FBN1

fibrillin 1, the group of Fibrillins

Basic information

Region (hg38): 15:48408313-48645721

Previous symbols: [ "FBN", "MFS1", "WMS" ]

Links

ENSG00000166147 ∙ NCBI:2200 ∙ OMIM:134797 ∙ HGNC:3603 ∙ Uniprot:P35555 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Shprintzen-Goldberg syndrome (Limited), mode of inheritance: Unknown
• Marfan syndrome (Definitive), mode of inheritance: AD
• Shprintzen-Goldberg syndrome (Definitive), mode of inheritance: AD
• ectopia lentis 1, isolated, autosomal dominant (Limited), mode of inheritance: AD
• Weill-Marchesani syndrome 2, dominant (Limited), mode of inheritance: AD
• MASS syndrome (Definitive), mode of inheritance: AD
• Marfan syndrome (Strong), mode of inheritance: AD
• Marfan syndrome (Strong), mode of inheritance: AD
• progeroid and marfanoid aspect-lipodystrophy syndrome (Moderate), mode of inheritance: AD
• Marfan syndrome (Definitive), mode of inheritance: AD
• isolated ectopia lentis (Supportive), mode of inheritance: AD
• Acromicric dysplasia (Supportive), mode of inheritance: AD
• geleophysic dysplasia (Supportive), mode of inheritance: AD
• Weill-Marchesani syndrome (Supportive), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Supportive), mode of inheritance: AD
• Marfan syndrome (Supportive), mode of inheritance: AD
• neonatal Marfan syndrome (Supportive), mode of inheritance: AD
• progeroid and marfanoid aspect-lipodystrophy syndrome (Supportive), mode of inheritance: AD
• stiff skin syndrome (Limited), mode of inheritance: AD
• Acromicric dysplasia (Strong), mode of inheritance: AD
• Marfan syndrome (Definitive), mode of inheritance: AR
• progeroid and marfanoid aspect-lipodystrophy syndrome (Strong), mode of inheritance: AD
• Marfan syndrome (Strong), mode of inheritance: AD
• stiff skin syndrome (Strong), mode of inheritance: AD
• Weill-Marchesani syndrome 2, dominant (Strong), mode of inheritance: AD
• familial thoracic aortic aneurysm and aortic dissection (Definitive), mode of inheritance: AD
• Shprintzen-Goldberg syndrome (Disputed Evidence), mode of inheritance: AD
• Marfan syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Marfan syndrome; MASS syndrome; Shprintzen-Goldberg syndrome; Marfanoid-progeroid-lipodystrophy syndrome; Ectopia lentis 1, familial; Geleophysic dysplasia 2; Weill-Marchesani syndrome 2	AD	Cardiovascular; Musculoskeletal; Ophthalmologic; Pharmacogenomic; Pulmonary	Medications that reduce aortic wall hemodynamic stress (eg, beta blockers) have been shown to be effective; Afterload-reducing agents can improve cardiovascular function in CHF; Surgical aortic repair is indicated depending on parameters such as size and rate of change of aorta; Other issues also require attention and may benefit from regular surveillance, such as those involving ophthalomologic, pulmonary, and skeletal complications; Certain agents and circumstances should be avoided, including activities that impose cardiovascular or musculoskeletal risk, as well as agents such as decongestants, caffeine; LASIK is typically contraindicated; Geleophysic dysplasia may frequently be clinically recognizable, but individuals can have cardiovascular manifestations such as progressive cardiac valve thickening necessitating surgical interventions very early in childhood, and early diagnosis may be beneficial to allow early treatment; In Weill-Marchesani syndrome, awareness of the risk of certain ophthalmological complications (including glaucoma) can allow prompt awareness and treatment	Cardiovascular; Craniofacial; Dental; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic; Pulmonary	1157278; 370588; 6182156; 2938007; 3189335; 2322060; 1852208; 2337033; 1864149; 1301946; 1569206; 1736263; 1542340; 8406497; 7802039; 7573130; 8152445; 8863159; 8733052; 8790089; 8563763; 9150726; 9761390; 10489951; 10219065; 11256662; 11700157; 12446365; 11845856; 11826022; 12525539; 14598350; 15054843; 15731757; 15517394; 16596670; 16202954; 17366579; 18579813; 19996017; 19353630; 20375004; 20301510; 20301776; 20886638; 20979188; 21063442; 21594992; 21594993; 21683322; 21883168; 21932315; 22034023; 22461464; 22736615; 22876116; 22950452; 24613577

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FBN1 gene.

• Marfan syndrome;Familial thoracic aortic aneurysm and aortic dissection (686 variants)
• Familial thoracic aortic aneurysm and aortic dissection;Marfan syndrome (408 variants)
• Marfan syndrome (346 variants)
• not provided (252 variants)
• Familial thoracic aortic aneurysm and aortic dissection (187 variants)
• Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections (28 variants)
• not specified (21 variants)
• Cardiovascular phenotype (19 variants)
• 8 conditions (11 variants)
• Progeroid and marfanoid aspect-lipodystrophy syndrome (10 variants)
• FBN1-related disorder (7 variants)
• Acromicric dysplasia (6 variants)
• Ectopia lentis 1, isolated, autosomal dominant (4 variants)
• Inborn genetic diseases (3 variants)
• Neonatal Marfan syndrome (3 variants)
• Connective tissue disorder (3 variants)
• See cases (2 variants)
• Geleophysic dysplasia 2 (2 variants)
• Congenital aneurysm of ascending aorta;Acute aortic dissection (2 variants)
• Weill-Marchesani syndrome 2, dominant (2 variants)
• Arthrogryposis, renal dysfunction, and cholestasis 1 (1 variants)
• Marfan syndrome, atypical (1 variants)
• Weill-Marchesani syndrome (1 variants)
• Familial ectopia lentis (1 variants)
• Marfan syndrome, autosomal recessive (1 variants)
• 9 conditions (1 variants)
• Thoracic aortic disease (1 variants)
• Congenital scoliosis (1 variants)
• Marfan syndrome;Progeroid and marfanoid aspect-lipodystrophy syndrome (1 variants)
• Aortic dissection;Lens subluxation;Arachnodactyly;High palate (1 variants)
• Ectopia lentis 1, isolated, autosomal dominant;Stiff skin syndrome;Geleophysic dysplasia 2;Familial thoracic aortic aneurysm and aortic dissection (1 variants)
• Brugada syndrome 1 (1 variants)
• Stiff skin syndrome (1 variants)
• MASS syndrome (1 variants)
• Loeys-Dietz syndrome (1 variants)
• Myopia;Tall stature;Pectus excavatum;Joint hypermobility;Inguinal hernia (1 variants)
• Isolated thoracic aortic aneurysm (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FBN1 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	2	3	29	886	10	930
missense	434	750	1795	43	15	3037
nonsense	301	73	3			377
start loss	7	1				8
frameshift	616	147	4			767
inframe indel	12	22	35			69
splice donor/acceptor (+/-2bp)	146	134	4			284
splice region	9	22	148	145	4	328
non coding	2	4	123	524	136	789
Total	1520	1134	1993	1453	161

Highest pathogenic variant AF is 0.00000658

Variants in FBN1

This is a list of pathogenic ClinVar variants found in the FBN1 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-48408316-A-T		Weill-Marchesani syndrome • Geleophysic dysplasia • Acromicric dysplasia • Marfan syndrome • Ectopia lentis 1, isolated, autosomal dominant • Stiff skin syndrome • Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (Jan 13, 2018)
15-48408352-A-G		Marfan syndrome • Familial thoracic aortic aneurysm and aortic dissection • Weill-Marchesani syndrome • Acromicric dysplasia • Ectopia lentis 1, isolated, autosomal dominant • Geleophysic dysplasia • Stiff skin syndrome	Uncertain significance (Jan 12, 2018)
15-48408396-C-A		Familial thoracic aortic aneurysm and aortic dissection • Marfan syndrome • Acromicric dysplasia • MASS syndrome • Geleophysic dysplasia • Ectopia lentis • Stiff skin syndrome • Weill-Marchesani syndrome	Uncertain significance (Jun 14, 2016)
15-48408398-A-G		Ectopia lentis 1, isolated, autosomal dominant • Weill-Marchesani syndrome • Marfan syndrome • Stiff skin syndrome • Acromicric dysplasia • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jan 12, 2018)
15-48408412-G-A		MASS syndrome • Stiff skin syndrome • Ectopia lentis • Familial thoracic aortic aneurysm and aortic dissection • Geleophysic dysplasia • Acromicric dysplasia • Weill-Marchesani syndrome • Marfan syndrome	Uncertain significance (Jun 14, 2016)
15-48408434-C-T		Acromicric dysplasia • Stiff skin syndrome • Familial thoracic aortic aneurysm and aortic dissection • Ectopia lentis 1, isolated, autosomal dominant • Weill-Marchesani syndrome • Geleophysic dysplasia • Marfan syndrome	Uncertain significance (Jan 13, 2018)
15-48408457-G-T		Marfan syndrome • MASS syndrome • Acromicric dysplasia • Stiff skin syndrome • Familial thoracic aortic aneurysm and aortic dissection • Geleophysic dysplasia • Ectopia lentis • Weill-Marchesani syndrome	Uncertain significance (Jun 14, 2016)
15-48408466-T-C		Ectopia lentis 1, isolated, autosomal dominant • Stiff skin syndrome • Geleophysic dysplasia • Weill-Marchesani syndrome • Marfan syndrome • Acromicric dysplasia • Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (May 18, 2021)
15-48408547-C-A		Familial thoracic aortic aneurysm and aortic dissection • Geleophysic dysplasia • Marfan syndrome • Weill-Marchesani syndrome • MASS syndrome • Stiff skin syndrome • Acromicric dysplasia • Ectopia lentis	Uncertain significance (Jun 14, 2016)
15-48408569-G-T		Weill-Marchesani syndrome • Geleophysic dysplasia • MASS syndrome • Ectopia lentis • Stiff skin syndrome • Marfan syndrome • Familial thoracic aortic aneurysm and aortic dissection • Acromicric dysplasia	Uncertain significance (Jun 14, 2016)
15-48408592-C-A		Stiff skin syndrome • Marfan syndrome • Weill-Marchesani syndrome • Familial thoracic aortic aneurysm and aortic dissection • Acromicric dysplasia • Ectopia lentis 1, isolated, autosomal dominant • Geleophysic dysplasia	Conflicting classifications of pathogenicity (Jan 13, 2018)
15-48408595-C-T		Geleophysic dysplasia • Stiff skin syndrome • Marfan syndrome • Ectopia lentis 1, isolated, autosomal dominant • Familial thoracic aortic aneurysm and aortic dissection • Acromicric dysplasia • Weill-Marchesani syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
15-48408630-G-C		Ectopia lentis • Geleophysic dysplasia • Weill-Marchesani syndrome • Acromicric dysplasia • Marfan syndrome • Stiff skin syndrome • MASS syndrome • Familial thoracic aortic aneurysm and aortic dissection	Likely benign (Jun 14, 2016)
15-48408730-G-T		Marfan syndrome • MASS syndrome • Familial thoracic aortic aneurysm and aortic dissection • Weill-Marchesani syndrome • Ectopia lentis • Stiff skin syndrome • Geleophysic dysplasia • Acromicric dysplasia	Uncertain significance (Jun 14, 2016)
15-48408769-T-C		Marfan syndrome • Familial thoracic aortic aneurysm and aortic dissection • Ectopia lentis 1, isolated, autosomal dominant • Stiff skin syndrome • Geleophysic dysplasia • Weill-Marchesani syndrome • Acromicric dysplasia	Uncertain significance (Jan 12, 2018)
15-48408832-C-T		Stiff skin syndrome • Ectopia lentis 1, isolated, autosomal dominant • Acromicric dysplasia • Familial thoracic aortic aneurysm and aortic dissection • Weill-Marchesani syndrome • Marfan syndrome • Geleophysic dysplasia	Benign (May 11, 2021)
15-48408837-T-C		Weill-Marchesani syndrome • Acromicric dysplasia • Stiff skin syndrome • Geleophysic dysplasia • Familial thoracic aortic aneurysm and aortic dissection • Marfan syndrome • Ectopia lentis 1, isolated, autosomal dominant	Benign/Likely benign (Jun 10, 2021)
15-48408876-A-T		Familial thoracic aortic aneurysm and aortic dissection • Stiff skin syndrome • Weill-Marchesani syndrome • Ectopia lentis 1, isolated, autosomal dominant • Geleophysic dysplasia • Marfan syndrome • Acromicric dysplasia	Uncertain significance (Jan 12, 2018)
15-48408899-C-T		Stiff skin syndrome • Geleophysic dysplasia • Familial thoracic aortic aneurysm and aortic dissection • Marfan syndrome • Ectopia lentis 1, isolated, autosomal dominant • Acromicric dysplasia • Weill-Marchesani syndrome	Conflicting classifications of pathogenicity (Apr 01, 2023)
15-48408912-C-A		Marfan syndrome • Ectopia lentis • Stiff skin syndrome • Weill-Marchesani syndrome • Acromicric dysplasia • Geleophysic dysplasia • MASS syndrome • Familial thoracic aortic aneurysm and aortic dissection	Uncertain significance (Jun 14, 2016)
15-48408945-C-T		Marfan syndrome • Geleophysic dysplasia • Familial thoracic aortic aneurysm and aortic dissection • Acromicric dysplasia • Ectopia lentis 1, isolated, autosomal dominant • Stiff skin syndrome • Weill-Marchesani syndrome	Conflicting classifications of pathogenicity (Jan 13, 2018)
15-48408946-G-A		Ectopia lentis 1, isolated, autosomal dominant • Weill-Marchesani syndrome • Stiff skin syndrome • Familial thoracic aortic aneurysm and aortic dissection • Marfan syndrome • Acromicric dysplasia	Uncertain significance (Jan 13, 2018)
15-48408950-A-G		Familial thoracic aortic aneurysm and aortic dissection • Stiff skin syndrome • Weill-Marchesani syndrome • Marfan syndrome • Acromicric dysplasia • Geleophysic dysplasia • Ectopia lentis 1, isolated, autosomal dominant	Benign (May 11, 2021)
15-48408953-A-G		Weill-Marchesani syndrome • Familial thoracic aortic aneurysm and aortic dissection • Acromicric dysplasia • Marfan syndrome • Ectopia lentis 1, isolated, autosomal dominant • Stiff skin syndrome	Uncertain significance (Jan 12, 2018)
15-48408966-T-C		Marfan syndrome • Geleophysic dysplasia • Weill-Marchesani syndrome • Acromicric dysplasia • Ectopia lentis 1, isolated, autosomal dominant • Familial thoracic aortic aneurysm and aortic dissection • Stiff skin syndrome	Conflicting classifications of pathogenicity (Apr 01, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FBN1	protein_coding	protein_coding	ENST00000316623	65	237544

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	4.09e-24	125733	0	14	125747	0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	5.06	1038	1.61e+3	0.645	0.0000932	19158
Missense in Polyphen		346	757.54	0.45674		8847
Synonymous	0.221	573	580	0.988	0.0000365	5163
Loss of Function	11.5	3	159	0.0189	0.00000894	1983

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000418	0.000416
European (Non-Finnish)	0.00000880	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.000131	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Fibrillin-1: Structural component of the 10-12 nm diameter microfibrils of the extracellular matrix, which conveys both structural and regulatory properties to load-bearing connective tissues (PubMed:1860873, PubMed:15062093). Fibrillin-1- containing microfibrils provide long-term force bearing structural support. In tissues such as the lung, blood vessels and skin, microfibrils form the periphery of the elastic fiber, acting as a scaffold for the deposition of elastin. In addition, microfibrils can occur as elastin-independent networks in tissues such as the ciliary zonule, tendon, cornea and glomerulus where they provide tensile strength and have anchoring roles. Fibrillin-1 also plays a key role in tissue homeostasis through specific interactions with growth factors, such as the bone morphogenetic proteins (BMPs), growth and differentiation factors (GDFs) and latent transforming growth factor-beta-binding proteins (LTBPs), cell- surface integrins and other extracellular matrix protein and proteoglycan components (PubMed:27026396). Regulates osteoblast maturation by controlling TGF-beta bioavailability and calibrating TGF-beta and BMP levels, respectively (By similarity). Negatively regulates osteoclastogenesis by binding and sequestering an osteoclast differentiation and activation factor TNFSF11. This leads to disruption of TNFSF11-induced Ca(2+) signaling and impairment of TNFSF11-mediated nuclear translocation and activation of transcription factor NFATC1 which regulates genes important for osteoclast differentiation and function (PubMed:24039232). Mediates cell adhesion via its binding to cell surface receptors integrins ITGAV:ITGB3 and ITGA5:ITGB1 (PubMed:12807887, PubMed:17158881). Binds heparin and this interaction has an important role in the assembly of microfibrils (PubMed:11461921). {ECO:0000250|UniProtKB:Q61554, ECO:0000269|PubMed:11461921, ECO:0000269|PubMed:12807887, ECO:0000269|PubMed:15062093, ECO:0000269|PubMed:17158881, ECO:0000269|PubMed:1860873, ECO:0000269|PubMed:24039232, ECO:0000303|PubMed:27026396}.
• Disease: DISEASE: Marfan syndrome (MFS) [MIM:154700]: A hereditary disorder of connective tissue that affects the skeletal, ocular, and cardiovascular systems. A wide variety of skeletal abnormalities occurs with Marfan syndrome, including scoliosis, chest wall deformity, tall stature, abnormal joint mobility. Ectopia lentis occurs in most of the patients and is almost always bilateral. The leading cause of premature death is progressive dilation of the aortic root and ascending aorta, causing aortic incompetence and dissection. Neonatal Marfan syndrome is the most severe form resulting in death from cardiorespiratory failure in the first few years of life. {ECO:0000269|PubMed:10425041, ECO:0000269|PubMed:10441597, ECO:0000269|PubMed:10694921, ECO:0000269|PubMed:11700157, ECO:0000269|PubMed:11826022, ECO:0000269|PubMed:12161601, ECO:0000269|PubMed:12203992, ECO:0000269|PubMed:12402346, ECO:0000269|PubMed:1301946, ECO:0000269|PubMed:14695540, ECO:0000269|PubMed:15161917, ECO:0000269|PubMed:15221638, ECO:0000269|PubMed:1569206, ECO:0000269|PubMed:16220557, ECO:0000269|PubMed:16222657, ECO:0000269|PubMed:17657824, ECO:0000269|PubMed:18435798, ECO:0000269|PubMed:1852208, ECO:0000269|PubMed:19533785, ECO:0000269|PubMed:19941982, ECO:0000269|PubMed:20803651, ECO:0000269|PubMed:21542060, ECO:0000269|PubMed:22772377, ECO:0000269|PubMed:7611299, ECO:0000269|PubMed:7738200, ECO:0000269|PubMed:7762551, ECO:0000269|PubMed:7870075, ECO:0000269|PubMed:7951214, ECO:0000269|PubMed:7977366, ECO:0000269|PubMed:8004112, ECO:0000269|PubMed:8040326, ECO:0000269|PubMed:8071963, ECO:0000269|PubMed:8136837, ECO:0000269|PubMed:8281141, ECO:0000269|PubMed:8406497, ECO:0000269|PubMed:8504310, ECO:0000269|PubMed:8863159, ECO:0000269|PubMed:8882780, ECO:0000269|PubMed:9016526, ECO:0000269|PubMed:9254848, ECO:0000269|PubMed:9338581, ECO:0000269|PubMed:9401003, ECO:0000269|PubMed:9452085, ECO:0000269|PubMed:9837823, ECO:0000269|Ref.68}. Note=The disease is caused by mutations affecting the gene represented in this entry. The majority of the more than thousand mutations in FBN1 currently known are point mutations, the rest are frameshifts and splice site mutations. Marfan syndrome has been suggested in at least 2 historical figures, Abraham Lincoln and Paganini.; DISEASE: Ectopia lentis 1, isolated, autosomal dominant (ECTOL1) [MIM:129600]: An ocular abnormality characterized by partial or complete displacement of the lens from its space resulting from defective zonule formation. {ECO:0000269|PubMed:11700157, ECO:0000269|PubMed:11826022, ECO:0000269|PubMed:12203992, ECO:0000269|PubMed:17657824, ECO:0000269|PubMed:8188302}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Weill-Marchesani syndrome 2 (WMS2) [MIM:608328]: A rare connective tissue disorder characterized by short stature, brachydactyly, joint stiffness, and eye abnormalities including microspherophakia, ectopia lentis, severe myopia and glaucoma. {ECO:0000269|PubMed:12525539}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Overlap connective tissue disease (OCTD) [MIM:604308]: Heritable disorder of connective tissue characterized by involvement of the mitral valve, aorta, skeleton, and skin. MASS syndrome is closely resembling both the Marfan syndrome and the Barlow syndrome. However, no dislocation of the lenses or aneurysmal changes occur in the aorta, and the mitral valve prolapse is by no means invariable. {ECO:0000269|PubMed:2739055}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Stiff skin syndrome (SSKS) [MIM:184900]: A syndrome characterized by hard, thick skin, usually over the entire body, which limits joint mobility and causes flexion contractures. Other occasional findings include lipodystrophy and muscle weakness. {ECO:0000269|PubMed:20375004}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Geleophysic dysplasia 2 (GPHYSD2) [MIM:614185]: An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have characteristic facial features including a 'happy' face with full cheeks, shortened nose, hypertelorism, long and flat philtrum, and thin upper lip. Other distinctive features include progressive cardiac valvular thickening often leading to an early death, toe walking, tracheal stenosis, respiratory insufficiency, and lysosomal-like storage vacuoles in various tissues. {ECO:0000269|PubMed:21683322}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Acromicric dysplasia (ACMICD) [MIM:102370]: An autosomal dominant disorder characterized by severe short stature, short hands and feet, joint limitations, and skin thickening. Radiologic features include delayed bone age, cone-shaped epiphyses, shortened long tubular bones, and ovoid vertebral bodies. Affected individuals have distinct facial features, including round face, well-defined eyebrows, long eyelashes, bulbous nose with anteverted nostrils, long and prominent philtrum, and thick lips with a small mouth. Other characteristic features include hoarse voice and pseudomuscular build, and there are distinct skeletal features as well, including an internal notch of the femoral head, internal notch of the second metacarpal, and external notch of the fifth metacarpal. {ECO:0000269|PubMed:21683322}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Marfan lipodystrophy syndrome (MFLS) [MIM:616914]: A syndrome characterized by congenital lipodystrophy, a progeroid facial appearance due to lack of subcutaneous fat, and variable signs of Marfan syndrome. Clinical features include premature birth with an accelerated linear growth disproportionate to the weight gain, ectopia lentis, aortic dilatation, dural ectasia, and arachnodactyly. Mental and motor development are within normal limits. {ECO:0000269|PubMed:20979188, ECO:0000269|PubMed:21594992, ECO:0000269|PubMed:21594993, ECO:0000269|PubMed:24039054, ECO:0000269|PubMed:24613577, ECO:0000269|PubMed:24665001, ECO:0000269|PubMed:26860060, ECO:0000269|PubMed:27087445}. Note=The disease is caused by mutations affecting the gene represented in this entry. Asprosin: Mutations specifically affect Asprosin, a hormone peptide present at the C-terminus of Fibrillin-1 chain, which is cleaved from Fibrillin-1 following secretion (PubMed:27087445). {ECO:0000269|PubMed:27087445}.
• Pathway: Hypothesized Pathways in Pathogenesis of Cardiovascular Disease;Post-translational protein phosphorylation;Integrin cell surface interactions;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Elastic fibre formation;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Beta3 integrin cell surface interactions;Beta5 beta6 beta7 and beta8 integrin cell surface interactions;Beta1 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.114

Intolerance Scores

• loftool: 0.00289
• rvis_EVS: -2.81
• rvis_percentile_EVS: 0.64

Haploinsufficiency Scores

• pHI: 0.834
• hipred: Y
• hipred_score: 0.837
• ghis: 0.635

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.748

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fbn1
• Phenotype: 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; renal/urinary system phenotype; immune system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); embryo phenotype; pigmentation phenotype; reproductive 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); 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); 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); hematopoietic system phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Gene ontology

• Biological process: skeletal system development;metanephros development;heart development;regulation of signaling receptor activity;extracellular matrix organization;cell adhesion mediated by integrin;sequestering of BMP in extracellular matrix;sequestering of TGFbeta in extracellular matrix;camera-type eye development;post-translational protein modification;cellular protein metabolic process;negative regulation of osteoclast differentiation;embryonic eye morphogenesis;post-embryonic eye morphogenesis;cellular response to transforming growth factor beta stimulus;cellular response to insulin-like growth factor stimulus;negative regulation of osteoclast development
• Cellular component: microfibril;extracellular region;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;collagen-containing extracellular matrix
• Molecular function: integrin binding;hormone activity;extracellular matrix structural constituent;calcium ion binding;protein binding;heparin binding;extracellular matrix constituent conferring elasticity;identical protein binding;protein-containing complex binding