FBLIM1

protein-coding

filamin binding LIM protein 1, the group of LIM domain containing

Gene summary

This gene encodes a protein with an N-terminal filamin-binding domain, a central proline-rich domain, and, multiple C-terminal LIM domains. This protein localizes at cell junctions and may link cell adhesion structures to the actin cytoskeleton. This protein may be involved in the assembly and stabilization of actin-filaments and likely plays a role in modulating cell adhesion, cell morphology and cell motility. This protein also localizes to the nucleus and may affect cardiomyocyte differentiation after binding with the CSX/NKX2-5 transcription factor. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

MANE transcript

NM_017556.4

Inheritance

—

ClinVar variants

U:58B:7

Top phenotype

EBV-positive nodal T- and NK-cell lymphoma

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr1:15,756,607-15,786,594

External References & Databases

Ensembl (ENSG00000162458)

Transcript & Mutation Effects

hg38 • Region Span ~30.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FBLIM1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 8

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017556.4. 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			3 clinvar		2 clinvar	5
missense			54 clinvar	3 clinvar	2 clinvar	59
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	58	3	4	65

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 179 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017556.4	RefSeq	NP_060026.2	7	MANE Select
ENST00000375766.8	Ensembl	ENSP00000364921.3	7	MANE Select
NM_001024215.1	RefSeq	NP_001019386.1	5	Standard
NM_001024216.3	RefSeq	NP_001019387.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cell-extracellular matrix interactions
Cell junction organization
Cell-Cell communication

Biological Process

regulation of cell shape
regulation of integrin activation
cell junction assembly
cell-cell adhesion

Molecular Function

protein binding
filamin binding
metal ion binding

Cellular Component

fibrillar center
stress fiber
cytosol
focal adhesion
cell junction

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000441801
Coding exons: 5
Length: 29988
Individuals with no LoFs: 125677
Homozygous LoFs: 0
Heterozygous LoFs: 64
Defined: 125741
p: 0.000255

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.526	198	220	0.900	0.0000133	2349
Missense (PolyPhen)		57	76.706	0.74309		828
Synonymous	0.266	88	91.2	0.965	0.00000585	792
Loss of Function	0.958	8	11.5	0.695	6.60e-7	124

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00067	0.00067	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00016	0.00016	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.000081	0.000079	rare
South Asian	0.00059	0.00059	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Serves as an anchoring site for cell-ECM adhesion proteins and filamin-containing actin filaments. Is implicated in cell shape modulation (spreading) and motility. May participate in the regulation of filamin-mediated cross-linking and stabilization of actin filaments. May also regulate the assembly of filamin- containing signaling complexes that control actin assembly. Promotes dissociation of FLNA from ITGB3 and ITGB7. Promotes activation of integrins and regulates integrin-mediated cell-cell adhesion. {ECO:0000269|PubMed:12496242, ECO:0000269|PubMed:12679033, ECO:0000269|PubMed:18829455, ECO:0000269|PubMed:19074766}.;

Recessive Scores

pRec: 0.106

Intolerance Scores

LoFtool: 0.229
RVIS EVS: 0.51
RVIS percentile EVS: 80.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.434

Gene Damage Prediction

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