LIMD1

Summary

LIMD1 (LIM domain containing 1, HGNC:6612) is a protein-coding gene on chromosome 3p21.31, encoding LIM domain-containing protein 1 (Q9UGP4). Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, prol….

Predicted to enable transcription corepressor activity. Involved in several processes, including negative regulation of hippo signaling; negative regulation of macromolecule biosynthetic process; and response to hypoxia. Acts upstream of or within P-body assembly and miRNA-mediated post-transcriptional gene silencing. Located in several cellular components, including P-body; adherens junction; and focal adhesion. Part of RISC complex.

Source: NCBI Gene 8994 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 118 total
• Druggable target: yes
• MANE Select transcript: NM_014240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6612
Approved symbol	LIMD1
Name	LIM domain containing 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000144791
Ensembl biotype	protein_coding
OMIM	604543
Entrez	8994

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000273317, ENST00000440097, ENST00000465039, ENST00000474665, ENST00000943035

RefSeq mRNA: 1 — MANE Select: NM_014240 NM_014240

CCDS: CCDS2729

Canonical transcript exons

ENST00000273317 — 8 exons

Exon	Start	End
ENSE00000967113	45594751	45596287
ENSE00001054371	45676922	45686341
ENSE00001767376	45674343	45674411
ENSE00003470336	45665650	45665717
ENSE00003520971	45636150	45636251
ENSE00003546473	45668294	45668356
ENSE00003600935	45672690	45672820
ENSE00003691876	45673454	45673505

Expression profiles

Bgee: expression breadth ubiquitous, 267 present calls, max score 94.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.2532 / max 597.0157, expressed in 1809 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36383	18.6402	1800
36384	4.1423	1610
36382	2.0049	1125
36385	1.4261	746
36380	0.0332	8
36381	0.0066	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	94.93	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.94	gold quality
superficial temporal artery	UBERON:0001614	92.03	gold quality
pigmented layer of retina	UBERON:0001782	91.34	gold quality
retina	UBERON:0000966	91.32	gold quality
visceral pleura	UBERON:0002401	90.14	gold quality
synovial joint	UBERON:0002217	89.41	gold quality
pylorus	UBERON:0001166	89.22	gold quality
oral cavity	UBERON:0000167	89.19	gold quality
germinal epithelium of ovary	UBERON:0001304	89.09	gold quality
superior surface of tongue	UBERON:0007371	89.00	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	88.35	gold quality
secondary oocyte	CL:0000655	88.30	gold quality
oocyte	CL:0000023	88.25	gold quality
tibia	UBERON:0000979	88.24	gold quality
bronchial epithelial cell	CL:0002328	87.75	gold quality
epithelium of nasopharynx	UBERON:0001951	87.70	gold quality
nasopharynx	UBERON:0001728	87.68	gold quality
right lung	UBERON:0002167	87.34	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.34	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.32	gold quality
trabecular bone tissue	UBERON:0002483	87.11	gold quality
colonic mucosa	UBERON:0000317	86.85	gold quality
jejunum	UBERON:0002115	86.58	gold quality
upper lobe of lung	UBERON:0008948	86.52	gold quality
cardia of stomach	UBERON:0001162	86.18	gold quality
gastrocnemius	UBERON:0001388	85.91	gold quality
saphenous vein	UBERON:0007318	85.90	gold quality
upper lobe of left lung	UBERON:0008952	85.88	gold quality
biceps brachii	UBERON:0001507	85.79	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.79
E-ENAD-27	no	3.75

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
HIF1A	Repression

Upstream regulators (CollecTRI, top): AP1, FOXC1, NFATC1, SPI1

miRNA regulators (miRDB)

175 targeting LIMD1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-485-3P	99.98	70.68	1585
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-LET-7A-5P	99.98	72.29	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-MIR-98-5P	99.98	72.33	1787
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650

Literature-anchored findings (GeneRIF, showing 21)

• LIMD1 is a tumor-suppressor gene, the protein product of which functionally interacts with pRB and the loss of which promotes lung carcinogenesis (PMID:15542589)
• analysis of hLIMD1 gene variants in breast cancer (PMID:17889706)
• These results suggest that some breast tumors have altered expression of LIMD1 RNA and that LIMD1 may be involved in cell anchoring via focal adhesions and in the cell cycle, particularly during mitosis. (PMID:18439753)
• study demonstrates that LIMD1 represents a novel prognostic marker for breast cancer. Combined with the fact that LIMD1 expression is downregulated in lung cancers this clearly indicates that LIMD1 may represent a critical tumor suppressor gene (PMID:18712738)
• LIMD1 is a validated chromosome 3p21.3 tumor-suppressor gene involved in human lung cancer development. (PMID:19060205)
• LIMD1 inactivation as primary event than inactivation of RB1 in head and neck squamous cell carcinoma development. (PMID:20226061)
• PU.1 is a major transcriptional activator of LIMD1 (PMID:21402070)
• Data show that the tumour suppressor protein LIMD1 acts as a molecular scaffold, simultaneously binding the PHDs and VHL, thereby assembling a PHD-LIMD1-VHL protein complex and creating an enzymatic niche that enables efficient degradation of HIF-1alpha. (PMID:22286099)
• LIMD1 prevents retinoblastoma phosphorylation and downregulates of E2F1 protein and blocks entry of cells into S-phase. (PMID:24523249)
• Cyclic stretch is associated with a JNK-dependent increase in binding of a LATS inhibitor, LIMD1, to the LATS1 kinase and that reduction of LIMD1 expression suppresses the activation of YAP by cyclic stretch. (PMID:25127217)
• Thus, the LIMD1-MYBL1 Index had considerable clinical value for DLBCL subtype classification and prognosis. (PMID:25940947)
• These results suggested that LIMD1 is a novel BRCA2-interacting protein and is involved in the centrosome localization of BRCA2 and suppression of LIMD1, causing abnormal cell division in EC cells. (PMID:27656835)
• LIMD1 coordinates the assembly of an AGO-TNRC6 containing miRISC complex by binding both proteins simultaneously at distinct interfaces. (PMID:28683311)
• that the reduced expression of LimD1 and VHL might have synergistic effect on induction of HIF1alpha resulting increased cellular proliferation and progression of the disease. (PMID:29033184)
• We show that all three mammalian Ajuba family proteins - AJUBA, LIMD1 and WTIP - exhibit tension-dependent localization to adherens junctions, and that both LATS family proteins, LATS1 and LATS2, exhibit an overlapping tension-dependent junctional localization (PMID:29440237)
• our data also suggests the importance ofLIMD1 and CDC25A in conjunction with HPV for use as diagnostic and prognostic markers of HNSCC, whereas RBSP3 as a prognostic marker only. (PMID:29672635)
• The lung tumor suppressor protein LIMD1 is a member of the Zyxin family of adaptor proteins, initially characterized as signal transducers shuttling between the cytoplasm and nucleus. LIMD1 expression promotes tumor growth. (PMID:29930174)
• Kaposi’s sarcoma-associated herpesvirus SOX binds to LIMD1 and shows RNA substrate selectivity (PMID:30321376)
• findings suggest that LIMD1 is a key regulator of mitotic progression, and that dysregulation of LIMD1 contributes to tumorigenesis (PMID:30600590)
• LIMD1 phase separation contributes to cellular mechanics and durotaxis by regulating focal adhesion dynamics in response to force. (PMID:33891898)
• Clinical implications of activation of the LIMD1-VHL-HIF1alpha pathway during head-&-neck squamous cell carcinoma development. (PMID:39382421)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	limd1a	ENSDARG00000110954
danio_rerio		ENSDARG00000112073
mus_musculus	Limd1	ENSMUSG00000025239
rattus_norvegicus	Limd1	ENSRNOG00000004837

Paralogs (2): AJUBA (ENSG00000129474), WTIP (ENSG00000142279)

Protein

Protein identifiers

LIM domain-containing protein 1 — Q9UGP4 (reviewed: Q9UGP4)

All UniProt accessions (2): Q9UGP4, C9JRJ5

UniProt curated annotations — full annotation on UniProt →

Function. Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation.

Subunit / interactions. Interacts (via LIM domains) with TRAF6. Found in a complex with TRAF6, PRKCZ and SQSTM1. Interacts (via LIM domains) SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain). Interacts with SQSTM1 and RB1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, EGLN1/PHD2, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM zinc-binding 2) with isoform 1 and isoform 3 of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain).

Subcellular location. Cytoplasm. Nucleus. P-body. Cell junction. Adherens junction. Focal adhesion.

Tissue specificity. Expressed in normal and breast cancer tissues (at protein level). Ubiquitous.

Post-translational modifications. Phosphorylated during mitosis.

Induction. Down-regulated in lung cancer.

Similarity. Belongs to the zyxin/ajuba family.

RefSeq proteins (1): NP_055055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001781	Znf_LIM	Domain
IPR047172	Ajuba-like	Family
IPR047245	Ajuba-like_LIM1	Domain
IPR047247	Ajuba-like_LIM2	Domain
IPR047248	Ajuba-like_LIM3	Domain

Pfam: PF00412

UniProt features (26 total): modified residue 9, region of interest 6, compositionally biased region 5, domain 3, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UGP4-F1	57.84	0.07

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 (9): 145, 233, 239, 272, 277, 304, 316, 421, 424

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1234176	Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1234174	Cellular response to hypoxia
R-HSA-2262752	Cellular responses to stress
R-HSA-8953897	Cellular responses to stimuli

MSigDB gene sets: 221 (showing top): GOBP_P_BODY_ASSEMBLY, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, ATACCTC_MIR202, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_HIPPO_SIGNALING, GOBP_NEGATIVE_REGULATION_OF_TRANSLATION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_OXYGEN_LEVELS, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_ORGANELLE_ASSEMBLY, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (15): response to hypoxia (GO:0001666), osteoblast development (GO:0002076), regulation of DNA-templated transcription (GO:0006355), cytoskeleton organization (GO:0007010), regulation of cell shape (GO:0008360), phosphorylation (GO:0016310), cell migration (GO:0016477), P-body assembly (GO:0033962), miRNA-mediated post-transcriptional gene silencing (GO:0035195), miRNA-mediated gene silencing by inhibition of translation (GO:0035278), negative regulation of hippo signaling (GO:0035331), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of canonical Wnt signaling pathway (GO:0090090), regulatory ncRNA-mediated gene silencing (GO:0031047)

GO Molecular Function (3): transcription corepressor activity (GO:0003714), metal ion binding (GO:0046872), protein binding (GO:0005515)

GO Cellular Component (11): P-body (GO:0000932), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), RISC complex (GO:0016442), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Cellular response to hypoxia	1
Cellular responses to stress	1
Cellular responses to stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
osteoblast differentiation	2
DNA-templated transcription	2
response to stress	1
response to decreased oxygen levels	1
cell development	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
organelle organization	1
regulation of cell morphogenesis	1
regulation of biological quality	1
phosphate-containing compound metabolic process	1
cell motility	1
membraneless organelle assembly	1
regulatory ncRNA-mediated post-transcriptional gene silencing	1
negative regulation of translation	1
miRNA-mediated post-transcriptional gene silencing	1
hippo signaling	1
regulation of hippo signaling	1
negative regulation of intracellular signal transduction	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
negative regulation of gene expression	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
cation binding	1
binding	1
cytoplasmic ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
protein-containing complex	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1266 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LIMD1	LARS2	Q15031	907
LIMD1	LATS1	O95835	860
LIMD1	RPH3AL	Q9UNE2	783
LIMD1	EGLN1	Q9GZT9	740
LIMD1	RPH3A	Q9Y2J0	680
LIMD1	SAV1	Q9H4B6	598
LIMD1	TRAF6	Q9Y4K3	593
LIMD1	RHOBTB3	O94955	546
LIMD1	VHL	P40337	543
LIMD1	RAB3A	P20336	527
LIMD1	PDLIM2	Q96JY6	522
LIMD1	TNRC6A	Q8NDV7	478
LIMD1	SNAI1	O95863	477
LIMD1	E2F1	Q01094	451
LIMD1	EIF4E	P06730	446

IntAct

133 interactions, top by confidence:

A	B	Type	Score
AGO2	TNRC6A	psi-mi:“MI:0403”(colocalization)	0.960
PPP2R3A	PPP2R1A	psi-mi:“MI:0914”(association)	0.920
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880
PPP2R1A	STRN	psi-mi:“MI:2364”(proximity)	0.880
AGO2	DDX6	psi-mi:“MI:0914”(association)	0.810
PDLIM7	BAG3	psi-mi:“MI:0914”(association)	0.800
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
AGO2	LIMD1	psi-mi:“MI:2364”(proximity)	0.690
AGO2	LIMD1	psi-mi:“MI:0915”(physical association)	0.690
AGO2	LIMD1	psi-mi:“MI:0407”(direct interaction)	0.690
AGO2	LIMD1	psi-mi:“MI:0403”(colocalization)	0.690
LIMD1	AGO2	psi-mi:“MI:0915”(physical association)	0.690
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
PPP2R3A	WTIP	psi-mi:“MI:0914”(association)	0.640
LPXN	PCNT	psi-mi:“MI:0914”(association)	0.640
ZNF576	ZBED1	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
MAP3K6	YWHAG	psi-mi:“MI:0914”(association)	0.640
DDX6	TNRC6A	psi-mi:“MI:0914”(association)	0.570

BioGRID (180): TRAF6 (Affinity Capture-Western), TRAF6 (Reconstituted Complex), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-MS), LIMD1 (Affinity Capture-Western), LIMD1 (Affinity Capture-Western), LIMD1 (Affinity Capture-Western), LIMD1 (Proximity Label-MS), LIMD1 (Proximity Label-MS), LIMD1 (Proximity Label-MS)

ESM2 similar proteins: A2ARK0, A3KN19, A6ND36, E9Q0S6, E9Q2Z1, G5E5X0, O70405, O75385, O94983, O95402, P42335, Q04205, Q08EC4, Q32PJ7, Q3UJB9, Q3ZAV8, Q5D1E7, Q5D1E8, Q5PQS0, Q5SSZ5, Q5SWY7, Q5XIS1, Q5XK72, Q63HR2, Q68CZ2, Q6P2E9, Q6PDH0, Q7TSI1, Q80Y50, Q86UU1, Q8BG26, Q8C2B3, Q8CGB6, Q8IUC6, Q8K1S6, Q8K2P2, Q8K330, Q8TE77, Q8TF72, Q8WUI4

Diamond homologs: A0JNI8, A0M8S5, A1ZA47, A2PZF9, A5H447, A6NIX2, A8DZE6, A9LS46, B5DEH0, B7ZUL2, E1BKA3, G5E5X0, G5EEA1, O43294, O60663, O88609, P35688, P37137, P48742, P53411, P53413, P61375, P61376, P61968, P61969, P63006, P63007, P63008, Q04584, Q06BR1, Q07E40, Q0VA45, Q15654, Q15942, Q1JQB5, Q2IBC3, Q3MHZ4, Q3SWZ8, Q3SX26, Q3SX40

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Regulation of RUNX1 Expression and Activity	5	39.5×	7e-06
Regulation of MITF-M-dependent genes involved in apoptosis	5	37.3×	9e-06
MicroRNA (miRNA) biogenesis	5	26.9×	4e-05
TGFBR3 expression	5	26.9×	4e-05
Regulation of MECP2 expression and activity	6	26.0×	6e-06
Transcriptional Regulation by MECP2	6	22.4×	1e-05
Gene Silencing by RNA	5	21.0×	1e-04
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	5	18.2×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
miRNA-mediated gene silencing by inhibition of translation	8	63.4×	2e-10
miRNA processing	5	47.0×	2e-05
mitotic spindle organization	6	14.6×	4e-04
positive regulation of non-canonical NF-kappaB signal transduction	5	11.4×	5e-03
intracellular protein localization	8	7.5×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	5
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2330 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45595078:G:GT	donor_gain	1.0000
3:45595097:G:GT	donor_gain	1.0000
3:45595097:G:T	donor_gain	1.0000
3:45636252:G:GG	donor_gain	1.0000
3:45665635:T:TA	acceptor_gain	1.0000
3:45665647:TA:T	acceptor_loss	1.0000
3:45665648:A:AG	acceptor_gain	1.0000
3:45665648:A:C	acceptor_loss	1.0000
3:45665648:AG:A	acceptor_gain	1.0000
3:45665648:AGGCC:A	acceptor_gain	1.0000
3:45665649:G:GG	acceptor_gain	1.0000
3:45665649:GG:G	acceptor_gain	1.0000
3:45665649:GGCC:G	acceptor_gain	1.0000
3:45665649:GGCCG:G	acceptor_gain	1.0000
3:45665715:CTGGT:C	donor_loss	1.0000
3:45665718:G:GG	donor_gain	1.0000
3:45665719:T:G	donor_loss	1.0000
3:45668291:CAGT:C	acceptor_loss	1.0000
3:45668292:A:AG	acceptor_gain	1.0000
3:45668292:AGT:A	acceptor_loss	1.0000
3:45668293:G:GA	acceptor_gain	1.0000
3:45668293:GT:G	acceptor_gain	1.0000
3:45668293:GTA:G	acceptor_gain	1.0000
3:45668293:GTAC:G	acceptor_gain	1.0000
3:45668293:GTACT:G	acceptor_gain	1.0000
3:45672821:G:GG	donor_gain	1.0000
3:45673450:ACAG:A	acceptor_gain	1.0000
3:45673452:AG:A	acceptor_gain	1.0000
3:45673453:GG:G	acceptor_gain	1.0000
3:45674334:T:TA	acceptor_gain	1.0000

AlphaMissense

4398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:45594920:T:C	F14S	1.000
3:45594932:T:C	L18P	1.000
3:45636230:T:C	C497R	1.000
3:45636233:T:C	F498L	1.000
3:45636234:T:C	F498S	1.000
3:45636234:T:G	F498C	1.000
3:45636235:C:A	F498L	1.000
3:45636235:C:G	F498L	1.000
3:45636239:T:C	C500R	1.000
3:45636240:G:A	C500Y	1.000
3:45636241:T:G	C500W	1.000
3:45636248:T:C	C503R	1.000
3:45636249:G:A	C503Y	1.000
3:45636250:C:G	C503W	1.000
3:45665673:T:C	F512L	1.000
3:45665675:T:A	F512L	1.000
3:45665675:T:G	F512L	1.000
3:45665676:T:G	Y513D	1.000
3:45665700:T:A	C521S	1.000
3:45665700:T:C	C521R	1.000
3:45665701:G:A	C521Y	1.000
3:45665701:G:C	C521S	1.000
3:45665701:G:T	C521F	1.000
3:45665702:T:G	C521W	1.000
3:45665712:T:C	F525L	1.000
3:45665713:T:C	F525S	1.000
3:45665714:C:A	F525L	1.000
3:45665714:C:G	F525L	1.000
3:45668324:T:A	C537S	1.000
3:45668324:T:C	C537R	1.000

dbSNP variants (sampled 300 via entrez): RS1000023870 (3:45612075 C>G,T), RS1000038919 (3:45594877 A>G), RS1000092219 (3:45662770 G>A,T), RS1000124140 (3:45594283 C>A), RS1000160114 (3:45598023 T>G), RS1000171368 (3:45642867 G>C), RS1000184937 (3:45662495 C>A,T), RS1000216948 (3:45619213 A>G), RS1000279693 (3:45601819 C>G), RS1000295012 (3:45625105 C>T), RS1000316945 (3:45657211 G>C), RS1000382101 (3:45668905 C>T), RS1000394480 (3:45675605 C>T), RS1000402183 (3:45644624 T>C), RS1000415484 (3:45638973 A>G)

Disease associations

OMIM: gene MIM:604543 | 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
GCST002481_7	Acne (severe)	3.000000e-06
GCST007267_97	Systolic blood pressure	1.000000e-09
GCST010698_35	Subcortical volume (min-P)	2.000000e-35
GCST010699_82	Brain morphology (min-P)	3.000000e-15
GCST010701_19	Cortical surface area (MOSTest)	5.000000e-08
GCST010702_119	Subcortical volume (MOSTest)	2.000000e-09
GCST010703_230	Brain morphology (MOSTest)	1.000000e-12
GCST012251_14	Macular telangiectasia type 2	1.000000e-09
GCST012252_5	Macular telangiectasia type 2	6.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0004346	neuroimaging measurement
EFO:1002009	macular telangiectasia type 2

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5465379 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs62242177	LIMD1		0.00	0
rs62242178	LIMD1		0.00	0

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
arsenite	affects binding, decreases reaction	1
sodium arsenite	affects splicing, increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
2-palmitoylglycerol	increases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
Bortezomib	increases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases methylation	1
Benzo(a)pyrene	increases methylation, decreases methylation	1
Caffeine	affects phosphorylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	increases expression	1
Methotrexate	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Levonorgestrel	affects cotreatment, decreases expression	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
CHEMBL5377690	Binding	PROTAC activity at CRBN/LIMD1 in human MV4-11 cells assessed as degradation of IKZF1 protein at 0.5 uM incubated for 18 hrs by Western blotting analysis	Discovery of Potent and Selective WDR5 Proteolysis Targeting Chimeras as Potential Therapeutics for Pancreatic Cancer. — J Med Chem

Clinical trials (associated diseases)

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