LSM12

Summary

LSM12 (LSM12 homolog, HGNC:26407) is a protein-coding gene on chromosome 17q21.31, encoding Protein LSM12 (Q3MHD2). Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein. It is a selective cancer dependency (DepMap: 51.7% of cell lines).

Predicted to enable RNA binding activity. Located in cytoplasm.

Source: NCBI Gene 124801 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• GTEx eGene: eQTL in 30 tissues, sQTL in 1 (q < 0.05)
• Cancer dependency (DepMap): dependent in 51.7% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.14 (highly constrained)
• MANE Select transcript: NM_001371445

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26407
Approved symbol	LSM12
Name	LSM12 homolog
Location	17q21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ30656
Ensembl gene	ENSG00000161654
Ensembl biotype	protein_coding
OMIM	611793
Entrez	124801

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 18 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000293406

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

ENST00000293406, ENST00000585388, ENST00000590563, ENST00000591247, ENST00000893747, ENST00000893748, ENST00000893749, ENST00000893750, ENST00000893751, ENST00000893752, ENST00000914321, ENST00000914322, ENST00000914323, ENST00000914324, ENST00000914325, ENST00000914326, ENST00000986806, ENST00001017138, ENST00001017139, ENST00001067723, ENST00001098827, ENST00001121509, ENST00001139359

RefSeq mRNA: 5 — MANE Select: NM_001371445 NM_001369484, NM_001369485, NM_001369486, NM_001371445, NM_152344

CCDS: CCDS11475, CCDS92334

Canonical transcript exons

ENST00000293406 — 5 exons

Exon	Start	End
ENSE00001059496	44066464	44066671
ENSE00001059502	44040147	44040256
ENSE00001059510	44063801	44063934
ENSE00003661961	44037412	44037538
ENSE00003897200	44034328	44036300

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 95.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 64.5318 / max 311.4238, expressed in 1825 samples.

Highest expression (Bgee): gingival epithelium, gingiva, triceps brachii, gluteal muscle, type B pancreatic cell.

Genetic regulation across tissues (GTEx eQTL / sQTL)

LSM12 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 31 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	5.1e-10	+0.45	17:44039482:C:T
Esophagus Mucosa	eqtl	3.3e-09	+0.52	17:44127491:G:A
Muscle Skeletal	eqtl	1.8e-08	+0.41	17:44039482:C:T
Colon Sigmoid	eqtl	2.6e-05	+0.53	17:44039482:C:T
Adipose Subcutaneous	eqtl	3.5e-05	+0.45	17:44039482:C:T
Cells EBV-transformed lymphocytes	eqtl	8.3e-05	+0.67	17:44083042:G:A
Whole Blood	eqtl	8.3e-05	+0.44	17:44039482:C:T
Thyroid	eqtl	1.4e-04	+0.43	17:44083042:G:A
Brain Hypothalamus	eqtl	3.9e-04	+0.70	17:44039482:C:T
Lung	eqtl	4.9e-04	+0.38	17:44127491:G:A
Nerve Tibial	eqtl	8.9e-04	+0.50	17:44039482:C:T
Spleen	eqtl	9.1e-04	+0.78	17:44039482:C:T
Adrenal Gland	eqtl	1.2e-03	+0.65	17:44039482:C:T
Skin Sun Exposed Lower leg	eqtl	2.3e-03	+0.39	17:44039482:C:T
Brain Cerebellum	eqtl	2.3e-03	+0.81	17:43989178:T:C
Artery Aorta	eqtl	4.7e-03	+0.45	17:44039482:C:T
Heart Left Ventricle	sqtl	4.7e-03	-1.78	17:44230015:G:A
Brain Caudate basal ganglia	eqtl	6.4e-03	+0.51	17:44293943:G:A
Esophagus Muscularis	eqtl	6.9e-03	+0.32	17:44039482:C:T
Brain Hippocampus	eqtl	7.2e-03	+0.76	17:43989178:T:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
166299	64.0760	1825
166298	0.3568	194
166296	0.0815	27
166297	0.0113	2
166300	0.0061	3

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
gingival epithelium	UBERON:0001949	95.50	gold quality
gingiva	UBERON:0001828	94.76	gold quality
triceps brachii	UBERON:0001509	94.45	gold quality
gluteal muscle	UBERON:0002000	93.93	gold quality
type B pancreatic cell	CL:0000169	93.21	silver quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.17	gold quality
palpebral conjunctiva	UBERON:0001812	93.12	gold quality
cartilage tissue	UBERON:0002418	92.99	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.90	gold quality
substantia nigra pars compacta	UBERON:0001965	92.37	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.24	gold quality
tongue squamous epithelium	UBERON:0006919	92.12	gold quality
stromal cell of endometrium	CL:0002255	91.98	gold quality
colonic epithelium	UBERON:0000397	91.96	gold quality
lateral globus pallidus	UBERON:0002476	91.93	gold quality
monocyte	CL:0000576	91.85	gold quality
mononuclear cell	CL:0000842	91.83	gold quality
leukocyte	CL:0000738	91.73	gold quality
diaphragm	UBERON:0001103	91.07	silver quality
ganglionic eminence	UBERON:0004023	90.96	gold quality
cortical plate	UBERON:0005343	90.85	gold quality
corpus epididymis	UBERON:0004359	90.76	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	90.56	gold quality
tonsil	UBERON:0002372	90.53	gold quality
islet of Langerhans	UBERON:0000006	90.46	gold quality
choroid plexus epithelium	UBERON:0003911	90.43	gold quality
right testis	UBERON:0004534	90.33	gold quality
decidua	UBERON:0002450	90.17	gold quality
eye	UBERON:0000970	90.15	gold quality
testis	UBERON:0000473	90.11	gold quality
olfactory bulb	UBERON:0002264	90.06	gold quality
pharyngeal mucosa	UBERON:0000355	90.02	gold quality
gastrocnemius	UBERON:0001388	89.96	gold quality
left testis	UBERON:0004533	89.95	gold quality
caput epididymis	UBERON:0004358	89.78	gold quality
cauda epididymis	UBERON:0004360	89.73	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	89.71	gold quality
smooth muscle tissue	UBERON:0001135	89.69	gold quality
esophagus squamous epithelium	UBERON:0006920	89.65	gold quality
muscle of leg	UBERON:0001383	89.62	gold quality
epithelium of nasopharynx	UBERON:0001951	89.62	gold quality
rectum	UBERON:0001052	89.52	gold quality
biceps brachii	UBERON:0001507	89.46	gold quality
penis	UBERON:0000989	89.37	gold quality
embryo	UBERON:0000922	89.35	gold quality
lower esophagus mucosa	UBERON:0035834	89.33	gold quality
body of tongue	UBERON:0011876	89.30	gold quality
epithelium of esophagus	UBERON:0001976	89.18	gold quality
bone marrow	UBERON:0002371	89.17	gold quality
muscle organ	UBERON:0001630	89.01	gold quality
skeletal muscle organ	UBERON:0014892	89.00	gold quality
body of pancreas	UBERON:0001150	88.87	gold quality
mucosa of transverse colon	UBERON:0004991	88.85	gold quality
thymus	UBERON:0002370	88.84	gold quality
vena cava	UBERON:0004087	88.82	silver quality
esophagus mucosa	UBERON:0002469	88.81	gold quality
prefrontal cortex	UBERON:0000451	88.74	gold quality
bone marrow cell	CL:0002092	88.60	gold quality
subthalamic nucleus	UBERON:0001906	88.53	gold quality
middle temporal gyrus	UBERON:0002771	88.46	gold quality
mucosa of sigmoid colon	UBERON:0004993	88.46	gold quality
dorsal plus ventral thalamus	UBERON:0001897	88.38	gold quality
heart right ventricle	UBERON:0002080	88.37	gold quality
skeletal muscle tissue	UBERON:0001134	88.32	gold quality
tongue	UBERON:0001723	88.31	gold quality
pancreas	UBERON:0001264	88.29	gold quality
ventricular zone	UBERON:0003053	88.29	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.23	gold quality
liver	UBERON:0002107	88.21	gold quality
colonic mucosa	UBERON:0000317	87.91	gold quality
placenta	UBERON:0001987	87.89	gold quality
cardia of stomach	UBERON:0001162	87.82	gold quality
granulocyte	CL:0000094	87.76	gold quality
right adrenal gland cortex	UBERON:0035827	87.74	gold quality
esophagus	UBERON:0001043	87.72	gold quality
nipple	UBERON:0002030	87.58	gold quality
adrenal gland	UBERON:0002369	87.58	gold quality
hypothalamus	UBERON:0001898	87.54	gold quality
right adrenal gland	UBERON:0001233	87.52	gold quality
left adrenal gland	UBERON:0001234	87.52	gold quality
cingulate cortex	UBERON:0003027	87.49	gold quality
anterior cingulate cortex	UBERON:0009835	87.47	gold quality
trachea	UBERON:0003126	87.45	gold quality
nephron tubule	UBERON:0001231	87.43	gold quality
lymph node	UBERON:0000029	87.42	gold quality
thoracic mammary gland	UBERON:0005200	87.33	gold quality
endometrium	UBERON:0001295	87.31	gold quality
bone element	UBERON:0001474	87.26	gold quality
mammary gland	UBERON:0001911	87.20	gold quality
adrenal cortex	UBERON:0001235	87.17	gold quality
buccal mucosa cell	CL:0002336	87.14	gold quality
left adrenal gland cortex	UBERON:0035825	87.12	gold quality
right lobe of liver	UBERON:0001114	87.11	gold quality
squamous epithelium	UBERON:0006914	87.06	gold quality
right atrium auricular region	UBERON:0006631	87.04	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.02	gold quality
cardiac ventricle	UBERON:0002082	86.93	gold quality
epithelium of mammary gland	UBERON:0003244	86.93	gold quality
vastus lateralis	UBERON:0001379	86.92	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.94

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Thalamus	tissue	87.6
Spinal cord	tissue	84.9
Cerebral cortex	tissue	84.4	high
Occipital cortex	tissue	84.4
Somatosensory cortex	tissue	82.4
Pons	tissue	81.6
Midbrain	tissue	79.3
Hippocampal formation	tissue	79.1
Superior colliculi	tissue	78.2
Medulla oblongata	tissue	78.1
Prefrontal cortex	tissue	77.8
Motor cortex	tissue	74.3
Substantia nigra	tissue	72.3
Entorhinal cortex	tissue	71.7
Hypothalamus	tissue	71.2
Temporal cortex	tissue	70.9
Septum	tissue	68.4
Retrosplenial and cingulate cortex	tissue	68.2
Putamen	tissue	67.8
Corpus callosum	tissue	66.2
Periaqueductal gray	tissue	65.0
Retrosplenial cortex	tissue	64.2
Ventral forebrain	tissue	62.8
Basal ganglia	tissue	59.4	medium
Olfactory bulb	tissue	57.8
Insular cortex	tissue	57.1
Amygdala	tissue	57.0
Cerebellum	tissue	56.8	high
Postcentral gyrus	tissue	37.8
Locus coeruleus	tissue	32.2
Hippocampus	tissue	30.0	not detected
Retina	tissue	28.9
Bone marrow	tissue	27.9	low
Liver	tissue	27.4	high
Choroid plexus	tissue	26.4
Skeletal muscle	tissue	26.3	high
Nucleus accumbens	tissue	26.3
Epididymis	tissue	23.6	high
Tonsil	tissue	23.2	high
Rectum	tissue	22.2	high
Tongue	tissue	22.1
Testis	tissue	21.9	high
Placenta	tissue	21.7	medium
Frontal cortex	tissue	21.5
Urinary bladder	tissue	21.3	high
Parathyroid gland	tissue	20.3	low
Pancreas	tissue	19.9	medium
Caudate putamen	tissue	19.9
Lymph node	tissue	19.4	high
Smooth muscle	tissue	19.0	low
Kidney	tissue	18.9	high
Adipose tissue	tissue	18.7	not detected
Thymus	tissue	18.6
Colon	tissue	18.5	high
Esophagus	tissue	18.2	high
Stomach 1	tissue	17.7	high
Heart muscle	tissue	17.5	medium
Breast	tissue	17.4	high
Salivary gland	tissue	17.1	medium
Thyroid gland	tissue	17.0	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Ventral spinal cord (84.9), Dorsal hippocampus (79.1), Dorsal spinal cord (75.7), Ventral hippocampus (72.9), Subiculum (68.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting LSM12 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 176 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6772-5P	99.94	67.01	577

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.145, missense Z 2.62 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000293406 — one region, missense o/e 0.45. DepMap (CRISPR cell-line fitness): dependent in 51.7% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KMS-20 (-1.923), MV4-11 (-1.529), MOLM-13 (-1.434), KMS-27 (-1.417), KARPAS-422 (-1.406), MM1-S (-1.393), RPMI 8226 (-1.385), NCI-H727 (-1.378), Hep G2 (-1.375), LS513 (-1.369), HUP-T4 (-1.355), G-402 (-1.349), L-363 (-1.333), SK-BR-3 (-1.329), HCC1419 (-1.318).

Literature-anchored findings (GeneRIF, showing 5)

• LSM12-EPAC1 defines a neuroprotective pathway that sustains the nucleocytoplasmic RAN gradient. (PMID:33362237)
• Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles. (PMID:34362892)
• Identification of RNA-splicing factor Lsm12 as a novel tumor-associated gene and a potent biomarker in Oral Squamous Cell Carcinoma (OSCC). (PMID:35449073)
• LSM12 facilitates the progression of colorectal cancer by activating the WNT/CTNNB1 signaling pathway. (PMID:37303493)
• Convergent activation of two-pore channels mediated by the NAADP-binding proteins JPT2 and LSM12. (PMID:37607218)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	lsm12a	ENSDARG00000028848
danio_rerio	lsm12b	ENSDARG00000109510
mus_musculus	Lsm12	ENSMUSG00000020922
rattus_norvegicus	Lsm12	ENSRNOG00000020894
drosophila_melanogaster	Lsm12a	FBGN0030364
drosophila_melanogaster	Hez	FBGN0036057
caenorhabditis_elegans		WBGENE00010922

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1919592) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
hyperactivity	1
abnormal auditory brainstem response	1
preweaning lethality, complete penetrance	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	Q0VCF9	100.0%	Diamond
Pongo abelii	Q5RAT5	100.0%	Diamond
Xenopus laevis	Q6GP89	95.9%	Diamond
Xenopus tropicalis	Q6P833	95.9%	Diamond
Gallus gallus	Q5ZML5	93.8%	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
HROB	protein-coding	78995
G6PC3	protein-coding	92579
HDAC5	protein-coding	10014
NAGS	protein-coding	162417
TMEM101	protein-coding	84336
PYY	protein-coding	5697

Protein

Protein identifiers

Protein LSM12 — Q3MHD2 (reviewed: Q3MHD2)

All UniProt accessions (2): Q3MHD2, K7ELG9

UniProt curated annotations — full annotation on UniProt →

Function. Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein. Confers NAADP sensitivity to the two pore channel complex (TPCs) by acting as TPC accessory protein necessary for NAADP-evoked Ca(2+) release.

Subunit / interactions. Found in a complex with LSM12, TPCN1 and TPCN2. Interacts with TPCN2.

Subcellular location. Cytoplasm.

Similarity. Belongs to the LSM12 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q3MHD2-1	1	yes
Q3MHD2-2	2

RefSeq proteins (5): NP_001356413, NP_001356414, NP_001356415, NP_001358374, NP_689557 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019181	LSM12_ABD	Domain
IPR039683	Lsm12-like	Family
IPR047574	AD	Domain
IPR047575	Sm	Domain
IPR048478	LSM12_LSM	Domain

Pfam: PF09793, PF21166

UniProt features (10 total): domain 2, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, region of interest 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3MHD2-F1	90.97	0.81

Human Protein Atlas

Protein class: Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH approved · 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 (2)

Type	Positions
N-acetylalanine	2
Phosphothreonine	75

Function

Pathways and Gene Ontology

Reactome pathways

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

MSigDB gene sets: 202 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MORF_RAGE, TGCGCANK_UNKNOWN, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, CHX10_01, CREB_Q4, MARTINEZ_RB1_TARGETS_UP, MORF_FANCG, DODD_NASOPHARYNGEAL_CARCINOMA_UP, MORF_PML, TCCAGAG_MIR518C, SENESE_HDAC1_TARGETS_UP, MORF_IKBKG, AGTCAGC_MIR345

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

4 GO namespaces:

Category	Terms
nucleic acid binding	1
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 3 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
cytoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,224 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM12	ZCCHC4	Q9H5U6	950
LSM12	JPT2	Q9H910	788
LSM12	LSM11	P83369	642
LSM12	LSM1	O15116	632
LSM12	LSM10	Q969L4	627
LSM12	LSM6	P62312	600
LSM12	LSM7	Q9UK45	592
LSM12	LSM5	Q9Y4Y9	586
LSM12	LSM3	P62310	582
LSM12	ATXN2	Q99700	567
LSM12	LSM8	O95777	565
LSM12	LSM14B	Q9BX40	556
LSM12	TPCN2	Q8NHX9	530
LSM12	LSM4	Q9Y4Z0	503
LSM12	PAIP1	Q9H074	471

IntAct

Human interaction partners of LSM12 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
LSM2	physical association	0.560	3
LSM3	physical association	0.560	3
NTAQ1	physical association	0.560	3
MCRIP1	association	0.350	1
DSTYK	physical association	0.000	1
GOLM1	physical association	0.000	1
IKBKE	physical association	0.000	1
VHL	physical association	0.000	1

BioGRID (215 interactions; top human partners by supporting records): DDX6 (Proximity Label-MS; 7 records), ATXN2 (Co-fractionation; 5 records), ATXN2L (Co-fractionation; 5 records), NUFIP2 (Affinity Capture-MS; 5 records), FAM195B (Proximity Label-MS; 3 records), CAND1 (Affinity Capture-MS; 2 records), CASC3 (Proximity Label-MS; 2 records), CTNNB1 (Affinity Capture-MS; 2 records), FAM195A (Proximity Label-MS; 2 records), G3BP2 (Proximity Label-MS; 2 records), LSM14A (Proximity Label-MS; 2 records), PABPC1 (Proximity Label-MS; 2 records), PABPC4 (Proximity Label-MS; 2 records), STK4 (Affinity Capture-MS; 2 records), AAMDC (Affinity Capture-MS)

Disease & clinical

Genetic variants

Variant evidence for LSM12: 16 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	11
Likely benign	1
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 41 predictions of 832):

Position(s)	Effect	Δscore	Sites
17:44040145–44040146	donor_loss	1.0000	4
17:44040257–44040258	acceptor_loss	1.0000	6
17:44063799–44063800	donor_loss	1.0000	5
17:44066467	donor_gain	1.0000
17:44036301–44036302	acceptor_loss	0.9900	6
17:44037407–44037411	donor_loss	0.9900	10
17:44037440	donor_gain	0.9900
17:44037539–44037540	acceptor_loss	0.9900	6
17:44040142	donor_loss	0.9900
17:44040145	donor_loss	0.9900

AlphaMissense

702 missense substitutions predicted likely pathogenic (of 1,273 scored), across 161 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
D33	8	0.988	0.997
H161	8	0.986	1.000
F9	8	0.984	0.998
F32	8	0.974	1.000
F117	8	0.957	1.000
D172	8	0.944	0.994
D54	8	0.942	0.994
N59	8	0.918	0.996
S13	8	0.872	0.996
W129	7	1.000	1.000
C151	7	0.995	1.000
H169	7	0.992	0.999
M137	7	0.990	0.998
C127	7	0.982	0.999
I134	7	0.972	1.000
I165	7	0.966	1.000
C17	7	0.960	0.997
K168	7	0.947	0.999
Q114	7	0.908	0.999
N83	7	0.865	0.991

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

5 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	unfavorable	0.000312
Lung Adenocarcinoma (validation)	unfavorable	0.000624
Lung Adenocarcinoma (TCGA)	unfavorable	0.000824
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000858
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000887

Disease associations

OMIM: gene MIM:611793 | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST008103_184	Bipolar disorder	2e-8

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295839 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.32	Kd	4.731	nM	CHEMBL3752910
8.29	ED50	5.186	nM	CHEMBL3752910
5.29	Kd	5089	nM	CHEMBL5653589
5.25	ED50	5578	nM	CHEMBL5653589

PubChem BioAssay actives

2 with measured affinity, of 5 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148670: Binding affinity to human LSM12 incubated for 45 mins by Kinobead based pull down assay	kd	0.0047	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148670: Binding affinity to human LSM12 incubated for 45 mins by Kinobead based pull down assay	kd	5.0889	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Smoke	decreases expression, increases abundance	2
Cadmium Chloride	increases abundance, decreases expression	2
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
sodium arsenite	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
bisphenol AF	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	decreases expression, increases abundance	1
Caffeine	decreases phosphorylation	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Methapyrilene	increases methylation	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Volatile Organic Compounds	affects cotreatment, increases oxidation	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
CHEMBL4118625	Binding	Binding affinity to LSM12 in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — *Bioorg Med Chem*

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E2BN	HAP1 LSM12 (-) 1	Cancer cell line	Male
CVCL_E2BP	HAP1 LSM12 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for LSM12 across ~30M SureChEMBL compounds — explore on Sugi Predict.