LIMS1

Summary

LIMS1 (LIM zinc finger domain containing 1, HGNC:6616) is a protein-coding gene on chromosome 2q12.3, encoding LIM and senescent cell antigen-like-containing domain protein 1 (P48059). Within the IPP (ILK-PINCH-PARVIN) complex, binds to F-actin, promoting F-actin bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration.

The protein encoded by this gene is an adaptor protein which contains five LIM domains, or double zinc fingers. The protein is likely involved in integrin signaling through its LIM domain-mediated interaction with integrin-linked kinase, found in focal adhesion plaques. It is also thought to act as a bridge linking integrin-linked kinase to NCK adaptor protein 2, which is involved in growth factor receptor kinase signaling pathways. Its localization to the periphery of spreading cells also suggests that this protein may play a role in integrin-mediated cell adhesion or spreading. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 3987 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 75 total
• Druggable target: yes
• MANE Select transcript: NM_001193483

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6616
Approved symbol	LIMS1
Name	LIM zinc finger domain containing 1
Location	2q12.3
Locus type	gene with protein product
Status	Approved
Aliases	PINCH, PINCH1
Ensembl gene	ENSG00000169756
Ensembl biotype	protein_coding
OMIM	602567
Entrez	3987

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 20 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000332345, ENST00000338045, ENST00000393310, ENST00000409441, ENST00000410093, ENST00000414829, ENST00000422797, ENST00000434274, ENST00000449684, ENST00000462817, ENST00000474038, ENST00000496653, ENST00000542845, ENST00000544547, ENST00000695516, ENST00000695517, ENST00000695518, ENST00000695519, ENST00000695520, ENST00000695521, ENST00000695522, ENST00000695523, ENST00000695524, ENST00000939438, ENST00000968506, ENST00000968507

RefSeq mRNA: 16 — MANE Select: NM_001193483 NM_001193482, NM_001193483, NM_001193484, NM_001193485, NM_001193488, NM_001371494, NM_001371495, NM_001371496, NM_001371497, NM_001371498, NM_001371499, NM_001371500, NM_001394896, NM_001394897, NM_001394898, NM_004987

CCDS: CCDS2078, CCDS54382, CCDS54383, CCDS54384, CCDS54385, CCDS92829, CCDS92830, CCDS92831, CCDS92832, CCDS92833

Canonical transcript exons

ENST00000544547 — 10 exons

Exon	Start	End
ENSE00002456591	108670781	108670847
ENSE00002493656	108675878	108676028
ENSE00003620191	108680695	108680770
ENSE00003625238	108659605	108659764
ENSE00003672911	108676606	108676698
ENSE00003686993	108672325	108672445
ENSE00003691742	108677979	108678027
ENSE00003789009	108672880	108673029
ENSE00003964133	108683885	108687246
ENSE00003964137	108534470	108534594

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 97.73.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 48.9412 / max 1076.2788, expressed in 1817 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21876	21.2090	1804
21884	16.1832	754
21886	3.1977	309
21875	1.6198	1089
21896	1.4129	305
21906	0.9382	370
21885	0.5737	157
21899	0.4472	132
21895	0.4386	156
21887	0.4093	147

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.73	gold quality
stromal cell of endometrium	CL:0002255	97.70	gold quality
mononuclear cell	CL:0000842	97.33	gold quality
leukocyte	CL:0000738	96.91	gold quality
adrenal tissue	UBERON:0018303	96.40	gold quality
endometrium	UBERON:0001295	95.51	gold quality
gastrocnemius	UBERON:0001388	95.40	gold quality
muscle of leg	UBERON:0001383	94.98	gold quality
ascending aorta	UBERON:0001496	94.47	gold quality
thoracic aorta	UBERON:0001515	94.31	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.81	gold quality
decidua	UBERON:0002450	93.43	gold quality
cauda epididymis	UBERON:0004360	93.41	gold quality
descending thoracic aorta	UBERON:0002345	93.36	gold quality
colonic epithelium	UBERON:0000397	93.14	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	92.91	gold quality
aorta	UBERON:0000947	92.90	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.86	gold quality
corpus epididymis	UBERON:0004359	92.56	gold quality
gall bladder	UBERON:0002110	92.41	gold quality
caput epididymis	UBERON:0004358	92.00	gold quality
left adrenal gland cortex	UBERON:0035825	91.92	gold quality
tibial artery	UBERON:0007610	91.89	gold quality
popliteal artery	UBERON:0002250	91.88	gold quality
biceps brachii	UBERON:0001507	91.82	gold quality
right coronary artery	UBERON:0001625	91.81	gold quality
calcaneal tendon	UBERON:0003701	91.79	gold quality
muscle organ	UBERON:0001630	91.77	gold quality
adrenal gland	UBERON:0002369	91.71	gold quality
adrenal cortex	UBERON:0001235	91.56	gold quality

Single-cell (SCXA)

Detected in 19 experiment(s), a significant marker in 19.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	3040.45
E-CURD-122	yes	2991.62
E-HCAD-10	yes	2602.14
E-CURD-98	yes	1837.56
E-MTAB-8271	yes	603.18
E-HCAD-6	yes	369.69
E-MTAB-10287	yes	49.14
E-MTAB-8142	yes	46.96
E-HCAD-4	yes	46.36
E-CURD-119	yes	34.91
E-MTAB-9221	yes	23.88
E-HCAD-1	yes	16.75
E-HCAD-25	yes	16.10
E-MTAB-6701	yes	15.16
E-MTAB-9067	yes	12.83

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
ILK	Activation

miRNA regulators (miRDB)

132 targeting LIMS1, 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-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 40)

• Assembly of the PINCH-ILK-CH-ILKBP complex precedes and is essential for localization of each component to cell-matrix adhesion sites (PMID:12432066)
• PINCH1 and ILK are essential for prompt cell spreading and motility; PINCH1 and ILK, like alpha-parvin, are crucial for cell survival; PINCH1 and ILK are required for optimal activating phosphorylation of PKB/Akt of the survival pathway (PMID:14551191)
• PINCH-1 functions as a molecular platform for coupling and uncoupling diverse cellular processes via overlapping but yet distinct domain interactions (PMID:15941716)
• Up-regulation of PINCH protein in stroma may be involved in promoting invasion and metastasis in oral squamous cell cacinoma. (PMID:16273248)
• PINCH-1, through its interaction with integrin-linked kinase, plays important role in regulating TGF-beta1-mediated epithelial-to-mesenchymal transition and could be potential future therapeutic target to prevent progression of renal disease. (PMID:17656471)
• PINCH-1 contributes to apoptosis resistance through suppression of Bim. Mechanistically, PINCH-1 suppresses Bim not only transcriptionally but also post-transcriptionally. (PMID:18063582)
• PINCH expression may be involved in glioma development and differentiation. (PMID:18187956)
• observations that PINCH is robustly expressed in the CNS of HIV patients suggests an important role for PINCH in HIV-associated neurodegenerative processes (PMID:18459134)
• PINCH protein is overexpressed in tumor-associated stroma of esophageal squamous cell carcinoma. (PMID:18957717)
• zincs are coordinated by PINCH1 LIM1, and suggests that conformational flexibility and twisting between the 2 zinc fingers within the LIM1 domain may be important for ILK binding. (PMID:19074270)
• Review provides an overview of the current knowledge of the molecular interactions of PINCH with other components of focal adhesions and discusses its potential implication for human heart disease. (PMID:19952891)
• Findings of increased PINCH protein in more advanced stages of human pancreatic ductal adenocarcinoma, as well as in metastatic tumours in the animal model, support the hypothesis that PINCH is an important controller of cell survival and migration. (PMID:20590912)
• PINCH may function as a neuron-specific host-mediated response to challenge by HIV-related factors in the CNS. (PMID:20689998)
• PINCH expression markedly increased in tumor-associated stroma in endometrioid carcinoma compared to normal endometrium and atypical endometrial hyperplasia; results suggest PINCH seems to play a role in tumorigenesis and development of endometrial cancer (PMID:20714146)
• data reveal how specific domains of PINCH-1 direct two independent pathways: one utilizing ILK to allow cell attachment, and the other recruiting Rsu-1 to activate Rac1 in order to promote cell spreading (PMID:20926685)
• Data suggest that the adapter protein PINCH1 critically participates in the regulation of the cellular radiosensitivity of normal and malignant cells similarly under adhesion and suspension conditions. (PMID:20927395)
• PINCH1 can shuttle into the nucleus from cytoplasm in podocytes, wherein it interacts with WT1 and suppresses podocyte-specific gene expression. (PMID:21390327)
• PINCH staining at the tumour invasive margin was related to survival in poorly differentiated tumours but not in better differentiated tumours, indicating that the impact of PINCH on prognosis was dependent on differentiation status. (PMID:21426571)
• PINCH mRNA overexpression in colorectal carcinomas is correlated with VEGF and FAS mRNA expression (PMID:22199270)
• Pinch-1 mRNA and protein were significantly up-regulated in acute lymphoblastic leukemia and acute myeloid leukemia bone marrow stromal cells compared to normal bone marrow stromal cells (p<0.01). (PMID:22310984)
• PINCH protein might play an important role in the tumourigenesis and metastasis of gastric adenocarcinoma. (PMID:22976000)
• PINCH is increased and binds to hp-Tau. These studies address a new mechanism by which AD and HIV may intersect and identify PINCH as a contributing factor to the accumulation of hyperphosphorylated Tau. (PMID:23554879)
• PINCH predicts survival in rectal cancer patients with RT, but not in patients without RT. The expression of PINCH may be regulated by radiation and by environmental factors surrounding the cells. (PMID:23970013)
• changes in CSF levels of PINCH appear to correlate with changes in blood CD4 count and with changes in CSF hyperphosphorylated Tau levels (PMID:24817145)
• two novel genes, galectin 9 and PINCH, were expressed at much higher levels in cancerous lesions than in normal tissues in all the patients with clear-cell carcinoma who were examined (PMID:24895689)
• Downregulation of PINCH1 is associated with metastatic breast cancer. (PMID:25647720)
• Data suggest that PINCH1 and Nck2 critically participate in the regulation of cellular radiosensitivity and EGFR function and downstream signaling in a cellular model of human squamous cell carcinoma. (PMID:26004008)
• our data suggest an essential role of PINCH1, ILK and ILKAP for the radioresistance of p53-wildtype glioblastoma multiforme cells (PMID:26460618)
• Mammalian cells have two functional PINCH proteins, PINCH1 and PINCH2. PINCH not only binds to Nck2 and engages in the signaling of growth factor receptors, but also forms a ternary complex with ILK and parvin (IPP complex). (PMID:27590440)
• that PINCH-1 may be playing an important role in etiopathogenesis of both subtypes breast cancer (PMID:29079319)
• High LIMS1 expression is associated with Neuroblastoma. (PMID:29695398)
• focal adhesion signaling to actin cytoskeleton is implicated in human laryngeal carcinogenesis and PINCH1 has prognostic significance in the disease. (PMID:29755929)
• We found that the LIMS1 locus appeared to encode a minor histocompatibility antigen. Genomic collision at this locus was associated with rejection of the kidney allograft and with production of anti-LIMS1 IgG2 and IgG3. (PMID:31091373)
• The PINCH-1 interacts with Smurf1, which inhibits the latter from interacting with BMPR2 and consequently suppresses BMPR2 degradation, resulting in augmented BMP signaling and MSC osteogenic differentiation (OD). (PMID:31578224)
• PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis. (PMID:31801973)
• Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons. (PMID:32746944)
• MicroRNA-Dependent Targeting of RSU1 and the IPP Adhesion Complex Regulates the PTEN/PI3K/AKT Signaling Pathway in Breast Cancer Cell Lines. (PMID:32751711)
• PINCH-1 regulates mitochondrial dynamics to promote proline synthesis and tumor growth. (PMID:33004813)
• A mechanoresponsive PINCH-1-Notch2 interaction regulates smooth muscle differentiation of human placental mesenchymal stem cells. (PMID:33529444)
• Complex structures of Rsu1 and PINCH1 reveal a regulatory mechanism of the ILK/PINCH/Parvin complex for F-actin dynamics. (PMID:33587032)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lims2	ENSDARG00000014976
danio_rerio	lims1	ENSDARG00000026985
drosophila_melanogaster	stck	FBGN0020249
drosophila_melanogaster	Zasp67	FBGN0036044
caenorhabditis_elegans		WBGENE00004030
caenorhabditis_elegans		WBGENE00006826

Paralogs (3): LIMS2 (ENSG00000072163), LIMS4 (ENSG00000256671), LIMS3 (ENSG00000256977)

Protein

Protein identifiers

LIM and senescent cell antigen-like-containing domain protein 1 — P48059 (reviewed: P48059)

Alternative names: Particularly interesting new Cys-His protein 1, Renal carcinoma antigen NY-REN-48

All UniProt accessions (11): A0A0M3HER1, A0A8Q3WKI3, A0A8Q3WKJ2, A0A8Q3WKK6, A0A8Q3WKP0, A0A8Q3WLN4, A0A8Q3WLX8, P48059, F8WB59, F8WC86, F8WE10

UniProt curated annotations — full annotation on UniProt →

Function. Within the IPP (ILK-PINCH-PARVIN) complex, binds to F-actin, promoting F-actin bundling, a process required to generate force for actin cytoskeleton reorganization and subsequent dynamic cell adhesion events such as cell spreading and migration.

Subunit / interactions. Component of the heterotrimeric IPP (ILK-PINCH-PARVIN) complex composed of ILK, LIMS1/PINCH and PARVA; the complex binds to F-actin via the C-terminal tail of LIMS1 and the N-terminal region of PARVA, promoting F-actin filament bundling. Formation of the IPP complex is dependent on protein kinase C and precedes integrin-mediated cell adhesion and spreading. Competes with LIMS2 for interaction with ILK. Interacts (via LIM zinc-binding 5) with TGFB1I1. Interacts with SH3/SH2 adapter NCK2, thereby linking the complex to cell surface receptors.

Subcellular location. Cell junction. Focal adhesion. Cell membrane.

Tissue specificity. Expressed in most tissues except in the brain.

Isoforms (5)

UniProt ID	Names	Canonical?
P48059-1	1	yes
P48059-2	2
P48059-3	3
P48059-4	4
P48059-5	5

RefSeq proteins (16): NP_001180411, NP_001180412, NP_001180413, NP_001180414, NP_001180417, NP_001358423, NP_001358424, NP_001358425, NP_001358426, NP_001358427, NP_001358428, NP_001358429, NP_001381825, NP_001381826, NP_001381827, NP_004978 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR017351	PINCH-1-4-like	Family
IPR047944	LIMS1/2-like_LIM1	Domain
IPR047946	PINCH-1/2-like	Family

Pfam: PF00412

UniProt features (65 total): strand 26, turn 11, mutagenesis site 7, helix 7, domain 5, splice variant 4, sequence conflict 2, initiator methionine 1, chain 1, modified residue 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4HI8	X-RAY DIFFRACTION	1.2
4HI9	X-RAY DIFFRACTION	1.2
3F6Q	X-RAY DIFFRACTION	1.6
7D2S	X-RAY DIFFRACTION	1.65
7D2T	X-RAY DIFFRACTION	2.2
7LT9	X-RAY DIFFRACTION	3.05
7D2U	X-RAY DIFFRACTION	3.15
1G47	SOLUTION NMR
1NYP	SOLUTION NMR
1U5S	SOLUTION NMR
2COR	SOLUTION NMR
2D8X	SOLUTION NMR
2KBX	SOLUTION NMR
6MIF	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48059-F1	88.24	0.48

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): 2

Mutagenesis-validated functional residues (7):

Position	Phenotype
40	loss of interaction with ilk and loss of localization to focal adhesions.
42	loss of interaction with ilk and loss of localization to focal adhesions.
56	alters interaction with ilk.
61	alters interaction with ilk.
62	alters interaction with ilk.
66	alters interaction with ilk.
307–313	reduced actin binding and reduced f-actin bundling. impaired cell spreading.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-446353	Cell-extracellular matrix interactions
R-HSA-446388	Regulation of cytoskeletal remodeling and cell spreading by IPP complex components
R-HSA-1500931	Cell-Cell communication
R-HSA-446728	Cell junction organization

MSigDB gene sets: 270 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_RESPONSE_TO_PEPTIDE, chr2q12, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_MATURE_CELL, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, MORI_IMMATURE_B_LYMPHOCYTE_UP, KYNG_DNA_DAMAGE_DN, GOBP_CELL_CELL_ADHESION, BROWNE_HCMV_INFECTION_48HR_DN, MARTINEZ_RB1_TARGETS_UP, GOBP_CELL_JUNCTION_ORGANIZATION

GO Biological Process (16): cell-matrix adhesion (GO:0007160), tumor necrosis factor-mediated signaling pathway (GO:0033209), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), cell-cell junction organization (GO:0045216), negative regulation of DNA-templated transcription (GO:0045892), cellular response to transforming growth factor beta stimulus (GO:0071560), cell-cell adhesion (GO:0098609), positive regulation of substrate adhesion-dependent cell spreading (GO:1900026), positive regulation of integrin-mediated signaling pathway (GO:2001046), cell surface receptor signaling pathway (GO:0007166), positive regulation of signal transduction (GO:0009967), positive regulation of gene expression (GO:0010628), positive regulation of cell-substrate adhesion (GO:0010811), positive regulation of GTPase activity (GO:0043547), establishment of protein localization (GO:0045184), positive regulation of focal adhesion assembly (GO:0051894)

GO Molecular Function (5): actin binding (GO:0003779), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (8): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), cell-cell junction (GO:0005911), focal adhesion (GO:0005925), perinuclear region of cytoplasm (GO:0048471), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cell junction organization	1
Cell-extracellular matrix interactions	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cell-substrate adhesion	2
signal transduction	2
cytoplasm	2
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
cell junction organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
cell adhesion	1
positive regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
integrin-mediated signaling pathway	1
positive regulation of signal transduction	1
regulation of integrin-mediated signaling pathway	1
regulation of signal transduction	1
positive regulation of cell communication	1
positive regulation of signaling	1
positive regulation of response to stimulus	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell-substrate adhesion	1
positive regulation of cell adhesion	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
establishment of localization	1
positive regulation of cell-matrix adhesion	1
focal adhesion assembly	1
regulation of focal adhesion assembly	1
positive regulation of cell-substrate junction organization	1
positive regulation of cell junction assembly	1

Protein interactions and networks

STRING

734 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMS1	PARVA	Q9NVD7	999
LIMS1	ILK	P57043	999
LIMS1	PARVB	Q9HBI1	998
LIMS1	PARVG	Q9HBI0	997
LIMS1	NCK2	O43639	990
LIMS1	TMSB4X	P01253	979
LIMS1	RSU1	Q15404	971
LIMS1	TLN1	Q9Y490	965
LIMS1	TLN2	Q9Y4G6	965
LIMS1	VCL	P18206	959
LIMS1	PXN	P49023	904
LIMS1	ANK1	P16157	785
LIMS1	ANK2	Q01484	773
LIMS1	ANK3	Q12955	772
LIMS1	FERMT2	Q96AC1	770

IntAct

82 interactions, top by confidence:

A	B	Type	Score
LIMS1	ILK	psi-mi:“MI:0915”(physical association)	0.960
ILK	LIMS1	psi-mi:“MI:0407”(direct interaction)	0.960
ILK	LIMS1	psi-mi:“MI:0914”(association)	0.960
ILK	LIMS1	psi-mi:“MI:0915”(physical association)	0.960
LIMS1	ILK	psi-mi:“MI:0914”(association)	0.960
RSU1	LIMS1	psi-mi:“MI:0915”(physical association)	0.850
LIMS1	RSU1	psi-mi:“MI:0915”(physical association)	0.850
RSU1	LIMS1	psi-mi:“MI:0914”(association)	0.850
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
LIMS1	Ilk	psi-mi:“MI:0915”(physical association)	0.710
Ilk	LIMS1	psi-mi:“MI:0915”(physical association)	0.710
LIMS1	Ilk	psi-mi:“MI:0407”(direct interaction)	0.710
Ilk	LIMS1	psi-mi:“MI:0407”(direct interaction)	0.710
PARVG	LIMS1	psi-mi:“MI:0914”(association)	0.640
PARVA	LIMS1	psi-mi:“MI:0914”(association)	0.640
LIMS1	NCK2	psi-mi:“MI:0407”(direct interaction)	0.620
LIMS1	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
Hoxa1	LIMS1	psi-mi:“MI:0915”(physical association)	0.570

BioGRID (161): RSU1 (Two-hybrid), LIMS1 (Affinity Capture-MS), LIMS1 (Affinity Capture-MS), TYMS (Affinity Capture-MS), MYO18A (Affinity Capture-MS), ILK (Affinity Capture-MS), PARVA (Affinity Capture-MS), PARVB (Affinity Capture-MS), CMAS (Affinity Capture-MS), SRRT (Affinity Capture-MS), RABGAP1 (Affinity Capture-MS), REPS1 (Affinity Capture-MS), MYH7 (Affinity Capture-MS), PXN (Affinity Capture-MS), TRIP6 (Affinity Capture-MS)

ESM2 similar proteins: A0A2R8RWN9, A5PKA5, O15294, O89050, P25791, P25801, P48059, P49136, P49139, P49336, P56558, P61201, P61202, P61203, P61968, P61969, P79101, P81436, Q08211, Q1LZ94, Q27HV0, Q28141, Q2KJ33, Q3SWZ8, Q3UHD6, Q5FVB2, Q5M8V8, Q5R874, Q5RB35, Q5SRY7, Q5ZIH0, Q6DJ06, Q7Z4I7, Q801P0, Q8AW92, Q8CGY8, Q8K4V4, Q8R3L8, Q90XH3, Q91854

Diamond homologs: A0A1L8F1M4, A0M8R4, A0M8S5, A0M8U6, A1Z6W3, A8WH69, O35115, O43294, O43900, O60711, O70433, O94929, P47226, P48059, P49023, P49024, P50464, P97447, Q00PK1, Q07DW1, Q07DX3, Q07DY3, Q07DZ4, Q07E27, Q07E40, Q07E51, Q09476, Q09YI0, Q09YJ2, Q09YK3, Q09YL5, Q09YN8, Q108U9, Q13642, Q13643, Q14192, Q174I2, Q17QE2, Q28FG2, Q292U2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
LIMS1	“form complex”	“IPP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 52 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
ESR-mediated signaling	5	16.4×	2e-03
Diseases of signal transduction by growth factor receptors and second messengers	6	8.7×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
substrate adhesion-dependent cell spreading	5	35.8×	2e-04
epidermal growth factor receptor signaling pathway	5	25.8×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	60
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1871 predictions. Top by Δscore:

Variant	Effect	Δscore
2:108659595:C:CA	acceptor_gain	1.0000
2:108659597:T:TA	acceptor_gain	1.0000
2:108659603:A:AG	acceptor_gain	1.0000
2:108659604:G:GA	acceptor_gain	1.0000
2:108659604:GC:G	acceptor_gain	1.0000
2:108659604:GCA:G	acceptor_gain	1.0000
2:108659604:GCAAC:G	acceptor_gain	1.0000
2:108659761:TGAGG:T	donor_loss	1.0000
2:108659762:GAG:G	donor_gain	1.0000
2:108659764:GGTG:G	donor_loss	1.0000
2:108659765:G:GG	donor_gain	1.0000
2:108659765:GTGA:G	donor_loss	1.0000
2:108659766:T:A	donor_loss	1.0000
2:108672312:T:A	acceptor_gain	1.0000
2:108672321:A:AG	acceptor_gain	1.0000
2:108672321:ACAG:A	acceptor_gain	1.0000
2:108672322:C:G	acceptor_gain	1.0000
2:108672322:CAGG:C	acceptor_loss	1.0000
2:108672323:A:AG	acceptor_gain	1.0000
2:108672323:AG:A	acceptor_gain	1.0000
2:108672323:AGGT:A	acceptor_gain	1.0000
2:108672324:G:A	acceptor_gain	1.0000
2:108672324:G:GC	acceptor_gain	1.0000
2:108672324:GGT:G	acceptor_gain	1.0000
2:108672324:GGTG:G	acceptor_gain	1.0000
2:108672324:GGTGA:G	acceptor_gain	1.0000
2:108672405:G:GT	donor_gain	1.0000
2:108672441:GGGAG:G	donor_gain	1.0000
2:108672442:GGAG:G	donor_gain	1.0000
2:108672442:GGAGG:G	donor_gain	1.0000

AlphaMissense

2270 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:108670796:T:G	Y58D	1.000
2:108670799:T:C	C59R	1.000
2:108670800:G:A	C59Y	1.000
2:108670801:T:G	C59W	1.000
2:108670811:T:C	F63L	1.000
2:108670813:T:A	F63L	1.000
2:108670813:T:G	F63L	1.000
2:108670823:T:C	F67L	1.000
2:108670825:T:A	F67L	1.000
2:108670825:T:G	F67L	1.000
2:108670827:C:A	A68D	1.000
2:108670835:T:C	C71R	1.000
2:108670836:G:A	C71Y	1.000
2:108670837:T:G	C71W	1.000
2:108672330:T:C	F77L	1.000
2:108672332:C:A	F77L	1.000
2:108672332:C:G	F77L	1.000
2:108672390:T:C	C97R	1.000
2:108672424:G:A	G108E	1.000
2:108672426:T:C	F109L	1.000
2:108672428:T:A	F109L	1.000
2:108672428:T:G	F109L	1.000
2:108672887:T:C	C118R	1.000
2:108672938:T:C	C135R	1.000
2:108672939:G:A	C135Y	1.000
2:108672940:C:G	C135W	1.000
2:108672947:T:C	C138R	1.000
2:108673016:T:A	C161S	1.000
2:108673016:T:C	C161R	1.000
2:108673017:G:A	C161Y	1.000

dbSNP variants (sampled 300 via entrez): RS1000001917 (2:108610219 T>C), RS1000051096 (2:108617347 A>G), RS1000051512 (2:108650172 G>A), RS1000077616 (2:108588053 C>A,T), RS1000087061 (2:108679217 G>A), RS1000093427 (2:108563231 C>T), RS1000186860 (2:108616746 A>G), RS1000261722 (2:108575640 G>A), RS1000276385 (2:108645066 A>G), RS1000283297 (2:108553217 C>A,T), RS1000360579 (2:108532961 C>T), RS1000391790 (2:108559413 C>T), RS1000398256 (2:108575321 A>G), RS1000437985 (2:108610592 C>T), RS1000460007 (2:108581962 A>G)

Disease associations

OMIM: gene MIM:602567 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST003474_7	Scalp hair shape	3.000000e-119
GCST003475_4	Beard thickness	1.000000e-15
GCST003476_3	Eyebrow thickness	1.000000e-07
GCST003477_5	Monobrow thickness	1.000000e-07
GCST006095_2	Excessive hairiness	2.000000e-09
GCST006612_16	LDL cholesterol	1.000000e-09
GCST008362_146	Birth weight	3.000000e-08
GCST010243_93	Apolipoprotein B levels	2.000000e-10
GCST010245_76	LDL cholesterol levels	3.000000e-10
GCST90002387_262	Immature fraction of reticulocytes	3.000000e-09
GCST90011900_130	Serum alkaline phosphatase levels	5.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004344	birth weight
EFO:0004615	apolipoprotein B measurement
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066888 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.09	Kd	8152	nM	CHEMBL5653589
5.05	ED50	8849	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 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
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148654: Binding affinity to human LIMS1 incubated for 45 mins by Kinobead based pull down assay	kd	8.1517	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases expression, decreases methylation	3
sodium arsenite	increases abundance, increases expression, affects cotreatment	2
Tretinoin	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
lead acetate	increases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
sodium bichromate	decreases expression	1
cobaltous chloride	increases expression	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Bortezomib	increases expression	1
Temozolomide	decreases expression	1
Decitabine	increases expression	1
Matrines	decreases expression, decreases reaction, affects expression, affects reaction	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Azacitidine	increases expression	1
Benzo(a)pyrene	increases methylation	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651696	Binding	Binding affinity to human LIMS1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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