LSM8

Summary

LSM8 (LSM8 homolog, U6 small nuclear RNA associated, HGNC:20471) is a protein-coding gene on chromosome 7q31.31, encoding U6 snRNA-associated Sm-like protein LSm8 (O95777). Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

This gene encodes a member of the like-Sm family of proteins. The encoded protein consists of a closed barrel shape, made up of five anti-parallel beta strands and an alpha helix. This protein partners with six paralogs to form a heteroheptameric ring which transiently binds U6 small nuclear RNAs and is involved in the general maturation of RNA in the nucleus.

Source: NCBI Gene 51691 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 7 total
• GTEx eGene: eQTL in 34 tissues, sQTL in 19 (q < 0.05)
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.42 (unconstrained)
• MANE Select transcript: NM_016200

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20471
Approved symbol	LSM8
Name	LSM8 homolog, U6 small nuclear RNA associated
Location	7q31.31
Locus type	gene with protein product
Status	Approved
Aliases	YJR022W
Ensembl gene	ENSG00000128534
Ensembl biotype	protein_coding
OMIM	607288
Entrez	51691

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 14 protein_coding, 7 nonsense_mediated_decay

MANE Select: ENST00000249299

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 3, TSL 3: 1

ENST00000249299, ENST00000411938, ENST00000422760, ENST00000424702, ENST00000915332, ENST00000915333, ENST00001051892, ENST00001081197, ENST00001081198, ENST00001081200, ENST00001081201, ENST00001081202, ENST00001081204, ENST00001081205, ENST00001081206, ENST00001092148, ENST00001092149, ENST00001092150, ENST00001092151, ENST00001092152, ENST00001139439

RefSeq mRNA: 1 — MANE Select: NM_016200 NM_016200

CCDS: CCDS5775

Canonical transcript exons

ENST00000249299 — 4 exons

Exon	Start	End
ENSE00001018687	118185654	118185694
ENSE00001129736	118184164	118184254
ENSE00003785688	118188278	118188405
ENSE00004794881	118191912	118204035

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 93.97.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 82.2435 / max 839.3366, expressed in 1827 samples.

Highest expression (Bgee): calcaneal tendon, colonic epithelium, heart right ventricle, ventricular zone, monocyte.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LSM8 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 34 tissues and its splicing (sQTL) in 19 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 53 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	eqtl	2.7e-22	-0.24	7:118113342:G:GA
Adipose Subcutaneous	eqtl	5.0e-20	+0.28	7:118287350:GA:G
Muscle Skeletal	eqtl	5.5e-20	-0.30	7:118182326:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.7e-18	+0.21	7:118234254:C:T
Adipose Subcutaneous	sqtl	2.3e-15	-2.52	7:118181666:C:G
Whole Blood	eqtl	6.5e-14	-0.13	7:118214417:C:T
Spleen	eqtl	2.5e-12	+0.33	7:118241816:T:C
Lung	eqtl	3.4e-12	-0.20	7:118235480:T:C
Skin Sun Exposed Lower leg	sqtl	4.9e-11	-1.96	7:118181666:C:G
Testis	eqtl	8.1e-11	-0.21	7:118121617:G:A
Nerve Tibial	sqtl	8.3e-11	-1.90	7:118181666:C:G
Cells Cultured fibroblasts	eqtl	7.6e-10	+0.18	7:118182816:T:C
Artery Tibial	sqtl	1.4e-09	-2.03	7:118498100:G:A
Thyroid	sqtl	2.0e-09	-1.92	7:118181666:C:G
Artery Tibial	eqtl	2.7e-09	+0.58	7:118339516:C:A
Nerve Tibial	eqtl	3.5e-09	-0.38	7:118320146:C:T
Esophagus Muscularis	eqtl	6.2e-09	-0.19	7:118182326:T:C
Skin Not Sun Exposed Suprapubic	sqtl	1.6e-08	-1.74	7:118610615:G:A
Colon Transverse	sqtl	1.8e-08	-2.19	7:118181666:C:G
Stomach	eqtl	2.3e-08	-0.27	7:118235480:T:C

FANTOM5 promoters

3 alternative TSS:

Promoter ID	TPM avg	Samples expressed
80732	50.3253	1824
80731	31.8865	1822
80733	0.0317	5

Top tissues by expression

showing 100 of 288 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	93.97	gold quality
colonic epithelium	UBERON:0000397	92.01	gold quality
heart right ventricle	UBERON:0002080	91.89	gold quality
ventricular zone	UBERON:0003053	91.43	gold quality
monocyte	CL:0000576	91.23	gold quality
bone marrow	UBERON:0002371	91.23	gold quality
leukocyte	CL:0000738	91.16	gold quality
mononuclear cell	CL:0000842	91.16	gold quality
bone marrow cell	CL:0002092	90.90	gold quality
upper leg skin	UBERON:0004262	90.79	gold quality
granulocyte	CL:0000094	90.74	gold quality
oocyte	CL:0000023	90.41	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	90.20	gold quality
cartilage tissue	UBERON:0002418	90.15	gold quality
corpus epididymis	UBERON:0004359	90.07	gold quality
embryo	UBERON:0000922	90.02	gold quality
ganglionic eminence	UBERON:0004023	89.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.47	gold quality
blood vessel layer	UBERON:0004797	89.46	gold quality
tendon	UBERON:0000043	89.28	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.27	gold quality
bone element	UBERON:0001474	88.89	gold quality
vermiform appendix	UBERON:0001154	88.66	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.52	gold quality
oral cavity	UBERON:0000167	88.49	gold quality
skin of hip	UBERON:0001554	88.34	gold quality
colonic mucosa	UBERON:0000317	88.25	gold quality
adrenal tissue	UBERON:0018303	88.22	gold quality
seminal vesicle	UBERON:0000998	87.82	gold quality
biceps brachii	UBERON:0001507	87.51	gold quality
cortical plate	UBERON:0005343	87.51	gold quality
spleen	UBERON:0002106	87.50	gold quality
nasal cavity mucosa	UBERON:0001826	87.24	gold quality
lymph node	UBERON:0000029	87.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.07	gold quality
cauda epididymis	UBERON:0004360	87.05	gold quality
mammalian vulva	UBERON:0000997	86.75	gold quality
trabecular bone tissue	UBERON:0002483	86.74	gold quality
jejunal mucosa	UBERON:0000399	86.65	gold quality
connective tissue	UBERON:0002384	86.63	gold quality
body of pancreas	UBERON:0001150	86.59	gold quality
adipose tissue	UBERON:0001013	86.55	gold quality
endometrium	UBERON:0001295	86.55	gold quality
tonsil	UBERON:0002372	86.55	gold quality
mucosa of stomach	UBERON:0001199	86.50	gold quality
periodontal ligament	UBERON:0008266	86.24	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.14	gold quality
caecum	UBERON:0001153	86.05	gold quality
penis	UBERON:0000989	85.97	gold quality
right lobe of thyroid gland	UBERON:0001119	85.76	gold quality
subcutaneous adipose tissue	UBERON:0002190	85.67	gold quality
mucosa of transverse colon	UBERON:0004991	85.62	gold quality
duodenum	UBERON:0002114	85.60	gold quality
small intestine	UBERON:0002108	85.47	gold quality
synovial joint	UBERON:0002217	85.41	gold quality
intestine	UBERON:0000160	85.38	gold quality
left lobe of thyroid gland	UBERON:0001120	85.33	gold quality
mucosa of paranasal sinus	UBERON:0005030	85.33	gold quality
rectum	UBERON:0001052	85.31	gold quality
large intestine	UBERON:0000059	85.23	gold quality
minor salivary gland	UBERON:0001830	85.23	gold quality
layer of synovial tissue	UBERON:0007616	85.11	gold quality
colon	UBERON:0001155	85.10	gold quality
superficial temporal artery	UBERON:0001614	85.09	gold quality
uterus	UBERON:0000995	85.05	gold quality
thyroid gland	UBERON:0002046	85.02	gold quality
adipose tissue of abdominal region	UBERON:0007808	84.91	gold quality
esophagus mucosa	UBERON:0002469	84.87	gold quality
transverse colon	UBERON:0001157	84.83	gold quality
right lung	UBERON:0002167	84.75	gold quality
mouth mucosa	UBERON:0003729	84.73	gold quality
tibial artery	UBERON:0007610	84.70	gold quality
lower lobe of lung	UBERON:0008949	84.70	gold quality
bronchial epithelial cell	CL:0002328	84.67	gold quality
popliteal artery	UBERON:0002250	84.67	gold quality
adult organism	UBERON:0007023	84.62	gold quality
descending thoracic aorta	UBERON:0002345	84.60	gold quality
caput epididymis	UBERON:0004358	84.60	gold quality
body of stomach	UBERON:0001161	84.53	gold quality
urethra	UBERON:0000057	84.52	gold quality
omental fat pad	UBERON:0010414	84.51	gold quality
peritoneum	UBERON:0002358	84.50	gold quality
zone of skin	UBERON:0000014	84.45	gold quality
pancreas	UBERON:0001264	84.39	gold quality
aorta	UBERON:0000947	84.38	gold quality
body of uterus	UBERON:0009853	84.38	gold quality
upper lobe of lung	UBERON:0008948	84.36	gold quality
skin of abdomen	UBERON:0001416	84.27	gold quality
upper lobe of left lung	UBERON:0008952	84.22	gold quality
female reproductive system	UBERON:0000474	84.21	gold quality
urinary bladder	UBERON:0001255	84.16	gold quality
esophagus	UBERON:0001043	84.12	gold quality
right ovary	UBERON:0002118	84.12	gold quality
metanephros cortex	UBERON:0010533	84.10	gold quality
muscle of leg	UBERON:0001383	84.05	gold quality
jejunum	UBERON:0002115	84.05	gold quality
ascending aorta	UBERON:0001496	84.04	gold quality
thoracic aorta	UBERON:0001515	84.04	gold quality
ectocervix	UBERON:0012249	84.02	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.77
E-MTAB-6386	no	291.18

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	47.4
Caudate putamen	tissue	43.7
Bone marrow	tissue	42.2	low
Putamen	tissue	27.2
Lymph node	tissue	26.9	medium
Pons	tissue	26.1
Tonsil	tissue	25.7	medium
Superior colliculi	tissue	24.0
Medulla oblongata	tissue	23.1
Thalamus	tissue	22.3
Hippocampal formation	tissue	22.2
Hypothalamus	tissue	22.0
Midbrain	tissue	21.8
Spinal cord	tissue	21.6
Septum	tissue	21.3
Appendix	tissue	21.0	low
Periaqueductal gray	tissue	20.7
Substantia nigra	tissue	20.6
Pancreas	tissue	19.8	medium
Corpus callosum	tissue	19.3
Spleen	tissue	18.8	low
Cerebellum	tissue	18.7	medium
Ventral forebrain	tissue	18.4
Basal ganglia	tissue	18.0	not detected
Nucleus accumbens	tissue	17.8
Cerebral cortex	tissue	17.5	low
Occipital cortex	tissue	17.5
Thymus	tissue	17.0
Somatosensory cortex	tissue	16.3
Motor cortex	tissue	15.8
Epididymis	tissue	15.7	medium
Postcentral gyrus	tissue	15.6
Retina	tissue	15.4
Choroid plexus	tissue	15.4
Skeletal muscle	tissue	15.3	medium
Hippocampus	tissue	14.8	low
Entorhinal cortex	tissue	14.8
Small intestine	tissue	14.6	medium
Duodenum	tissue	14.5	medium
Olfactory bulb	tissue	14.5
Retrosplenial cortex	tissue	14.4
Vagina	tissue	14.3	medium
Retrosplenial and cingulate cortex	tissue	14.2
Colon	tissue	13.9	medium
Breast	tissue	13.6	low
Stomach 1	tissue	13.4	medium
Skin 1	tissue	13.3	medium
Rectum	tissue	13.3	medium
Locus coeruleus	tissue	13.3
Prefrontal cortex	tissue	13.2
Temporal cortex	tissue	13.2
Amygdala	tissue	13.0
Insular cortex	tissue	12.2
Pituitary gland	tissue	11.7
Adipose tissue	tissue	11.3	low
Endometrium 1	tissue	11.3	low
Urinary bladder	tissue	10.6	medium
Adrenal gland	tissue	10.3	high
Lung	tissue	10.1	medium
Ovary	tissue	9.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Cerebellar cortex (36.8), Flocculonodular lobe (35.0), Vermis (31.3), Parieto-temporal junction (white matter) (23.5), Temporal white matter (23.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LSM8 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 426 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-4668-3P	100.00	68.74	2635

Functional genomics

gnomAD constraint: pLI 6.25e-05, LOEUF 1.42, missense Z 0.964 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000249299 — one region, missense o/e 0.78. DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): DAN-G (-3.277), SNU-475 (-3.085), SCC-4 (-2.947), TE-10 (-2.945), HCC1143 (-2.945), Detroit 562 (-2.908), JHH-6 (-2.877), CAL-120 (-2.858), NIH:OVCAR-3 (-2.789), NCI-N87 (-2.778), TUHR14TKB (-2.716), COR-L311 (-2.71), LU99 (-2.694), KP-N-SI9s (-2.653), SNU-245 (-2.634).

Literature-anchored findings (GeneRIF, showing 1)

• LSm8 controls nuclear accumulation of all LSm2-7 proteins and the number of cytoplasmic processing bodies. (PMID:22875987)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm8	ENSDARG00000091656
mus_musculus	Lsm8	ENSMUSG00000044155
rattus_norvegicus	Lsm8	ENSRNOG00000070946
drosophila_melanogaster	CG2021	FBGN0035271
caenorhabditis_elegans		WBGENE00003082

Paralogs (1): LSM1 (ENSG00000175324)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1923772) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
enlarged lymph nodes	1
small seminal vesicle	1
abnormal seminal vesicle morphology	1
abnormal lymph node morphology	1
increased circulating alanine transaminase level	1
increased circulating serum albumin level	1
increased circulating creatinine level	1
increased blood urea nitrogen level	1
increased circulating total protein level	1
preweaning lethality, complete penetrance	1
embryonic lethality prior to organogenesis	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZCE0	100.0%	Diamond
Pongo abelii	Q5R6I0	100.0%	Diamond
Macaca fascicularis	Q60HD3	100.0%	Diamond
Erinaceus europaeus	Q9TU67	98.8%	Diamond
Monodelphis domestica	Q9TU66	95.0%	Diamond
Notamacropus eugenii	Q9N1Q0	94.8%	Diamond
Thermoplasma volcanium GSS1	Q97BU5	92.6%	Diamond
Gallus gallus	Q9PV94	92.1%	Diamond
Medicago sativa	P24715	86.8%	Diamond
Methanococcoides burtonii DSM 6242	Q12U30	80.6%	Diamond
Arabidopsis thaliana	Q8LFL8	79.7%	Diamond
Methanocella arvoryzae MRE50	Q0W8R9	72.2%	Diamond
Schizosaccharomyces pombe 972h-	P87173	61.0%	Diamond
Dictyostelium discoideum	Q54HF6	60.0%	Diamond
Saccharomyces cerevisiae S288C	Q12330	58.9%	Diamond
Aeropyrum pernix K1	Q9YEQ5	46.8%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SQH7	40.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
ANKRD7	protein-coding	56311
CFTR	protein-coding	1080
CFTR-AS1	ncRNA	111082987
CFTR-AS2	ncRNA	140577507
CTTNBP2	protein-coding	83992

Protein

Protein identifiers

U6 snRNA-associated Sm-like protein LSm8 — O95777 (reviewed: O95777)

All UniProt accessions (5): O95777, A4D0W0, C9JIZ0, C9JNV3, F2Z2Y6

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3’-terminal U-tract of U6 snRNA.

Subunit / interactions. Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome.

Subcellular location. Nucleus.

Similarity. Belongs to the snRNP Sm proteins family.

RefSeq proteins (1): NP_057284* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR034103	Lsm8	Domain
IPR044642	PTHR15588	Family
IPR047575	Sm	Domain

Pfam: PF01423

UniProt features (16 total): strand 7, helix 3, turn 2, initiator methionine 1, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

21 structures by resolution:

PDB	Title	Method	Resolution (Å)
8H6L	Cryo-EM structure of human exon-defined spliceosome in the early B state.	ELECTRON MICROSCOPY	2.6
8H6K	Cryo-EM structure of human exon-defined spliceosome in the mature B state.	ELECTRON MICROSCOPY	2.7
6QW6	Structure of the human U5.U4/U6 tri-snRNP at 2.9A resolution.	ELECTRON MICROSCOPY	2.92
9XU3	Human minor spliceosome exon-ligation-ready C* complex (prior to step-II)	ELECTRON MICROSCOPY	3
8H6E	Cryo-EM structure of human exon-defined spliceosome in the late pre-B state.	ELECTRON MICROSCOPY	3.2
8H6J	Cryo-EM structure of human exon-defined spliceosome in the mature pre-B state.	ELECTRON MICROSCOPY	3.25
6QX9	Structure of a human fully-assembled precatalytic spliceosome (pre-B complex).	ELECTRON MICROSCOPY	3.28
6AHD	The Cryo-EM Structure of Human Pre-catalytic Spliceosome (B complex) at 3.8 angstrom …	ELECTRON MICROSCOPY	3.8
8QZS	Cryo-EM structure of the cross-exon B-like complex	ELECTRON MICROSCOPY	4.1
8R09	Cryo-EM structure of the cross-exon pre-B+5’ss+ATPgammaS complex	ELECTRON MICROSCOPY	4.3
8R0B	Cryo-EM structure of the cross-exon pre-B+ATP complex	ELECTRON MICROSCOPY	4.4
5O9Z	Cryo-EM structure of a pre-catalytic human spliceosome primed for activation (B complex)	ELECTRON MICROSCOPY	4.5
8QO9	Cryo-EM structure of a human spliceosomal B complex protomer	ELECTRON MICROSCOPY	5.29
6AH0	The Cryo-EM Structure of the Precusor of Human Pre-catalytic Spliceosome (pre-B complex)	ELECTRON MICROSCOPY	5.7
8R0A	Cryo-EM structure of the cross-exon pre-B+5’ss complex	ELECTRON MICROSCOPY	5.8
8R08	Cryo-EM structure of the cross-exon pre-B+AMPPNP complex	ELECTRON MICROSCOPY	6.1
8RM5	Cryo-EM structure of the cross-exon pre-B+5’ssLNG+ATPyS complex	ELECTRON MICROSCOPY	6.9
3JCR	3D structure determination of the human*U4/U6.U5* tri-snRNP complex	ELECTRON MICROSCOPY	7
7ABG	Human pre-Bact-1 spliceosome	ELECTRON MICROSCOPY	7.8
9R8V	Cryo-EM structure of the human pre-Bact-OTS complex (whole map)	ELECTRON MICROSCOPY	8.5
8QXD	Cryo-EM structure of the cross-exon pre-B complex	ELECTRON MICROSCOPY	9.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95777-F1	95.53	0.94

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; vesicles

Antibody reliability (HPA): IH uncertain · IF approved

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 (1)

Type	Positions
N-acetylthreonine	2

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—

MSigDB gene sets: 161 (showing top): TGCGCANK_UNKNOWN, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GNF2_FBL, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_13, REACTOME_MRNA_SPLICING, DODD_NASOPHARYNGEAL_CARCINOMA_UP, BASAKI_YBX1_TARGETS_DN, SCHLINGEMANN_SKIN_CARCINOGENESIS_TPA_UP, DANG_BOUND_BY_MYC, RIGGI_EWING_SARCOMA_PROGENITOR_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS

GO Biological Process (5): spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (4): RNA binding (GO:0003723), mRNA binding (GO:0003729), U6 snRNA binding (GO:0017070), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), U6 snRNP (GO:0005688), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), precatalytic spliceosome (GO:0071011), Lsm2-8 complex (GO:0120115), spliceosomal complex (GO:0005681), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

3 top-level categories:

Category	Pathways
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

29 GO namespaces:

Category	Terms
RNA processing	2
spliceosomal snRNP assembly	1
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
RNA binding	1
snRNA binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal snRNP complex	1
Lsm2-8 complex	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
spliceosomal complex	1
Sm-like protein family complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA splicing, via spliceosome	BP	direct assay
Lsm2-8 complex	CC	direct assay
U2-type precatalytic spliceosome	CC	direct assay
U4/U6 x U5 tri-snRNP complex	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,558 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM8	LSM7	Q9UK45	995
LSM8	LSM4	Q9Y4Z0	994
LSM8	LSM3	P62310	993
LSM8	LSM6	P62312	993
LSM8	LSM5	Q9Y4Y9	990
LSM8	LSM2	Q9Y333	986
LSM8	SNRPD2	P43330	953
LSM8	XRN1	Q8IZH2	911
LSM8	SNRPE	P08578	899
LSM8	SNRPD3	P43331	891
LSM8	SNRPD1	P13641	884
LSM8	NAA38	Q9BRA0	810
LSM8	LSM10	Q969L4	642
LSM8	USB1	Q9BQ65	627
LSM8	SART3	Q15020	615

IntAct

Human interaction partners of LSM8 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 59 partners by confidence:

Partner	Interaction type	MIscore	Records
LSM2	physical association	0.790	8
LSM3	physical association	0.780	6
HTT	physical association	0.560	15
PRKN	physical association	0.560	6
TARDBP	physical association	0.560	6
DCTN1	physical association	0.560	3
PMP22	physical association	0.560	3
SNCA	physical association	0.560	3
SOD1	physical association	0.560	3
UCHL1	physical association	0.560	3
SNRPB	physical association	0.550	1
ARNT	physical association	0.370	1
BCKDK	physical association	0.370	1
ECHDC2	physical association	0.370	1
EFTUD2	physical association	0.370	1
HSPA9	physical association	0.370	1
MAPK8IP2	physical association	0.370	1
MGA	physical association	0.370	1
MPRIP	physical association	0.370	1
NME4	physical association	0.370	1
PHF11	physical association	0.370	1
RBM5	physical association	0.370	1
RSC1A1	physical association	0.370	1
SEPTIN10	physical association	0.370	1
SMU1	physical association	0.370	1
SNRNP200	physical association	0.370	1
UBE2E3	physical association	0.370	1
LSM4	physical association	0.000	5
LSM6	physical association	0.000	3
ALYREF	physical association	0.000	1

BioGRID (153 interactions; top human partners by supporting records): LSM2 (Two-hybrid; 8 records), LSM4 (Affinity Capture-MS; 8 records), LSM6 (Affinity Capture-MS; 7 records), LSM3 (Affinity Capture-MS; 6 records), SART3 (Affinity Capture-MS; 5 records), PRPF4 (Affinity Capture-MS; 4 records), EFTUD2 (Affinity Capture-MS; 3 records), LSM5 (Affinity Capture-MS; 3 records), LSM7 (Affinity Capture-MS; 3 records), SNRPB (Affinity Capture-MS; 3 records), SNRPF (Affinity Capture-MS; 3 records), PRPF3 (Affinity Capture-MS; 2 records), RBM5 (Two-hybrid; 2 records), SMU1 (Two-hybrid; 2 records), SNRNP200 (Two-hybrid; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
LSM8	“form complex”	“U4/U6.U5 snRNP complex”	binding

Protein complexes (CORUM) (5)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

5 complexes by size:

Complex	Subunits	Members
Spliceosome, B complex	43	EFTUD2, MFAP1, PRPF3, PRPF6, SF3B3, SF3B4, SF3B6, SNRNP40, LSM2, LSM4, LSM7, SF3B1, SNRPB, SNRPD1, SNRPD3, SNRPE, LSM6, SMU1, SNU13, PHF5A, SNRPB2, SNRPF, SF3A1, SNRPD2, TXNL4A, UBL5, WBP4, LSM3, PPIH, PRPF38A, SF3A3, LSM5, PRPF4, PRPF8, SF3A2, SF3B2, SNRNP200, SNRPA1, SNRPG, LSM8, PRPF31, SART1, ZMAT2
Spliceosome, pre-B complex	38	SF3A3, SF3B4, SNRPD1, EFTUD2, LSM8, PRPF8, PRPF31, SF3A1, SF3A2, LSM3, PHF5A, SF3B1, SF3B2, SNRPA1, SNRPD2, SNRPF, SNU13, PRPF4, SF3B6, SNRNP200, SNRPB2, SNRPE, USP39, LSM4, LSM5, PRPF3, PRPF6, SF3B3, SNRNP40, SNRPG, TXNL4A, DDX23, LSM6, LSM7, SF3B5, SNRPD3, SNRPB, LSM2
★ Emerin complex 52	23	DDX39A, ILF3, LEMD3, RBL2, H1-1, HNRNPK, HNRNPU, IQGAP1, NMI, PDCD4, SNRPD1, THRA, API5, CKB, EMD, HDGF, LSM8, YWHAQ, ACTB, C1QBP, HNRNPL, LMNB1, YWHAE
Emerin complex 25	16	EMD, G3BP1, SAP130, SSB, BCCIP, LMNB1, LSM8, SNRPD1, YWHAE, BANF1, CDC37, LSM2, ACTB, HNRNPK, YWHAB, ZRANB2
LSm2-8 complex	7	LSM5, LSM6, LSM7, LSM8, LSM2, LSM3, LSM4

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
mRNA decay by 5’ to 3’ exoribonuclease	6	101.5×	1e-09
mRNA Splicing	8	19.5×	2e-07
mRNA Splicing - Major Pathway	15	18.2×	2e-13
Processing of Capped Intron-Containing Pre-mRNA	8	14.6×	2e-06
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	5	10.8×	2e-03
Metabolism of RNA	8	7.4×	3e-04
Dengue Virus-Host Interactions	6	6.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	15	25.4×	6e-15
RNA splicing	9	14.7×	2e-06

Disease & clinical

Genetic variants

Variant evidence for LSM8: 7 ClinVar records (0 pathogenic / likely pathogenic); 13 GWAS associations.

ClinVar

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

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 21 predictions of 614):

Position(s)	Effect	Δscore	Sites
7:118184298	donor_gain	0.9900
7:118184323	donor_gain	0.9900
7:118188275–118188277	acceptor_loss	0.9900	7
7:118188406–118188407	donor_loss	0.9900	6
7:118188410	donor_loss	0.9800
7:118192005	donor_gain	0.9800
7:118192032	donor_gain	0.9800
7:118188410	donor_loss	0.9700
7:118192087	donor_gain	0.9700
7:118184278	donor_gain	0.9600

AlphaMissense

330 missense substitutions predicted likely pathogenic (of 615 scored), across 80 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D31	8	0.996	0.998
D19	8	0.976	0.994
N35	8	0.949	0.999
D65	8	0.875	0.982
D78	8	0.841	0.965
E43	7	0.986	0.996
F46	7	0.986	0.996
F30	7	0.935	0.995
Q32	7	0.840	0.900
D74	7	0.720	0.862
G64	6	0.997	0.999
R63	6	0.986	0.999
G29	6	0.984	0.999
R21	6	0.982	0.997
G20	6	0.980	0.998
I37	6	0.949	0.998
T17	6	0.914	0.993
K28	6	0.889	0.983
N66	6	0.836	0.983
H42	6	0.783	0.992

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Chromophobe (TCGA)	unfavorable	4.38e-05
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000254

Disease associations

OMIM: gene MIM:607288 | disease phenotypes:

GWAS associations

13 associations:

Study	Trait	p-value
GCST90011770_37	Glaucoma (primary open-angle)	8e-17
GCST011703_84	Smoking initiation	5e-16
GCST011704_5	Smoking status (current vs never)	7e-9
GCST90011766_7	Glaucoma (primary open-angle)	9e-9
GCST006065_3	Glaucoma (primary open-angle)	1e-8
GCST005580_255	Intraocular pressure	2e-8
GCST006436_4	Triglyceride levels	2e-8
GCST007831_1	Anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	2e-7
GCST002408_2	Response to methotrexate in juvenile idiopathic arthritis	5e-7
GCST007624_6	Positive urgency	9e-7
GCST007851_2	Anti-thyroid peroxidase (TPOAb) and anti-thyroglobulin (TgAb) levels in Hashimoto’s thyroiditis	2e-6
GCST008368_3	Plasma anti-thyroid peroxidase levels	4e-6
GCST002408_3	Response to methotrexate in juvenile idiopathic arthritis	6e-6

EFO canonical traits (from GWAS)

5 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0004530	triglyceride measurement
EFO:0006946	behavioural disinhibition measurement
EFO:0005670	smoking initiation
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465283 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	5
bisphenol A	increases expression, increases methylation	2
trichostatin A	affects cotreatment, decreases expression	2
entinostat	decreases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
methylmercuric chloride	decreases expression	1
sodium arsenate	increases expression	1
arsenite	affects binding, increases reaction	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Hydrogen Peroxide	decreases expression, affects cotreatment	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	increases abundance, affects expression	1
Plant Extracts	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Theophylline	affects cotreatment, decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5338445	Binding	Binding affinity to Lsm8 (unknown origin) at 200 uM preincubated for 2 hrs followed by pronase addition and measured after 30 mins by coomassie blue staining based SDS-PAGE gel analysis	Structurally Diverse Alkaloids with Anti-Renal-Fibrosis Activity from the Centipede Scolopendra subspinipes mutilans. — *J Nat Prod*

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LSM8 across ~30M SureChEMBL compounds — explore on Sugi Predict.