SYT11

Summary

SYT11 (synaptotagmin 11, HGNC:19239) is a protein-coding gene on chromosome 1q22, encoding Synaptotagmin-11 (Q9BT88). Synaptotagmin family member involved in vesicular and membrane trafficking which does not bind Ca(2+).

This gene is a member of the synaptotagmin gene family and encodes a protein similar to other family members that are known calcium sensors and mediate calcium-dependent regulation of membrane trafficking in synaptic transmission. The encoded protein is also a substrate for ubiquitin-E3-ligase parkin. The gene has previously been referred to as synaptotagmin XII but has been renamed synaptotagmin XI to be consistent with mouse and rat official nomenclature.

Source: NCBI Gene 23208 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 53 total
• MANE Select transcript: NM_152280

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19239
Approved symbol	SYT11
Name	synaptotagmin 11
Location	1q22
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0080, MGC10881, MGC17226, DKFZp781D015
Ensembl gene	ENSG00000132718
Ensembl biotype	protein_coding
OMIM	608741
Entrez	23208

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000368324, ENST00000874873, ENST00000916077, ENST00000916078

RefSeq mRNA: 1 — MANE Select: NM_152280 NM_152280

CCDS: CCDS1122

Canonical transcript exons

ENST00000368324 — 4 exons

Exon	Start	End
ENSE00000961234	155867965	155868791
ENSE00001446874	155881198	155885199
ENSE00001446877	155859567	155859795
ENSE00003553355	155880500	155880623

Expression profiles

Bgee: expression breadth ubiquitous, 243 present calls, max score 99.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 68.1997 / max 1498.8044, expressed in 1522 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5636	33.7565	1355
5635	33.4790	1478
5647	0.5240	168
5646	0.4402	181

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.11	gold quality
lateral globus pallidus	UBERON:0002476	98.77	gold quality
lateral nuclear group of thalamus	UBERON:0002736	98.75	gold quality
inferior vagus X ganglion	UBERON:0005363	98.65	gold quality
substantia nigra pars reticulata	UBERON:0001966	98.56	gold quality
postcentral gyrus	UBERON:0002581	98.56	gold quality
prefrontal cortex	UBERON:0000451	98.54	gold quality
parietal lobe	UBERON:0001872	98.54	gold quality
Brodmann (1909) area 46	UBERON:0006483	98.49	gold quality
substantia nigra pars compacta	UBERON:0001965	98.40	gold quality
ventral tegmental area	UBERON:0002691	98.39	gold quality
ganglionic eminence	UBERON:0004023	98.29	gold quality
superior frontal gyrus	UBERON:0002661	98.19	gold quality
frontal cortex	UBERON:0001870	98.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.10	gold quality
dorsal plus ventral thalamus	UBERON:0001897	98.08	gold quality
subthalamic nucleus	UBERON:0001906	98.06	gold quality
right frontal lobe	UBERON:0002810	98.05	gold quality
caudate nucleus	UBERON:0001873	98.04	gold quality
corpus callosum	UBERON:0002336	98.03	gold quality
entorhinal cortex	UBERON:0002728	98.02	gold quality
putamen	UBERON:0001874	98.01	gold quality
nucleus accumbens	UBERON:0001882	97.91	gold quality
superior vestibular nucleus	UBERON:0007227	97.91	gold quality
neocortex	UBERON:0001950	97.89	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.86	gold quality
telencephalon	UBERON:0001893	97.83	gold quality
cerebral cortex	UBERON:0000956	97.79	gold quality
pons	UBERON:0000988	97.73	gold quality
dorsal root ganglion	UBERON:0000044	97.68	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

Upstream regulators (CollecTRI, top): SP1, YY1

miRNA regulators (miRDB)

203 targeting SYT11, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-3617-3P	99.98	67.86	918
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-507	99.97	70.11	1915
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 16)

• parkin interacts with and ubiquitinates synaptotagmin XI (PMID:12925569)
• Lack of disease-causing mutations in a detailed analysis of a large sample of familial and sporadic Parkinson’s disease patients argues against a major role of mutations in the synaptotagmin XI gene in PD. (PMID:15354386)
• Excessive expression of Syt11 can be associated with schizophrenia. (PMID:17192956)
• The genetic variations of VAMP2, Synaptotagmin XI might be indication of the relationship between these genes and idiopathic generalized epilepsy (PMID:24164654)
• In summary, This study supports the existence of association between Parkinson disease and markers in or around SYT11 (PMID:26944171)
• ATP13A2 and SYT11 form a functional network in the regulation of the autophagy-lysosome pathway, which may contribute to forms of Parkinson’s Disease-associated neurodegeneration. (PMID:27278822)
• parkin deficiency induces synaptotagmin-11 accumulation and PD-like neurotoxicity in mouse models, which is reversed by SYT11 knockdown in the SNpc or knockout of SYT11 restricted to dopaminergic neuron (PMID:29311685)
• The rs3129882/rs4248166 in HLA-DRA and rs34372695 in SYT11 are not associated with sporadic Parkinson’s disease in Central Chinese population. (PMID:32253955)
• Targeted sequencing of Parkinson’s disease loci genes highlights SYT11, FGF20 and other associations. (PMID:33349842)
• Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson’s disease. (PMID:34674384)
• Atlas of RNA editing events affecting protein expression in aged and Alzheimer’s disease human brain tissue. (PMID:34857756)
• The highly expressed calcium-insensitive synaptotagmin-11 and synaptotagmin-13 modulate insulin secretion. (PMID:35753051)
• Synaptotagmin 11 scaffolds MKK7-JNK signaling process to promote stem-like molecular subtype gastric cancer oncogenesis. (PMID:35768842)
• Impad1 and Syt11 work in an epistatic pathway that regulates EMT-mediated vesicular trafficking to drive lung cancer invasion and metastasis. (PMID:36170810)
• Palmitoylation of the Parkinson’s disease-associated protein synaptotagmin-11 links its turnover to alpha-synuclein homeostasis. (PMID:36787382)
• Role of SYT11 in human pan-cancer using comprehensive approaches. (PMID:38890718)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	syt11b	ENSDARG00000056105
danio_rerio	syt11a	ENSDARG00000057913
mus_musculus	Syt11	ENSMUSG00000068923
rattus_norvegicus	Syt11	ENSRNOG00000020279

Paralogs (31): SYT7 (ENSG00000011347), SYT13 (ENSG00000019505), SYT1 (ENSG00000067715), RPH3A (ENSG00000089169), SYTL4 (ENSG00000102362), SYT17 (ENSG00000103528), SYT10 (ENSG00000110975), SYT5 (ENSG00000129990), SYT4 (ENSG00000132872), SYT6 (ENSG00000134207), SYTL2 (ENSG00000137501), SYT16 (ENSG00000139973), SYTL1 (ENSG00000142765), SYT14 (ENSG00000143469), SYT2 (ENSG00000143858), SYTL5 (ENSG00000147041), SYT8 (ENSG00000149043), DOC2A (ENSG00000149927), SYTL3 (ENSG00000164674), TC2N (ENSG00000165929), SYT9 (ENSG00000170743), SYT12 (ENSG00000173227), RPH3AL (ENSG00000181031), C2CD4C (ENSG00000183186), C2CD4A (ENSG00000198535), SYT15 (ENSG00000204176), C2CD4B (ENSG00000205502), SYT3 (ENSG00000213023), C2CD4D (ENSG00000225556), DOC2B (ENSG00000272636), SYT15B (ENSG00000277758)

Protein

Protein identifiers

Synaptotagmin-11 — Q9BT88 (reviewed: Q9BT88)

Alternative names: Synaptotagmin XI

All UniProt accessions (1): Q9BT88

UniProt curated annotations — full annotation on UniProt →

Function. Synaptotagmin family member involved in vesicular and membrane trafficking which does not bind Ca(2+). Inhibits clathrin-mediated and bulk endocytosis, functions to ensure precision in vesicle retrieval. Plays an important role in dopamine transmission by regulating endocytosis and the vesicle-recycling process. Essential component of a neuronal vesicular trafficking pathway that differs from the synaptic vesicle trafficking pathway but is crucial for development and synaptic plasticity. In macrophages and microglia, inhibits the conventional cytokine secretion, of at least IL6 and TNF, and phagocytosis. In astrocytes, regulates lysosome exocytosis, mechanism required for the repair of injured astrocyte cell membrane. Required for the ATP13A2-mediated regulation of the autophagy-lysosome pathway.

Subunit / interactions. Homodimer. Can also form heterodimers. Interacts with PRKN. Interacts (via C2 2 domain) with AGO2 and SND1; the interaction with SND1 is direct. Interacts with KIF1A; the interaction increases in presence of calcium.

Subcellular location. Cytoplasmic vesicle membrane. Perikaryon. Golgi apparatus. trans-Golgi network membrane. Recycling endosome membrane. Lysosome membrane. Cytoplasmic vesicle. Phagosome. Cell projection. Axon. Dendrite. Postsynaptic density. Clathrin-coated vesicle membrane.

Post-translational modifications. Ubiquitinated, at least by PRKN, and targeted to the proteasome complex for degradation. Ubiquitination is inhibited by ATP13A2.

Domain organisation. The second C2 domain/C2B is required for the inhibitory role in both clathrin-mediated and bulk endocytosis. The transmembrane domain and the first C2 domain/C2A are critical for the inhibitory role in clathrin-mediated endocytosis or bulk endocytosis, respectively. Unlike in other synaptotagmin family members, the first C2 domain/C2A does not bind Ca(2+) neither mediates Ca(2+)-dependent phospholipid binding. An aspartate-to-serine substitution in this domain inactivates Ca(2+)/phospho-lipid binding.

Similarity. Belongs to the synaptotagmin family.

RefSeq proteins (1): NP_689493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR001565	Synaptotagmin	Domain
IPR035892	C2_domain_sf	Homologous_superfamily

Pfam: PF00168

UniProt features (18 total): sequence conflict 4, binding site 3, topological domain 2, sequence variant 2, domain 2, chain 1, modified residue 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT88-F1	75.98	0.48

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 (3): 256; 250; 253

Post-translational modifications (1): 134

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-8856825	Cargo recognition for clathrin-mediated endocytosis
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-199991	Membrane Trafficking
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 405 (showing top): GOBP_MEMORY, GOBP_REGULATION_OF_CELL_ACTIVATION, E2F_Q4_01, GOBP_REGULATION_OF_VESICLE_FUSION, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_VESICLE_LOCALIZATION, GOBP_INFLAMMATORY_RESPONSE, GOCC_VACUOLAR_MEMBRANE, GOBP_VESICLE_ORGANIZATION, MAZ_Q6, GOBP_MEMBRANE_FUSION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_PLASMA_MEMBRANE_ORGANIZATION

GO Biological Process (24): plasma membrane repair (GO:0001778), negative regulation of cytokine production (GO:0001818), vesicle fusion (GO:0006906), autophagy (GO:0006914), learning (GO:0007612), memory (GO:0007613), vesicle-mediated transport (GO:0016192), regulation of calcium ion-dependent exocytosis (GO:0017158), negative regulation of interleukin-6 production (GO:0032715), negative regulation of tumor necrosis factor production (GO:0032720), negative regulation of dopamine secretion (GO:0033602), negative regulation of endocytosis (GO:0045806), negative regulation of neurotransmitter secretion (GO:0046929), negative regulation of phagocytosis (GO:0050765), establishment of vesicle localization (GO:0051650), calcium-dependent activation of synaptic vesicle fusion (GO:0099502), regulation of synaptic vesicle endocytosis (GO:1900242), regulation of defense response to bacterium (GO:1900424), negative regulation of microglial cell activation (GO:1903979), regulation of phagosome maturation (GO:1905162), positive regulation of protein localization to phagocytic vesicle (GO:1905171), calcium ion regulated lysosome exocytosis (GO:1990927), response to wounding (GO:0009611), negative regulation of secretion by cell (GO:1903531)

GO Molecular Function (9): SNARE binding (GO:0000149), calcium-dependent phospholipid binding (GO:0005544), translation initiation factor binding (GO:0031369), ubiquitin protein ligase binding (GO:0031625), identical protein binding (GO:0042802), metal ion binding (GO:0046872), beta-tubulin binding (GO:0048487), calcium ion sensor activity (GO:0061891), protein binding (GO:0005515)

GO Cellular Component (32): phagocytic cup (GO:0001891), lysosome (GO:0005764), lysosomal membrane (GO:0005765), trans-Golgi network (GO:0005802), plasma membrane (GO:0005886), synaptic vesicle (GO:0008021), postsynaptic density (GO:0014069), axon (GO:0030424), dendrite (GO:0030425), clathrin-coated vesicle membrane (GO:0030665), vesicle (GO:0031982), early phagosome (GO:0032009), neuron projection (GO:0043005), dendritic spine (GO:0043197), perikaryon (GO:0043204), synapse (GO:0045202), phagocytic vesicle (GO:0045335), presynaptic active zone membrane (GO:0048787), recycling endosome (GO:0055037), recycling endosome membrane (GO:0055038), excitatory synapse (GO:0060076), inhibitory synapse (GO:0060077), exocytic vesicle (GO:0070382), dopaminergic synapse (GO:0098691), presynapse (GO:0098793), cytoplasm (GO:0005737), endosome (GO:0005768), Golgi apparatus (GO:0005794), membrane (GO:0016020), cytoplasmic vesicle membrane (GO:0030659), cytoplasmic vesicle (GO:0031410), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Clathrin-mediated endocytosis	1
Membrane Trafficking	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	3
learning or memory	2
regulation of endocytosis	2
cellular anatomical structure	2
neuron projection	2
plasma membrane organization	1
wound healing	1
cytokine production	1
regulation of cytokine production	1
negative regulation of gene expression	1
negative regulation of multicellular organismal process	1
vesicle organization	1
vesicle-mediated transport	1
organelle membrane fusion	1
catabolic process	1
transmembrane transport	1
process utilizing autophagic mechanism	1
transport	1
cellular process	1
calcium-ion regulated exocytosis	1
regulation of regulated secretory pathway	1
negative regulation of cytokine production	1
interleukin-6 production	1
regulation of interleukin-6 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
dopamine secretion	1
regulation of dopamine secretion	1
negative regulation of catecholamine secretion	1
endocytosis	1
negative regulation of transport	1
negative regulation of cellular component organization	1
neurotransmitter secretion	1
regulation of neurotransmitter secretion	1
negative regulation of neurotransmitter transport	1
negative regulation of secretion by cell	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1

Protein interactions and networks

STRING

1638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SYT11	PRKN	O60260	877
SYT11	CCDC62	Q6P9F0	721
SYT11	ACMSD	Q8TDX5	662
SYT11	LRRK2	Q5S007	658
SYT11	SNCAIP	Q9Y6H5	645
SYT11	GPR37	O15354	637
SYT11	MCCC1	Q96RQ3	630
SYT11	STX1B	P61266	626
SYT11	SH3GL2	Q99962	609
SYT11	DGKQ	P52824	603
SYT11	GAK	O14976	587
SYT11	HIP1R	O75146	583
SYT11	STK39	Q9UEW8	581
SYT11	PINK1	Q9BXM7	570
SYT11	PARK7	Q99497	568

IntAct

60 interactions, top by confidence:

A	B	Type	Score
SGTA	SYT11	psi-mi:“MI:0915”(physical association)	0.780
SYT11	SGTA	psi-mi:“MI:0915”(physical association)	0.780
SYT11	TTC1	psi-mi:“MI:0914”(association)	0.640
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
APPBP2	SYT11	psi-mi:“MI:0915”(physical association)	0.620
SGTB	SYT11	psi-mi:“MI:0915”(physical association)	0.560
SYT11	PRKN	psi-mi:“MI:0915”(physical association)	0.560
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
LDLRAD1	ADAM10	psi-mi:“MI:0914”(association)	0.530
TNFRSF13B	TNFRSF10B	psi-mi:“MI:0914”(association)	0.530
ATP13A2	SYT11	psi-mi:“MI:0915”(physical association)	0.510
SYT11	GPR35	psi-mi:“MI:0915”(physical association)	0.370
	SNAP23	psi-mi:“MI:0914”(association)	0.350
SCN2A	IGLL5	psi-mi:“MI:0914”(association)	0.350
DYRK1A	TEX13D	psi-mi:“MI:0914”(association)	0.350
ITM2B	ILVBL	psi-mi:“MI:0914”(association)	0.350
CACNA1C	SYT5	psi-mi:“MI:0914”(association)	0.350
RIMS1	KIF2A	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350

BioGRID (45): SYT11 (Two-hybrid), TTC1 (Affinity Capture-MS), UBE2O (Affinity Capture-MS), PDLIM7 (Affinity Capture-MS), PRKAR1B (Affinity Capture-MS), PDLIM5 (Affinity Capture-MS), SYT11 (Two-hybrid), SYT11 (Affinity Capture-MS), SGTA (Two-hybrid), TTC1 (Affinity Capture-MS), PDLIM7 (Affinity Capture-MS), SYT11 (Two-hybrid), SYT11 (Affinity Capture-Western), PARK2 (Reconstituted Complex), SYT11 (Two-hybrid)

ESM2 similar proteins: A0A075F932, A8KBH6, F1LM93, K8FE10, O08625, O08835, P04409, P05126, P05130, P05696, P05771, P05772, P10102, P13217, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P25455, P29101, P34693, P40749, P41823, P46096, P46097, P47191, P47861, P48018, P50232, P68403, P68404, P70169, P70610, P90980, Q14184, Q5FWL4

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRKN	“down-regulates quantity by destabilization”	SYT11	polyubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

742 predictions. Top by Δscore:

Variant	Effect	Δscore
1:155859791:CTTTG:C	donor_gain	1.0000
1:155859794:TGGTA:T	donor_loss	1.0000
1:155859796:G:GG	donor_gain	1.0000
1:155859796:GTAA:G	donor_loss	1.0000
1:155859797:T:A	donor_loss	1.0000
1:155868792:G:GC	donor_loss	1.0000
1:155868793:T:G	donor_loss	1.0000
1:155880498:A:AG	acceptor_gain	1.0000
1:155880499:G:GG	acceptor_gain	1.0000
1:155880499:GAA:G	acceptor_gain	1.0000
1:155880616:CTCAG:C	donor_loss	1.0000
1:155880617:TCAGG:T	donor_loss	1.0000
1:155880618:CAG:C	donor_loss	1.0000
1:155880619:AGGTA:A	donor_loss	1.0000
1:155880620:GGTAG:G	donor_loss	1.0000
1:155880621:GT:G	donor_loss	1.0000
1:155880622:T:A	donor_loss	1.0000
1:155881186:T:A	acceptor_gain	1.0000
1:155881187:G:A	acceptor_gain	1.0000
1:155859792:TTTG:T	donor_gain	0.9900
1:155859793:TTG:T	donor_gain	0.9900
1:155859794:TG:T	donor_gain	0.9900
1:155859795:GG:G	donor_gain	0.9900
1:155867959:CTTCA:C	acceptor_loss	0.9900
1:155867960:TTCA:T	acceptor_loss	0.9900
1:155867961:TCA:T	acceptor_loss	0.9900
1:155867962:CAG:C	acceptor_loss	0.9900
1:155867963:A:AC	acceptor_loss	0.9900
1:155867963:A:AG	acceptor_gain	0.9900
1:155867964:G:GG	acceptor_gain	0.9900

AlphaMissense

2835 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:155868406:G:A	G159E	1.000
1:155868412:T:A	L161H	1.000
1:155868412:T:C	L161P	1.000
1:155868451:T:C	L174P	1.000
1:155868457:T:A	V176E	1.000
1:155868519:T:C	Y197H	1.000
1:155868519:T:G	Y197D	1.000
1:155868525:A:G	K199E	1.000
1:155868527:A:C	K199N	1.000
1:155868527:A:T	K199N	1.000
1:155868563:G:C	K211N	1.000
1:155868563:G:T	K211N	1.000
1:155868565:C:T	T212I	1.000
1:155868568:G:T	R213I	1.000
1:155868569:A:C	R213S	1.000
1:155868569:A:T	R213S	1.000
1:155868592:C:A	P221H	1.000
1:155868597:T:C	F223L	1.000
1:155868599:T:A	F223L	1.000
1:155868599:T:G	F223L	1.000
1:155868604:A:T	E225V	1.000
1:155868609:T:C	F227L	1.000
1:155868610:T:C	F227S	1.000
1:155868611:C:A	F227L	1.000
1:155868611:C:G	F227L	1.000
1:155868655:T:C	L242P	1.000
1:155868667:T:A	V246D	1.000
1:155868670:T:C	L247P	1.000
1:155868675:T:C	F249L	1.000
1:155868677:T:A	F249L	1.000

dbSNP variants (sampled 300 via entrez): RS1000057973 (1:155879516 A>G), RS1000202077 (1:155875463 G>T), RS1000520410 (1:155858768 G>A,C), RS1000588592 (1:155860292 C>A,T), RS1000888528 (1:155875754 C>T), RS1001052162 (1:155865740 C>T), RS1001254538 (1:155881729 T>A), RS1001282633 (1:155872861 G>A,C), RS1001283200 (1:155867058 G>T), RS1001339547 (1:155880457 G>A), RS1001485990 (1:155866075 G>A), RS1001571958 (1:155859559 C>A), RS1001613614 (1:155873567 C>G,T), RS1001775510 (1:155873203 G>A), RS1001883408 (1:155874013 G>A,C,T)

Disease associations

OMIM: gene MIM:608741 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000959_4	Parkinson’s disease	4.000000e-12
GCST002544_10	Parkinson’s disease	1.000000e-29
GCST004131_70	Inflammatory bowel disease	6.000000e-08
GCST004132_44	Crohn’s disease	2.000000e-07
GCST004904_249	Body mass index	1.000000e-09
GCST006585_876	Blood protein levels	5.000000e-26
GCST007294_124	Body fat distribution (trunk fat ratio)	8.000000e-35
GCST007294_3	Body fat distribution (trunk fat ratio)	6.000000e-21
GCST007294_50	Body fat distribution (trunk fat ratio)	1.000000e-15
GCST007295_17	Body fat distribution (leg fat ratio)	3.000000e-13
GCST007295_37	Body fat distribution (leg fat ratio)	7.000000e-17
GCST007295_72	Body fat distribution (leg fat ratio)	1.000000e-28
GCST009649_6	Serum cancer antigen 15.3 levels	3.000000e-08
GCST010696_19	Cortical thickness (min-P)	2.000000e-10
GCST010697_10	Cortical surface area (min-P)	3.000000e-10
GCST010698_59	Subcortical volume (min-P)	9.000000e-10
GCST010699_20	Brain morphology (min-P)	7.000000e-10
GCST010700_5	Cortical thickness (MOSTest)	8.000000e-17
GCST010701_66	Cortical surface area (MOSTest)	1.000000e-09
GCST010702_43	Subcortical volume (MOSTest)	3.000000e-10
GCST010703_253	Brain morphology (MOSTest)	4.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004341	body fat distribution
EFO:0010585	cancer antigen 15.3 measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression, affects expression	4
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	increases expression	2
sodium arsenite	decreases expression, increases abundance, increases expression	2
entinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
zinc chromate	increases abundance, increases expression	1
manganese chloride	increases abundance, increases expression	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	increases 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
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
licochalcone B	increases expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases abundance, increases expression	1

Clinical trials (associated diseases)

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