LIMK1

LIM domain kinase 1, the group of LIM domain containing|PDZ domain containing|LIMK/TESK kinase family

Basic information

Region (hg38): 7:74082933-74122525

Links

ENSG00000106683 ∙ NCBI:3984 ∙ OMIM:601329 ∙ HGNC:6613 ∙ Uniprot:P53667 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LIMK1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LIMK1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				25	3	28
missense			28	4	2	34
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				5	3	8
non coding				1	1	2
Total	0	0	28	30	6

Variants in LIMK1

This is a list of pathogenic ClinVar variants found in the LIMK1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-74085752-C-T			Benign (Sep 19, 2018)
7-74085762-G-A		not specified	Likely benign (Nov 10, 2022)
7-74085792-G-C		not specified	Uncertain significance (Feb 14, 2023)
7-74085819-G-A		See cases	Likely pathogenic (-)
7-74085836-C-T			Likely benign (Dec 31, 2019)
7-74096649-G-A			Likely benign (Jun 19, 2017)
7-74096663-A-G		not specified	Uncertain significance (Dec 15, 2022)
7-74096666-A-C			Benign (Dec 31, 2019)
7-74096701-G-A		not specified	Uncertain significance (Jun 29, 2022)
7-74096707-T-C		not specified	Uncertain significance (May 23, 2024)
7-74096755-G-A		not specified	Uncertain significance (Jan 27, 2022)
7-74097072-C-G		LIMK1-related disorder	Benign (Dec 31, 2019)
7-74097072-C-T			Likely benign (Aug 01, 2023)
7-74097127-G-A			Likely benign (Dec 12, 2017)
7-74097172-G-A			Likely benign (Aug 01, 2023)
7-74097180-A-G		not specified	Uncertain significance (Feb 16, 2023)
7-74099063-C-G		not specified	Uncertain significance (Jan 09, 2024)
7-74099179-C-T		LIMK1-related disorder	Likely benign (Dec 31, 2019)
7-74099184-C-A		not specified	Uncertain significance (Oct 06, 2022)
7-74099197-G-A			Likely benign (Sep 01, 2022)
7-74099199-G-C			Benign (Dec 31, 2019)
7-74099225-G-A		not specified	Uncertain significance (Feb 22, 2023)
7-74099230-C-A			Likely benign (Jan 02, 2019)
7-74099237-G-C		not specified	Uncertain significance (Nov 06, 2023)
7-74099248-C-T			Benign (Apr 11, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LIMK1	protein_coding	protein_coding	ENST00000336180	16	39593

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000629	125738	0	5	125743	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.63	276	429	0.643	0.0000283	4198
Missense in Polyphen		84	168.7	0.49793		1630
Synonymous	-0.167	190	187	1.02	0.0000137	1277
Loss of Function	4.97	3	34.5	0.0870	0.00000181	377

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000123	0.000123
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00000911	0.00000879
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin- 2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. Stimulates axonal outgrowth and may be involved in brain development. Isoform 3 has a dominant negative effect on actin cytoskeletal changes. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1). {ECO:0000269|PubMed:10196227, ECO:0000269|PubMed:10436159, ECO:0000269|PubMed:11832213, ECO:0000269|PubMed:12807904, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:16230460, ECO:0000269|PubMed:18028908, ECO:0000269|PubMed:23633677}.
• Disease: DISEASE: Note=LIMK1 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
• Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Axon guidance - Homo sapiens (human);Regulation of Microtubule Cytoskeleton;VEGFA-VEGFR2 Signaling Pathway;Regulation of Actin Cytoskeleton;G13 Signaling Pathway;Developmental Biology;Signal Transduction;ccr3 signaling in eosinophils;rho cell motility signaling pathway;rac1 cell motility signaling pathway;Fcgamma receptor (FCGR) dependent phagocytosis;EPH-Ephrin signaling;Innate Immune System;Immune System;EPHB-mediated forward signaling;RHO GTPases Activate ROCKs;RHO GTPases activate PAKs;RHO GTPase Effectors;Signaling by Rho GTPases;Sema4D induced cell migration and growth-cone collapse;Sema4D in semaphorin signaling;role of mal in rho-mediated activation of srf;CXCR4-mediated signaling events;Sema3A PAK dependent Axon repulsion;Semaphorin interactions;Regulation of actin dynamics for phagocytic cup formation;Axon guidance;Leptin;Caspase Cascade in Apoptosis;RAC1 signaling pathway;CDC42 signaling events;RhoA signaling pathway (Consensus)

Recessive Scores

• pRec: 0.327

Intolerance Scores

• loftool: 0.0812
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.88

Haploinsufficiency Scores

• pHI: 0.309
• hipred: Y
• hipred_score: 0.825
• ghis: 0.525

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.452

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Limk1
• Phenotype: cellular phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: protein phosphorylation;signal transduction;Rho protein signal transduction;nervous system development;actin cytoskeleton organization;positive regulation of actin filament bundle assembly;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of axon extension;negative regulation of ubiquitin-protein transferase activity;positive regulation of stress fiber assembly
• Cellular component: nucleus;cytoplasm;cytosol;focal adhesion;membrane;nuclear speck;lamellipodium;neuron projection
• Molecular function: protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;heat shock protein binding;metal ion binding;protein heterodimerization activity