LIMD2

Summary

LIMD2 (LIM domain containing 2, HGNC:28142) is a protein-coding gene on chromosome 17q23.3, encoding LIM domain-containing protein 2 (Q9BT23). Acts as an activator of the protein-kinase ILK, thereby regulating cell motility.

Predicted to enable actin filament binding activity. Predicted to be involved in actin filament bundle assembly. Located in cytosol and nucleoplasm.

Source: NCBI Gene 80774 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 24 total
• MANE Select transcript: NM_030576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28142
Approved symbol	LIMD2
Name	LIM domain containing 2
Location	17q23.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC10986
Ensembl gene	ENSG00000136490
Ensembl biotype	protein_coding
Entrez	80774

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 21 protein_coding, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000259006, ENST00000578061, ENST00000578067, ENST00000578297, ENST00000578402, ENST00000578993, ENST00000579329, ENST00000579814, ENST00000580222, ENST00000582055, ENST00000583211, ENST00000584645, ENST00000851314, ENST00000851315, ENST00000851316, ENST00000851317, ENST00000851318, ENST00000851319, ENST00000851320, ENST00000851321, ENST00000851322, ENST00000923159, ENST00000923160, ENST00000923161, ENST00000953954, ENST00000953955

RefSeq mRNA: 1 — MANE Select: NM_030576 NM_030576

CCDS: CCDS11641

Canonical transcript exons

ENST00000259006 — 5 exons

Exon	Start	End
ENSE00001249271	63695888	63698711
ENSE00001249295	63699028	63699069
ENSE00001374895	63700032	63700125
ENSE00003462804	63698799	63698938
ENSE00003485978	63699257	63699348

Expression profiles

Bgee: expression breadth ubiquitous, 174 present calls, max score 99.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 84.3363 / max 1796.4419, expressed in 1735 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167476	59.7851	1725
167473	22.5557	905
167470	0.6639	290
167477	0.6219	291
167475	0.2160	104
167478	0.2085	110
167474	0.1065	45
167471	0.0990	45
167472	0.0797	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.47	gold quality
monocyte	CL:0000576	98.87	gold quality
leukocyte	CL:0000738	98.78	gold quality
mononuclear cell	CL:0000842	98.75	gold quality
spleen	UBERON:0002106	96.75	gold quality
blood	UBERON:0000178	95.59	gold quality
lymph node	UBERON:0000029	94.38	gold quality
vermiform appendix	UBERON:0001154	93.72	gold quality
bone marrow cell	CL:0002092	93.63	gold quality
ganglionic eminence	UBERON:0004023	92.36	gold quality
cortical plate	UBERON:0005343	92.34	gold quality
bone marrow	UBERON:0002371	89.96	gold quality
caudate nucleus	UBERON:0001873	89.81	gold quality
putamen	UBERON:0001874	89.23	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.90	gold quality
right frontal lobe	UBERON:0002810	88.56	gold quality
caecum	UBERON:0001153	88.43	gold quality
nucleus accumbens	UBERON:0001882	88.28	gold quality
anterior cingulate cortex	UBERON:0009835	87.91	gold quality
cingulate cortex	UBERON:0003027	87.90	gold quality
gall bladder	UBERON:0002110	87.72	gold quality
right lung	UBERON:0002167	87.11	gold quality
prefrontal cortex	UBERON:0000451	86.78	gold quality
upper lobe of left lung	UBERON:0008952	86.68	gold quality
ventricular zone	UBERON:0003053	86.32	gold quality
mucosa of transverse colon	UBERON:0004991	86.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	86.02	gold quality
embryo	UBERON:0000922	85.95	gold quality
small intestine	UBERON:0002108	85.60	gold quality
tibial nerve	UBERON:0001323	85.38	gold quality

Single-cell (SCXA)

Detected in 18 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	93.45
E-CURD-122	yes	64.50
E-HCAD-4	yes	55.57
E-CURD-88	yes	47.73
E-MTAB-8410	yes	37.42
E-HCAD-10	yes	29.17
E-ANND-3	yes	19.04
E-MTAB-10042	yes	16.45
E-MTAB-9067	yes	13.66
E-CURD-112	yes	11.62
E-MTAB-9388	yes	10.41
E-MTAB-9801	yes	5.03
E-CURD-79	no	648.13
E-MTAB-7606	no	633.82
E-CURD-97	no	396.30

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB

miRNA regulators (miRDB)

125 targeting LIMD2, 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-6127	100.00	66.76	2188
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-6759-5P	99.99	66.54	785
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 4)

• Our data suggest that LIMD2 may play an important role in the metastatic process of papillary thyroid carcinoma (PMID:29560564)
• the results of the present study revealed that LIMD2 promoted nonsmall cell lung cancer (NSCLC)progression and was regulated by miR34a. (PMID:30221696)
• LIM domain-containing 2 (LIMD2) promotes the progress of ovarian cancer via the focal adhesion signaling pathway. (PMID:34724866)
• LIMD2 is the Signature of Cell Aging-immune/Inflammation in Acute Myocardial Infarction. (PMID:37936458)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	LIMD2	ENSDARG00000112015
mus_musculus	Limd2	ENSMUSG00000040699
rattus_norvegicus	Limd2	ENSRNOG00000025448
rattus_norvegicus		ENSRNOG00000069052
drosophila_melanogaster	Tes	FBGN0034223
caenorhabditis_elegans		WBGENE00004112
caenorhabditis_elegans		WBGENE00015217

Paralogs (3): LMCD1 (ENSG00000071282), TES (ENSG00000135269), PRICKLE1 (ENSG00000139174)

Protein

Protein identifiers

LIM domain-containing protein 2 — Q9BT23 (reviewed: Q9BT23)

All UniProt accessions (5): A0A140VJN0, Q9BT23, J3KRR0, J3QL69, J3QQM5

UniProt curated annotations — full annotation on UniProt →

Function. Acts as an activator of the protein-kinase ILK, thereby regulating cell motility.

Subunit / interactions. Interacts with ILK.

Subcellular location. Cytoplasm. Nucleus.

Induction. Over-expressed in breast, bladder, melanoma and thyroid cancer cell lines and tumors (at protein level).

Miscellaneous. May play a role in tumor progression via its ability to activate the ILK protein-kinase activity.

RefSeq proteins (1): NP_085053* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR044115	LIM_LIMD2	Domain

Pfam: PF00412

UniProt features (22 total): binding site 8, strand 5, turn 3, chain 1, domain 1, modified residue 1, sequence conflict 1, region of interest 1, helix 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2LZU	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BT23-F1	73.04	0.25

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 91; 40; 43; 61; 64; 67; 70; 88

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 219 (showing top): GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GTGCCTT_MIR506, HOWLIN_PUBERTAL_MAMMARY_GLAND, GOBP_ACTIN_FILAMENT_ORGANIZATION, MODULE_171, RYTTCCTG_ETS2_B, GOMF_ACTIN_BINDING, AGTCAGC_MIR345, HAMAI_APOPTOSIS_VIA_TRAIL_DN, NIKOLSKY_BREAST_CANCER_17Q21_Q25_AMPLICON, NERF_Q2, TTTGCAC_MIR19A_MIR19B, CP2_01, GINESTIER_BREAST_CANCER_ZNF217_AMPLIFIED_DN, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (1): actin filament bundle assembly (GO:0051017)

GO Molecular Function (3): metal ion binding (GO:0046872), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (6): nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular component assembly	1
actin filament bundle organization	1
cation binding	1
actin binding	1
protein-containing complex binding	1
binding	1
nuclear lumen	1
cytoplasm	1
membrane	1
cell periphery	1
cytoskeleton	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

828 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMD2	PDLIM2	Q96JY6	680
LIMD2	ZNF771	Q7L3S4	460
LIMD2	MPP7	Q5T2T1	433
LIMD2	FHL2	Q14192	425
LIMD2	MRPL35	Q9NZE8	418
LIMD2	MED14	O60244	408
LIMD2	MRPS11	P82912	402
LIMD2	TMEM160	Q9NX00	390
LIMD2	ZNF584	Q8IVC4	370
LIMD2	MIDN	Q504T8	368
LIMD2	KCNE1	P15382	367
LIMD2	MTRF1	O75570	362
LIMD2	CCDC18	Q5T9S5	352
LIMD2	LIMD1	Q9UGP4	338
LIMD2	DENND4B	O75064	334

IntAct

5 interactions, top by confidence:

A	B	Type	Score
LIMD2	PSMA6	psi-mi:“MI:0915”(physical association)	0.560
LIMD2	carB	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): LIMD2 (Two-hybrid), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Affinity Capture-MS), LIMD2 (Biochemical Activity), LIMD2 (Protein-peptide), LIMD2 (Proximity Label-MS)

ESM2 similar proteins: O00151, O04193, O35115, O70400, O70433, O80839, P21291, P29675, P36201, P47875, P50238, P50461, P50462, P50463, P50464, P52943, P52944, P53777, P63254, P63255, P67966, P67967, P97315, Q0VFX8, Q14192, Q16527, Q1ECF5, Q1LZA7, Q24400, Q2KI95, Q3MHY1, Q4KM31, Q4U0T9, Q500W4, Q56K04, Q5E9E1, Q5R7Y1, Q5RCT4, Q5RGJ5, Q5ZLR4

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

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	18
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

868 predictions. Top by Δscore:

Variant	Effect	Δscore
17:63698575:C:CT	donor_gain	1.0000
17:63698580:T:TA	donor_gain	1.0000
17:63698707:CCAGG:C	acceptor_gain	1.0000
17:63698708:CAGG:C	acceptor_gain	1.0000
17:63698708:CAGGC:C	acceptor_gain	1.0000
17:63698709:AGG:A	acceptor_gain	1.0000
17:63698710:GG:G	acceptor_gain	1.0000
17:63698711:GC:G	acceptor_loss	1.0000
17:63698712:C:A	acceptor_loss	1.0000
17:63698712:C:CC	acceptor_gain	1.0000
17:63698713:T:G	acceptor_loss	1.0000
17:63698722:C:CT	acceptor_gain	1.0000
17:63699255:A:AC	donor_gain	1.0000
17:63699256:C:CC	donor_gain	1.0000
17:63698521:T:TA	donor_gain	0.9900
17:63698547:AGG:A	donor_gain	0.9900
17:63698554:AGG:A	donor_gain	0.9900
17:63698576:C:CT	donor_gain	0.9900
17:63698715:C:CT	acceptor_gain	0.9900
17:63698722:C:T	acceptor_gain	0.9900
17:63698937:GA:G	acceptor_gain	0.9900
17:63698939:C:CC	acceptor_gain	0.9900
17:63699025:TA:T	donor_loss	0.9900
17:63699026:ACCTT:A	donor_loss	0.9900
17:63699250:CACTT:C	donor_loss	0.9900
17:63699251:ACTTA:A	donor_loss	0.9900
17:63699253:TTA:T	donor_loss	0.9900
17:63699254:TACAT:T	donor_loss	0.9900
17:63699255:A:AT	donor_loss	0.9900
17:63699256:CA:C	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000382701 (17:63697967 G>T), RS1001641022 (17:63697930 C>G,T), RS1001658462 (17:63696916 T>C), RS1001693440 (17:63697729 G>A,C), RS1001826585 (17:63702647 T>C), RS1001877326 (17:63701816 C>A,G,T), RS1001936756 (17:63695553 C>T), RS1002003069 (17:63696683 G>A,T), RS1002389124 (17:63695717 T>C,G), RS1002568030 (17:63701156 G>A,T), RS1002694357 (17:63697022 T>C), RS1002882175 (17:63700162 A>C,G), RS1003550245 (17:63700513 C>T), RS1003574788 (17:63700211 C>A), RS1003759883 (17:63695858 C>T)

Disease associations

OMIM: gene `` | 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
GCST90002397_583	Mean spheric corpuscular volume	2.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	increases expression, increases methylation	2
Nickel	increases expression	2
Valproic Acid	decreases expression, increases methylation	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
titanium dioxide	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
CMF regimen	affects response to substance	1
abrine	decreases expression	1
jinfukang	increases expression, affects cotreatment	1
Sunitinib	decreases expression	1
Arsenic Trioxide	increases response to substance	1
Arsenic	affects methylation	1
Calcitriol	decreases expression	1
Cisplatin	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diuron	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Rotenone	decreases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	increases expression	1
Aflatoxin B1	increases expression	1
Gold Compounds	increases expression	1
Sodium Selenite	increases expression	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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