LIMA1

Summary

LIMA1 (LIM domain and actin binding 1, HGNC:24636) is a protein-coding gene on chromosome 12q13.12, encoding LIM domain and actin-binding protein 1 (Q9UHB6). Actin-binding protein involved in actin cytoskeleton regulation and dynamics.

This gene encodes a cytoskeleton-associated protein that inhibits actin filament depolymerization and cross-links filaments in bundles. It is downregulated in some cancer cell lines. Alternatively spliced transcript variants encoding different isoforms have been described for this gene, and expression of some of the variants maybe independently regulated.

Source: NCBI Gene 51474 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 117 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_016357

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24636
Approved symbol	LIMA1
Name	LIM domain and actin binding 1
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	EPLIN
Ensembl gene	ENSG00000050405
Ensembl biotype	protein_coding
OMIM	608364
Entrez	51474

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 20 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000341247, ENST00000394943, ENST00000547825, ENST00000549064, ENST00000550592, ENST00000550611, ENST00000551486, ENST00000551691, ENST00000552008, ENST00000552045, ENST00000552338, ENST00000552491, ENST00000552720, ENST00000552783, ENST00000552823, ENST00000552909, ENST00000872657, ENST00000872658, ENST00000872659, ENST00000872660, ENST00000872661, ENST00000872662, ENST00000872663, ENST00000872664, ENST00000872665, ENST00000956833, ENST00000956834

RefSeq mRNA: 12 — MANE Select: NM_016357 NM_001113546, NM_001113547, NM_001243775, NM_001394886, NM_001394887, NM_001394888, NM_001394889, NM_001394890, NM_001394891, NM_001394892, NM_001394893, NM_016357

CCDS: CCDS44877, CCDS55826, CCDS58230, CCDS8802

Canonical transcript exons

ENST00000341247 — 11 exons

Exon	Start	End
ENSE00000837648	50231665	50231710
ENSE00001060480	50222021	50222485
ENSE00001379043	50248633	50248774
ENSE00002388713	50283420	50283520
ENSE00002405286	50175788	50178069
ENSE00003466996	50181904	50182037
ENSE00003480448	50205984	50206068
ENSE00003491342	50204552	50204700
ENSE00003589225	50200777	50200884
ENSE00003659950	50192452	50192561
ENSE00003661687	50195830	50195887

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 99.78.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 71.0279 / max 1817.1032, expressed in 1779 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130907	56.6514	1633
130913	12.3611	1626
130904	0.6707	388
130906	0.4699	254
130905	0.3183	189
130911	0.1861	85
130912	0.1680	75
130903	0.1106	30
130910	0.0575	23
130908	0.0275	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	99.78	gold quality
secondary oocyte	CL:0000655	99.71	gold quality
tendon of biceps brachii	UBERON:0008188	99.46	gold quality
tendon	UBERON:0000043	98.86	gold quality
calcaneal tendon	UBERON:0003701	98.80	gold quality
rectum	UBERON:0001052	98.62	gold quality
colonic mucosa	UBERON:0000317	98.53	gold quality
mucosa of sigmoid colon	UBERON:0004993	98.34	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.29	gold quality
jejunal mucosa	UBERON:0000399	98.09	gold quality
mucosa of stomach	UBERON:0001199	98.03	gold quality
adipose tissue	UBERON:0001013	98.02	gold quality
gall bladder	UBERON:0002110	97.98	gold quality
colonic epithelium	UBERON:0000397	97.91	gold quality
ileal mucosa	UBERON:0000331	97.89	gold quality
skin of hip	UBERON:0001554	97.79	gold quality
connective tissue	UBERON:0002384	97.77	gold quality
mucosa of transverse colon	UBERON:0004991	97.69	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.66	gold quality
pylorus	UBERON:0001166	97.63	gold quality
omental fat pad	UBERON:0010414	97.61	gold quality
cerebellar hemisphere	UBERON:0002245	97.59	gold quality
peritoneum	UBERON:0002358	97.59	gold quality
duodenum	UBERON:0002114	97.58	gold quality
cerebellar cortex	UBERON:0002129	97.57	gold quality
right coronary artery	UBERON:0001625	97.56	gold quality
synovial joint	UBERON:0002217	97.21	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.15	gold quality
cerebellum	UBERON:0002037	97.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.07	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-GEOD-75367	yes	162.45
E-MTAB-8142	yes	98.83
E-MTAB-6701	yes	75.64
E-CURD-114	yes	58.78
E-HCAD-10	yes	45.72
E-MTAB-6678	yes	16.66
E-CURD-119	yes	11.49
E-CURD-112	yes	6.26
E-GEOD-130148	yes	5.43
E-MTAB-7249	yes	4.53
E-MTAB-7051	no	1056.16
E-GEOD-99795	no	126.08
E-GEOD-137537	no	3.32
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, CUX1, LEF1, SRF

miRNA regulators (miRDB)

73 targeting LIMA1, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-4679	99.76	69.19	1229

Literature-anchored findings (GeneRIF, showing 24)

• EPLIN functions to link the cadherin-catenin complex to F-actin and simultaneously stabilizes this population of actin fibers, resulting in the establishment of the adhesion (PMID:18093941)
• expression of EPLIN-alpha in breast cancer is down-regulated in breast cancer cells . (PMID:18796137)
• EPLIN protein may function during cytokinesis to maintain local accumulation of key cytokinesis proteins at the furrow. (PMID:19221476)
• EPLINalpha over-expression can regulate HECV cell motility, matrix adhesion and tubule formation in vitro and slow in vivo tumour formation, suggesting an anti-angiogenic role for EPLINalpha. (PMID:20848180)
• EPLIN downregulation promotes epithelial-mesenchymal transition in prostate cancer cells and correlates with clinical lymph node metastasis. (PMID:21625216)
• EPLIN clutch is necessary for stabilization of capillary structures in an angiogenesis model. (PMID:22194609)
• Together with the findings that EPLIN-alpha inhibits cellular growth and invasion, we conclude that EPLIN-alpha is a tumour suppressor of oesophageal cancer (PMID:22493360)
• EGF promotes epithelial-mesenchymal transition and induces degradation of EPLIN, a putative suppressor of prostate cancer metastasis. (PMID:23188829)
• a major activity of DNp73 is to establish initiation of the invasion-metastasis cascade via EPLIN-dependent IGF1R regulation (PMID:24135282)
• EPLIN is functionally linked to molecules like actin and paxillin and has been implicated in a number of potential pathways to enhance metastatic potential (PMID:26350886)
• Data provide evidence that downregulation of EPLIN-alpha may be associated with poor prognosis for patients with epithelial ovarian cancer (EOC), and that this molecule appears to play a tumour suppressor role by inhibition of EOC growth and migration. (PMID:27035883)
• Reduction in the levels of hCDC14A and eplin mRNA is frequently associated with colorectal carcinoma and is correlated with poor prognosis. Authors therefore propose that eplin dephosphorylation by hCDC14A reduces actin dynamics to restrict tumor malignancy. (PMID:28465438)
• this study identifies LIMA1 as a key protein regulating intestinal cholesterol absorption. (PMID:29880681)
• Study proposes a role for EPLIN’s ability to regulate the aggressive characteristics of prostate cancer cells partially through regulating FAK/Src signaling. (PMID:30098000)
• EPLIN-alpha and -beta Isoforms Modulate Endothelial Cell Dynamics through a Spatiotemporally Differentiated Interaction with Actin. (PMID:31644899)
• LUZP1 and the tumor suppressor EPLIN modulate actin stability to restrict primary cilia formation. (PMID:32496561)
• Rab40-Cullin5 complex regulates EPLIN and actin cytoskeleton dynamics during cell migration. (PMID:33999101)
• Epithelial Protein Lost in Neoplasm, EPLIN, the Cellular and Molecular Prospects in Cancers. (PMID:34356662)
• CAF-Released Exosomal miR-20a-5p Facilitates HCC Progression via the LIMA1-Mediated beta-Catenin Pathway. (PMID:36497115)
• EPLIN-beta is a novel substrate of ornithine decarboxylase antizyme 1 and mediates cellular migration. (PMID:37325974)
• MAD2 activates IGF1R/PI3K/AKT pathway and promotes cholangiocarcinoma progression by interfering USP44/LIMA1 complex. (PMID:37752233)
• Nuclear-cytoplasmic translocation of SQSTM1/p62 protein enhances ESCC cell migration and invasion by stabilizing EPLIN expression. (PMID:38185251)
• The concerted action of SEPT9 and EPLIN modulates the adhesion and migration of human fibroblasts. (PMID:38719752)
• Expression and molecular insights of lima1 in cholangiocarcinoma. (PMID:39076043)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lima1a	ENSDARG00000101441
mus_musculus	Lima1	ENSMUSG00000023022
rattus_norvegicus	Lima1	ENSRNOG00000059801

Protein

Protein identifiers

LIM domain and actin-binding protein 1 — Q9UHB6 (reviewed: Q9UHB6)

Alternative names: Epithelial protein lost in neoplasm

All UniProt accessions (6): F8VQE1, F8VRN8, F8VS07, F8VTU2, F8VVQ7, Q9UHB6

UniProt curated annotations — full annotation on UniProt →

Function. Actin-binding protein involved in actin cytoskeleton regulation and dynamics. Increases the number and size of actin stress fibers and inhibits membrane ruffling. Inhibits actin filament depolymerization. Bundles actin filaments, delays filament nucleation and reduces formation of branched filaments. Acts as a negative regulator of primary cilium formation. Plays a role in cholesterol homeostasis. Influences plasma cholesterol levels through regulation of intestinal cholesterol absorption. May act as a scaffold protein by regulating NPC1L1 transportation, an essential protein for cholesterol absorption, to the plasma membrane by recruiting MYO5B to NPC1L1, and thus facilitates cholesterol uptake.

Subunit / interactions. Interacts with NPC1L1; bridges NPC1L1 with MYO5B. Interacts with MYO5B; bridges NPC1L1 with MYO5B. Interacts with PXN; this complex stabilizes actin dynamics. Interacts with F-actin and G-actin. Interacts with LUZP1 (via C-terminus); both proteins restrict ciliation and may work together to regulate this process. Binds RAB40B (GTP-bound); interaction influences LIMA1 subcellular localization in lamellipodia during cell migration.

Subcellular location. Cytoplasm. Cell junction. Focal adhesion. Cytoskeleton. Stress fiber. Cell membrane. Cell projection. Ruffle. Lamellipodium.

Tissue specificity. Highly expressed in placenta, kidney, pancreas, prostate, ovary, spleen and heart. Also detected in lung, liver, brain, skeletal muscle, thymus, testis and intestine. Not detected in leukocytes. Isoform Beta expressed generally at very low levels. Isoform Alpha abundant in epithelial cells from mammary gland, prostate and in normal oral keratinocytes. Low levels in aortic endothelial cells and dermal fibroblasts. Not detectable in myocardium.

Post-translational modifications. Ubiquitinated by the ECS(RAB40B) complex leading to its degradation. Phosphorylation of the C-terminal region by MAPK1/MAPK3 reduces its association with F-actin and contributes to actin filament reorganization and enhances cell motility.

Domain organisation. Contains at least 2 actin-binding domains, one on each side of the LIM domain. Both domains bind actin monomers and filaments. The C-terminal domain binds filaments more efficiently than the N-terminus.

Induction. Down-regulated in some cancer cell lines. Isoform Alpha is induced by serum. Isoform Beta is constitutively expressed.

Polymorphism. Genetic variations in LIMA1 influence low density lipoprotein cholesterol (LDL-C) variability and contribute to the low density lipoprotein cholesterol level quantitative trait locus 8 (LDLCQ8) [MIM:618079].

Miscellaneous. Produced by alternative promoter usage. Produced by alternative promoter usage. Produced by alternative splicing of isoform Beta. Produced by alternative splicing.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9UHB6-1	Beta	yes
Q9UHB6-2	Alpha
Q9UHB6-3	3
Q9UHB6-4	4
Q9UHB6-5	5

RefSeq proteins (12): NP_001107018, NP_001107019, NP_001230704, NP_001381815, NP_001381816, NP_001381817, NP_001381818, NP_001381819, NP_001381820, NP_001381821, NP_001381822, NP_057441* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR028740	EPLIN_Lim_dom	Domain

Pfam: PF00412

UniProt features (69 total): modified residue 31, compositionally biased region 11, region of interest 6, sequence conflict 5, strand 4, turn 4, splice variant 3, chain 1, domain 1, sequence variant 1, helix 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2D8Y	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UHB6-F1	52.12	0.09

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 (31): 1, 4, 15, 55, 132, 225, 229, 230, 242, 263, 343, 350, 362, 365, 369, 374, 439, 490, 601, 604 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 368 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_DIGESTION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_STEROL_HOMEOSTASIS, GCANCTGNY_MYOD_Q6, AREB6_03, GOBP_NEGATIVE_REGULATION_OF_ACTIN_FILAMENT_DEPOLYMERIZATION, TAL1ALPHAE47_01, GOCC_RUFFLE, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_LIPID_DIGESTION, GOBP_NEGATIVE_REGULATION_OF_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS

GO Biological Process (13): cholesterol metabolic process (GO:0008203), cell migration (GO:0016477), intestinal cholesterol absorption (GO:0030299), negative regulation of cell migration (GO:0030336), negative regulation of actin filament depolymerization (GO:0030835), ruffle organization (GO:0031529), positive regulation of actin filament bundle assembly (GO:0032233), cholesterol homeostasis (GO:0042632), actin filament bundle assembly (GO:0051017), negative regulation of cilium assembly (GO:1902018), regulation of lamellipodium organization (GO:1902743), lipid metabolic process (GO:0006629), steroid metabolic process (GO:0008202)

GO Molecular Function (7): actin monomer binding (GO:0003785), cadherin binding (GO:0045296), metal ion binding (GO:0046872), actin filament binding (GO:0051015), microtubule stabilizing activity (GO:0140778), actin binding (GO:0003779), protein binding (GO:0005515)

GO Cellular Component (16): stress fiber (GO:0001725), ruffle (GO:0001726), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), lamellipodium (GO:0030027), brush border membrane (GO:0031526), cleavage furrow (GO:0032154), cytoplasm (GO:0005737), cytoskeleton (GO:0005856), brush border (GO:0005903), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
actin binding	2
cell leading edge	2
plasma membrane bounded cell projection	2
sterol metabolic process	1
secondary alcohol metabolic process	1
cell motility	1
lipid digestion	1
intestinal lipid absorption	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
actin filament depolymerization	1
regulation of actin filament depolymerization	1
negative regulation of cytoskeleton organization	1
negative regulation of protein depolymerization	1
negative regulation of supramolecular fiber organization	1
plasma membrane bounded cell projection organization	1
regulation of actin filament bundle assembly	1
positive regulation of cellular component biogenesis	1
actin filament bundle assembly	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
sterol homeostasis	1
cellular component assembly	1
actin filament bundle organization	1
cilium assembly	1
negative regulation of plasma membrane bounded cell projection assembly	1
regulation of cilium assembly	1
negative regulation of organelle assembly	1
lamellipodium organization	1
regulation of plasma membrane bounded cell projection organization	1
primary metabolic process	1
lipid metabolic process	1
cell adhesion molecule binding	1
cation binding	1
protein-containing complex binding	1
protein-containing complex stabilizing activity	1
cytoskeletal protein binding	1
binding	1

Protein interactions and networks

STRING

1216 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMA1	CTNNB1	P35222	931
LIMA1	CTNND1	O60716	800
LIMA1	VCL	P18206	725
LIMA1	CDH17	Q12864	712
LIMA1	CTNNA1	P35221	669
LIMA1	CDH1	P12830	636
LIMA1	TJP1	Q07157	615
LIMA1	DUSP5	Q16690	614
LIMA1	RHOA	P06749	610
LIMA1	PXN	P49023	584
LIMA1	FLNA	P21333	572
LIMA1	CDH5	P33151	571
LIMA1	FLNB	O75369	564
LIMA1	PLEC	Q15149	560
LIMA1	GSN	P06396	560

IntAct

240 interactions, top by confidence:

A	B	Type	Score
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
LIMA1	DAPK1	psi-mi:“MI:0407”(direct interaction)	0.590
CANX	PGRMC1	psi-mi:“MI:0914”(association)	0.570
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
LIMA1	CTNNA1	psi-mi:“MI:0915”(physical association)	0.560
TWF1	MYO1C	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480

BioGRID (557): LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-RNA), LIMA1 (Affinity Capture-RNA), LIMA1 (Affinity Capture-RNA), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS), LIMA1 (Affinity Capture-MS)

ESM2 similar proteins: A0P8Z5, A4IGN8, B0KYV5, D3ZUI5, F1LR10, O00515, O46385, O54931, O75128, O75152, O75410, O95425, P42167, P57016, Q13625, Q1RMS0, Q3U1C4, Q3UMF0, Q53SF7, Q5NBX1, Q5PQN4, Q5PR69, Q5RC32, Q5RDC1, Q5REG6, Q5U301, Q5U5Q9, Q5ZJ26, Q5ZJJ1, Q5ZMW6, Q641Q2, Q6A098, Q6INC4, Q6NZF1, Q6Y685, Q7TNY7, Q80XI1, Q8CG79, Q8K3I4, Q8K4L3

Diamond homologs: B0KYV5, D4A1F2, E7F9T0, F1LR10, F1MF74, F1MH07, F1QH17, F1QWK4, F1RA39, F6QZ15, G3MWR8, O04193, O60952, O80839, O94851, P29675, P34416, P50461, P50462, P50463, Q0E908, Q1ECF5, Q1LZA7, Q4KM31, Q4U0T9, Q4U4S6, Q500W4, Q7F9R9, Q7RTP6, Q8BGB5, Q8BML1, Q8CJ19, Q8I7C3, Q94JX5, Q9BT23, Q9ERG0, Q9M047, Q9UHB6, A5D7D1, A8MU46

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
MAPK1	“down-regulates quantity by destabilization”	LIMA1	phosphorylation
ERK1/2	“down-regulates quantity by destabilization”	LIMA1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 193 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	41.0×	1e-09
Activation of BAD and translocation to mitochondria	7	40.7×	1e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	35.9×	4e-08
RHO GTPases activate PKNs	12	29.1×	1e-12
Activation of BH3-only proteins	7	26.5×	3e-07
RHO GTPases activate PAKs	6	24.9×	4e-06
Signaling by cytosolic FGFR1 fusion mutants	5	24.2×	3e-05
Signaling by RAS mutants	6	19.4×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	6	12.7×	1e-03
substantia nigra development	6	12.7×	1e-03
cellular response to insulin stimulus	7	6.9×	9e-03
actin cytoskeleton organization	14	6.4×	6e-05
intracellular protein localization	10	6.0×	1e-03
protein phosphorylation	13	5.1×	8e-04
cell migration	13	4.6×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2566 predictions. Top by Δscore:

Variant	Effect	Δscore
12:50178065:CTAGA:C	acceptor_gain	1.0000
12:50178070:C:CC	acceptor_gain	1.0000
12:50178076:T:TC	acceptor_gain	1.0000
12:50181900:TTA:T	donor_loss	1.0000
12:50181901:TACCT:T	donor_loss	1.0000
12:50181902:A:AC	donor_gain	1.0000
12:50181902:A:AT	donor_loss	1.0000
12:50181902:AC:A	donor_gain	1.0000
12:50181903:C:CA	donor_gain	1.0000
12:50181903:CC:C	donor_gain	1.0000
12:50181903:CCT:C	donor_gain	1.0000
12:50181903:CCTG:C	donor_gain	1.0000
12:50181903:CCTGA:C	donor_gain	1.0000
12:50182033:AACTT:A	acceptor_gain	1.0000
12:50182034:ACTT:A	acceptor_loss	1.0000
12:50182034:ACTTC:A	acceptor_gain	1.0000
12:50182035:CTT:C	acceptor_gain	1.0000
12:50182035:CTTCT:C	acceptor_gain	1.0000
12:50182036:TT:T	acceptor_gain	1.0000
12:50182038:C:A	acceptor_loss	1.0000
12:50182038:C:CC	acceptor_gain	1.0000
12:50195828:A:AC	donor_gain	1.0000
12:50195829:C:CC	donor_gain	1.0000
12:50195883:GAAAT:G	acceptor_gain	1.0000
12:50195885:AAT:A	acceptor_gain	1.0000
12:50195885:AATC:A	acceptor_loss	1.0000
12:50195886:AT:A	acceptor_gain	1.0000
12:50195886:ATC:A	acceptor_loss	1.0000
12:50195887:TCTAC:T	acceptor_loss	1.0000
12:50195888:C:CA	acceptor_loss	1.0000

AlphaMissense

5039 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:50178030:A:C	C438W	1.000
12:50178032:A:G	C438R	1.000
12:50181929:A:G	C417R	1.000
12:50181988:A:T	V397D	1.000
12:50182010:A:G	C390R	1.000
12:50177750:A:G	W532R	0.999
12:50177750:A:T	W532R	0.999
12:50177976:A:C	F456L	0.999
12:50177976:A:T	F456L	0.999
12:50177978:A:G	F456L	0.999
12:50178006:A:C	F446L	0.999
12:50178006:A:T	F446L	0.999
12:50178007:A:G	F446S	0.999
12:50178008:A:G	F446L	0.999
12:50178010:A:G	L445P	0.999
12:50178018:G:C	F442L	0.999
12:50178018:G:T	F442L	0.999
12:50178020:A:G	F442L	0.999
12:50178031:C:A	C438F	0.999
12:50178031:C:G	C438S	0.999
12:50178031:C:T	C438Y	0.999
12:50178032:A:T	C438S	0.999
12:50178035:A:C	Y437D	0.999
12:50178059:A:C	Y429D	0.999
12:50181918:G:C	C420W	0.999
12:50181919:C:A	C420F	0.999
12:50181919:C:T	C420Y	0.999
12:50181920:A:G	C420R	0.999
12:50181927:G:C	C417W	0.999
12:50181928:C:G	C417S	0.999

dbSNP variants (sampled 300 via entrez): RS1000044839 (12:50229308 G>A), RS1000065145 (12:50239274 A>G), RS1000130837 (12:50257546 C>T), RS1000182514 (12:50211197 C>T), RS1000188748 (12:50203340 T>C), RS1000221559 (12:50203439 A>G), RS1000228300 (12:50268314 C>A), RS1000248608 (12:50220550 C>G), RS1000277944 (12:50226796 G>T), RS1000279246 (12:50275299 T>C), RS1000364771 (12:50176689 G>A), RS1000365195 (12:50220112 G>A), RS1000386090 (12:50282151 A>C,G,T), RS1000424977 (12:50181393 T>C), RS1000456777 (12:50184239 G>A,C)

Disease associations

OMIM: gene MIM:608364 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST003209_14	Colorectal or endometrial cancer	3.000000e-06
GCST007293_76	Body fat distribution (arm fat ratio)	4.000000e-07
GCST007294_123	Body fat distribution (trunk fat ratio)	2.000000e-09
GCST007294_2	Body fat distribution (trunk fat ratio)	1.000000e-18
GCST007295_152	Body fat distribution (leg fat ratio)	4.000000e-13
GCST010204_206	Low density lipoprotein cholesterol levels	7.000000e-15
GCST010243_47	Apolipoprotein B levels	1.000000e-15
GCST010245_165	LDL cholesterol levels	4.000000e-17
GCST010703_176	Brain morphology (MOSTest)	5.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004230	endometrial neoplasm
EFO:0004341	body fat distribution
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725027 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.55	IC50	280	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178840: Inhibition of LIMA1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2800	uM

CTD chemical–gene interactions

106 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	7
bisphenol A	decreases expression	4
trichostatin A	affects cotreatment, increases expression	4
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression, increases expression	3
Valproic Acid	affects expression, increases expression	3
Particulate Matter	affects cotreatment, increases abundance, increases expression, affects expression	3
perfluorooctanoic acid	decreases expression, affects cotreatment, increases expression	2
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
chloropicrin	affects expression, decreases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	decreases expression, affects cotreatment, increases abundance, increases oxidation	2
Doxorubicin	decreases expression, affects response to substance	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Progesterone	decreases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
sodium arsenate	decreases expression	1
decabromobiphenyl ether	decreases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697570	Binding	Inhibition of LIMA1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8PA	Ubigene HCT 116 LIMA1 KO	Cancer cell line	Male
CVCL_E7VL	ARCaPE-shEPLIN	Cancer cell line	Male

Clinical trials (associated diseases)

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