FLNB

filamin B, the group of Filamins

Basic information

Region (hg38): 3:58008398-58172251

Previous symbols: [ "FLN1L", "LRS1" ]

Links

ENSG00000136068 ∙ NCBI:2317 ∙ OMIM:603381 ∙ HGNC:3755 ∙ Uniprot:O75369 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• spondylocarpotarsal synostosis syndrome (Definitive), mode of inheritance: AR
• Larsen syndrome (Definitive), mode of inheritance: AD
• atelosteogenesis type III (Definitive), mode of inheritance: AD
• atelosteogenesis type I (Definitive), mode of inheritance: AD
• atelosteogenesis type I (Supportive), mode of inheritance: AD
• spondylocarpotarsal synostosis syndrome (Supportive), mode of inheritance: AR
• Larsen syndrome (Supportive), mode of inheritance: AD
• atelosteogenesis type III (Supportive), mode of inheritance: AD
• Larsen syndrome (Definitive), mode of inheritance: Mitochondrial
• atelosteogenesis type I (Strong), mode of inheritance: AD
• Boomerang dysplasia (Strong), mode of inheritance: AD
• spondylocarpotarsal synostosis syndrome (Strong), mode of inheritance: AR
• Larsen syndrome (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Larsen syndrome; Spondylocarpotarsal synostosis syndrome	AD/AR	Audiologic/Otolaryngologic; Musculoskeletal	Surveillance and early intervention related to cervical spine stability can allow early detection and treatment of manifestations; Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Dental; Musculoskeletal	8609132; 12955767; 14991055; 15994868; 17202879; 16801345; 18257094; 18377309; 18386804; 20301736; 22190451; 22354125

ClinVar

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

• not provided (37 variants)
• Spondylocarpotarsal synostosis syndrome (11 variants)
• Larsen syndrome (4 variants)
• Atelosteogenesis type I (2 variants)
• FLNB-Related Spectrum Disorders (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLNB 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			15	381	21	417
missense	10	21	647	148	18	844
nonsense	15	4				19
start loss						0
frameshift	21	8	2			31
inframe indel		1	10			11
splice donor/acceptor (+/-2bp)	1	15	1			17
splice region			51	56	4	111
non coding			40	245	126	411
Total	47	49	715	774	165

Highest pathogenic variant AF is 0.0000394

Variants in FLNB

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

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

Position	Type	Phenotype	Significance	ClinVar
3-58008405-C-G		FLNB-Related Spectrum Disorders	Uncertain significance (Apr 27, 2017)
3-58008420-G-T		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008434-G-C		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 13, 2018)
3-58008458-T-G		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008462-A-G		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008468-C-T		FLNB-Related Spectrum Disorders	Likely benign (Jan 12, 2018)
3-58008470-C-G		FLNB-Related Spectrum Disorders	Likely benign (Jan 13, 2018)
3-58008477-C-A		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008484-G-C		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 13, 2018)
3-58008489-C-A		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008534-C-T		FLNB-Related Spectrum Disorders • not specified	Benign (Jan 12, 2018)
3-58008560-C-T			Uncertain significance (Jun 15, 2022)
3-58008561-C-T		FLNB-Related Spectrum Disorders	Uncertain significance (Jan 12, 2018)
3-58008570-G-A			Likely benign (Dec 05, 2021)
3-58008573-A-G		not specified • FLNB-Related Spectrum Disorders • FLNB-related disorder	Conflicting classifications of pathogenicity (Aug 04, 2023)
3-58008606-G-GA			Pathogenic (Dec 12, 2022)
3-58008626-C-G			Uncertain significance (Mar 04, 2023)
3-58008627-G-A			Likely benign (Sep 13, 2022)
3-58008645-C-T			Likely benign (Sep 05, 2023)
3-58008647-A-T			Uncertain significance (May 06, 2022)
3-58008652-C-CT			Pathogenic (Feb 09, 2023)
3-58008665-A-G			Uncertain significance (Nov 19, 2023)
3-58008671-G-A		not specified • Connective tissue disorder • FLNB-related disorder	Conflicting classifications of pathogenicity (Jan 19, 2024)
3-58008671-G-T		Inborn genetic diseases	Uncertain significance (Sep 23, 2023)
3-58008682-C-T			Likely benign (Jun 28, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLNB	protein_coding	protein_coding	ENST00000490882	47	163856

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.05e-10	1.00	125628	0	120	125748	0.000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.14	1326	1.56e+3	0.848	0.0000973	17224
Missense in Polyphen		553	773.42	0.71501		8482
Synonymous	-0.129	666	662	1.01	0.0000486	5349
Loss of Function	6.50	38	112	0.338	0.00000586	1356

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000506	0.000503
Ashkenazi Jewish	0.000198	0.000198
East Asian	0.00109	0.00109
Finnish	0.000323	0.000323
European (Non-Finnish)	0.000497	0.000492
Middle Eastern	0.00109	0.00109
South Asian	0.000523	0.000523
Other	0.000821	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Connects cell membrane constituents to the actin cytoskeleton. May promote orthogonal branching of actin filaments and links actin filaments to membrane glycoproteins. Anchors various transmembrane proteins to the actin cytoskeleton. Interaction with FLNA may allow neuroblast migration from the ventricular zone into the cortical plate. Various interactions and localizations of isoforms affect myotube morphology and myogenesis. Isoform 6 accelerates muscle differentiation in vitro.
• Disease: DISEASE: Note=Interaction with FLNA may compensate for dysfunctional FLNA homodimer in the periventricular nodular heterotopia (PVNH) disorder.; DISEASE: Atelosteogenesis 1 (AO1) [MIM:108720]: A lethal chondrodysplasia characterized by distal hypoplasia of the humeri and femurs, hypoplasia of the mid-thoracic spine, occasionally complete lack of ossification of single hand bones, and the finding in cartilage of multiple degenerated chondrocytes which are encapsulated in fibrous tissue. {ECO:0000269|PubMed:14991055}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atelosteogenesis 3 (AO3) [MIM:108721]: A short-limb lethal skeletal dysplasia with vertebral abnormalities, disharmonious skeletal maturation, poorly modeled long bones and joint dislocations. Recurrent respiratory insufficiency and/or infections usually result in early death. {ECO:0000269|PubMed:14991055}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Boomerang dysplasia (BOOMD) [MIM:112310]: A perinatal lethal osteochondrodysplasia characterized by absence or underossification of the limb bones and vertebrae. Patients manifest dwarfism with short, bowed, rigid limbs and characteristic facies. Boomerang dysplasia is distinguished from atelosteogenesis on the basis of a more severe defect in mineralization, with complete absence of ossification in some limb elements and vertebral segments. {ECO:0000269|PubMed:15994868}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Larsen syndrome (LRS) [MIM:150250]: An osteochondrodysplasia characterized by large-joint dislocations and characteristic craniofacial abnormalities. The cardinal features of the condition are dislocations of the hip, knee and elbow joints, with equinovarus or equinovalgus foot deformities. Spatula-shaped fingers, most marked in the thumb, are also present. Craniofacial anomalies include hypertelorism, prominence of the forehead, a depressed nasal bridge, and a flattened midface. Cleft palate and short stature are often associated features. Spinal anomalies include scoliosis and cervical kyphosis. Hearing loss is a well-recognized complication. {ECO:0000269|PubMed:14991055, ECO:0000269|PubMed:16801345}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spondylocarpotarsal synostosis syndrome (SCT) [MIM:272460]: Disorder characterized by short stature and vertebral, carpal and tarsal fusions. {ECO:0000269|PubMed:14991055}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Focal adhesion - Homo sapiens (human);Salmonella infection - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Focal Adhesion;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Cytokine Signaling in Immune system;TCR;Immune System;EGFR1;ISG15 antiviral mechanism;Antiviral mechanism by IFN-stimulated genes;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.216

Intolerance Scores

• loftool: 0.00269
• rvis_EVS: -1.44
• rvis_percentile_EVS: 3.94

Haploinsufficiency Scores

• pHI: 0.452
• hipred: Y
• hipred_score: 0.698
• ghis: 0.514

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Flnb
• Phenotype: growth/size/body region phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system 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); limbs/digits/tail phenotype; skeleton phenotype

Gene ontology

• Biological process: keratinocyte development;epithelial cell morphogenesis;cytoskeletal anchoring at plasma membrane;signal transduction;skeletal muscle tissue development;actin cytoskeleton organization;cellular response to interferon-gamma
• Cellular component: stress fiber;cytoplasm;cytosol;plasma membrane;brush border;focal adhesion;cell cortex;actin cytoskeleton;integral component of membrane;Z disc;phagocytic vesicle;extracellular exosome
• Molecular function: RNA binding;actin binding;protein binding;identical protein binding;cadherin binding