LIMA1

protein-coding

LIM domain and actin binding 1, the group of MicroRNA protein coding host genes|LIM domain containing

Gene summary

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. [provided by RefSeq, Aug 2011]

MANE transcript

NM_016357.5

Inheritance

ClinVar variants

U:103B:12

Top phenotype

Low density lipoprotein cholesterol level quantitative trait locus

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr12:50,175,788-50,283,520

External References & Databases

Ensembl (ENSG00000050405)

Transcript & Mutation Effects

hg38 • Region Span ~107.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Low density lipoprotein cholesterol level quantitative trait locusAD

Manifestation: Gastrointestinal

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29880681

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LIMA1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 109

LIMA1-related disorderTotal: 4

LOW DENSITY LIPOPROTEIN CHOLESTEROL LEVEL QUANTITATIVE TRAIT LOCUS 8Total: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016357.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				9 clinvar		9
missense			101 clinvar	3 clinvar		104
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	103	12	0	115

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 58 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016357.5	RefSeq	NP_057441.1	10	MANE Select
ENST00000341247.9	Ensembl	ENSP00000340184.4	10	MANE Select
NM_001113546.2	RefSeq	NP_001107018.1	10	Standard
NM_001113547.2	RefSeq	NP_001107019.1	8	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Stabilization and expansion of the E-cadherin adherens junction

Biological Process

cholesterol metabolic process
cell migration
intestinal cholesterol absorption
negative regulation of actin filament depolymerization
ruffle organization

Molecular Function

actin monomer binding
protein binding
cadherin binding
metal ion binding
actin filament binding

Cellular Component

stress fiber
ruffle
cytosol
plasma membrane
focal adhesion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000394943
Coding exons: 10
Length: 107759
Individuals with no LoFs: 125662
Homozygous LoFs: 0
Heterozygous LoFs: 85
Defined: 125747
p: 0.000338

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.51	316	401	0.788	0.0000201	5035
Missense (PolyPhen)		59	94.758	0.62264		1173
Synonymous	-0.297	150	145	1.03	0.00000758	1414
Loss of Function	2.24	21	35.4	0.594	0.00000199	423

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00049	0.00049	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00019	0.00018	rare
European (Non-Finnish)	0.00036	0.00036	rare
South Asian	0.00030	0.00029	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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 (PubMed:12566430). 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 (By similarity). {ECO:0000250|UniProtKB:Q9ERG0, ECO:0000269|PubMed:12566430}.;

Recessive Scores

pRec: 0.139

Intolerance Scores

LoFtool: 0.137
RVIS EVS: -1
RVIS percentile EVS: 8.37

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.923

Gene Damage Prediction

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