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 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 16 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 51.7% of screened cell lines
• 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: 16 — 15 protein_coding, 1 retained_intron

ENST00000293406, ENST00000585388, ENST00000590563, ENST00000591247, ENST00000893747, ENST00000893748, ENST00000893749, ENST00000893750, ENST00000893751, ENST00000893752, ENST00000914321, ENST00000914322, ENST00000914323, ENST00000914324, ENST00000914325, ENST00000914326

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.

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

291 total, 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

Single-cell (SCXA)

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

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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

176 targeting LSM12, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-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

DepMap (CRISPR cell-line fitness): dependent in 51.7% of screened cell lines.

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

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

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

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

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): 2, 75

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

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 Biological Process (0):

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

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

GO top-level categories

Rollup of top GO terms by namespace:

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

Protein interactions and networks

STRING

1442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LSM12	ZCCHC4	Q9H5U6	952
LSM12	ATXN2	Q99700	715
LSM12	LSM1	O15116	648
LSM12	LSM6	P62312	637
LSM12	LSM7	Q9UK45	625
LSM12	JPT2	Q9H910	620
LSM12	LSM3	P62310	616
LSM12	ILF2	Q12905	604
LSM12	LSM5	Q9Y4Y9	604
LSM12	DDX6	P26196	592
LSM12	LSM8	O95777	590
LSM12	LSM11	P83369	589
LSM12	LSM2	Q9Y333	585
LSM12	KHSRP	Q92945	580
LSM12	LSM14B	Q9BX40	545

IntAct

98 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
ATXN2	PABPC1	psi-mi:“MI:0915”(physical association)	0.820
DDX6	RPS3	psi-mi:“MI:0915”(physical association)	0.690
LSM3	LSM12	psi-mi:“MI:0915”(physical association)	0.560
LSM2	LSM12	psi-mi:“MI:0915”(physical association)	0.560
LSM12	NTAQ1	psi-mi:“MI:0915”(physical association)	0.560
LSM12	LSM2	psi-mi:“MI:0915”(physical association)	0.560
DDX6	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.540
MCRIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
NUFIP2	RELA	psi-mi:“MI:0914”(association)	0.530
NUFIP2	CASC3	psi-mi:“MI:0914”(association)	0.530
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
YWHAE	HNRNPA1	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	RPLP0	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
DCP1B	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
ACTA1	PABPC1	psi-mi:“MI:0915”(physical association)	0.400
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (209): LSM12 (Affinity Capture-MS), LSM12 (Affinity Capture-MS), LSM12 (Co-fractionation), LSM12 (Co-fractionation), LSM12 (Co-fractionation), LSM12 (Co-fractionation), LSM12 (Co-fractionation), LSM12 (Co-fractionation), LSM12 (Co-fractionation), PCBP1 (Co-fractionation), LSM12 (Affinity Capture-MS), LSM12 (Proximity Label-MS), LSM12 (Affinity Capture-MS), LSM12 (Affinity Capture-MS), LSM12 (Affinity Capture-MS)

ESM2 similar proteins: A6QPR9, B1H2P5, B5X165, O42611, O95707, P32780, P59764, Q03123, Q08CL8, Q0VCF9, Q0VCL9, Q2KHW8, Q2KIB9, Q2T9V5, Q3MHD2, Q3TTL0, Q498D5, Q502M5, Q5JPI3, Q5M882, Q5PPG7, Q5R7B0, Q5RAT5, Q5RHQ8, Q5XH48, Q5XIA4, Q5ZML5, Q61211, Q66H33, Q6DE97, Q6GP89, Q6NSN1, Q6NU53, Q6P833, Q6PBA2, Q8BH15, Q8CG73, Q8IZC4, Q8N1I0, Q8QFR2

Diamond homologs: Q0VCF9, Q3MHD2, Q5RAT5, Q5ZML5, Q6GP89, Q6NSN1, Q6P833, Q6PBA2, Q9D0R8, Q9VT67, Q9VYR0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 103 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
Translation initiation complex formation	6	16.1×	5e-04
Formation of the ternary complex, and subsequently, the 43S complex	5	15.2×	1e-03
SARS-CoV-1-host interactions	6	14.8×	5e-04
Ribosomal scanning and start codon recognition	5	13.4×	2e-03
SARS-CoV-1 Infection	6	12.1×	8e-04
mRNA Splicing	7	10.8×	5e-04
L13a-mediated translational silencing of Ceruloplasmin expression	7	10.0×	6e-04
Formation of a pool of free 40S subunits	6	9.5×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
stress granule assembly	6	41.0×	5e-06
mRNA splicing, via spliceosome	8	8.3×	2e-03

Disease & clinical

Clinical variants and AI predictions

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1543 predictions. Top by Δscore:

Variant	Effect	Δscore
17:44036297:CAAC:C	acceptor_gain	1.0000
17:44036301:C:CC	acceptor_gain	1.0000
17:44036301:CTG:C	acceptor_loss	1.0000
17:44037410:A:AC	donor_gain	1.0000
17:44037411:C:CG	donor_gain	1.0000
17:44037411:CT:C	donor_gain	1.0000
17:44037411:CTA:C	donor_gain	1.0000
17:44037411:CTAT:C	donor_gain	1.0000
17:44037411:CTATT:C	donor_gain	1.0000
17:44037537:TG:T	acceptor_gain	1.0000
17:44037539:C:CC	acceptor_gain	1.0000
17:44040140:AACTC:A	donor_loss	1.0000
17:44040142:CTCAC:C	donor_loss	1.0000
17:44040143:T:TC	donor_loss	1.0000
17:44040144:C:CC	donor_loss	1.0000
17:44040145:A:AC	donor_gain	1.0000
17:44040145:ACGT:A	donor_gain	1.0000
17:44040146:C:CC	donor_gain	1.0000
17:44040146:CGT:C	donor_gain	1.0000
17:44040146:CGTC:C	donor_gain	1.0000
17:44040146:CGTCT:C	donor_gain	1.0000
17:44040253:CAAG:C	acceptor_gain	1.0000
17:44040254:AAG:A	acceptor_gain	1.0000
17:44040255:AG:A	acceptor_gain	1.0000
17:44040255:AGCT:A	acceptor_loss	1.0000
17:44040256:GC:G	acceptor_loss	1.0000
17:44040257:C:CC	acceptor_gain	1.0000
17:44040258:T:C	acceptor_loss	1.0000
17:44040262:G:GC	acceptor_gain	1.0000
17:44063795:CCTTA:C	donor_loss	1.0000

AlphaMissense

1273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:44036299:A:T	V166D	1.000
17:44037413:A:T	I165K	1.000
17:44037422:A:T	V162E	1.000
17:44037426:G:C	H161D	1.000
17:44037454:A:C	C151W	1.000
17:44037455:C:T	C151Y	1.000
17:44037456:A:G	C151R	1.000
17:44037471:A:C	Y146D	1.000
17:44037471:A:G	Y146H	1.000
17:44037482:A:C	I142S	1.000
17:44037482:A:G	I142T	1.000
17:44037482:A:T	I142N	1.000
17:44037488:A:T	V140D	1.000
17:44037500:A:T	V136D	1.000
17:44037506:A:C	I134S	1.000
17:44037506:A:G	I134T	1.000
17:44037506:A:T	I134N	1.000
17:44037520:C:A	W129C	1.000
17:44037520:C:G	W129C	1.000
17:44037521:C:G	W129S	1.000
17:44037522:A:G	W129R	1.000
17:44037522:A:T	W129R	1.000
17:44040149:C:A	K122N	1.000
17:44040149:C:G	K122N	1.000
17:44040151:T:C	K122E	1.000
17:44040156:A:C	I120S	1.000
17:44040156:A:T	I120N	1.000
17:44040164:G:C	F117L	1.000
17:44040164:G:T	F117L	1.000
17:44040165:A:G	F117S	1.000

dbSNP variants (sampled 300 via entrez): RS1000008182 (17:44059039 G>A), RS1000037423 (17:44045322 G>A,T), RS1000103326 (17:44048115 T>C), RS1000162475 (17:44054138 T>A,C), RS1000235787 (17:44053897 GAA>G), RS1000313918 (17:44041618 A>C), RS1000366458 (17:44042425 G>C), RS1000402240 (17:44054236 G>A), RS1000403407 (17:44048362 G>C), RS1000418978 (17:44042180 A>G), RS1000510946 (17:44058511 G>A,C), RS1000786659 (17:44064021 A>G), RS1000802589 (17:44046887 C>A,G,T), RS1000916003 (17:44039992 C>T), RS1000934573 (17:44063173 T>A,G)

Disease associations

OMIM: gene MIM:611793 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_24	Bipolar disorder	2.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295839 (SINGLE PROTEIN)

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

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	increases abundance, increases oxidation, decreases expression, affects cotreatment	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	increases abundance, affects cotreatment, increases oxidation	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)

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