FLNB

Summary

FLNB (filamin B, HGNC:3755) is a protein-coding gene on chromosome 3p14.3, encoding Filamin-B (O75369). Connects cell membrane constituents to the actin cytoskeleton.

This gene encodes a member of the filamin family. The encoded protein interacts with glycoprotein Ib alpha as part of the process to repair vascular injuries. The platelet glycoprotein Ib complex includes glycoprotein Ib alpha, and it binds the actin cytoskeleton. Mutations in this gene have been found in several conditions: atelosteogenesis type 1 and type 3; boomerang dysplasia; autosomal dominant Larsen syndrome; and spondylocarpotarsal synostosis syndrome. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Source: NCBI Gene 2317 — RefSeq curated summary.

At a glance

• Gene–disease (curated): FLNB-associated autosomal dominant filamin related bone disorder (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 35
• Clinical variants (ClinVar): 2,910 total — 81 pathogenic, 72 likely-pathogenic
• Phenotypes (HPO): 199
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001457

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3755
Approved symbol	FLNB
Name	filamin B
Location	3p14.3
Locus type	gene with protein product
Status	Approved
Aliases	TAP, TABP, ABP-278, FH1
Ensembl gene	ENSG00000136068
Ensembl biotype	protein_coding
OMIM	603381
Entrez	2317

Gene structure

Transcript identifiers

Ensembl transcripts: 29 — 13 retained_intron, 8 protein_coding, 6 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000295956, ENST00000358537, ENST00000419752, ENST00000429972, ENST00000466455, ENST00000468939, ENST00000470231, ENST00000475487, ENST00000477629, ENST00000481470, ENST00000484981, ENST00000490882, ENST00000491408, ENST00000493452, ENST00000682097, ENST00000682297, ENST00000682503, ENST00000682868, ENST00000682871, ENST00000682987, ENST00000683114, ENST00000683511, ENST00000683925, ENST00000684107, ENST00000684439, ENST00000684506, ENST00000684517, ENST00000684607, ENST00000946856

RefSeq mRNA: 4 — MANE Select: NM_001457 NM_001164317, NM_001164318, NM_001164319, NM_001457

CCDS: CCDS2885, CCDS54599, CCDS54600, CCDS54601

Canonical transcript exons

ENST00000295956 — 46 exons

Exon	Start	End
ENSE00000000021	58008422	58008856
ENSE00000861937	58126602	58126762
ENSE00001077198	58123093	58123690
ENSE00001077200	58125581	58125743
ENSE00001077282	58121241	58121503
ENSE00001180344	58109576	58109699
ENSE00001180346	58109179	58109322
ENSE00001180347	58108458	58108571
ENSE00001180356	58103959	58104085
ENSE00001180363	58110010	58110170
ENSE00001180390	58124332	58124505
ENSE00001180403	58118872	58118989
ENSE00001212911	58112149	58112318
ENSE00001212915	58111791	58111881
ENSE00001295364	58102203	58102340
ENSE00001295579	58096141	58096218
ENSE00001296552	58105080	58105216
ENSE00001298400	58077046	58077294
ENSE00001299267	58081629	58081776
ENSE00001302065	58141858	58141929
ENSE00001306228	58132808	58132931
ENSE00001312484	58097815	58097977
ENSE00001313345	58106680	58106873
ENSE00001315475	58078717	58078814
ENSE00001316025	58098711	58098908
ENSE00001328202	58130741	58130908
ENSE00002261435	58094836	58094954
ENSE00003471268	58168440	58168658
ENSE00003475600	58134616	58134772
ENSE00003477276	58148206	58148364
ENSE00003517404	58150105	58150227
ENSE00003539711	58145921	58146049
ENSE00003545942	58138282	58138529
ENSE00003559224	58163154	58163330
ENSE00003579347	58142650	58142752
ENSE00003579837	58135979	58136168
ENSE00003586110	58154791	58154928
ENSE00003605580	58146820	58146993
ENSE00003605790	58143473	58143613
ENSE00003606803	58159554	58159686
ENSE00003639438	58148649	58148852
ENSE00003672987	58169590	58169793
ENSE00003681625	58155960	58156075
ENSE00003691128	58149850	58150002
ENSE00003790285	58153375	58153641
ENSE00003900804	58170575	58172251

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 99.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.1674 / max 1356.0635, expressed in 1804 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
37011	92.9571	1804
202783	0.3796	200
202785	0.3176	168
202786	0.2736	146
202787	0.1387	50
202784	0.1007	24

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.03	gold quality
tibial nerve	UBERON:0001323	98.86	gold quality
transverse colon	UBERON:0001157	98.26	gold quality
body of uterus	UBERON:0009853	98.11	gold quality
right uterine tube	UBERON:0001302	97.99	gold quality
sural nerve	UBERON:0015488	97.89	gold quality
adrenal tissue	UBERON:0018303	97.77	gold quality
prostate gland	UBERON:0002367	97.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.66	gold quality
ileal mucosa	UBERON:0000331	97.59	gold quality
colon	UBERON:0001155	97.57	gold quality
left lobe of thyroid gland	UBERON:0001120	97.48	gold quality
sigmoid colon	UBERON:0001159	97.46	gold quality
large intestine	UBERON:0000059	97.45	gold quality
left uterine tube	UBERON:0001303	97.45	gold quality
skin of leg	UBERON:0001511	97.45	gold quality
skin of abdomen	UBERON:0001416	97.43	gold quality
body of pancreas	UBERON:0001150	97.38	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.36	gold quality
right lobe of thyroid gland	UBERON:0001119	97.34	gold quality
thyroid gland	UBERON:0002046	97.34	gold quality
right coronary artery	UBERON:0001625	97.32	gold quality
intestine	UBERON:0000160	97.17	gold quality
mucosa of stomach	UBERON:0001199	97.13	gold quality
rectum	UBERON:0001052	97.06	gold quality
colonic mucosa	UBERON:0000317	97.00	gold quality
zone of skin	UBERON:0000014	96.78	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.70	gold quality
tibia	UBERON:0000979	96.66	gold quality
body of stomach	UBERON:0001161	96.65	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	871.83
E-GEOD-135922	yes	34.91
E-GEOD-125970	yes	15.49
E-HCAD-9	yes	13.12
E-MTAB-8498	yes	12.80
E-HCAD-13	yes	7.24
E-MTAB-6678	yes	6.98
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting FLNB, 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-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-504-3P	99.30	67.18	1745

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits (PMID:11807098)
• role in vertebral segmentation, joint formation and endochondral ossification (PMID:14991055)
• mutations cause four distinct disorders of skeletal development (PMID:15054484)
• We report the identification of mutations in FLNB in two unrelated individuals with boomerang dysplasia. The resultant substitutions, L171R and S235P, lie within the calponin homology 2 region of the actin binding domain and occur at conserved sites. (PMID:15994868)
• Novel missense mutations within exon 2 and exon 3 of the FLNB gene are associated with atelosteogenesis I and III. (PMID:16752402)
• Mutations within the FLNB gene is non-random, with clusters of mutations leading to substitutions in the actin-binding domain and filamin repeats 13-17 being the most common cause of Larsen syndrome. (PMID:16801345)
• Spondylocarpotarsal synostosis syndrome in a patient with a causal FLNB mutation. (PMID:18257094)
• ASB2 may regulate hematopoietic cell differentiation by modulating cell spreading and actin remodeling through targeting of filamins A and B for degradation. (PMID:18799729)
• identifies filamin B as a molecular linker that mediates ICAM-1-driven transendothelial migration (PMID:18809679)
• These results establish a novel function of filamin B as a molecular scaffold in the JNK signaling pathway for type I IFN-induced apoptosis. (PMID:18815275)
• FLNB and SBF2 are associated with human stature. (PMID:19039035)
• anti-inflammatory activity of Serp-1 is mediated through modification of uPAR-linked beta-integrin and filamin B in monocytes, identifying this interaction as a central regulatory axis for inflammation (PMID:19052145)
• findings suggest common variants in FLNB have effects on bone structure in women. Although the location of variants having effects is not entirely consistent, variation at 5’ end of the gene may reflect effects on levels of FLNB transcription efficiency (PMID:19453265)
• High-resolution X-ray crystal structures of the human filamin B wild type actin-binding domain, plus W148R and M202V mutants. (PMID:19505475)
• Multiple single nucleotide polymorphisms and haplotypes in FLNB were significantly associated with bone mineral density, with the strongest association between lumbar spine BMD and rs9828717 (p = 0.005). (PMID:19727905)
• Maternal genes FLNB, HIC1 and ZNF189 were strongly associated with risk of clefting. (PMID:20634891)
• these data demonstrate that coordinated expression of GPIbalpha and filamin is required for efficient trafficking of either protein to the cell surface, and for production of normal-sized platelets. (PMID:22174152)
• skeletal dysplasias -associated mutations in the actin-binding domain of filamin B cause cytoplasmic focal accumulations correlating with disease severity. (PMID:22190451)
• study indicates that filamins are important regulators of polycystin-2 channel function, and further links actin cytoskeletal dynamics to the regulation of this channel protein (PMID:22802962)
• The structure reveals a new hinge in the linker region between actin binding domain (ABD) and the first filamin repeat that is ideally positioned to orient the ABD for actin binding. (PMID:23036857)
• study presents two patients with Atelosteogenesis Type I caused by two novel Filamin B (FLNB) mutations affecting the same FLNB residue: c.542G > A, predicting p.Gly181Asp and c.542G > C, predicting p.Gly181Arg (PMID:23401428)
• VEGF and PKC promote degradation-independent protein ubiquitination of FLNB to control intracellular trafficking of HDAC7. (PMID:23401860)
• Polymorphism at rs11720285, rs11130605 and rs9809315, all of which are located either 5’ of the transcription start site or in intron 1 of the FLNB gene has been identified as significantly associated with BMD in Caucasian women. (PMID:24176111)
• FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK. (PMID:25925610)
• F-actin clustering through the interaction with the mutant FLNB actin-binding domain may limit the cytoskeletal reorganization, preventing normal skeletal development. (PMID:26491051)
• Our results provide evidence for the involvement of FLNB in the pathogenesis of isolated Congenital talipes equinovarusand have expanded the clinical spectrum of FLNB mutations. (PMID:27395407)
• splicing variants of FLNB are differentially expressed in giant cell tumor cells and may play a role in the proliferation and differentiation of tumor cells. (PMID:27779699)
• This is the first identified mutation in the dimerization domain of FLNB. This loss-of-function frameshift mutation in FLNB causes autosomal-recessive SCT with rarely reported rib anomalies. This report demonstrates the involvement of rib anomaly in SCT and its causative mutation in the dimerization domain of FLNB. (PMID:28145000)
• FlnA more strongly binds RhoA, although both filamins overlap with RhoA expression in the cell cytoplasm. FlnA promotes RhoA activation whereas FlnB indirectly inhibits this pathway. Moreover, FlnA loss leads to diminished expression of b1-integrin, whereas FlnB loss promotes integrin expression (PMID:28175289)
• We report the case of a male patient with Larsen syndrome found to be mosaic for a novel point mutation in FLNB in whom it was possible to provide evidence-based personalized counseling on transmission risk to future offspring. Using dideoxy sequencing, a low-level FLNB c.698A>G, encoding p.(Tyr233Cys) mutation was detected in buccal mucosa and fibroblast DNA. (PMID:28639312)
• Data show mutations in Filamin genes known to cause Larsen syndrome and Frontometaphyseal dysplasia can affect the structure and therefore function of Filamin domains 16 and 17. (PMID:28652603)
• These mutations increased binding of FLNB protein to the MAP3K1 and RAC1 signal transduction complex and activated beta-catenin and had different effects on phosphorylation of MAP kinase pathway intermediates and SOX9 expression. Direct activation of beta-catenin through the FLNB-MAP3K1-RAC1 complex by FLNB mutations is a novel mechanism for causing 46,XY gonadal dysgenesis (PMID:29095481)
• Our report validates key clinical (fused thoracic vertebrae and carpal and tarsal coalition) and molecular (truncating variants in FLNB) characteristics of this condition. (PMID:29566257)
• In conclusion, the authors identify filamin B as a novel host factor that can interact with core protein to promote hepatitis B virus replication in hepatocytes. (PMID:29594956)
• FLNB mutation is associated with Piepkorn type of osteochondrodysplasia. (PMID:29797497)
• skipping of FLNB exon 30 is strongly associated with epithelial-to-mesenchymal transition gene signatures in basal-like breast cancer patient samples. (PMID:30059005)
• Studied expression levels of Filamin b (FLN-b) in the placenta of patients with pre-eclampsia (PE). Found down-regulation of FLN-b inhibits the ERK/matrix metallopeptidase 9 (MMP-9) pathways, leading to trophoblastic invasion disorders in the PE placenta. (PMID:30756369)
• Exome sequencing analysis identifies frequent oligogenic involvement and FLNB variants in adolescent idiopathic scoliosis. (PMID:32381728)
• circRNAome Profiling in Oral Carcinoma Unveils a Novel circFLNB that Mediates Tumour Growth-Regulating Transcriptional Response. (PMID:32785098)
• The variants at FLNA and FLNB contribute to the susceptibility of hypertension and stroke with differentially expressed mRNA. (PMID:33649519)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	flnbl	ENSDARG00000098374
danio_rerio	flnbl	ENSDARG00000112527
mus_musculus	Flnb	ENSMUSG00000025278
rattus_norvegicus	Flnb	ENSRNOG00000009470
drosophila_melanogaster	CG5984	FBGN0039500

Paralogs (36): SYNE2 (ENSG00000054654), SPTB (ENSG00000070182), ACTN1 (ENSG00000072110), ACTN2 (ENSG00000077522), DSP (ENSG00000096696), DRP2 (ENSG00000102385), SPTBN1 (ENSG00000115306), MACF1 (ENSG00000127603), FLNC (ENSG00000128591), ACTN4 (ENSG00000130402), SYNE1 (ENSG00000131018), MICAL2 (ENSG00000133816), DTNA (ENSG00000134769), MICAL1 (ENSG00000135596), SPTBN5 (ENSG00000137877), DTNB (ENSG00000138101), GAS2L3 (ENSG00000139354), DST (ENSG00000151914), UTRN (ENSG00000152818), SPTBN4 (ENSG00000160460), SPTA1 (ENSG00000163554), CLMN (ENSG00000165959), PKHD1 (ENSG00000170927), SPTBN2 (ENSG00000173898), SYNE3 (ENSG00000176438), PLEC (ENSG00000178209), SMTNL2 (ENSG00000188176), FLNA (ENSG00000196924), SPTAN1 (ENSG00000197694), DMD (ENSG00000198947), PKHD1L1 (ENSG00000205038), DYTN (ENSG00000232125), MICAL3 (ENSG00000243156), ACTN3 (ENSG00000248746), EPPK1 (ENSG00000261150), GAS2L2 (ENSG00000270765)

Protein

Protein identifiers

Filamin-B — O75369 (reviewed: O75369)

Alternative names: ABP-278, ABP-280 homolog, Actin-binding-like protein, Beta-filamin, Filamin homolog 1, Filamin-3, Thyroid autoantigen, Truncated actin-binding protein

All UniProt accessions (7): A0A0C4DGA1, A0A804HJC2, A0A804HK76, A0A804HL72, O75369, E7EN95, H7C5L4

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homodimer. Interacts with MICALL2. Interacts with RFLNA and RFLNB. Isoform 1 interacts with FBLP1, FLNA, FLNC, GP1BA, INPPL1, ITGB1A, PSEN1 and PSEN2. Isoform 3 interacts with ITGB1A, ITGB1D, ITGB3 and ITGB6. Interacts with MYOT and MYOZ1. Interacts with HBV capsid protein. Interacts with ASB2 isoform 1; the interaction targets FLNB for proteasomal degradation.

Subcellular location. Cytoplasm. Cell cortex. Cytoskeleton. Stress fiber. Myofibril. Sarcomere. Z line Cytoplasm. Stress fiber Cytoplasm.

Tissue specificity. Ubiquitous. Isoform 1 and isoform 2 are expressed in placenta, bone marrow, brain, umbilical vein endothelial cells (HUVEC), retina and skeletal muscle. Isoform 1 is predominantly expressed in prostate, uterus, liver, thyroid, stomach, lymph node, small intestine, spleen, skeletal muscle, kidney, placenta, pancreas, heart, lung, platelets, endothelial cells, megakaryocytic and erythroleukemic cell lines. Isoform 2 is predominantly expressed in spinal cord, platelet and Daudi cells. Also expressed in thyroid adenoma, neurofibrillary tangles (NFT), senile plaques in the hippocampus and cerebral cortex in Alzheimer disease (AD). Isoform 3 and isoform 6 are expressed predominantly in lung, heart, skeletal muscle, testis, spleen, thymus and leukocytes. Isoform 4 and isoform 5 are expressed in heart.

Post-translational modifications. ISGylation prevents ability to interact with the upstream activators of the JNK cascade and inhibits IFNA-induced JNK signaling. Ubiquitination by a SCF-like complex containing ASB2 isoform 1 leads to proteasomal degradation which promotes muscle differentiation.

Disease relevance. Interaction with FLNA may compensate for dysfunctional FLNA homodimer in the periventricular nodular heterotopia (PVNH) disorder. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. 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. The disease is caused by variants affecting the gene represented in this entry. Spondylocarpotarsal synostosis syndrome (SCT) [MIM:272460] Disorder characterized by short stature and vertebral, carpal and tarsal fusions. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Comprised of a NH2-terminal actin-binding domain, 24 internally homologous repeats and two hinge regions. Repeat 24 and the second hinge domain are important for dimer formation. The first hinge region prevents binding to ITGA and ITGB subunits.

Miscellaneous. May be due to exon skipping. May be due to exon skipping. May be due to competing donor splice sites. May be due to exon skipping.

Similarity. Belongs to the filamin family.

Isoforms (9)

UniProt ID	Names	Canonical?
O75369-1	1, ABP-278	yes
O75369-2	2, ABP-276
O75369-3	3, Var-1
O75369-7	7
O75369-4	4, Var-3
O75369-5	5, Var-2
O75369-6	6, Var-1-DeltaH1
O75369-8	8
O75369-9	9

RefSeq proteins (4): NP_001157789, NP_001157790, NP_001157791, NP_001448* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001298	Filamin/ABP280_rpt	Repeat
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR014756	Ig_E-set	Homologous_superfamily
IPR017868	Filamin/ABP280_rpt-like	Repeat
IPR036872	CH_dom_sf	Homologous_superfamily
IPR044801	Filamin	Family

Pfam: PF00307, PF00630

UniProt features (294 total): strand 131, helix 32, sequence variant 27, modified residue 26, repeat 24, turn 17, sequence conflict 12, region of interest 10, splice variant 10, domain 2, chain 1, mutagenesis site 1, cross-link 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
2WA7	X-RAY DIFFRACTION	1.85
2WA5	X-RAY DIFFRACTION	1.9
2WA6	X-RAY DIFFRACTION	1.95
4B7L	X-RAY DIFFRACTION	2.05
3FER	X-RAY DIFFRACTION	2.4
5DCP	X-RAY DIFFRACTION	2.49
2DI8	SOLUTION NMR
2DI9	SOLUTION NMR
2DIA	SOLUTION NMR
2DIB	SOLUTION NMR
2DIC	SOLUTION NMR
2DJ4	SOLUTION NMR
2DLG	SOLUTION NMR
2DMB	SOLUTION NMR
2DMC	SOLUTION NMR
2E9I	SOLUTION NMR
2E9J	SOLUTION NMR
2EE6	SOLUTION NMR
2EE9	SOLUTION NMR
2EEA	SOLUTION NMR
2EEB	SOLUTION NMR
2EEC	SOLUTION NMR
2EED	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75369-F1	76.96	0.07

Functional residue map

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

Post-translational modifications (27): 1474, 216, 519, 681, 730, 886, 932, 983, 1028, 1307, 1316, 1433, 1505, 1602, 1780, 2083, 2107, 2113, 2369, 2465 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
2468	cytoplasmic localization.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1169408	ISG15 antiviral mechanism

MSigDB gene sets: 720 (showing top): VERHAAK_AML_WITH_NPM1_MUTATED_DN, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_EPITHELIAL_CELL_DEVELOPMENT, KEGG_MAPK_SIGNALING_PATHWAY, AREB6_03, AREB6_01, PARK_TRETINOIN_RESPONSE_AND_RARA_PLZF_FUSION, BRUECKNER_TARGETS_OF_MIRLET7A3_DN, RODRIGUES_NTN1_TARGETS_DN, BILD_HRAS_ONCOGENIC_SIGNATURE, KANG_FLUOROURACIL_RESISTANCE_DN

GO Biological Process (8): keratinocyte development (GO:0003334), epithelial cell morphogenesis (GO:0003382), signal transduction (GO:0007165), skeletal muscle tissue development (GO:0007519), actin cytoskeleton organization (GO:0030036), cellular response to type II interferon (GO:0071346), muscle organ development (GO:0007517), cell differentiation (GO:0030154)

GO Molecular Function (6): RNA binding (GO:0003723), actin binding (GO:0003779), identical protein binding (GO:0042802), cadherin binding (GO:0045296), actin filament binding (GO:0051015), protein binding (GO:0005515)

GO Cellular Component (14): stress fiber (GO:0001725), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), brush border (GO:0005903), focal adhesion (GO:0005925), cell cortex (GO:0005938), actin cytoskeleton (GO:0015629), membrane (GO:0016020), Z disc (GO:0030018), neuronal cell body (GO:0043025), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
epithelial cell development	2
cytoplasm	2
cell periphery	2
keratinocyte differentiation	1
cell morphogenesis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
striated muscle tissue development	1
skeletal muscle organ development	1
cytoskeleton organization	1
actin filament-based process	1
response to type II interferon	1
cellular response to cytokine stimulus	1
animal organ development	1
muscle structure development	1
cellular developmental process	1
nucleic acid binding	1
cytoskeletal protein binding	1
protein binding	1
cell adhesion molecule binding	1
actin binding	1
protein-containing complex binding	1
binding	1
actomyosin	1
contractile actin filament bundle	1
intracellular anatomical structure	1
membrane	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
cell-substrate junction	1
cytoskeleton	1
I band	1
somatodendritic compartment	1
cell body	1
endocytic vesicle	1

Protein interactions and networks

STRING

2358 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FLNB	TLN1	Q9Y490	996
FLNB	TLN2	Q9Y4G6	996
FLNB	VCL	P18206	994
FLNB	FBLIM1	Q8WUP2	994
FLNB	PXN	P49023	981
FLNB	GP1BA	P07359	906
FLNB	CAV1	Q03135	860
FLNB	CFL1	P23528	827
FLNB	CFL2	Q9Y281	817
FLNB	INPPL1	O15357	806
FLNB	RALA	P11233	785
FLNB	FSCN1	Q16658	783
FLNB	AR	P10275	779
FLNB	RHOA	P06749	772
FLNB	FERMT3	Q86UX7	771

IntAct

162 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:2364”(proximity)	0.900
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
TANC2	TAX1BP3	psi-mi:“MI:0914”(association)	0.690
ISG15	FLNB	psi-mi:“MI:0915”(physical association)	0.590
FLNB	ISG15	psi-mi:“MI:0915”(physical association)	0.590
FLNB	GRB2	psi-mi:“MI:0915”(physical association)	0.560
FLNB	FLNA	psi-mi:“MI:0915”(physical association)	0.540
FLNB	FLNA	psi-mi:“MI:0403”(colocalization)	0.540
TUBB3	POTEF	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
PSEN1	FLNB	psi-mi:“MI:0915”(physical association)	0.510
PSEN2	FLNB	psi-mi:“MI:0915”(physical association)	0.510
FLNB	PSEN2	psi-mi:“MI:0915”(physical association)	0.510
FLNB	RAC1	psi-mi:“MI:0914”(association)	0.500
RAC1	FLNB	psi-mi:“MI:0915”(physical association)	0.500
FLNB	MAP3K1	psi-mi:“MI:0915”(physical association)	0.500
MAP3K4	FLNB	psi-mi:“MI:0915”(physical association)	0.500

BioGRID (407): FLNB (Two-hybrid), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Affinity Capture-MS), FLNB (Two-hybrid), AP1G1 (Co-fractionation), BASP1 (Co-fractionation), EIF4EBP1 (Co-fractionation), FLNA (Co-fractionation), FLNB (Co-fractionation), FLNB (Co-fractionation)

ESM2 similar proteins: A0A087WV53, A1CS92, A2ABU4, A2Q908, A2RUH7, A4QZL9, D3ZHA0, O01761, O70468, O75369, O88599, P05548, P11275, P11730, P11798, P13466, P21333, P56276, P56741, P70402, P79280, Q05623, Q13177, Q13203, Q13557, Q14315, Q2GM53, Q2HJF7, Q2URB7, Q5FW53, Q5PQM4, Q5RCC4, Q5VTT5, Q5ZJJ9, Q5ZKI0, Q62422, Q63518, Q6C1H8, Q6P686, Q6PHZ2

Diamond homologs: A4IF63, A5D7F8, A5D8S5, D2GXS7, D3ZHA0, D3ZQG6, F7H9X2, O70277, O75369, O75382, P13466, P21333, Q14315, Q1XHU0, Q28E95, Q3UIW8, Q5RBR0, Q60953, Q69ZI1, Q6NRD3, Q71F54, Q7Z6J0, Q80X90, Q80XJ2, Q8BTM8, Q8C120, Q8TEJ3, Q8VHX6, Q9C040, Q9ESN6, Q9HCM9, Q9R1R2, Q9VEN1, A5D7D1, D3ZEN0, D3ZHV2, D3ZQL6, E1BBG2, F1MF74, F1RA39

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FBLIM1	“up-regulates activity”	FLNB	binding
“Elongin E3-Cul-5”	“down-regulates quantity by destabilization”	FLNB	polyubiquitination
ASB2	“down-regulates quantity by destabilization”	FLNB	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 144 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by ERBB2 ECD mutants	5	31.4×	6e-05
Downstream signal transduction	8	28.5×	2e-07
FCERI mediated MAPK activation	7	22.6×	8e-06
Signaling by ERBB2 KD Mutants	5	19.8×	2e-04
RHO GTPases activate IQGAPs	6	19.4×	6e-05
DAP12 signaling	5	17.2×	3e-04
Signaling by RAF1 mutants	6	15.6×	1e-04
Signaling by high-kinase activity BRAF mutants	5	14.8×	6e-04

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to reactive oxygen species	5	15.8×	5e-03
negative regulation of translation	7	10.6×	3e-03
Ras protein signal transduction	6	9.5×	9e-03
cell migration	11	5.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2910 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	81
Likely pathogenic	72
Uncertain significance	1201
Likely benign	984
Benign	166

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098338	NM_001457.4(FLNB):c.1740dup (p.Ser581fs)	Pathogenic
126375	NM_001457.4(FLNB):c.517G>A (p.Ala173Thr)	Pathogenic
1332749	NM_001457.4(FLNB):c.1243C>T (p.Arg415Ter)	Pathogenic
1332815	NM_001457.4(FLNB):c.1204del (p.Val402fs)	Pathogenic
1332839	NM_001457.4(FLNB):c.1493del (p.Glu498fs)	Pathogenic
1332844	NM_001457.4(FLNB):c.1429delinsCT (p.Val477fs)	Pathogenic
1370778	NM_001457.4(FLNB):c.1109del (p.Ile370fs)	Pathogenic
1383728	NM_001457.4(FLNB):c.5842C>T (p.Arg1948Ter)	Pathogenic
1414987	NM_001457.4(FLNB):c.4439_4440dup (p.Val1481fs)	Pathogenic
1426583	NM_001457.4(FLNB):c.4470_4473dup (p.Met1492fs)	Pathogenic
1452279	NM_001457.4(FLNB):c.613G>T (p.Ala205Ser)	Pathogenic
1453088	NM_001457.4(FLNB):c.89dup (p.Lys31fs)	Pathogenic
1453267	NM_001457.4(FLNB):c.7472_7473del (p.Glu2491fs)	Pathogenic
1457383	NM_001457.4(FLNB):c.501C>G (p.Asp167Glu)	Pathogenic
1685823	NM_001457.4(FLNB):c.4807C>T (p.Pro1603Ser)	Pathogenic
1925259	NM_001457.4(FLNB):c.1006C>T (p.Gln336Ter)	Pathogenic
2008393	NM_001457.4(FLNB):c.5337del (p.Asn1779fs)	Pathogenic
2030487	NM_001457.4(FLNB):c.1665G>A (p.Trp555Ter)	Pathogenic
2032895	NM_001457.4(FLNB):c.5745C>A (p.Cys1915Ter)	Pathogenic
2053849	NM_001457.4(FLNB):c.4738T>G (p.Tyr1580Asp)	Pathogenic
2088065	NM_001457.4(FLNB):c.4014del (p.Glu1340fs)	Pathogenic
2119358	NM_001457.4(FLNB):c.3695_3696del (p.Lys1232fs)	Pathogenic
21278	NM_001457.4(FLNB):c.1081G>A (p.Gly361Ser)	Pathogenic
21280	NM_001457.4(FLNB):c.1945C>T (p.Arg649Ter)	Pathogenic
21292	NM_001457.4(FLNB):c.5500G>A (p.Gly1834Arg)	Pathogenic
2130925	NM_001457.4(FLNB):c.910C>T (p.Gln304Ter)	Pathogenic
2190805	NM_001457.4(FLNB):c.2911dup (p.Ala971fs)	Pathogenic
2696954	NM_001457.4(FLNB):c.1351_1370del (p.Asn451fs)	Pathogenic
2706113	NM_001457.4(FLNB):c.623G>A (p.Trp208Ter)	Pathogenic
2734542	NM_001457.4(FLNB):c.4781A>C (p.Tyr1594Ser)	Pathogenic

SpliceAI

6966 predictions. Top by Δscore:

Variant	Effect	Δscore
3:58008856:GGT:G	donor_loss	1.0000
3:58008857:G:C	donor_loss	1.0000
3:58008857:G:GG	donor_gain	1.0000
3:58008858:T:A	donor_loss	1.0000
3:58077044:A:AG	acceptor_gain	1.0000
3:58077044:A:G	acceptor_loss	1.0000
3:58077045:G:GT	acceptor_gain	1.0000
3:58077045:GAT:G	acceptor_gain	1.0000
3:58077045:GATA:G	acceptor_gain	1.0000
3:58077293:AGGT:A	donor_loss	1.0000
3:58077294:GGTA:G	donor_loss	1.0000
3:58077295:G:GA	donor_loss	1.0000
3:58077295:G:GG	donor_gain	1.0000
3:58078708:T:A	acceptor_gain	1.0000
3:58078711:TAACA:T	acceptor_gain	1.0000
3:58078712:A:AG	acceptor_gain	1.0000
3:58078712:AACAG:A	acceptor_gain	1.0000
3:58078713:ACAGG:A	acceptor_gain	1.0000
3:58078715:A:AG	acceptor_gain	1.0000
3:58078715:AG:A	acceptor_gain	1.0000
3:58078716:G:GA	acceptor_gain	1.0000
3:58078716:GG:G	acceptor_gain	1.0000
3:58078716:GGT:G	acceptor_gain	1.0000
3:58078716:GGTC:G	acceptor_gain	1.0000
3:58078716:GGTCT:G	acceptor_gain	1.0000
3:58078813:AGGT:A	donor_loss	1.0000
3:58078814:GG:G	donor_loss	1.0000
3:58078816:T:G	donor_loss	1.0000
3:58081774:GAG:G	donor_gain	1.0000
3:58081774:GAGGT:G	donor_loss	1.0000

AlphaMissense

17064 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:58008604:T:A	W14R	1.000
3:58008604:T:C	W14R	1.000
3:58008606:G:C	W14C	1.000
3:58008606:G:T	W14C	1.000
3:58008637:T:A	W25R	1.000
3:58008637:T:C	W25R	1.000
3:58077096:T:A	W115R	1.000
3:58077096:T:C	W115R	1.000
3:58077103:T:C	L117P	1.000
3:58077109:T:C	L119P	1.000
3:58077187:T:C	L145P	1.000
3:58077195:T:A	W148R	1.000
3:58077195:T:C	W148R	1.000
3:58077235:T:C	F161S	1.000
3:58077246:T:A	W165R	1.000
3:58077246:T:C	W165R	1.000
3:58077247:G:C	W165S	1.000
3:58077248:G:C	W165C	1.000
3:58077248:G:T	W165C	1.000
3:58077265:T:C	L171P	1.000
3:58077274:T:C	L174P	1.000
3:58078731:T:A	W186R	1.000
3:58078731:T:C	W186R	1.000
3:58078733:G:C	W186C	1.000
3:58078733:G:T	W186C	1.000
3:58078740:T:A	W189R	1.000
3:58078740:T:C	W189R	1.000
3:58078742:G:C	W189C	1.000
3:58078742:G:T	W189C	1.000
3:58078801:T:C	L209P	1.000

dbSNP variants (sampled 300 via entrez): RS1000007469 (3:58045571 T>C), RS1000047478 (3:58087378 G>A,C), RS1000074950 (3:58064389 T>C), RS1000076405 (3:58009517 G>A,C), RS1000098671 (3:58105205 T>TG), RS1000106766 (3:58094050 T>C), RS1000110892 (3:58084398 C>T), RS1000126854 (3:58061789 T>A), RS1000134283 (3:58081667 C>A,T), RS1000161236 (3:58169755 G>A), RS1000185099 (3:58129224 C>T), RS1000199603 (3:58129559 T>A), RS1000220780 (3:58033618 C>A), RS1000269961 (3:58045985 C>G,T), RS1000302672 (3:58037307 C>A,T)

Disease associations

OMIM: gene MIM:603381 | disease phenotypes: MIM:108720, MIM:112310, MIM:150250, MIM:108721, MIM:272460

GenCC curated gene-disease

Disease	Classification	Inheritance
atelosteogenesis type I	Definitive	Autosomal dominant
spondylocarpotarsal synostosis syndrome	Definitive	Autosomal recessive
atelosteogenesis type III	Definitive	Autosomal dominant
Boomerang dysplasia	Strong	Autosomal dominant
Larsen syndrome	Strong	Autosomal dominant
filamin-related bone disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
FLNB-associated autosomal dominant filamin related bone disorder	Definitive	AD

Mondo (10): atelosteogenesis type I (MONDO:0007167), Boomerang dysplasia (MONDO:0007208), Larsen syndrome (MONDO:0007875), connective tissue disorder (MONDO:0003900), atelosteogenesis type III (MONDO:0007168), spondylocarpotarsal synostosis syndrome (MONDO:0010094), skeletal dysplasia (MONDO:0018230), arthrogryposis syndrome (MONDO:0015225), arthrogryposis (MONDO:0008779), filamin-related bone disorder (MONDO:0019690)

Orphanet (7): Atelosteogenesis type I (Orphanet:1190), Boomerang dysplasia (Orphanet:1263), Larsen syndrome (Orphanet:503), Spondylocarpotarsal synostosis (Orphanet:3275), Atelosteogenesis type III (Orphanet:56305), Primary bone dysplasia (Orphanet:364526), Arthrogryposis syndrome (Orphanet:109007)

HPO phenotypes

199 total (30 of 199 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000107	Renal cyst
HP:0000175	Cleft palate
HP:0000204	Cleft upper lip
HP:0000218	High palate
HP:0000269	Prominent occiput
HP:0000272	Malar flattening
HP:0000283	Broad face
HP:0000316	Hypertelorism
HP:0000327	Hypoplasia of the maxilla
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000384	Preauricular skin tag
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000410	Mixed hearing impairment
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000506	Telecanthus
HP:0000518	Cataract
HP:0000520	Proptosis
HP:0000586	Shallow orbits
HP:0000668	Hypodontia

GWAS associations

35 associations (top):

Study	Trait	p-value
GCST001959_3	Eating disorders (purging via substances)	1.000000e-06
GCST002004_7	Adverse response to chemotherapy (neutropenia/leucopenia) (carboplatin)	4.000000e-06
GCST002764_16	Optic cup area	7.000000e-06
GCST002764_4	Optic cup area	1.000000e-08
GCST003875_39	Gut microbiota (bacterial taxa)	3.000000e-08
GCST004075_18	Vertical cup-disc ratio	5.000000e-06
GCST004075_9	Vertical cup-disc ratio	2.000000e-08
GCST004137_1	Optic cup area	5.000000e-06
GCST004137_8	Optic cup area	6.000000e-11
GCST004611_52	High light scatter reticulocyte count	4.000000e-18
GCST004612_60	High light scatter reticulocyte percentage of red cells	9.000000e-19
GCST004619_196	Reticulocyte fraction of red cells	2.000000e-13
GCST004622_163	Reticulocyte count	5.000000e-12
GCST004628_62	Immature fraction of reticulocytes	1.000000e-16
GCST007269_87	Pulse pressure	5.000000e-08
GCST008053_180	Height	1.000000e-06
GCST008053_181	Height	1.000000e-06
GCST008053_33	Height	5.000000e-11
GCST009131_6	Systemic sclerosis	1.000000e-10
GCST009404_23	Optic cup area	1.000000e-08
GCST009723_94	Vertical cup-disc ratio (adjusted for vertical disc diameter)	2.000000e-07
GCST009724_30	Vertical cup-disc ratio (multi-trait analysis)	2.000000e-11
GCST011440_2	Glaucoma (low intraocular pressure)	2.000000e-08
GCST90002385_433	High light scatter reticulocyte count	2.000000e-27
GCST90002386_553	High light scatter reticulocyte percentage of red cells	1.000000e-29
GCST90002387_76	Immature fraction of reticulocytes	8.000000e-26
GCST90002388_199	Lymphocyte count	6.000000e-10
GCST90002398_123	Neutrophil count	1.000000e-14
GCST90002405_20	Reticulocyte count	5.000000e-19
GCST90002406_39	Reticulocyte fraction of red cells	2.000000e-21

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0007883	taxonomic microbiome measurement
EFO:0006939	cup-to-disc ratio measurement
EFO:0007986	reticulocyte count
EFO:0005763	pulse pressure measurement
EFO:0004587	lymphocyte count
EFO:0004833	neutrophil count
EFO:0007789	BMI-adjusted waist circumference

MeSH disease descriptors (7)

Descriptor	Name	Tree numbers
D001176	Arthrogryposis	C05.550.150; C05.651.102; C05.660.077; C16.131.621.077
D003240	Connective Tissue Diseases	C17.300
C579928	Atelosteogenesis Type 3 (supp.)
C535396	Atelosteogenesis, type 1 (supp.)
C536573	Boomerang dysplasia (supp.)
C580241	Larsen Syndrome (supp.)
C535780	Spondylocarpotarsal synostosis (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295677 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.03	Kd	93.08	nM	CHEMBL5653589
7.01	ED50	96.85	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 3 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148394: Binding affinity to human FLNB incubated for 45 mins by Kinobead based pull down assay	kd	0.0931	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects methylation, decreases expression, increases expression, affects cotreatment	5
Valproic Acid	affects cotreatment, increases expression	5
trichostatin A	affects cotreatment, increases expression, affects expression	3
Arsenic Trioxide	decreases response to substance, decreases expression, increases expression	3
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	3
Tretinoin	increases expression	3
bisphenol F	decreases expression, increases expression, affects cotreatment	2
cobaltous chloride	decreases expression, increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
chloropicrin	decreases expression	2
entinostat	affects cotreatment, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	decreases expression	2
Copper	affects binding, increases expression	2
Estradiol	affects cotreatment, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
Raloxifene Hydrochloride	decreases expression, affects expression, affects cotreatment, affects reaction	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
glycidyl methacrylate	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, decreases expression, increases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
dimethylselenide	decreases expression, increases oxidation	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118962	Binding	Binding affinity to FLNB in human NCI-H358 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D7PY	Ubigene A-549 FLNB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01042158	PHASE4	COMPLETED	A Clinical Trial of Ambrisentan and Tadalafil in Pulmonary Arterial Hypertension Associated With Systemic Sclerosis
NCT03688191	PHASE4	UNKNOWN	Study of Sirolimus in CTD-TP in China
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04197050	PHASE4	UNKNOWN	Effect of Sacubitril/Valsartan on Reduced Right Ventricular Ejection Fraction in Patients With CTD
NCT04928586	PHASE4	UNKNOWN	Immunosuppressant Combined With Pirfenidone in CTD-ILD
NCT05440240	PHASE4	RECRUITING	Percutaneous Needle Fasciotomy +/- Corticosteroid Injection for Dupuytren’s Contracture
NCT05505409	PHASE4	UNKNOWN	Efficacy and Safety of Pirfenidone in CTD-ILD
NCT06499233	PHASE4	RECRUITING	Efficacy and Safety of Prophylactic Treatment for Pneumocystis Jirovecii Pneumonia in Patients With Autoimmune Inflammatory Rheumatic Disease
NCT00864201	PHASE3	UNKNOWN	A Study to Evaluate the Use of Bosentan in Patients With Exercise Induced Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
NCT01196091	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01205438	PHASE3	COMPLETED	A Study of LY2127399 in Participants With Systemic Lupus Erythematosus
NCT01488708	PHASE3	TERMINATED	On Open-Label Study in Participants With Systemic Lupus Erythematosus
NCT03626688	PHASE3	COMPLETED	A Study Evaluating the Efficacy and Safety of Ralinepag to Improve Treatment Outcomes in PAH Patients
NCT03683186	PHASE3	ENROLLING_BY_INVITATION	A Study Evaluating the Long-Term Efficacy and Safety of Ralinepag in Subjects With PAH Via an Open-Label Extension
NCT04084678	PHASE3	TERMINATED	A Study of Ralinepag to Evaluate Effects on Exercise Capacity by CPET in Subjects With WHO Group 1 PH
NCT06716606	PHASE3	RECRUITING	A Study to Investigate the Long-term Safety and Efficacy of Belimumab in Adults With Interstitial Lung Disease (ILD) Associated With Systemic Sclerosis (SSc) and Other Connective Tissue Diseases (CTD) (BLISSconneCTD-OLE)
NCT06917690	PHASE3	RECRUITING	A Study to Learn About the Safety and Efficacy of the Drug Oleogel-S10 in Japanese Patients With Epidermolysis Bullosa
NCT00004357	PHASE2	COMPLETED	Absorption of Corticosteroids in Children With Juvenile Dermatomyositis
NCT00005675	PHASE2	COMPLETED	Oral Type I Collagen for Relieving Scleroderma
NCT01808196	PHASE2	COMPLETED	Testing Effectiveness of Losartan in Patients With EoE With or Without a CTD
NCT02682511	PHASE2	ACTIVE_NOT_RECRUITING	Oral Ifetroban to Treat Diffuse Cutaneous Systemic Sclerosis (SSc) or SSc-associated Pulmonary Arterial Hypertension
NCT04993885	PHASE2	RECRUITING	Avatrombopag in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT05516758	PHASE2	TERMINATED	A Study of Peresolimab (LY3462817) in Participants With Moderately-to-Severely Active Rheumatoid Arthritis
NCT05998759	PHASE2	RECRUITING	Telitacicept for the Treatment of Connective Tissue Disease-associated Thrombocytopenia
NCT06104228	PHASE2	RECRUITING	129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH)
NCT01028833	PHASE2	COMPLETED	Effects of Power Mobility on Young Children With Severe Motor Impairments
NCT05052554	PHASE1	WITHDRAWN	Study With QR-504a to Evaluate Safety, Tolerability & Corneal Endothelium Molecular Biomarker(s) in Subjects With FECD3
NCT01093911	PHASE1	COMPLETED	Safety Study of CDP7657 in Healthy Volunteers and Patients With Systemic Lupus Erythematosus (SLE)
NCT01764594	PHASE1	COMPLETED	Safety Study of CDP7657 in Patients With Systemic Lupus Erythematosus
NCT02392130	PHASE1	COMPLETED	A Clinical Trial to Assess the Potential of LEO 130852A Gel to Reduce Steroid Induced Skin Atrophy on Healthy Skin
NCT03337165	PHASE1	COMPLETED	Autologous Tolerogenic Dendritic Cells for Treatment of Patients With Rheumatoid Arthritis
NCT03929120	PHASE1	COMPLETED	Allogeneic Bone Marrow Mesenchymal Stem Cells for Patients With Interstitial Lung Disease (ILD) & Connective Tissue Disorders (CTD)
NCT02872662	Not specified	COMPLETED	Individual Molecular MRD Monitoring for MDS Patients After Allo-SCT
NCT03821727	Not specified	COMPLETED	SCT in Ph Positive Acute Lymphoblastic Leukemia
NCT01424033	PHASE2/PHASE3	TERMINATED	A Clinical Trial for CTD-ILD Treatment
NCT04915482	PHASE2/PHASE3	UNKNOWN	TPO-RAs Combined With Anti-CD20 Antibody in the Treatment of Adult Immune Thrombocytopenia With Autoantibodies
NCT06574581	PHASE1/PHASE2	RECRUITING	ADSCs Therapy in Patients With CTD-ILD
NCT00001330	Not specified	COMPLETED	Study of Silicone-Associated Connective Tissue Diseases
NCT00001641	Not specified	COMPLETED	Study of Heritable Connective Tissue Disorders
NCT00001978	Not specified	TERMINATED	Determination of Kidney Function