FBLN5
fibulin 5, the group of Fibulins
Basic information
Region (hg38): 14:91869411-91947987
Links
Phenotypes
GenCC
Source:
- cutis laxa, autosomal recessive, type 1A (Strong), mode of inheritance: AR
- cutis laxa, autosomal dominant 2 (Strong), mode of inheritance: AD
- cutis laxa, autosomal recessive, type 1A (Strong), mode of inheritance: AR
- cutis laxa, autosomal recessive, type 1A (Moderate), mode of inheritance: Semidominant
- macular degeneration, age-related, 3 (Moderate), mode of inheritance: AD
- autosomal dominant cutis laxa (Supportive), mode of inheritance: AD
- autosomal recessive cutis laxa type 1 (Supportive), mode of inheritance: AR
- hereditary sensorimotor neuropathy with hyperelastic skin (Supportive), mode of inheritance: AD
- cutis laxa, autosomal recessive, type 1A (Strong), mode of inheritance: AR
- cutis laxa, autosomal dominant 2 (Definitive), mode of inheritance: AD
- Charcot-Marie-Tooth disease, demyelinating, IIA 1H (Strong), mode of inheritance: AD
- demyelinating hereditary motor and sensory neuropathy (Moderate), mode of inheritance: AD
- cutis laxa, autosomal recessive, type 1A (Definitive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Neuropathy, hereditary, with or witout age-related macular degeneration; Macular degeneration, age-related, 3; Cutis laxa, autosomal dominant 2; Cutis laxa, autosomal recessive, type IA | AD/AR | General | 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 | Dermatologic; Cardiovascular; Gastrointestinal; Genitourinary; Neurologic; Ophthalmologic; Pulmonary | 12189163; 12618961; 15269314; 20301756; 22829427 |
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (523 variants)
- Inborn_genetic_diseases (41 variants)
- Macular_degeneration,_age-related,_3 (40 variants)
- Cutis_laxa (27 variants)
- not_specified (26 variants)
- FBLN5-related_disorder (23 variants)
- Cutis_laxa,_autosomal_recessive,_type_1A (18 variants)
- Cutis_laxa,_autosomal_dominant_2 (14 variants)
- Charcot-Marie-Tooth_disease,_demyelinating,_IIA_1H (11 variants)
- Age-related_macular_degeneration (10 variants)
- Cutis_laxa,_autosomal_dominant (7 variants)
- Retinal_dystrophy (5 variants)
- Optic_atrophy (2 variants)
- Hereditary_sensorimotor_neuropathy_with_hyperelastic_skin (2 variants)
- Autosomal_recessive_cutis_laxa_type_1 (1 variants)
- Cutis_Laxa,_Dominant/Recessive (1 variants)
- Peripheral_axonal_neuropathy (1 variants)
- Age_related_macular_degeneration_1 (1 variants)
- Tip-toe_gait (1 variants)
- Proximal_spinal_muscular_atrophy (1 variants)
- See_cases (1 variants)
- Macular_degeneration (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBLN5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000006329.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 119 | 124 | ||||
| missense | 250 | 265 | ||||
| nonsense | 12 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 2 | |||||
| Total | 4 | 10 | 267 | 125 | 1 |
Highest pathogenic variant AF is 0.0000545274
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| FBLN5 | protein_coding | protein_coding | ENST00000342058 | 11 | 78576 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 0.000301 | 125741 | 0 | 2 | 125743 | 0.00000795 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.56 | 199 | 271 | 0.734 | 0.0000175 | 2947 |
| Missense in Polyphen | 39 | 90.043 | 0.43313 | 1090 | ||
| Synonymous | 0.419 | 100 | 105 | 0.948 | 0.00000747 | 843 |
| Loss of Function | 4.70 | 1 | 27.6 | 0.0362 | 0.00000153 | 302 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.00000898 | 0.00000879 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Essential for elastic fiber formation, is involved in the assembly of continuous elastin (ELN) polymer and promotes the interaction of microfibrils and ELN (PubMed:18185537). Stabilizes and organizes elastic fibers in the skin, lung and vasculature (By similarity). Promotes adhesion of endothelial cells through interaction of integrins and the RGD motif. Vascular ligand for integrin receptors which may play a role in vascular development and remodeling (PubMed:10428823). May act as an adapter that mediates the interaction between FBN1 and ELN (PubMed:17255108). {ECO:0000250|UniProtKB:Q9WVH9, ECO:0000269|PubMed:10428823, ECO:0000269|PubMed:17255108, ECO:0000269|PubMed:18185537}.;
- Disease
- DISEASE: Neuropathy, hereditary, with or without age-related macular degeneration (HNARMD) [MIM:608895]: An autosomal dominant neuropathy of the Charcot-Marie-Tooth disease group, characterized by distal muscle weakness and atrophy variably affecting the lower and upper limbs. Distal sensory impairment and decreased nerve conduction velocities are present in most but not all patients. Additional variable features are age-related macular degeneration, joint hypermobility, and hyperelastic skin. {ECO:0000269|PubMed:21576112, ECO:0000269|PubMed:23328402}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cutis laxa, autosomal dominant, 2 (ADCL2) [MIM:614434]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. Additional variable clinical features are gastrointestinal diverticula, hernia, and genital prolapse. Rare manifestations are pulmonary artery stenosis, aortic aneurysm, bronchiectasis, and emphysema. {ECO:0000269|PubMed:12618961}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Cutis laxa, autosomal recessive, 1A (ARCL1A) [MIM:219100]: A connective tissue disorder characterized by loose, hyperextensible skin with decreased resilience and elasticity leading to a premature aged appearance. Face, hands, feet, joints, and torso may be differentially affected. The clinical spectrum of autosomal recessive cutis laxa is highly heterogeneous with respect to organ involvement and severity. Type I autosomal recessive cutis laxa is a specific, life-threatening disorder with organ involvement, lung atelectasis and emphysema, diverticula of the gastrointestinal and genitourinary systems, and vascular anomalies. Associated cranial anomalies, late closure of the fontanel, joint laxity, hip dislocation, and inguinal hernia have been observed but are uncommon. {ECO:0000269|PubMed:12189163, ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:16691202, ECO:0000269|PubMed:17035250, ECO:0000269|PubMed:18185537, ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547}. Note=The disease is caused by mutations affecting the gene represented in this entry. Mutations affecting this gene can modify the phenotype of diseases caused by ELN mutations. {ECO:0000269|PubMed:19194475}.; DISEASE: Macular degeneration, age-related, 3 (ARMD3) [MIM:608895]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269|PubMed:15269314, ECO:0000269|PubMed:16652333, ECO:0000269|PubMed:20007835, ECO:0000269|PubMed:20599547}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.;
- Pathway
- Extracellular matrix organization;Molecules associated with elastic fibres;Elastic fibre formation
(Consensus)
Recessive Scores
- pRec
- 0.175
Intolerance Scores
- loftool
- 0.0398
- rvis_EVS
- -0.58
- rvis_percentile_EVS
- 18.59
Haploinsufficiency Scores
- pHI
- 0.338
- hipred
- Y
- hipred_score
- 0.685
- ghis
- 0.591
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.545
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Fbln5
- Phenotype
- neoplasm; 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); respiratory system phenotype; muscle phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; craniofacial phenotype;
Gene ontology
- Biological process
- regulation of cell growth;cell-matrix adhesion;extracellular matrix organization;protein localization to cell surface;secretion;elastic fiber assembly;regulation of removal of superoxide radicals
- Cellular component
- extracellular region;extracellular space;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome;elastic fiber
- Molecular function
- integrin binding;calcium ion binding;protein binding;protein C-terminus binding;extracellular matrix constituent conferring elasticity;protein homodimerization activity