FBLN1

Summary

FBLN1 (fibulin 1, HGNC:3600) is a protein-coding gene on chromosome 22q13.31, encoding Fibulin-1 (P23142). Incorporated into fibronectin-containing matrix fibers.

Fibulin 1 is a secreted glycoprotein that becomes incorporated into a fibrillar extracellular matrix. Calcium-binding is apparently required to mediate its binding to laminin and nidogen. It mediates platelet adhesion via binding fibrinogen. Four splice variants which differ in the 3’ end have been identified. Each variant encodes a different isoform, but no functional distinctions have been identified among the four variants.

Source: NCBI Gene 2192 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 14
• Clinical variants (ClinVar): 344 total
• Phenotypes (HPO): 18
• MANE Select transcript: NM_006486

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3600
Approved symbol	FBLN1
Name	fibulin 1
Location	22q13.31
Locus type	gene with protein product
Status	Approved
Aliases	FBLN
Ensembl gene	ENSG00000077942
Ensembl biotype	protein_coding
OMIM	135820
Entrez	2192

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 25 protein_coding, 3 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000262722, ENST00000327858, ENST00000340923, ENST00000402984, ENST00000411478, ENST00000437711, ENST00000439835, ENST00000442170, ENST00000445110, ENST00000450975, ENST00000451475, ENST00000454279, ENST00000455233, ENST00000460300, ENST00000460538, ENST00000465578, ENST00000476366, ENST00000484531, ENST00000869150, ENST00000869151, ENST00000869152, ENST00000869153, ENST00000869154, ENST00000869155, ENST00000869157, ENST00000869160, ENST00000869162, ENST00000869164, ENST00000920060, ENST00000947320, ENST00000947321, ENST00000947322

RefSeq mRNA: 4 — MANE Select: NM_006486 NM_001996, NM_006485, NM_006486, NM_006487

CCDS: CCDS14067, CCDS14068, CCDS14069, CCDS43028

Canonical transcript exons

ENST00000327858 — 17 exons

Exon	Start	End
ENSE00001823520	45600307	45601135
ENSE00001873674	45502883	45503064
ENSE00002209135	45548613	45548744
ENSE00002234132	45533063	45533164
ENSE00002265445	45535200	45535337
ENSE00002268867	45527847	45528009
ENSE00002275257	45574511	45574653
ENSE00002300640	45576977	45577108
ENSE00003515324	45547085	45547204
ENSE00003544709	45541229	45541372
ENSE00003562824	45542155	45542283
ENSE00003585659	45543401	45543526
ENSE00003648838	45518682	45518787
ENSE00003669715	45550492	45550615
ENSE00003786053	45525543	45525678
ENSE00003790821	45533761	45533898
ENSE00003790950	45531265	45531324

Expression profiles

Bgee: expression breadth ubiquitous, 264 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.5527 / max 2851.1392, expressed in 1317 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
192723	96.2649	1312
192752	0.7337	328
192727	0.5708	290
192721	0.4652	257
192726	0.4033	208
192731	0.2323	120
192720	0.1938	84
192732	0.1698	88
192722	0.1340	66
192728	0.1319	54

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endocervix	UBERON:0000458	99.76	gold quality
gall bladder	UBERON:0002110	99.67	gold quality
pericardium	UBERON:0002407	99.61	gold quality
vena cava	UBERON:0004087	99.61	gold quality
mucosa of stomach	UBERON:0001199	99.57	gold quality
vagina	UBERON:0000996	99.53	gold quality
ectocervix	UBERON:0012249	99.53	gold quality
left uterine tube	UBERON:0001303	99.44	gold quality
right atrium auricular region	UBERON:0006631	99.43	gold quality
tendon of biceps brachii	UBERON:0008188	99.43	gold quality
cardiac atrium	UBERON:0002081	99.41	gold quality
right coronary artery	UBERON:0001625	99.37	gold quality
saphenous vein	UBERON:0007318	99.37	gold quality
body of uterus	UBERON:0009853	99.37	gold quality
right uterine tube	UBERON:0001302	99.33	gold quality
urinary bladder	UBERON:0001255	99.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	99.25	gold quality
urethra	UBERON:0000057	99.21	gold quality
popliteal artery	UBERON:0002250	99.21	gold quality
tibial artery	UBERON:0007610	99.21	gold quality
fundus of stomach	UBERON:0001160	99.18	gold quality
descending thoracic aorta	UBERON:0002345	99.18	gold quality
upper arm skin	UBERON:0004263	99.17	gold quality
upper lobe of left lung	UBERON:0008952	99.15	gold quality
cardiac muscle of right atrium	UBERON:0003379	99.12	gold quality
aorta	UBERON:0000947	99.11	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.09	gold quality
lower esophagus	UBERON:0013473	99.08	gold quality
coronary artery	UBERON:0001621	99.07	gold quality
placenta	UBERON:0001987	99.07	gold quality

Single-cell (SCXA)

Detected in 35 experiment(s), a significant marker in 34.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	5800.03
E-CURD-126	yes	4719.07
E-HCAD-15	yes	4617.18
E-HCAD-36	yes	4289.33
E-MTAB-6653	yes	4169.91
E-HCAD-1	yes	3759.09
E-MTAB-8410	yes	2893.99
E-ANND-2	yes	2812.32
E-MTAB-9906	yes	2571.09
E-GEOD-135922	yes	2206.51
E-MTAB-10885	yes	2193.95
E-HCAD-11	yes	2163.23
E-MTAB-10662	yes	1957.77
E-MTAB-8322	yes	1722.40
E-MTAB-8142	yes	1684.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
FBLN1	Activation
FN1	Activation
HSPG2	Activation

Upstream regulators (CollecTRI, top): DNMT1, ESR1, ESR2, FBLN1, SP1, SP3, TFAP2A, TP53

miRNA regulators (miRDB)

34 targeting FBLN1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-149-5P	99.25	67.16	1315
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-3926	98.95	69.26	1438
HSA-MIR-6737-3P	98.95	68.56	1577
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-421	98.90	67.04	1883
HSA-MIR-3908	98.75	67.31	1160
HSA-MIR-5008-3P	98.73	67.50	1433
HSA-MIR-6894-5P	98.70	63.78	809
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-548S	98.50	67.17	1213
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-3614-3P	97.81	67.15	582
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-376C-3P	97.63	68.88	1263
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-4314	97.50	67.30	1369

Literature-anchored findings (GeneRIF, showing 40)

• Fibulin-1 has pronounced inhibitory effects on cell attachment and spreading promoted by fibronectin (FN) and suppresses the motility of a variety of cell types on FN substrates. (PMID:11792823)
• structural and functional characterization of promoter (PMID:11829738)
• FBLN1 disrupted by a t(12;22) translocation is associated with a complex type of synpolydactyly. (PMID:11836357)
• binding of HPV E6 protein to fibulin-1 (PMID:12200142)
• findings indicate that elevated expression and altered processing of fibulin-1 is associated with human breast cancer (PMID:12644824)
• The gene responsible for a unique vitreoretinal dystrophy is located on chromosome 22q13. (PMID:12912698)
• mutations in the splice acceptor site of fibulin-1 exon 19, but no MYH9 mutations,were found in family individuals affected by autosomal-dominant giant platelet syndromes associated with aberrant antisense gene regulation of the fibulin-1 gene. (PMID:14635206)
• FBLN seems to have an immunological and pathobiological role in breast neoplasm surveillance. (PMID:14691454)
• The preferential induction of the fibulin-1C variant, which is overexpressed in ovarian and breast cancer, might play an important role in estrogen-promoted carcinogenesis. (PMID:15528301)
• fiblin-1 is an important molecule that mediates progesterone action in human endometrial stromal cells differentiation towards implantation (PMID:15774544)
• fibulin-1 is a new regulator of ADAMTS-1-mediated proteoglycan proteolysis and may play an important role in proteoglycan turnover in tissues where there is overlapping expression (PMID:16061471)
• Coexpression of fibulin-1 with GROalpha abrogates key aspects of the transformed phenotype, including colonic tumor formation in a murine xenograft model. (PMID:17062666)
• degradation of basement membrane by cathepsin D liberates both fibulin-1 fragments and fibulin-5, which function to inhibit angiogenesis (PMID:18222970)
• FBLN1 was identified as a novel candidate tmour suppressor gene epigenetically downregulated in gastric cancer (PMID:18985039)
• Like tenascin-C, fibulin-1 inhibits fibroblast spreading and cell-mediated contraction of a fibrin-fibronectin matrix. (PMID:19109427)
• fibulin-1 and -2 respond differentially to single and repeated damaging noxae, and their expression is differently present in liver cells (PMID:19609566)
• the pattern of fibulin-1 within human atherosclerotic lesions and the potential for fibulin-1, perhaps derived from the blood and acting in conjunction with fibrinogen, to play a role in the etiology and cardiovascular disease progression (PMID:19693531)
• Fibulin-1 protein was expressed in guinea pig sclera and cultured human scleral fibroblasts. (PMID:20405022)
• Fibulin-1 is down-regulated in atrial tissue from patients with atrial fibrillation, perhaps reflecting the myocardial structural changes that may have taken place during arrhythmia. (PMID:20451270)
• data collectively suggest fibulin-1C may be worthy of further investigation as a target for airway remodeling in asthma (PMID:20967215)
• Promoter hypermethylation of FBLN1 was significantly associated with advanced stage hepatocellular carcinoma, multiple tumors and increased tumor size. (PMID:21268132)
• plasma levels of fibulin-1 could serve as a potential indicator to monitor kidney malfunction or kidney damage (PMID:21888404)
• Fibulin-1 accumulates in the arterial wall and in plasma of patients with type 2 diabetes, and appears to be a factor associated with arterial extracellular matrix changes in type 2 diabetes. (PMID:21926180)
• In single regression analysis, NT-proBNP was significantly associated with fibulin-1 in African men and Caucasian women. (PMID:22349089)
• Increased plasma fibulin-1 levels are associated with diabetes and impaired kidney function. (PMID:23294625)
• Fibulin-1 is down regulated in renal cell carcinoma through promoter hypermethylation. (PMID:23391467)
• Plasma fibulin-1 is independently associated with pulse wave velocity in type 2 diabetics. (PMID:23866070)
• FBLN1 functions as a novel candidate tumor suppressor gene in CM, and its downregulation may be due to promoter hypermethylation. (PMID:23907575)
• Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues. (PMID:24084572)
• Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. (PMID:24739800)
• Increased levels of fibulin-1 were independently associated with higher levels of suPAR and NT-proBNP especially in patients with lower aortic valve stenosis (PMID:25014213)
• fibulin-1 expression is associated with NMIBC grade and recurrence, it is epigenetically down-regulated and functions as a tumor suppressor gene and angiogenesis inhibitor in bladder cancer. (PMID:25234557)
• The purpose of this study was to develop and characterize robust quantitative assays for the emerging cardiovascular biomarker fibulin-1 and its circulating isoforms in human plasma. (PMID:25331251)
• Extracellular matrix biomarker, fibulin-1 and its association with soluble uPAR in a bi-ethnic South African population (PMID:25456503)
• Study identifies a novel fibulin-1D variant, named fibulin-1D’, comprising 638 amino acids with molecular weight of 70.5 kDa. Fibulin-1D’ lacks a secretion sequence, has a truncated N-terminus domain and binds to the intracellular domain of integrin beta1. (PMID:25661773)
• LDH associated positively with fibulin-1 (beta = 0.23; p < 0.001) and ROS (beta = 0.11; p = 0.30) in blacks only with cardiovascular disease. (PMID:26631026)
• Low expression of fibulin-1 is associated with gastric cancer. (PMID:26779638)
• The procedure described is the first to our knowledge that enables a large scale purification of Fibulin-1 from human plasma. (PMID:26826315)
• The FBLN1/FGF8 interaction may also be involved in the survival of neural crest cell population during development. (PMID:27402846)
• Serum and vitreous fibulin-1 concentrations are elevated under diabetic retinopathy condition. (PMID:27422995)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbln1	ENSDARG00000103311
mus_musculus	Fbln1	ENSMUSG00000006369
rattus_norvegicus	Fbln1	ENSRNOG00000014137
caenorhabditis_elegans		WBGENE00001403

Paralogs (6): EFEMP1 (ENSG00000115380), FBLN5 (ENSG00000140092), VWDE (ENSG00000146530), FBLN2 (ENSG00000163520), EFEMP2 (ENSG00000172638), EYS (ENSG00000188107)

Protein

Protein identifiers

Fibulin-1 — P23142 (reviewed: P23142)

All UniProt accessions (11): P23142, A0A0U1RRA4, A0A8S0LWY1, B1AHL2, B1AHM5, B1AHM6, B1AHM7, B1AHM8, B1AHM9, B1AHN3, H7C1M6

UniProt curated annotations — full annotation on UniProt →

Function. Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes. Has been implicated in a role in cellular transformation and tumor invasion, it appears to be a tumor suppressor. May play a role in haemostasis and thrombosis owing to its ability to bind fibrinogen and incorporate into clots. Could play a significant role in modulating the neurotrophic activities of APP, particularly soluble APP.

Subunit / interactions. Homomultimerizes and interacts with various extracellular matrix components such as FN1, LAMA1, LAMA2, NID, ACAN, CSPG2 and type IV collagen. Also interacts with APP and FGB. Interacts with FBLN7. Interacts with CCN3. (Microbial infection) Interacts with human papillomavirus/HPV type 16, 18 and 31 proteins E6.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Isoform A and isoform B are only expressed in placenta. Isoform C and isoform D are expressed in a variety of tissues and cultured cells.

Disease relevance. A chromosomal aberration involving FBLN1 is found in a complex type of synpolydactyly referred to as 3/3-prime/4 synpolydactyly associated with metacarpal and metatarsal synostoses. Reciprocal translocation t(12;22)(p11.2;q13.3) with RASSF8. Fibroblasts derived from a patient with synpolydactyly displayed alterations in the level of isoform D splice variant incorporated into the ECM and secreted into the conditioned culture medium. By contrast, the expression of isoform C was not perturbed in the patients fibroblasts. Furthermore, no aberrant polypeptides were detected in extracts of cultured patients fibroblasts. The translocation t(12;22) may result in haploinsufficiency of the isoform D splice variant, which could lead to the observed limb malformation. Elevated expression and altered processing of FBLN1 protein is associated with human breast cancer.

Induction. Expression increased by estrogen in ovarian cancer cells.

Similarity. Belongs to the fibulin family.

Isoforms (4)

UniProt ID	Names	Canonical?
P23142-1	D	yes
P23142-2	A
P23142-3	B
P23142-4	C

RefSeq proteins (4): NP_001987, NP_006476, NP_006477, NP_006478 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000020	Anaphylatoxin/fibulin	Domain
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR017048	Fibulin-1	Family
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR026823	cEGF	Domain
IPR049883	NOTCH1_EGF-like	Domain
IPR052235	Nephronectin_domain	Family
IPR055088	Fibulin_C	Domain

Pfam: PF01821, PF07645, PF12662, PF22914

UniProt features (68 total): disulfide bond 35, domain 12, sequence conflict 8, sequence variant 4, glycosylation site 3, splice variant 3, signal peptide 1, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23142-F1	79.49	0.33

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (35): 36–61, 37–68, 50–69, 78–109, 91–110, 112–136, 113–143, 126–144, 180–190, 186–199, 201–214, 220–233, 227–242, 248–260, 266–279, 273–288, 294–306, 312–325, 319–334, 341–354 …

Glycosylation sites (3): 98, 535, 539

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-2129379	Molecules associated with elastic fibres

MSigDB gene sets: 363 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_PROTEIN_ACTIVATION_CASCADE, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_POSITIVE_REGULATION_OF_FIBROBLAST_PROLIFERATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, TGACCTY_ERR1_Q2, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_STEM_CELL_PROLIFERATION, COUP_01, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, PUJANA_CHEK2_PCC_NETWORK, GOBP_NEGATIVE_REGULATION_OF_CELL_SUBSTRATE_ADHESION, GOBP_WOUND_HEALING

GO Biological Process (14): negative regulation of protein phosphorylation (GO:0001933), negative regulation of cell adhesion (GO:0007162), embryo implantation (GO:0007566), positive regulation of gene expression (GO:0010628), extracellular matrix organization (GO:0030198), positive regulation of fibroblast proliferation (GO:0048146), negative regulation of ERK1 and ERK2 cascade (GO:0070373), negative regulation of transforming growth factor beta production (GO:0071635), blood coagulation, fibrin clot formation (GO:0072378), negative regulation of substrate adhesion-dependent cell spreading (GO:1900025), negative regulation of transformation of host cell by virus (GO:1904188), positive regulation of substrate-dependent cell migration, cell attachment to substrate (GO:1904237), negative regulation of cell motility (GO:2000146), negative regulation of stem cell proliferation (GO:2000647)

GO Molecular Function (9): fibronectin binding (GO:0001968), integrin binding (GO:0005178), extracellular matrix structural constituent (GO:0005201), calcium ion binding (GO:0005509), peptidase activator activity (GO:0016504), identical protein binding (GO:0042802), protein-containing complex binding (GO:0044877), fibrinogen binding (GO:0070051), protein binding (GO:0005515)

GO Cellular Component (6): extracellular region (GO:0005576), basement membrane (GO:0005604), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), extracellular exosome (GO:0070062), elastic fiber (GO:0071953)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Elastic fibre formation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
negative regulation of cellular process	2
protein binding	2
protein-containing complex binding	2
extracellular matrix	2
binding	2
regulation of protein phosphorylation	1
protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
cell adhesion	1
regulation of cell adhesion	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
extracellular structure organization	1
external encapsulating structure organization	1
positive regulation of cell population proliferation	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
negative regulation of cytokine production	1
transforming growth factor beta production	1
regulation of transforming growth factor beta production	1
blood coagulation	1
protein activation cascade	1
negative regulation of cell-substrate adhesion	1
substrate adhesion-dependent cell spreading	1
regulation of substrate adhesion-dependent cell spreading	1
symbiont-mediated transformation of host cell	1
negative regulation of biological process	1
regulation of transformation of host cell by virus	1
substrate-dependent cell migration, cell attachment to substrate	1
positive regulation of cell-substrate adhesion	1
positive regulation of cell migration	1
regulation of substrate-dependent cell migration, cell attachment to substrate	1

Protein interactions and networks

STRING

2490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBLN1	FN1	P02751	988
FBLN1	ACAN	P16112	951
FBLN1	RASSF8	Q8NHQ8	926
FBLN1	HSPG2	P98160	883
FBLN1	ELN	P15502	834
FBLN1	VCAN	P13611	828
FBLN1	GSTT2B	P0CG30	772
FBLN1	ADAMTS3	O15072	670
FBLN1	ADAMTS4	O75173	667
FBLN1	HOXD13	P35453	663
FBLN1	THBS1	P07996	653
FBLN1	ADAMTS1	Q9UHI8	652
FBLN1	MFAP2	P55001	634
FBLN1	ADAMTS5	Q9UNA0	632
FBLN1	DCN	P07585	631

IntAct

106 interactions, top by confidence:

A	B	Type	Score
FBXO6	MAN2B1	psi-mi:“MI:0914”(association)	0.640
CDA	LIN7A	psi-mi:“MI:0914”(association)	0.640
DEFA1	MANBA	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
ELSPBP1	PFDN1	psi-mi:“MI:0914”(association)	0.530
ZFP41	LRP4	psi-mi:“MI:0914”(association)	0.530
OCLN	DNAJC13	psi-mi:“MI:0914”(association)	0.530
ZNF517	GGPS1	psi-mi:“MI:0914”(association)	0.530
WNT7A	LDLR	psi-mi:“MI:0914”(association)	0.530
ZNF764	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
C8A	IDE	psi-mi:“MI:0914”(association)	0.530
CRP	QSOX1	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
MID1IP1	ACACB	psi-mi:“MI:0914”(association)	0.530
NOTCH2	ZNF316	psi-mi:“MI:0914”(association)	0.530
PIP	TBKBP1	psi-mi:“MI:0914”(association)	0.530
FBLN1	APOA1	psi-mi:“MI:0915”(physical association)	0.490
SMAD3	FBLN1	psi-mi:“MI:0915”(physical association)	0.490
FBLN1	FAM20C	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FBLN1	YWHAQ	psi-mi:“MI:0915”(physical association)	0.440
YWHAQ	FBLN1	psi-mi:“MI:0403”(colocalization)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
Tubb4b	MGST3	psi-mi:“MI:0915”(physical association)	0.400
FBLN1	NLGN3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (160): FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), FBLN1 (Two-hybrid), FBLN1 (Two-hybrid), FBLN1 (Affinity Capture-MS)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A6BM72, A6QR11, E9QJQ6, O42182, O70534, O88281, P23142, P35555, P35953, P80370, P97607, P98133, P98155, P98156, P98165, P98166, Q08879, Q09163, Q28832, Q2VWQ2, Q5R3Z7, Q5VY43, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8R4Y4, Q8VIK5, Q90827

Diamond homologs: A8WGB1, B3EWY9, B5DFC9, E1BMV3, G3V928, O19045, O43897, O57382, O73775, O75095, O88322, O88947, P00743, P07204, P07225, P10493, P13497, P14543, P15306, P21941, P23142, P25155, P25723, P35951, P37889, P48960, P51942, P53813, P98063, P98069, P98070, P98095, P98118, P98157, P98163, Q07954, Q08761, Q08879, Q09165, Q14112

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

344 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	141
Likely benign	81
Benign	87

Top pathogenic / likely-pathogenic (0)

SpliceAI

3801 predictions. Top by Δscore:

Variant	Effect	Δscore
22:45518678:A:AG	acceptor_gain	1.0000
22:45518678:ACAGT:A	acceptor_gain	1.0000
22:45518679:C:G	acceptor_gain	1.0000
22:45518680:A:AG	acceptor_gain	1.0000
22:45518680:AGT:A	acceptor_gain	1.0000
22:45518681:G:GA	acceptor_gain	1.0000
22:45518681:GT:G	acceptor_gain	1.0000
22:45518681:GTG:G	acceptor_gain	1.0000
22:45518784:GCAG:G	donor_gain	1.0000
22:45518785:CAGG:C	donor_loss	1.0000
22:45518786:AGGTA:A	donor_loss	1.0000
22:45518788:GT:G	donor_loss	1.0000
22:45518789:T:A	donor_loss	1.0000
22:45531260:CTTA:C	acceptor_loss	1.0000
22:45531261:TTA:T	acceptor_loss	1.0000
22:45531263:A:AC	acceptor_loss	1.0000
22:45531263:A:AG	acceptor_gain	1.0000
22:45531264:G:GG	acceptor_gain	1.0000
22:45531264:GATAA:G	acceptor_gain	1.0000
22:45533759:A:AG	acceptor_gain	1.0000
22:45533760:G:GG	acceptor_gain	1.0000
22:45533760:GAT:G	acceptor_gain	1.0000
22:45533894:CAAAG:C	donor_loss	1.0000
22:45533895:AAAGG:A	donor_loss	1.0000
22:45533896:AAGGT:A	donor_loss	1.0000
22:45533897:AGGT:A	donor_loss	1.0000
22:45533899:G:GC	donor_loss	1.0000
22:45533900:T:G	donor_loss	1.0000
22:45535189:T:G	acceptor_gain	1.0000
22:45535189:T:TA	acceptor_gain	1.0000

AlphaMissense

4669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:45533772:T:A	C220S	0.999
22:45533773:G:C	C220S	0.999
22:45533838:T:A	C242S	0.999
22:45533839:G:C	C242S	0.999
22:45533865:G:T	G251C	0.999
22:45533892:T:A	C260S	0.999
22:45533893:G:C	C260S	0.999
22:45535211:T:A	C266S	0.999
22:45535211:T:C	C266R	0.999
22:45535212:G:C	C266S	0.999
22:45535232:T:C	C273R	0.999
22:45535250:T:A	C279S	0.999
22:45535250:T:C	C279R	0.999
22:45535251:G:A	C279Y	0.999
22:45535251:G:C	C279S	0.999
22:45535257:A:T	N281I	0.999
22:45535268:T:C	S285P	0.999
22:45535271:T:C	F286L	0.999
22:45535272:T:G	F286C	0.999
22:45535273:C:A	F286L	0.999
22:45535273:C:G	F286L	0.999
22:45535277:T:A	C288S	0.999
22:45535277:T:C	C288R	0.999
22:45535278:G:C	C288S	0.999
22:45541240:T:A	C312S	0.999
22:45541240:T:C	C312R	0.999
22:45541241:G:C	C312S	0.999
22:45541366:T:A	C354S	0.999
22:45541366:T:C	C354R	0.999
22:45541367:G:C	C354S	0.999

dbSNP variants (sampled 300 via entrez): RS1000012154 (22:45584940 G>C), RS1000043417 (22:45514456 G>A), RS1000048151 (22:45544331 C>T), RS1000049107 (22:45597916 C>A,G,T), RS1000083326 (22:45556319 T>C), RS1000106956 (22:45592749 T>C), RS1000108084 (22:45521015 C>T), RS1000171611 (22:45517060 G>A), RS1000214506 (22:45592931 C>G), RS1000230212 (22:45538580 G>A), RS1000316925 (22:45597709 C>T), RS1000321523 (22:45516063 C>G), RS1000339488 (22:45545974 C>G,T), RS1000340986 (22:45593656 C>T), RS1000394258 (22:45582987 C>T)

Disease associations

OMIM: gene MIM:135820 | disease phenotypes: MIM:608180, MIM:617468, MIM:208150

GenCC curated gene-disease

Disease	Classification	Inheritance
FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome	Supportive	Autosomal recessive
synpolydactyly type 2	Limited	Unknown

Mondo (4): synpolydactyly type 2 (MONDO:0011984), arthrogryposis multiplex congenita (MONDO:0015168), fetal akinesia deformation sequence 1 (MONDO:0100101), FBLN1-related developmental delay-central nervous system anomaly-syndactyly syndrome (MONDO:0018443)

Orphanet (4): Synpolydactyly type 2 (Orphanet:295197), Syndactyly type 2 (Orphanet:93403), Arthrogryposis multiplex congenita (Orphanet:1037), Fetal akinesia deformation sequence (Orphanet:994)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000028	Cryptorchidism
HP:0000608	Macular degeneration
HP:0000750	Delayed speech and language development
HP:0001159	Syndactyly
HP:0001260	Dysarthria
HP:0001270	Motor delay
HP:0001285	Spastic tetraparesis
HP:0001332	Dystonia
HP:0002120	Cerebral cortical atrophy
HP:0002200	Pseudobulbar signs
HP:0002307	Drooling
HP:0002342	Moderate intellectual disability
HP:0003396	Syringomyelia
HP:0007030	Nonprogressive encephalopathy
HP:0008780	Congenital bilateral hip dislocation
HP:0011506	Choroidal neovascularization
HP:0012469	Infantile spasms
HP:0031936	Delayed ability to walk

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001419_6	Temperament (bipolar disorder)	2.000000e-08
GCST004251_9	Paneth cell defects in Crohn’s disease	4.000000e-06
GCST004601_209	Red blood cell count	3.000000e-14
GCST004604_7	Hematocrit	1.000000e-15
GCST004615_76	Hemoglobin concentration	1.000000e-13
GCST005171_17	QT interval	3.000000e-06
GCST006585_2576	Blood protein levels	6.000000e-08
GCST006585_2579	Blood protein levels	5.000000e-08
GCST010083_332	Hemoglobin levels	2.000000e-25
GCST010204_152	Low density lipoprotein cholesterol levels	4.000000e-10
GCST012203_3	Colon cancer	3.000000e-08
GCST012205_7	Distal colorectal cancer	2.000000e-06
GCST012490_20	Femur bone mineral density x serum urate levels interaction	7.000000e-13
GCST90000015_8	Parkinson’s disease motor subtype (tremor to postural instability/gait difficulty score ratio)	2.000000e-06

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004365	personality trait
EFO:0007963	abnormal paneth cell measurement
EFO:0004305	erythrocyte count
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0004682	QT interval
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004531	urate measurement
EFO:0600011	Parkinson’s disease symptom measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564278	Synpolydactyly 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

85 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, decreases methylation, increases abundance, increases expression	5
bisphenol A	affects expression, affects cotreatment, increases methylation, decreases methylation, increases expression	4
Valproic Acid	affects expression, decreases expression	4
trichostatin A	affects cotreatment, increases expression	3
Benzo(a)pyrene	affects methylation, decreases methylation, increases expression	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
belinostat	affects cotreatment, decreases expression	2
Zoledronic Acid	increases expression	2
Air Pollutants	increases abundance, increases expression, decreases expression	2
Doxorubicin	affects expression, decreases expression	2
Estradiol	increases expression	2
Fluorouracil	affects expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Mifepristone	decreases reaction, increases expression, decreases expression	2
Aflatoxin B1	increases expression, affects methylation	2
Particulate Matter	increases abundance, increases expression, affects cotreatment	2
afuresertib	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
ginger extract	decreases expression, increases abundance	1
methylmercuric chloride	increases expression	1
glycidyl methacrylate	decreases expression	1
cobaltous chloride	decreases secretion	1
benzo(e)pyrene	decreases methylation	1
potassium chromate(VI)	decreases expression	1
cadmium acetate	decreases expression	1
cupric chloride	decreases expression	1
4-phenylbutyric acid	increases expression	1
corosolic acid	increases expression	1

Clinical trials (associated diseases)

4 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05393375	Not specified	COMPLETED	Arthrogryposis Multiplex Congenita in Pediatric Age: Correlation Between MUScular MRI and Functional Evaluation
NCT05673265	Not specified	UNKNOWN	Pediatric and Adult Registry for Patients With ARThrogryposis
NCT06130592	Not specified	UNKNOWN	Technical Feasibility Study of Ultrasound Muscle Imaging in Antenatal Ultrasound
NCT07360574	Not specified	NOT_YET_RECRUITING	Piezo2-related Arthrogryposis & physiopathOLOgy 3