LSM10

Summary

LSM10 (LSM10, U7 small nuclear RNA associated, HGNC:17562) is a protein-coding gene on chromosome 1p34.3, encoding U7 snRNA-associated Sm-like protein LSm10 (Q969L4). Appears to function in the U7 snRNP complex that is involved in histone 3’-end processing. It is a selective cancer dependency (DepMap: 32.3% of cell lines).

Enables U7 snRNA binding activity. Involved in positive regulation of G1/S transition of mitotic cell cycle. Located in Cajal body. Part of U7 snRNP.

Source: NCBI Gene 84967 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 20 total
• Cancer dependency (DepMap): dependent in 32.3% of screened cell lines
• MANE Select transcript: NM_032881

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17562
Approved symbol	LSM10
Name	LSM10, U7 small nuclear RNA associated
Location	1p34.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC15749
Ensembl gene	ENSG00000181817
Ensembl biotype	protein_coding
OMIM	617909
Entrez	84967

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000315732, ENST00000476041, ENST00000489912, ENST00000861455, ENST00000861456, ENST00000861457, ENST00000861458, ENST00000861459, ENST00000861460, ENST00000861461, ENST00000861462, ENST00000861463, ENST00000861464, ENST00000916574, ENST00000916575, ENST00000916576, ENST00000916577, ENST00000967723

RefSeq mRNA: 1 — MANE Select: NM_032881 NM_032881

CCDS: CCDS408

Canonical transcript exons

ENST00000315732 — 2 exons

Exon	Start	End
ENSE00001274385	36397767	36397908
ENSE00001274393	36393436	36394153

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 97.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2106 / max 190.5982, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11726	32.2106	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.36	gold quality
gastrocnemius	UBERON:0001388	96.95	gold quality
granulocyte	CL:0000094	96.42	gold quality
muscle of leg	UBERON:0001383	96.26	gold quality
apex of heart	UBERON:0002098	95.95	gold quality
leukocyte	CL:0000738	95.63	gold quality
monocyte	CL:0000576	95.55	gold quality
right atrium auricular region	UBERON:0006631	94.66	gold quality
skeletal muscle tissue	UBERON:0001134	94.57	gold quality
tibialis anterior	UBERON:0001385	94.52	gold quality
quadriceps femoris	UBERON:0001377	94.49	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.27	gold quality
deltoid	UBERON:0001476	94.23	gold quality
vastus lateralis	UBERON:0001379	94.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.15	gold quality
lower esophagus	UBERON:0013473	94.12	gold quality
heart left ventricle	UBERON:0002084	93.95	gold quality
cardiac atrium	UBERON:0002081	93.90	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.86	gold quality
cardiac ventricle	UBERON:0002082	93.78	gold quality
prefrontal cortex	UBERON:0000451	93.44	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.44	gold quality
biceps brachii	UBERON:0001507	93.21	gold quality
muscle tissue	UBERON:0002385	93.20	gold quality
anterior cingulate cortex	UBERON:0009835	93.11	gold quality
lymph node	UBERON:0000029	93.07	gold quality
mucosa of stomach	UBERON:0001199	93.00	gold quality
spleen	UBERON:0002106	92.83	gold quality
heart	UBERON:0000948	92.70	gold quality
adenohypophysis	UBERON:0002196	92.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

22 targeting LSM10, 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-4455	100.00	65.48	1587
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-5100	99.11	67.52	1098
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-1288-5P	98.85	67.01	734
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-6730-5P	98.03	68.12	1299
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-146B-3P	97.83	65.29	782
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-3192-5P	96.98	65.76	1926

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 32.3% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 6)

• Purified U7 snRNPs lack the Sm proteins D1 and D2 but contain Lsm10, a new 14 kDa Sm D1-like protein. (PMID:11574479)
• 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)
• The subnuclear organization of histone gene regulatory proteins and 3’ end processing factors (NPAT/LSM10) of normal somatic and embryonic stem cells is compromised in selected human cancer cell types. (PMID:19277982)
• FLASH plays two roles in 3’ end processing of histone pre-mRNAs: It interacts with Lsm11 to form a docking platform for the polyadenylation factors, and it cooperates with SLBP to recruit U7 snRNP to histone pre-mRNA. (PMID:28289156)
• 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)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm10	ENSDARG00000101222
		ENSDARG00000109563
mus_musculus	Lsm10	ENSMUSG00000050188
drosophila_melanogaster	Lsm10	FBGN0033554
caenorhabditis_elegans	K07A1.15	WBGENE00010619

Protein

Protein identifiers

U7 snRNA-associated Sm-like protein LSm10 — Q969L4 (reviewed: Q969L4)

All UniProt accessions (1): Q969L4

UniProt curated annotations — full annotation on UniProt →

Function. Appears to function in the U7 snRNP complex that is involved in histone 3’-end 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 U7 snRNA. Binds to the downstream cleavage product (DCP) of histone pre-mRNA in a U7 snRNP dependent manner.

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. Interacts with CLNS1A and SMN.

Subcellular location. Nucleus.

Post-translational modifications. Not methylated. Methylation is not necessary for interaction with SMN.

Similarity. Belongs to the snRNP Sm proteins family.

RefSeq proteins (1): NP_116270* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR047575	Sm	Domain
IPR052840	U7_snRNA_Sm-like	Family

Pfam: PF01423

UniProt features (14 total): strand 8, helix 3, chain 1, domain 1, turn 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9NH5	ELECTRON MICROSCOPY	2.82
9NH6	ELECTRON MICROSCOPY	2.82
9N96	ELECTRON MICROSCOPY	3.18
6V4X	ELECTRON MICROSCOPY	3.2
9NB1	ELECTRON MICROSCOPY	3.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969L4-F1	88.30	0.73

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: 139 (showing top): 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, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_MRNA_3_END_PROCESSING, GOBP_REGULATION_OF_CELL_CYCLE_G1_S_PHASE_TRANSITION, chr1p34, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_CELL_CYCLE_G1_S_PHASE_TRANSITION, GOBP_RNA_CAPPING, GOBP_RNA_SPLICING

GO Biological Process (4): mRNA 3’-end processing by stem-loop binding and cleavage (GO:0006398), RNA splicing (GO:0008380), positive regulation of G1/S transition of mitotic cell cycle (GO:1900087), mRNA processing (GO:0006397)

GO Molecular Function (4): histone pre-mRNA DCP binding (GO:0071208), U7 snRNA binding (GO:0071209), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (7): nucleoplasm (GO:0005654), U7 snRNP (GO:0005683), Cajal body (GO:0015030), nuclear body (GO:0016604), cytoplasmic U snRNP body (GO:0071254), nucleus (GO:0005634), 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
RNA processing	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
mRNA metabolic process	1
RNA binding	1
snRNA binding	1
nucleic acid binding	1
binding	1
nuclear lumen	1
cellular anatomical structure	1
small nuclear ribonucleoprotein complex	1
nuclear ribonucleoprotein granule	1
nucleoplasm	1
intracellular membraneless organelle	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1673 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM10	LSM11	P83369	997
LSM10	SNRPD3	P43331	832
LSM10	SNRPD1	P13641	815
LSM10	SNRPE	P08578	809
LSM10	SNRPD2	P43330	795
LSM10	SLBP	Q14493	794
LSM10	ZNF473	Q8WTR7	781
LSM10	SYMPK	Q92797	743
LSM10	CPSF3	Q9UKF6	719
LSM10	NPAT	Q14207	715
LSM10	SNRPB	P14678	702
LSM10	CPSF2	Q9P2I0	684
LSM10	HINFP	Q9BQA5	635
LSM10	DDX20	Q9UHI6	631
LSM10	LSM1	O15116	624

IntAct

19 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
LSM10	LSM3	psi-mi:“MI:0915”(physical association)	0.780
LSM3	LSM10	psi-mi:“MI:0915”(physical association)	0.780
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
LSM6	PRMT5	psi-mi:“MI:0914”(association)	0.530
SNRPF	SNRPGP15	psi-mi:“MI:0914”(association)	0.530
SNRPE	PRMT5	psi-mi:“MI:0914”(association)	0.530
Smn1	CLNS1A	psi-mi:“MI:0914”(association)	0.350
TGS1	SEPTIN10	psi-mi:“MI:0914”(association)	0.350
Fbxo21	ESYT2	psi-mi:“MI:0914”(association)	0.350
SNRPGP15	GEMIN2	psi-mi:“MI:0914”(association)	0.350
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.350
SNRPD3	PRMT5	psi-mi:“MI:0914”(association)	0.350
CASP4	LSM10	psi-mi:“MI:0915”(physical association)	0.000
LSM3	LSM10	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (32): LSM10 (Affinity Capture-RNA), LSM10 (Affinity Capture-RNA), LSM10 (Two-hybrid), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Affinity Capture-MS), LSM10 (Protein-RNA), LSM10 (Protein-RNA), LSM10 (Protein-RNA), LSM10 (Protein-RNA), LSM10 (Two-hybrid)

ESM2 similar proteins: A1CE19, A1DM27, A4RQ29, A5DRQ6, A6R363, A6S5C9, A7F5M4, A7UXE4, A8NHT8, B0DWN3, O22823, O26745, O43080, O59734, O74966, O82221, O95777, P0CR24, P0CR25, P24715, P34659, P38203, P54999, P57743, P62312, P62313, Q0UWI9, Q0W8R9, Q12U30, Q1DRN0, Q24297, Q2HAN0, Q3ZCE0, Q465S1, Q4PG71, Q4WNI0, Q54RX0, Q54XP2, Q5RCP3, Q6BR90

Diamond homologs: F4K4E3, O14352, O35900, O44437, O59734, P40070, P43321, P62306, P62307, P62321, Q17348, Q19952, Q24297, Q3T0Z8, Q3ZBK6, Q43582, Q54KX4, Q552U1, Q55EX5, Q8QZX5, Q969L4, Q9LGE6, Q9LM92, Q9QXA5, Q9S7E6, Q9SUM2, Q9Y333, Q9Y4Z0, Q9ZRU9, A9CTE0, O94408, P38203, Q02260, Q1H595, Q54F84, Q54TF6, Q8SQK1, A5DRQ6, A6S5C9, A7F5M4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 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	6	292.8×	3e-13
snRNP Assembly	8	130.1×	1e-14
SARS-CoV-2 modulates host translation machinery	5	86.1×	2e-08
mRNA Splicing	6	50.7×	8e-09
Processing of Capped Intron-Containing Pre-mRNA	6	37.9×	3e-08
Metabolism of RNA	9	28.9×	3e-11
mRNA Splicing - Major Pathway	6	25.2×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	8	332.1×	5e-18
mRNA splicing, via spliceosome	6	39.2×	7e-08
RNA splicing	6	37.8×	7e-08

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

631 predictions. Top by Δscore:

Variant	Effect	Δscore
1:36397681:T:TA	donor_gain	1.0000
1:36397777:T:TA	donor_gain	1.0000
1:36397781:T:TA	donor_gain	1.0000
1:36397788:T:A	donor_gain	1.0000
1:36394150:CTTG:C	acceptor_gain	0.9900
1:36394154:C:CC	acceptor_gain	0.9900
1:36397682:C:A	donor_gain	0.9900
1:36397698:T:TA	donor_gain	0.9900
1:36397742:C:CA	donor_gain	0.9900
1:36397782:C:A	donor_gain	0.9900
1:36397789:C:A	donor_gain	0.9900
1:36394152:TG:T	acceptor_gain	0.9800
1:36397616:A:AC	donor_gain	0.9800
1:36397617:C:CC	donor_gain	0.9800
1:36397655:A:AC	donor_gain	0.9800
1:36397656:C:CC	donor_gain	0.9800
1:36397766:CCACG:C	donor_gain	0.9800
1:36397702:T:TA	donor_gain	0.9700
1:36397766:C:CT	donor_gain	0.9700
1:36394154:C:CA	acceptor_loss	0.9600
1:36394155:T:G	acceptor_loss	0.9600
1:36397766:CCA:C	donor_gain	0.9600
1:36394151:TTG:T	acceptor_gain	0.9500
1:36397617:CT:C	donor_gain	0.9400
1:36397761:ACCC:A	donor_loss	0.9400
1:36397763:CCA:C	donor_loss	0.9400
1:36397764:CACCA:C	donor_loss	0.9400
1:36397765:A:AC	donor_gain	0.9400
1:36397765:A:AT	donor_loss	0.9400
1:36397766:C:CC	donor_gain	0.9400

AlphaMissense

804 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:36393885:A:T	V82D	0.992
1:36393980:C:A	M50I	0.991
1:36393980:C:G	M50I	0.991
1:36393980:C:T	M50I	0.991
1:36393894:A:T	V79D	0.988
1:36394032:A:G	L33P	0.987
1:36393983:G:C	F49L	0.985
1:36393983:G:T	F49L	0.985
1:36393985:A:G	F49L	0.985
1:36394008:C:T	G41E	0.985
1:36393977:G:C	N51K	0.984
1:36393977:G:T	N51K	0.984
1:36394014:G:T	A39D	0.983
1:36393909:A:T	V74E	0.977
1:36393911:A:C	F73L	0.977
1:36393911:A:T	F73L	0.977
1:36393913:A:G	F73L	0.977
1:36393989:A:C	D47E	0.976
1:36393989:A:T	D47E	0.976
1:36394038:A:T	V31E	0.976
1:36394101:C:G	R10P	0.976
1:36393993:A:T	V46D	0.974
1:36393892:G:T	R80S	0.972
1:36394008:C:A	G41V	0.972
1:36394082:G:C	S16R	0.971
1:36394082:G:T	S16R	0.971
1:36394084:T:G	S16R	0.971
1:36393969:A:G	L54P	0.968
1:36393978:T:A	N51I	0.968
1:36394009:C:G	G41R	0.968

dbSNP variants (sampled 300 via entrez): RS1000103786 (1:36397878 C>T), RS1000966588 (1:36397649 A>C,G), RS1001250204 (1:36397896 G>A,C), RS1002101570 (1:36397061 C>G,T), RS1002153929 (1:36397378 G>A), RS1003624384 (1:36396040 T>G), RS1003831737 (1:36396057 C>A,T), RS1003958175 (1:36394213 C>T), RS1004393676 (1:36394480 C>G,T), RS1004481545 (1:36395213 T>A,C), RS1004535461 (1:36399713 C>A), RS1004917787 (1:36395440 C>A), RS1006883463 (1:36394188 A>C,G), RS1006962833 (1:36398160 G>C), RS1007577714 (1:36393537 T>C)

Disease associations

OMIM: gene MIM:617909 | disease phenotypes: MIM:617667

GenCC curated gene-disease

Mondo (1): Fraser syndrome 3 (MONDO:0054739)

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST005974_10	Neutrophil count	4.000000e-16
GCST008256_6	Diverticulitis	2.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
ICG 001	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
jinfukang	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Arsenic	affects methylation	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases expression	1
Asbestos, Crocidolite	increases expression	1
Sodium Selenite	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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