acceptor_gain	1.0000
2:17592069:G:GT	acceptor_gain	1.0000
2:17592069:GGCA:G	acceptor_gain	1.0000
2:17592232:TGAAG:T	donor_gain	1.0000
2:17592233:GAAG:G	donor_gain	1.0000
2:17592233:GAAGG:G	donor_gain	1.0000
2:17592234:AAGG:A	donor_loss	1.0000
2:17592235:AG:A	donor_gain	1.0000
2:17592236:GG:G	donor_gain	1.0000
2:17592237:G:GA	donor_loss	1.0000
2:17592237:G:GG	donor_gain	1.0000
2:17649406:GCA:G	acceptor_loss	1.0000
2:17649407:CAGT:C	acceptor_loss	1.0000
2:17649408:A:AG	acceptor_gain	1.0000
2:17649408:AGTT:A	acceptor_loss	1.0000
2:17649409:G:GG	acceptor_gain	1.0000
2:17649409:GT:G	acceptor_gain	1.0000
2:17649409:GTT:G	acceptor_gain	1.0000
2:17649409:GTTC:G	acceptor_gain	1.0000
2:17649409:GTTCT:G	acceptor_gain	1.0000
2:17649623:GAG:G	donor_gain	1.0000
2:17649626:G:GG	donor_gain	1.0000
2:17649626:GTGAG:G	donor_loss	1.0000
2:17649627:T:G	donor_loss	1.0000
2:17655195:A:G	acceptor_gain	1.0000
2:17549144:A:AG	donor_gain	0.9900
2:17592069:GGC:G	acceptor_gain	0.9900
2:17655194:A:AG	acceptor_gain	0.9900
2:17655194:AAG:A	acceptor_gain	0.9900
2:17592068:AG:A	acceptor_gain	0.9800

AlphaMissense

1302 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:17592174:T:C	F34L	1.000
2:17592176:T:A	F34L	1.000
2:17592176:T:G	F34L	1.000
2:17649549:T:C	L101P	1.000
2:17649560:T:C	F105L	1.000
2:17649562:C:A	F105L	1.000
2:17649562:C:G	F105L	1.000
2:17592121:T:C	L16P	0.999
2:17592139:T:C	F22S	0.999
2:17592154:T:A	L27H	0.999
2:17592154:T:C	L27P	0.999
2:17592175:T:C	F34S	0.999
2:17592202:T:C	L43P	0.999
2:17592216:T:C	F48L	0.999
2:17592217:T:C	F48S	0.999
2:17592218:T:A	F48L	0.999
2:17592218:T:G	F48L	0.999
2:17649413:T:C	F56L	0.999
2:17649415:T:A	F56L	0.999
2:17649415:T:G	F56L	0.999
2:17649423:G:A	G59E	0.999
2:17649423:G:T	G59V	0.999
2:17649437:T:C	F64L	0.999
2:17649438:T:C	F64S	0.999
2:17649438:T:G	F64C	0.999
2:17649439:T:A	F64L	0.999
2:17649439:T:G	F64L	0.999
2:17649441:C:A	A65D	0.999
2:17649450:C:A	A68D	0.999
2:17649452:T:C	F69L	0.999

dbSNP variants (sampled 300 via entrez): RS1000006256 (2:17571149 T>A,C), RS1000016763 (2:17603215 G>A), RS1000041972 (2:17581777 G>A), RS1000047055 (2:17657471 C>T), RS1000050809 (2:17538792 T>G), RS1000095763 (2:17609196 G>T), RS1000137016 (2:17644477 G>A,T), RS1000147870 (2:17566646 T>C), RS1000155594 (2:17553653 C>A), RS1000161858 (2:17649966 A>G,T), RS1000190261 (2:17644929 C>G), RS1000237497 (2:17639669 C>T), RS1000283020 (2:17558934 T>G), RS1000291000 (2:17587906 T>C), RS1000333047 (2:17637900 C>T)

Disease associations

OMIM: gene MIM:600817 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): disease (MONDO:0000001)

Orphanet (1): (Orphanet:377788)

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001285_6	Psychosis and Alzheimer’s disease	6.000000e-07
GCST003487_17	Response to fenofibrate (total cholesterol levels)	5.000000e-06
GCST004750_100	Squamous cell lung carcinoma	2.000000e-06
GCST005173_66	Coronary artery calcified atherosclerotic plaque (130 HU threshold) in type 2 diabetes	8.000000e-08
GCST006403_6	Energy expenditure	3.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0005940	psychotic symptoms
EFO:0007806	total cholesterol change measurement
EFO:0004723	coronary artery calcification

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D004194	Disease	C23.550.288

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	7
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation	6
sodium arsenite	affects methylation, decreases expression, increases expression	4
bisphenol A	decreases methylation, decreases expression, affects expression, affects cotreatment	3
trichostatin A	affects cotreatment, decreases expression	3
Acetaminophen	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	decreases expression, decreases reaction	3
Cyclosporine	decreases expression	3
sodium arsenate	increases abundance, decreases expression	2
Cadmium	decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression	2
Hydrogen Peroxide	affects expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
Rotenone	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
3,19-(2-bromobenzylidene)andrographolide	decreases response to substance, increases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
methyleugenol	decreases expression	1
uranyl acetate	affects expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression	1
arsenite	increases methylation	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
hydroquinone	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00502970	PHASE4	COMPLETED	Short Course of Interferon Treatment in Patients With HCV Infection
NCT00632554	PHASE4	COMPLETED	The Efficacy of Three Months-prednisolone Therapy for Chronic Eosinophilic Pneumonia
NCT01179191	PHASE4	TERMINATED	Conversion to Embeda With Rescue Trial
NCT01968161	PHASE4	UNKNOWN	Investigator Initiated Study - Asenapine Early Psychosis
NCT02436980	PHASE4	COMPLETED	Premedication for ERCP With Midazolam or Tramadol
NCT03702361	PHASE4	COMPLETED	Rapid Intravenous Infusion of Velaglucerase Alfa (VPRIV) in Treatment-naive Patients With Type 1 Gaucher Disease
NCT06271538	PHASE4	RECRUITING	Evaluation of Efficacy of Skål Pro Powder on Symptoms of Irritable Bowel Syndrome
NCT06390436	PHASE4	NOT_YET_RECRUITING	Therapeutic Drug Monitoring-baSed adalimuMab De-escalatiOn in nOn-infecTious cHronic Uveitis
NCT06750471	PHASE4	ACTIVE_NOT_RECRUITING	Dupixent Study for Alternate Administration
NCT00096785	PHASE3	COMPLETED	Comparative Trial of Entecavir Versus Adefovir in the Treatment of Chronic Hepatitis B Infection
NCT00569595	PHASE3	COMPLETED	Improving Health Habits in Impoverished Populations
NCT00787956	PHASE3	COMPLETED	Internet Chronic Disease Self-Management Program for Australia
NCT00803244	PHASE3	COMPLETED	Safety and Efficacy on Phase III Study on 300 IR SLIT to Patients Suffering From Grass Pollen Rhinoconjunctivitis
NCT00813189	PHASE3	COMPLETED	Efficacy Study of Recombinant Growth Hormone on Muscle Function in Children Long-term Treated With Glucocorticoid
NCT00911287	PHASE3	COMPLETED	Oxymorphone Extended Release (ER) in Opioid-Naive Patients With Chronic Pain
NCT01237860	PHASE3	COMPLETED	Evaluation of the Safety and Performance of the NESS L300 Plus System
NCT01477281	PHASE3	UNKNOWN	Study to Evaluate the Efficacy and Tolerability of Venaflon Use in Reducing the Symptoms Caused by Chronic Venous Insufficiency When Compared With Daflon
NCT02137772	PHASE3	COMPLETED	Letermovir (MK-8228) Versus Placebo in the Prevention of Clinically-Significant Cytomegalovirus (CMV) Infection in Adult, CMV-Seropositive Allogeneic Hematopoietic Stem Cell Transplant Recipients (MK-8228-001)
NCT04007848	PHASE3	COMPLETED	Cobimetinib for BRAF-wild-type or Mutated Histiocytoses
NCT04264897	PHASE3	COMPLETED	Antecedent Metabolic Health and Metformin Aging Study
NCT04639310	PHASE3	TERMINATED	XEN496 (Ezogabine) in Children With KCNQ2 Developmental and Epileptic Encephalopathy
NCT04912856	PHASE3	TERMINATED	An Open-Label Extension of the Study XEN496 (Ezogabine) in Children With KCNQ2-DEE
NCT00003145	PHASE2	COMPLETED	Fludarabine Phosphate, Low-Dose Total-Body Irradiation, and Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Older Patients With Chronic Myeloid Leukemia
NCT00036738	PHASE2	COMPLETED	Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib
NCT00408252	PHASE2	TERMINATED	Efficacy of SU 011248 in Head And Neck Carcinoma
NCT00552461	PHASE2	COMPLETED	Prospective Trial of Rituximab for Primary Pulmonary Alveolar Proteinosis
NCT00795132	PHASE2	COMPLETED	Hematopoietic Cell Transplantation for Pediatric Patients With Hematologic Malignancies
NCT00889499	PHASE2	COMPLETED	Modulation of Central Hypersensitivity in Chronic Musculoskeletal Pain by Intravenous Tropisetron
NCT01047514	PHASE2	COMPLETED	Healthier Living Canada
NCT01047774	PHASE2	TERMINATED	The Effect of Soy Protein on Post- Breast Cancer Surgery Pain
NCT01215578	PHASE2	TERMINATED	Predictive Biomarkers of Response to Sunitinib in the Treatment of Poorly-differentiated NEURO-Endocrine Tumors
NCT01267253	PHASE2	COMPLETED	Brivanib Alaninate in Treating Patients With Persistent or Recurrent Cervical Cancer
NCT01325194	PHASE2	COMPLETED	CHemoImmunotherapy With Early Central Nervous System (CNS) Prophylaxis
NCT01326897	PHASE2	COMPLETED	Healthy Homes/Healthy Families
NCT01635270	PHASE2	COMPLETED	Phase 2 Study Evaluating Mid-position Strategy in Radiotherapy Treatment for Patients With a Locally Advanced Non-small Cell Lung Carcinoma
NCT01664663	PHASE2	TERMINATED	Phase II Randomized Study on Locally Advanced NSCLC Escalated Dose on Individual Basis Treatment With Radiochemotherapy
NCT01687777	PHASE2	UNKNOWN	Mensenchymal Stem Cell (MSC) Included in OrthADAPT Membrane for Rotator Cuff Tears Repair
NCT01737450	PHASE2	COMPLETED	Activity and Safety Study of BKM120 in Monotherapy in Patient With Metastatic Head and Neck Cancer Recurrent or Progressive
NCT01794845	PHASE2	TERMINATED	Cetuximab + Taxotere With Low Dose Fractionated Radiation for Head and Neck Carcinoma
NCT01884389	PHASE2	COMPLETED	Randomized Trial of an HIV Navigation Program for Early Palliative Care