LSM7

Summary

LSM7 (LSM7 homolog, U6 small nuclear RNA and mRNA degradation associated, HGNC:20470) is a protein-coding gene on chromosome 19p13.3, encoding U6 snRNA-associated Sm-like protein LSm7 (Q9UK45). 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 99.8% of cancer cell lines).

Sm-like proteins were identified in a variety of organisms based on sequence homology with the Sm protein family (see SNRPD2; MIM 601061). Sm-like proteins contain the Sm sequence motif, which consists of 2 regions separated by a linker of variable length that folds as a loop. The Sm-like proteins are thought to form a stable heteromer present in tri-snRNP particles, which are important for pre-mRNA splicing.

Source: NCBI Gene 51690 — RefSeq curated summary.

At a glance

• Gene–disease (curated): leukodystrophy (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 19 total — 2 pathogenic, 1 likely-pathogenic
• GTEx eGene: eQTL in 49 tissues, sQTL in 14 (q < 0.05)
• Phenotypes (HPO): 29
• Cancer dependency (DepMap): dependent in 99.8% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.73 (unconstrained)
• MANE Select transcript: NM_016199
• Interaction hub: 2,151 STRING partners (top 6% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20470
Approved symbol	LSM7
Name	LSM7 homolog, U6 small nuclear RNA and mRNA degradation associated
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	YNL147W
Ensembl gene	ENSG00000130332
Ensembl biotype	protein_coding
OMIM	607287
Entrez	51690

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 12 protein_coding, 8 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000252622

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 2

ENST00000252622, ENST00000585395, ENST00000585409, ENST00000587502, ENST00000589532, ENST00000591515, ENST00000591745, ENST00000932498, ENST00000932499, ENST00001006753, ENST00001026094, ENST00001059905, ENST00001059906, ENST00001059908, ENST00001059909, ENST00001059913, ENST00001059919, ENST00001059923, ENST00001103393, ENST00001103394, ENST00001103395, ENST00001103396, ENST00001142748

RefSeq mRNA: 1 — MANE Select: NM_016199 NM_016199

CCDS: CCDS45907

Canonical transcript exons

ENST00000252622 — 4 exons

Exon	Start	End
ENSE00000876654	2328387	2328477
ENSE00001623592	2328561	2328586
ENSE00003542372	2324125	2324196
ENSE00003627718	2321521	2321822

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 98.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.9422 / max 553.9949, expressed in 1815 samples.

Highest expression (Bgee): mucosa of transverse colon, granulocyte, ganglionic eminence, pituitary gland, embryo.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LSM7 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 49 tissues and its splicing (sQTL) in 14 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 63 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	7.8e-64	+0.37	19:2325420:CCT:C
Lung	eqtl	1.3e-53	+0.31	19:2325420:CCT:C
Nerve Tibial	eqtl	2.9e-47	+0.28	19:2326898:C:T
Whole Blood	eqtl	8.2e-40	+0.21	19:2325420:CCT:C
Adipose Subcutaneous	eqtl	3.7e-38	+0.24	19:2326898:C:T
Spleen	eqtl	3.0e-37	+0.44	19:2325420:CCT:C
Skin Sun Exposed Lower leg	eqtl	1.2e-31	+0.21	19:2326898:C:T
Adipose Visceral Omentum	eqtl	1.3e-30	+0.24	19:2325420:CCT:C
Artery Tibial	eqtl	5.2e-30	+0.18	19:2326903:G:A
Skin Not Sun Exposed Suprapubic	eqtl	2.1e-29	+0.24	19:2326898:C:T
Pituitary	eqtl	4.8e-28	+0.45	19:2329604:C:G
Heart Atrial Appendage	eqtl	8.7e-26	+0.28	19:2326903:G:A
Brain Cerebellum	eqtl	1.2e-25	+0.45	19:2325420:CCT:C
Prostate	eqtl	1.2e-24	+0.41	19:2326903:G:A
Esophagus Mucosa	eqtl	2.9e-24	+0.22	19:2325420:CCT:C
Brain Frontal Cortex BA9	eqtl	1.6e-23	+0.36	19:2325420:CCT:C
Breast Mammary Tissue	eqtl	1.1e-20	+0.21	19:2325420:CCT:C
Brain Cerebellar Hemisphere	eqtl	1.6e-20	+0.27	19:2346442:G:A
Esophagus Muscularis	eqtl	5.3e-20	+0.21	19:2326898:C:T
Pancreas	eqtl	7.1e-20	+0.29	19:2325420:CCT:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
178162	31.9422	1815

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	98.37	gold quality
granulocyte	CL:0000094	98.32	gold quality
ganglionic eminence	UBERON:0004023	97.82	gold quality
pituitary gland	UBERON:0000007	97.76	gold quality
embryo	UBERON:0000922	97.76	gold quality
ventricular zone	UBERON:0003053	97.70	gold quality
spleen	UBERON:0002106	97.60	gold quality
adenohypophysis	UBERON:0002196	97.60	gold quality
lower esophagus mucosa	UBERON:0035834	97.46	gold quality
monocyte	CL:0000576	97.33	gold quality
cortical plate	UBERON:0005343	97.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.25	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.23	gold quality
left ovary	UBERON:0002119	97.22	gold quality
mononuclear cell	CL:0000842	97.12	gold quality
lymph node	UBERON:0000029	97.10	gold quality
endocervix	UBERON:0000458	97.10	gold quality
adult organism	UBERON:0007023	97.10	gold quality
leukocyte	CL:0000738	97.07	gold quality
right ovary	UBERON:0002118	96.95	gold quality
ectocervix	UBERON:0012249	96.92	gold quality
transverse colon	UBERON:0001157	96.89	gold quality
right uterine tube	UBERON:0001302	96.73	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.67	gold quality
spinal cord	UBERON:0002240	96.60	gold quality
colonic mucosa	UBERON:0000317	96.59	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.57	gold quality
oral cavity	UBERON:0000167	96.51	gold quality
left uterine tube	UBERON:0001303	96.48	gold quality
caudate nucleus	UBERON:0001873	96.46	gold quality
body of uterus	UBERON:0009853	96.40	gold quality
stromal cell of endometrium	CL:0002255	96.38	gold quality
vermiform appendix	UBERON:0001154	96.37	gold quality
small intestine	UBERON:0002108	96.37	gold quality
nucleus accumbens	UBERON:0001882	96.30	gold quality
esophagus mucosa	UBERON:0002469	96.29	gold quality
skin of abdomen	UBERON:0001416	96.25	gold quality
metanephros cortex	UBERON:0010533	96.14	gold quality
caecum	UBERON:0001153	96.02	gold quality
body of stomach	UBERON:0001161	96.02	gold quality
amygdala	UBERON:0001876	96.01	gold quality
left coronary artery	UBERON:0001626	96.00	gold quality
sigmoid colon	UBERON:0001159	95.97	gold quality
trabecular bone tissue	UBERON:0002483	95.97	gold quality
right lobe of thyroid gland	UBERON:0001119	95.92	gold quality
ascending aorta	UBERON:0001496	95.91	gold quality
large intestine	UBERON:0000059	95.88	gold quality
peritoneum	UBERON:0002358	95.88	gold quality
omental fat pad	UBERON:0010414	95.88	gold quality
coronary artery	UBERON:0001621	95.87	gold quality
colon	UBERON:0001155	95.86	gold quality
thoracic aorta	UBERON:0001515	95.86	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.84	gold quality
bone marrow	UBERON:0002371	95.83	gold quality
right lobe of liver	UBERON:0001114	95.77	gold quality
intestine	UBERON:0000160	95.74	gold quality
skin of leg	UBERON:0001511	95.74	gold quality
cerebellar hemisphere	UBERON:0002245	95.74	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.73	gold quality
minor salivary gland	UBERON:0001830	95.72	gold quality
cerebellar cortex	UBERON:0002129	95.71	gold quality
right coronary artery	UBERON:0001625	95.69	gold quality
duodenum	UBERON:0002114	95.64	gold quality
esophagus	UBERON:0001043	95.58	gold quality
tibial nerve	UBERON:0001323	95.44	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.44	gold quality
left lobe of thyroid gland	UBERON:0001120	95.42	gold quality
right adrenal gland	UBERON:0001233	95.40	gold quality
mouth mucosa	UBERON:0003729	95.39	gold quality
upper lobe of left lung	UBERON:0008952	95.39	gold quality
putamen	UBERON:0001874	95.36	gold quality
nasal cavity mucosa	UBERON:0001826	95.35	gold quality
aorta	UBERON:0000947	95.34	gold quality
body of pancreas	UBERON:0001150	95.30	gold quality
lower esophagus	UBERON:0013473	95.27	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.26	gold quality
right adrenal gland cortex	UBERON:0035827	95.25	gold quality
cerebellum	UBERON:0002037	95.21	gold quality
fundus of stomach	UBERON:0001160	95.12	gold quality
cingulate cortex	UBERON:0003027	95.10	gold quality
zone of skin	UBERON:0000014	95.09	gold quality
left adrenal gland cortex	UBERON:0035825	95.05	gold quality
right frontal lobe	UBERON:0002810	95.03	gold quality
anterior cingulate cortex	UBERON:0009835	95.03	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.02	gold quality
right atrium auricular region	UBERON:0006631	95.02	gold quality
upper lobe of lung	UBERON:0008948	94.98	gold quality
popliteal artery	UBERON:0002250	94.97	gold quality
tibial artery	UBERON:0007610	94.97	gold quality
left adrenal gland	UBERON:0001234	94.96	gold quality
myometrium	UBERON:0001296	94.96	gold quality
apex of heart	UBERON:0002098	94.94	gold quality
pericardium	UBERON:0002407	94.91	gold quality
skin of hip	UBERON:0001554	94.85	gold quality
penis	UBERON:0000989	94.83	gold quality
adrenal cortex	UBERON:0001235	94.83	gold quality
thymus	UBERON:0002370	94.79	gold quality
mammalian vulva	UBERON:0000997	94.78	gold quality
oocyte	CL:0000023	94.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	50.08
E-CURD-122	yes	19.06
E-MTAB-10042	yes	13.51
E-ANND-3	no	0.00

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	122.8
Bone marrow	tissue	105.4	low
Caudate putamen	tissue	101.4
Pituitary gland	tissue	87.1
Ovary	tissue	73.7	not detected
Vagina	tissue	73.7	not detected
Thymus	tissue	72.2
Colon	tissue	66.6	medium
Lymph node	tissue	66.1	low
Duodenum	tissue	58.4	not detected
Small intestine	tissue	57.6	medium
Stomach 1	tissue	49.8	medium
Appendix	tissue	48.5	low
Skeletal muscle	tissue	47.7	low
Spleen	tissue	46.7	low
Tonsil	tissue	43.2	low
Urinary bladder	tissue	42.0	medium
Fallopian tube	tissue	39.2	low
Salivary gland	tissue	37.4	low
Placenta	tissue	36.1	medium
Cervix	tissue	34.3	not detected
Adipose tissue	tissue	33.3	medium
Breast	tissue	32.1	medium
Liver	tissue	31.2	low
Parathyroid gland	tissue	31.1	medium
Postcentral gyrus	tissue	31.1
Rectum	tissue	30.6	low
Adrenal gland	tissue	30.5	high
Seminal vesicle	tissue	30.0	medium
Tongue	tissue	28.8
Locus coeruleus	tissue	27.4
Pancreas	tissue	26.7	not detected
Endometrium 1	tissue	26.7	low
Prostate	tissue	26.7	low
Smooth muscle	tissue	26.4	medium
Nucleus accumbens	tissue	23.5
Heart muscle	tissue	23.1	low
Lung	tissue	22.6	high
Esophagus	tissue	22.3	not detected
Kidney	tissue	22.1	medium
Skin 1	tissue	21.9	low
Epididymis	tissue	21.6	not detected
Hippocampus	tissue	20.7	high
Choroid plexus	tissue	19.9
Gallbladder	tissue	19.4	low
Testis	tissue	18.6	high
Thyroid gland	tissue	18.1	low
Spinal cord	tissue	16.3
Medulla oblongata	tissue	16.0
Pons	tissue	15.5
Midbrain	tissue	15.3
Substantia nigra	tissue	15.1
Superior colliculi	tissue	15.0
Thalamus	tissue	14.5
Retina	tissue	14.0
Cerebral cortex	tissue	13.4	medium
Occipital cortex	tissue	13.4
Cerebellum	tissue	13.1	medium
Periaqueductal gray	tissue	13.1
Hypothalamus	tissue	13.0

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (70.7), Lateral funiculus (white matter) (38.5), Dorsal funiculus (white matter) (34.8), Lateral hypothalamic area (32.6), Nucleus raphe pallidus (32.6).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LSM7 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

10 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1284	99.67	73.56	1353
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-4714-3P	96.53	67.44	452

Functional genomics

gnomAD constraint: pLI 1.08e-05, LOEUF 1.73, missense Z -0.0221 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000252622 — one region, missense o/e 0.77. DepMap (CRISPR cell-line fitness): dependent in 99.8% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): S-117 (-3.178), CAL-120 (-3.0), IMR-32 (-2.621), TE-10 (-2.605), SW 1990 (-2.595), NCI-H1915 (-2.565), BICR 31 (-2.563), Detroit 562 (-2.554), NCI-H1693 (-2.438), HPAF-II (-2.388), A-673 (-2.37), D283 Med (-2.368), RD-ES (-2.362), Hs 729 (-2.359), KP-3 (-2.333).

Literature-anchored findings (GeneRIF, showing 2)

• LSm1-7 proteins colocalize with DCP1,DCP2 and Xrn1 in cytoplasmic foci (PMID:12515382)
• RNA-binding protein LSM7 facilitates breast cancer metastasis through mediating alternative splicing of CD44. (PMID:39182568)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm7	ENSDARG00000058328
mus_musculus	Lsm7	ENSMUSG00000035215
rattus_norvegicus	Lsm7	ENSRNOG00000019552
drosophila_melanogaster	LSm7	FBGN0261068
caenorhabditis_elegans		WBGENE00003081

Paralogs (1): SNRPG (ENSG00000143977)

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	Q3ZBL0	100.0%	Diamond
Pongo abelii	Q5RCP3	100.0%	Diamond
Methanosarcina barkeri str. Fusaro	Q465S1	98.6%	Diamond
Methanosarcina mazei Go1	Q8PZZ9	98.6%	Diamond
Methanosarcina acetivorans C2A	Q8TL47	98.6%	Diamond
Arabidopsis thaliana	O82221	86.8%	Diamond
Medicago sativa	P24715	86.8%	Diamond
Methanococcoides burtonii DSM 6242	Q12U30	80.6%	Diamond
Archaeoglobus fulgidus DSM 4304	O29386	75.4%	Diamond
Methanocella arvoryzae MRE50	Q0W8R9	72.2%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O26745	65.2%	Diamond
Dictyostelium discoideum	Q54RX0	61.8%	Diamond
Schizosaccharomyces pombe 972h-	P87173	61.0%	Diamond
Saccharomyces cerevisiae S288C	P40204	56.2%	Diamond
Aeropyrum pernix K1	Q9YEQ5	46.8%	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
PEAK3	protein-coding	374872
OAZ1	protein-coding	4946
SPPL2B	protein-coding	56928
LINGO3	protein-coding	645191
MIR7108	ncRNA	102466806
TIMM13	protein-coding	26517
TMPRSS9	protein-coding	360200
LMNB2	protein-coding	84823
LINC01775	ncRNA	101928602

Protein

Protein identifiers

U6 snRNA-associated Sm-like protein LSm7 — Q9UK45 (reviewed: Q9UK45)

All UniProt accessions (4): Q9UK45, A0A087X2I5, K7EML7, K7ENY5

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. Interacts with TACC1.

Subcellular location. Nucleus.

Disease relevance. Leukodystrophy and cerebellar atrophy (LDCA) [MIM:621191] An autosomal recessive disorder characterized by neurodevelopmental features including developmental delay, limited speech, axial hypotonia, and white matter abnormalities with cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the snRNP Sm proteins family.

RefSeq proteins (1): NP_057283* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001163	Sm_dom_euk/arc	Domain
IPR010920	LSM_dom_sf	Homologous_superfamily
IPR017132	Lsm7	Family
IPR044641	Lsm7/SmG-like	Family
IPR047575	Sm	Domain

Pfam: PF01423

UniProt features (15 total): strand 5, sequence variant 3, turn 2, initiator methionine 1, chain 1, helix 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-Q9UK45-F1	89.33	0.70

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli fibrillar center

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-acetylalanine	2

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-429914	Deadenylation-dependent mRNA decay	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—
R-HSA-430039	mRNA decay by 5’ to 3’ exoribonuclease	electronic

MSigDB gene sets: 179 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, KAAB_FAILED_HEART_ATRIUM_DN, MORF_UBE2I, REACTOME_MRNA_DECAY_BY_5_TO_3_EXORIBONUCLEASE, MORF_HDAC1, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, MUELLER_PLURINET, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GNF2_FBL, MORF_BUB3

GO Biological Process (7): spliceosomal tri-snRNP complex assembly (GO:0000244), deadenylation-dependent decapping of nuclear-transcribed mRNA (GO:0000290), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), nuclear-transcribed mRNA catabolic process (GO:0000956), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): U6 snRNA binding (GO:0017070), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (15): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U6 snRNP (GO:0005688), U12-type spliceosomal complex (GO:0005689), cytoplasm (GO:0005737), cytosol (GO:0005829), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type prespliceosome (GO:0071004), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013), spliceosomal tri-snRNP complex (GO:0097526), Lsm2-8 complex (GO:0120115), Lsm1-7-Pat1 complex (GO:1990726), ribonucleoprotein complex (GO:1990904)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Metabolism of RNA	2
Deadenylation-dependent mRNA decay	1
mRNA Splicing	1
Processing of Capped Intron-Containing Pre-mRNA	1

GO top-level categories

37 GO namespaces:

Category	Terms
cellular anatomical structure	3
RNA processing	2
spliceosomal snRNP complex	2
spliceosomal complex	2
U5 snRNP	2
U2-type spliceosomal complex	2
U1 snRNP	2
U2 snRNP	2
Sm-like protein family complex	2
spliceosomal snRNP assembly	1
nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay	1
nuclear-transcribed mRNA catabolic process	1
mRNA methylguanosine-cap decapping	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 catabolic process	1
mRNA metabolic process	1
snRNA binding	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
Lsm2-8 complex	1
intracellular anatomical structure	1
cytoplasm	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
prespliceosome	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
Prp19 complex	1
catalytic complex	1
protein-containing complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 25 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 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
cytoplasm	CC	physical interaction
nucleus	CC	direct assay
spliceosomal complex	CC	mutant phenotype

Protein interactions and networks

STRING

showing 15 of 2,151 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM7	LSM8	O95777	995
LSM7	LSM6	P62312	995
LSM7	LSM5	Q9Y4Y9	992
LSM7	LSM1	O15116	991
LSM7	LSM3	P62310	991
LSM7	LSM4	Q9Y4Z0	991
LSM7	LSM2	Q9Y333	983
LSM7	SNRPD2	P43330	955
LSM7	XRN1	Q8IZH2	936
LSM7	SNRPE	P08578	886
LSM7	SNRPD3	P43331	868
LSM7	SNRPD1	P13641	867
LSM7	NAA38	Q9BRA0	837
LSM7	DCP2	Q8IU60	668
LSM7	EDC3	Q96F86	628

IntAct

Human interaction partners of LSM7 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

23 partners by confidence:

Partner	Interaction type	MIscore	Records
LSM5	physical association	0.900	18
LSM2	physical association	0.900	11
LSM4	physical association	0.890	11
LSM3	physical association	0.800	9
LSM6	physical association	0.800	4
DDIT4L	physical association	0.780	10
SNRPF	physical association	0.740	6
SNRPD3	physical association	0.670	3
TACC1	physical association	0.630	7
SYT17	physical association	0.560	3
TCL1B	physical association	0.560	3
EPHA2	physical association	0.370	1
LDB1	physical association	0.370	1
PFKM	physical association	0.370	1
RASSF5	physical association	0.370	1
ZSCAN26	physical association	0.370	1
GEMIN2	association	0.350	1
SART1	association	0.350	1
EXOSC8	physical association	0.000	1
LSM8	physical association	0.000	1
MYH13	physical association	0.000	1
NPY1R	physical association	0.000	1
RAB29	physical association	0.000	1

BioGRID (193 interactions; top human partners by supporting records): LSM5 (Two-hybrid; 13 records), LSM4 (Co-fractionation; 12 records), LSM2 (Two-hybrid; 11 records), LSM6 (Co-fractionation; 9 records), LSM3 (Co-fractionation; 8 records), SNRPD3 (Co-fractionation; 5 records), SNRPF (Two-hybrid; 5 records), TACC1 (Two-hybrid; 5 records), SART3 (FRET; 4 records), LSM8 (Affinity Capture-MS; 3 records), PRPF4 (Affinity Capture-MS; 3 records), SNRPD2 (Co-fractionation; 3 records), DDIT4L (Two-hybrid; 2 records), FKBP4 (Affinity Capture-Luminescence; 2 records), LSM1 (Proximity Label-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
LSM7	“form complex”	“U4/U6.U5 snRNP complex”	binding

Protein complexes (CORUM) (4)

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

4 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
LSm1-7 complex	7	LSM2, LSM3, LSM4, LSM5, LSM6, LSM7, LSM1
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 23 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	5	237.9×	1e-10
mRNA Splicing	9	61.8×	2e-13
Processing of Capped Intron-Containing Pre-mRNA	9	46.2×	1e-12
mRNA Splicing - Major Pathway	9	30.7×	4e-11
Metabolism of RNA	9	23.4×	2e-10

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	5	126.3×	3e-08
mRNA splicing, via spliceosome	9	35.8×	2e-10
RNA splicing	5	19.2×	3e-04

Disease & clinical

Genetic variants

Variant evidence for LSM7: 19 ClinVar records (3 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	9
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
996338	NM_016199.3(LSM7):c.206G>C (p.Arg69Pro)	Likely pathogenic	criteria provided, single submitter	2
996070	NM_016199.3(LSM7):c.121G>A (p.Asp41Asn)	Pathogenic	no assertion criteria provided	2
3897536	LSM7, ARG69TRP	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore LSM7’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 323):

Position(s)	Effect	Δscore	Sites
19:2321823–2321824	acceptor_loss	1.0000	4
19:2324211–2324212	acceptor_gain	1.0000	2
19:2321823–2321824	acceptor_loss	0.9900	2
19:2324123–2324124	donor_loss	0.9900	4
19:2324198	acceptor_gain	0.9900
19:2328398	donor_gain	0.9900
19:2324124	donor_loss	0.9800
19:2324209	acceptor_gain	0.9800
19:2328385–2328386	donor_loss	0.9800	6
19:2324197–2324198	acceptor_loss	0.9700	5

AlphaMissense

474 missense substitutions predicted likely pathogenic (of 676 scored), across 94 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
D41	8	0.999	1.000
N45	8	0.995	1.000
D49	8	0.974	0.996
F97	8	0.973	1.000
N95	8	0.963	0.999
F27	8	0.962	0.999
D57	8	0.894	0.948
D14	8	0.881	0.985
D60	8	0.874	0.985
E53	7	0.996	0.999
C76	7	0.986	1.000
F40	7	0.982	0.999
I93	7	0.981	0.999
E32	7	0.978	0.997
C85	7	0.919	0.999
I12	7	0.916	0.998
E91	7	0.820	0.973
R31	6	0.999	1.000
G39	6	0.999	1.000
G78	6	0.999	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	5.6e-05
Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma (TCGA)	favorable	0.00053
Kidney Renal Clear Cell Carcinoma (TCGA)	unfavorable	0.000843

Disease associations

OMIM: gene MIM:607287 | disease phenotypes: MIM:621191, MIM:312080, MIM:618763

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
leukodystrophy	Moderate	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (8 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

8 panels:

Panel	Rating
Ataxia and cerebellar anomalies - childhood onset	amber
Hereditary ataxia and cerebellar anomalies, childhood onset	amber
Hereditary spastic paraplegia, childhood onset	amber
Hypotonic infant	amber
Intellectual disability	amber
Leukodystrophy, childhood onset	amber
Paediatric disorders	amber
White matter disorders and cerebral calcification - childhood onset	amber

Mondo (3): LSM7-related leukodystrophy and cerebellar atrophy (MONDO:0978294), leukodystrophy (MONDO:0019046), Joubert syndrome 36 (MONDO:0032902)

Orphanet (1): Leukodystrophy (Orphanet:68356)

HPO phenotypes

29 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000047	Hypospadias
HP:0000407	Sensorineural hearing impairment
HP:0000486	Strabismus
HP:0000639	Nystagmus
HP:0000739	Anxiety
HP:0000952	Jaundice
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001285	Spastic tetraparesis
HP:0001321	Cerebellar hypoplasia
HP:0001337	Tremor
HP:0001622	Premature birth
HP:0002084	Encephalocele
HP:0002098	Respiratory distress
HP:0002172	Postural instability
HP:0002186	Apraxia
HP:0002273	Tetraparesis
HP:0002360	Sleep disturbance
HP:0002415	Leukodystrophy
HP:0007308	Extrapyramidal dyskinesia
HP:0008936	Axial hypotonia
HP:0010865	Age-inappropriate oppositional behavior
HP:0010880	Increased nuchal translucency
HP:0011968	Feeding difficulties
HP:0034197	Third trimester onset

GWAS associations

1 associations:

Study	Trait	p-value
GCST004902_12	Parkinson’s disease	7e-7

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	3
cobaltous chloride	decreases expression	2
Doxorubicin	decreases expression, affects response to substance	2
bisphenol A	affects expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
LDN 193189	increases expression, affects cotreatment	1
PP242	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	decreases expression	1
Irinotecan	increases response to substance	1
Atrazine	decreases expression	1
Coumestrol	increases expression	1
Diazinon	increases methylation	1
Lead	increases expression	1
Smoke	decreases expression	1
Dronabinol	decreases expression	1
Valproic Acid	increases methylation	1
Vinblastine	affects response to substance	1
Vitamin E	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

8 trials:

NCT	Phase	Status	Title
NCT00889174	Not specified	COMPLETED	The Nosology and Etiology of Leukodystrophies of Unknown Causes
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT02843555	Not specified	COMPLETED	Natural History of the Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT03639285	Not specified	RECRUITING	Natural History, Diagnosis, and Outcomes for Leukodystrophies
NCT05443906	Not specified	RECRUITING	Home Exercise for Individuals With Neurodegenerative Disease