LSM11

Summary

LSM11 (LSM11, U7 small nuclear RNA associated, HGNC:30860) is a protein-coding gene on chromosome 5q33.3, encoding U7 snRNA-associated Sm-like protein LSm11 (P83369). Component of the U7 snRNP complex that is involved in the histone 3’-end pre-mRNA processing. It is a selective cancer dependency (DepMap: 83.6% of cell lines).

Enables U7 snRNA binding activity. Involved in mRNA 3’-end processing by stem-loop binding activity and cleavage; positive regulation of G1/S transition of mitotic cell cycle; and regulation of chromatin organization. Located in nuclear body. Part of U7 snRNP and telomerase holoenzyme complex. Implicated in Aicardi-Goutieres syndrome.

Source: NCBI Gene 134353 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Aicardi-Goutieres syndrome 8 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 2
• Clinical variants (ClinVar): 59 total — 1 pathogenic
• Phenotypes (HPO): 80
• Cancer dependency (DepMap): dependent in 83.6% of screened cell lines
• MANE Select transcript: NM_173491

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30860
Approved symbol	LSM11
Name	LSM11, U7 small nuclear RNA associated
Location	5q33.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ38273
Ensembl gene	ENSG00000155858
Ensembl biotype	protein_coding
OMIM	617910
Entrez	134353

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000286307

RefSeq mRNA: 1 — MANE Select: NM_173491 NM_173491

CCDS: CCDS4342

Canonical transcript exons

ENST00000286307 — 4 exons

Exon	Start	End
ENSE00001023124	157754004	157754087
ENSE00001233466	157751390	157751529
ENSE00001233474	157754854	157760709
ENSE00001233480	157743712	157744198

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 95.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.8349 / max 48.0852, expressed in 1533 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59839	3.8349	1533

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	95.30	gold quality
endothelial cell	CL:0000115	94.85	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.32	gold quality
middle temporal gyrus	UBERON:0002771	91.81	gold quality
oocyte	CL:0000023	91.27	gold quality
cortical plate	UBERON:0005343	90.94	gold quality
Brodmann (1909) area 46	UBERON:0006483	85.56	gold quality
superior frontal gyrus	UBERON:0002661	84.91	gold quality
postcentral gyrus	UBERON:0002581	84.90	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.57	gold quality
adrenal tissue	UBERON:0018303	84.42	gold quality
entorhinal cortex	UBERON:0002728	84.29	gold quality
cerebellar vermis	UBERON:0004720	84.23	gold quality
primary visual cortex	UBERON:0002436	83.87	gold quality
parietal lobe	UBERON:0001872	83.53	gold quality
cauda epididymis	UBERON:0004360	82.68	gold quality
cartilage tissue	UBERON:0002418	82.65	gold quality
occipital lobe	UBERON:0002021	81.92	gold quality
tibialis anterior	UBERON:0001385	80.79	silver quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	80.58	gold quality
lower esophagus	UBERON:0013473	80.48	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.25	gold quality
pigmented layer of retina	UBERON:0001782	78.47	gold quality
skin of hip	UBERON:0001554	78.09	gold quality
prefrontal cortex	UBERON:0000451	77.77	gold quality
colonic mucosa	UBERON:0000317	77.63	gold quality
urinary bladder	UBERON:0001255	77.60	gold quality
embryo	UBERON:0000922	77.55	gold quality
ganglionic eminence	UBERON:0004023	77.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.37

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

274 targeting LSM11, 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-3613-3P	100.00	76.36	7965
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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
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

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 5)

• Lsm10 and Lsm11, which replace the Sm proteins D1 and D2 in the histone RNA processing U7 snRNPs, associate with pICln in vitro and in vivo without receiving sDMA modifications and with PRMT5 and SMN complexes (PMID:16087681)
• The overexpression of Lsm10 and Lsm11 increases the cellular levels of U7 snRNP but has no effect on histone pre-mRNA processing. (PMID:16914750)
• FLASH/Lsm11 complex bind a unique combination of polyadenylation factors (PMID:23071092)
• While the molecular basis for this altered cleavage activity is unknown, one possibility is that binding of Lsm10 and Lsm11 to the spliceosomal Sm site affects the overall geometry of the U7-specific Sm ring, resulting in misalignment of the CPSF73 endonuclease with the substrate. (PMID:31819999)
• cGAS-mediated induction of type I interferon due to inborn errors of histone pre-mRNA processing. (PMID:33230297)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm11	ENSDARG00000090854
mus_musculus	Lsm11	ENSMUSG00000044847
rattus_norvegicus	Lsm11	ENSRNOG00000005450
drosophila_melanogaster	Lsm11	FBGN0033450
caenorhabditis_elegans		WBGENE00016791

Protein

Protein identifiers

U7 snRNA-associated Sm-like protein LSm11 — P83369 (reviewed: P83369)

All UniProt accessions (1): P83369

UniProt curated annotations — full annotation on UniProt →

Function. Component of the U7 snRNP complex that is involved in the histone 3’-end pre-mRNA processing. Increases U7 snRNA levels but not histone 3’-end pre-mRNA processing activity, when overexpressed. Required for cell cycle progression from G1 to S phases. Binds specifically to the Sm-binding site of U7 snRNA.

Subunit / interactions. Component of the heptameric ring U7 snRNP complex, or U7 Sm protein core complex, at least composed of LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF, SNRPG and U7 snRNA. Formation of the U7 snRNP is an ATP-dependent process mediated by a specialized SMN complex containing at least the Sm protein core complex and additionally, the U7-specific LSM10 and LSM11 proteins. Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Interacts (via the Sm domains) with CLNS1A. Interacts with SMN and ZNF473. Interacts with PRMT5 and WDR77.

Subcellular location. Nucleus.

Disease relevance. Aicardi-Goutieres syndrome 8 (AGS8) [MIM:619486] A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. AGS8 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry. Impaired histone 3’-end pre-mRNA processing caused by disease variants affects chromatin structure, relieving CGAS inhibition by nucleosomes. This activates the cGAS-STING pathway, triggering type-I interferon production and autoinflammation.

Domain organisation. The C-terminal SM 1 domain is both necessary for the binding to the Sm-binding site of U7 snRNA and U7 snRNP assembly. The N-terminal domain is essential for histone pre-mRNA cleavage. Amino acids 63-82 are sufficient to interact with ZNF473.

Similarity. Belongs to the snRNP Sm proteins family.

RefSeq proteins (1): NP_775762* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR034109	Lsm11_M	Domain
IPR039267	Lsm11	Family
IPR047575	Sm	Domain

UniProt features (28 total): strand 8, modified residue 5, region of interest 5, helix 3, compositionally biased region 2, chain 1, domain 1, cross-link 1, sequence variant 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9NH5	ELECTRON MICROSCOPY	2.82
9NH6	ELECTRON MICROSCOPY	2.82
8G1U	ELECTRON MICROSCOPY	2.83
6V4X	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P83369-F1	65.63	0.18

Functional residue map

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

Post-translational modifications (6): 21, 41, 154, 280, 120, 15

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-111367	SLBP independent Processing of Histone Pre-mRNAs
R-HSA-73856	RNA Polymerase II Transcription Termination
R-HSA-77588	SLBP Dependent Processing of Replication-Dependent Histone Pre-mRNAs
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-75067	Processing of Capped Intronless Pre-mRNA
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 330 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GSE45365_NK_CELL_VS_CD8A_DC_DN, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_MITOTIC_CELL_CYCLE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_RNA_METHYLATION, GOBP_POSITIVE_REGULATION_OF_G1_S_TRANSITION_OF_MITOTIC_CELL_CYCLE, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MRNA_3_END_PROCESSING, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION

GO Biological Process (4): mRNA 3’-end processing by stem-loop binding and cleavage (GO:0006398), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), regulation of chromatin organization (GO:1902275), mRNA processing (GO:0006397)

GO Molecular Function (3): U7 snRNA binding (GO:0071209), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), U7 snRNP (GO:0005683), telomerase holoenzyme complex (GO:0005697), nuclear body (GO:0016604), histone pre-mRNA 3’end processing complex (GO:0071204), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Processing of Capped Intronless Pre-mRNA	2
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear protein-containing complex	2
ribonucleoprotein complex	2
histone mRNA metabolic process	1
mRNA 3’-end processing	1
G1/S transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G1/S phase transition	1
regulation of G1/S transition of mitotic cell cycle	1
chromatin organization	1
regulation of cellular component organization	1
RNA processing	1
mRNA metabolic process	1
snRNA binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
small nuclear ribonucleoprotein complex	1
catalytic complex	1
nucleoplasm	1
intracellular membraneless organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM11	LSM10	Q969L4	997
LSM11	CASP8AP2	Q9UKL3	943
LSM11	CPSF3	Q9UKF6	911
LSM11	ZNF473	Q8WTR7	877
LSM11	NPAT	Q14207	874
LSM11	SLBP	Q14493	868
LSM11	SYMPK	Q92797	867
LSM11	SNRPE	P08578	843
LSM11	CSTF2	P33240	828
LSM11	SNRPD1	P13641	757
LSM11	SNRPD2	P43330	729
LSM11	CPSF1	Q10570	729
LSM11	COIL	P38432	721
LSM11	CPSF2	Q9P2I0	695
LSM11	SNRPB	P14678	681

IntAct

58 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SMN1	PRMT5	psi-mi:“MI:0914”(association)	0.600
RAB19	LSM11	psi-mi:“MI:0915”(physical association)	0.560
DDX20	GAPDHS	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPN	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPE	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
GEMIN7	GEMIN2	psi-mi:“MI:0914”(association)	0.530
Snrnp70	GEMIN2	psi-mi:“MI:0914”(association)	0.350
Fbl	COPS8	psi-mi:“MI:0914”(association)	0.350
Ppp2ca	DKFZP586J0619	psi-mi:“MI:0914”(association)	0.350
Hnrnpf	MATR3	psi-mi:“MI:0914”(association)	0.350
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
GEMIN7	CSNK1D	psi-mi:“MI:0914”(association)	0.350
GEMIN5	PFDN1	psi-mi:“MI:0914”(association)	0.350
ATL2	ACRBP	psi-mi:“MI:0914”(association)	0.350
KRAS		psi-mi:“MI:0914”(association)	0.350
Tgs1	EFCAB5	psi-mi:“MI:0914”(association)	0.350
TGS1	SEPTIN10	psi-mi:“MI:0914”(association)	0.350
FOSL2	RECQL5	psi-mi:“MI:0914”(association)	0.350
Katna1	RIMS1	psi-mi:“MI:0914”(association)	0.350
GPSM2	AASDH	psi-mi:“MI:0914”(association)	0.350
ILK	ELOC	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350

BioGRID (74): LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS), LSM11 (Affinity Capture-MS)

ESM2 similar proteins: A1A4I4, A2SXS5, A5PJV8, A6NFY7, A6QPI4, A8PU71, B0K036, O00192, O00255, O02718, O43189, O60232, O75208, O88559, P12755, P83369, Q0P5I0, Q16512, Q2KJ58, Q2NL34, Q32Q90, Q3MII6, Q3U276, Q504T8, Q5C9Z4, Q5QQ50, Q5RB75, Q5T6X4, Q68EN5, Q6DVA0, Q6WVG3, Q7T076, Q7Z6J2, Q86UD0, Q86UK7, Q8CEG5, Q8IVD9, Q8N6N2, Q8NC56, Q8QZV0

Diamond homologs: P83369, Q54HH8, Q7T076, Q8BUV6, P62310, P62311, Q32PE9, Q9LMN4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 70 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Metabolism of non-coding RNA	8	126.9×	6e-14
snRNP Assembly	13	68.7×	3e-19
SARS-CoV-2 modulates host translation machinery	10	56.0×	8e-14
mRNA Splicing - Minor Pathway	5	28.0×	2e-05
RNA Polymerase II Transcription Termination	5	27.4×	2e-05
SARS-CoV-2-host interactions	6	17.8×	2e-05
mRNA Splicing	6	16.5×	3e-05
CHD1 and CHD2 subfamily	6	16.3×	3e-05

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	13	137.3×	2e-23
U2-type prespliceosome assembly	5	56.7×	2e-06
mRNA splicing, via spliceosome	9	15.0×	9e-07
RNA splicing	6	9.6×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	47
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1202617	NM_173491.4(LSM11):c.631G>A (p.Gly211Ser)	Pathogenic

SpliceAI

842 predictions. Top by Δscore:

Variant	Effect	Δscore
5:157744114:G:GT	donor_gain	1.0000
5:157751382:T:TA	acceptor_gain	1.0000
5:157751387:CAGT:C	acceptor_loss	1.0000
5:157751388:A:AG	acceptor_gain	1.0000
5:157751388:AG:A	acceptor_loss	1.0000
5:157751388:AGT:A	acceptor_gain	1.0000
5:157751389:G:GG	acceptor_gain	1.0000
5:157751389:GTG:G	acceptor_gain	1.0000
5:157751389:GTGC:G	acceptor_gain	1.0000
5:157751526:TATGG:T	donor_loss	1.0000
5:157751528:TGG:T	donor_loss	1.0000
5:157751531:T:A	donor_loss	1.0000
5:157753988:T:TA	acceptor_gain	1.0000
5:157753989:G:A	acceptor_gain	1.0000
5:157754086:GG:G	donor_gain	1.0000
5:157754087:GG:G	donor_gain	1.0000
5:157754853:GCT:G	acceptor_gain	1.0000
5:157754958:G:GT	donor_gain	1.0000
5:157754958:G:T	donor_gain	1.0000
5:157744194:GCCCT:G	donor_gain	0.9900
5:157744199:G:GG	donor_gain	0.9900
5:157751389:GT:G	acceptor_gain	0.9900
5:157751389:GTGCA:G	acceptor_gain	0.9900
5:157751523:GAA:G	donor_gain	0.9900
5:157751530:G:GG	donor_gain	0.9900
5:157753998:CTCTA:C	acceptor_loss	0.9900
5:157753999:TCTA:T	acceptor_loss	0.9900
5:157754000:CTA:C	acceptor_loss	0.9900
5:157754001:TAGGC:T	acceptor_loss	0.9900
5:157754002:A:AG	acceptor_gain	0.9900

AlphaMissense

2275 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:157751453:T:A	V171D	1.000
5:157751461:C:A	R174S	1.000
5:157751462:G:C	R174P	1.000
5:157751482:G:C	G181R	1.000
5:157751483:G:A	G181D	1.000
5:157751488:T:C	C183R	1.000
5:157751489:G:A	C183Y	1.000
5:157751490:T:G	C183W	1.000
5:157751494:G:C	G185R	1.000
5:157751495:G:A	G185D	1.000
5:157751495:G:T	G185V	1.000
5:157751497:T:C	F186L	1.000
5:157751499:C:A	F186L	1.000
5:157751499:C:G	F186L	1.000
5:157751501:T:A	L187H	1.000
5:157751509:T:C	F190L	1.000
5:157751510:T:C	F190S	1.000
5:157751511:C:A	F190L	1.000
5:157751511:C:G	F190L	1.000
5:157751512:G:C	D191H	1.000
5:157751513:A:C	D191A	1.000
5:157751513:A:G	D191G	1.000
5:157751513:A:T	D191V	1.000
5:157751514:C:A	D191E	1.000
5:157751514:C:G	D191E	1.000
5:157751518:T:C	F193L	1.000
5:157751520:C:A	F193L	1.000
5:157751520:C:G	F193L	1.000
5:157751521:T:A	W194R	1.000
5:157751521:T:C	W194R	1.000

dbSNP variants (sampled 300 via entrez): RS1000335952 (5:157751292 G>A,T), RS1000368492 (5:157751616 G>T), RS1000472120 (5:157745442 A>G), RS1000567971 (5:157757465 C>T), RS1000574947 (5:157743303 G>A), RS1000682356 (5:157749294 T>C,G), RS1000821584 (5:157744987 C>T), RS1000903011 (5:157757186 A>G), RS1001345784 (5:157751468 T>C,G), RS1001345848 (5:157752630 G>A,T), RS1001570083 (5:157758922 G>A), RS1001795413 (5:157751186 T>C), RS1001837463 (5:157756063 C>T), RS1002006354 (5:157752448 G>C,T), RS1002136892 (5:157748423 A>G)

Disease associations

OMIM: gene MIM:617910 | disease phenotypes: MIM:619486

GenCC curated gene-disease

Disease	Classification	Inheritance
Aicardi-Goutieres syndrome 8	Limited	Unknown
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (2): Aicardi-Goutieres syndrome 8 (MONDO:0030361), Tourette syndrome (MONDO:0007661)

Orphanet (0):

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000050	Hypoplastic male external genitalia
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000625	Eyelid coloboma
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000958	Dry skin
HP:0000965	Cutis marmorata
HP:0001063	Acrocyanosis
HP:0001087	Developmental glaucoma
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001357	Plagiocephaly
HP:0001369	Arthritis
HP:0001433	Hepatosplenomegaly
HP:0001609	Hoarse voice
HP:0001639	Hypertrophic cardiomyopathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90002396_315	Mean reticulocyte volume	9.000000e-16
GCST90002397_50	Mean spheric corpuscular volume	1.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases expression, affects cotreatment	3
FR900359	increases phosphorylation	1
triphenyl phosphate	affects expression	1
trichostatin A	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
butyraldehyde	decreases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	decreases phosphorylation	1
pentanal	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Lead	affects expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Smoke	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome