FBLN7

Summary

FBLN7 (fibulin 7, HGNC:26740) is a protein-coding gene on chromosome 2q13, encoding Fibulin-7 (Q53RD9). An adhesion molecule that interacts with extracellular matrix molecules in developing teeth and may play important roles in differentiation and maintenance of odontoblasts as well as in dentin formation.

Predicted to enable calcium ion binding activity; heparan sulfate proteoglycan binding activity; and heparin binding activity. Predicted to be involved in cell adhesion. Located in focal adhesion.

Source: NCBI Gene 129804 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 116 total
• MANE Select transcript: NM_153214

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26740
Approved symbol	FBLN7
Name	fibulin 7
Location	2q13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37440, TM14
Ensembl gene	ENSG00000144152
Ensembl biotype	protein_coding
OMIM	611551
Entrez	129804

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 9 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000272559, ENST00000331203, ENST00000409450, ENST00000409667, ENST00000409903, ENST00000441565, ENST00000472377, ENST00000865641, ENST00000865642, ENST00000865643

RefSeq mRNA: 2 — MANE Select: NM_153214 NM_001128165, NM_153214

CCDS: CCDS2095, CCDS46391

Canonical transcript exons

ENST00000331203 — 8 exons

Exon	Start	End
ENSE00000963780	112182791	112182928
ENSE00001009514	112181739	112181876
ENSE00001009516	112175714	112175839
ENSE00001071590	112185201	112185339
ENSE00001252519	112138385	112138730
ENSE00001310253	112187134	112188218
ENSE00003461848	112165001	112165171
ENSE00003542972	112159676	112159835

Expression profiles

Bgee: expression breadth ubiquitous, 179 present calls, max score 91.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 6.7974 / max 116.0639, expressed in 1170 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
21973	5.6245	1100
21974	1.1729	132

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	91.40	gold quality
oocyte	CL:0000023	90.22	gold quality
cartilage tissue	UBERON:0002418	89.63	gold quality
stromal cell of endometrium	CL:0002255	87.28	gold quality
tibia	UBERON:0000979	85.83	gold quality
primary visual cortex	UBERON:0002436	82.18	gold quality
prefrontal cortex	UBERON:0000451	82.17	gold quality
popliteal artery	UBERON:0002250	81.57	gold quality
tibial artery	UBERON:0007610	81.55	gold quality
ventricular zone	UBERON:0003053	80.09	gold quality
pituitary gland	UBERON:0000007	79.47	gold quality
middle temporal gyrus	UBERON:0002771	79.16	gold quality
aorta	UBERON:0000947	79.08	gold quality
right coronary artery	UBERON:0001625	78.88	gold quality
right frontal lobe	UBERON:0002810	78.71	gold quality
frontal cortex	UBERON:0001870	78.69	gold quality
left lobe of thyroid gland	UBERON:0001120	78.62	gold quality
thyroid gland	UBERON:0002046	78.62	gold quality
occipital lobe	UBERON:0002021	78.16	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.65	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.59	gold quality
ectocervix	UBERON:0012249	77.52	gold quality
lymph node	UBERON:0000029	77.22	gold quality
neocortex	UBERON:0001950	77.10	gold quality
upper arm skin	UBERON:0004263	76.89	gold quality
endocervix	UBERON:0000458	76.81	gold quality
right lobe of thyroid gland	UBERON:0001119	76.80	gold quality
tendon of biceps brachii	UBERON:0008188	76.66	gold quality
decidua	UBERON:0002450	76.53	gold quality
descending thoracic aorta	UBERON:0002345	76.42	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	25.50
E-ANND-3	no	2.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting FBLN7, 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-3924	100.00	72.09	2394
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-556-3P	99.74	68.75	1203
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-4502	99.65	66.99	1021
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-331-3P	98.76	64.91	793
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-1910-3P	98.44	67.51	1695
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-6511A-5P	98.13	67.47	1770
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-212-5P	96.83	67.43	950
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-601	95.98	67.59	421

Literature-anchored findings (GeneRIF, showing 8)

• Dysregulation of fibulin expression by anti-Ro/SSA antibodiess may contribute to disorganization of the extracellular environment and thus cause injury to the salivary gland architecture and functionality observed in Sjogren syndrome (PMID:19229767)
• Fbln7-C terminal fragment inhibited the HUVEC tube formation and the vessel sprouting in aortic ring assays. (PMID:24480309)
• Heterozygous loss of FBLN7 and TMEM87B account for some of the clinical features, including cardiac defects and craniofacial abnormalities associated with 2q13 deletion syndrome. (PMID:24694933)
• fibulin-7 (Fbln7) bound to angiopoietin-1 through interaction between the N-terminal portions of Fbln7 and angiopoietin-1. (PMID:30924128)
• this is the first report which confirms the presence of ligatin and fibulin-7 in human aqueous humor, quantified their differential expression, and indicated the possibility of their involvement in the maintenance of the trabecular meshwork structure in glaucoma progression. (PMID:30958601)
• Novel progressive acrodysostosis-like skeletal dysplasia, cerebellar atrophy, and ichthyosis. (PMID:32783359)
• Fibulin7 aggravates calcium oxalate-induced acute kidney injury by binding to calcium oxalate crystals. (PMID:36370444)
• Fibulin7 Mediated Pathological Cardiac Remodeling through EGFR Binding and EGFR-Dependent FAK/AKT Signaling Activation. (PMID:37344348)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	fbln7	ENSDARG00000089519
mus_musculus	Fbln7	ENSMUSG00000027386
rattus_norvegicus	Fbln7	ENSRNOG00000017550
caenorhabditis_elegans		WBGENE00000168
caenorhabditis_elegans		WBGENE00012018
caenorhabditis_elegans		WBGENE00013480
caenorhabditis_elegans		WBGENE00013486
caenorhabditis_elegans		WBGENE00013487
caenorhabditis_elegans		WBGENE00018906
caenorhabditis_elegans		WBGENE00019901
caenorhabditis_elegans		WBGENE00022858

Paralogs (8): DLL3 (ENSG00000090932), CD93 (ENSG00000125810), WIF1 (ENSG00000156076), CRELD1 (ENSG00000163703), DLK2 (ENSG00000171462), CD248 (ENSG00000174807), CLEC14A (ENSG00000176435), CRELD2 (ENSG00000184164)

Protein

Protein identifiers

Fibulin-7 — Q53RD9 (reviewed: Q53RD9)

All UniProt accessions (4): Q53RD9, B8ZZC1, H7BZ65, Q8IY13

UniProt curated annotations — full annotation on UniProt →

Function. An adhesion molecule that interacts with extracellular matrix molecules in developing teeth and may play important roles in differentiation and maintenance of odontoblasts as well as in dentin formation.

Subunit / interactions. Interacts with heparin, FBLN1, FN1 and DSPP. Preferentially binds dental mesenchyme cells and odontoblasts but not dental epithelial cells or nondental cells. Binding requires a heparan sulfate-containing receptor on the cell surface as well as an integrin.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the fibulin family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q53RD9-1	1	yes
Q53RD9-2	2
Q53RD9-3	3
Q53RD9-4	4

RefSeq proteins (2): NP_001121637, NP_694946* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000436	Sushi_SCR_CCP_dom	Domain
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR035976	Sushi/SCR/CCP_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR050751	ECM_structural_protein	Family
IPR055088	Fibulin_C	Domain

Pfam: PF00008, PF00084, PF07645, PF14670, PF22914

UniProt features (24 total): disulfide bond 11, domain 4, splice variant 3, glycosylation site 2, signal peptide 1, chain 1, sequence variant 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q53RD9-F1	82.78	0.40

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 (11): 107–134, 140–151, 145–160, 162–171, 228–244, 240–253, 255–268, 274–287, 281–296, 301–318, 81–121

Glycosylation sites (2): 124, 307

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 76 (showing top): BENPORATH_ES_WITH_H3K27ME3, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOMF_HEPARIN_BINDING, CUI_TCF21_TARGETS_2_UP, LEIN_MEDULLA_MARKERS, GOCC_ANCHORING_JUNCTION, GOMF_SULFUR_COMPOUND_BINDING, GOMF_PROTEOGLYCAN_BINDING, GOMF_HEPARAN_SULFATE_PROTEOGLYCAN_BINDING, DODD_NASOPHARYNGEAL_CARCINOMA_DN, CHEN_METABOLIC_SYNDROM_NETWORK, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, MEISSNER_BRAIN_HCP_WITH_H3K4ME3_AND_H3K27ME3, MCBRYAN_PUBERTAL_BREAST_4_5WK_UP

GO Biological Process (1): cell adhesion (GO:0007155)

GO Molecular Function (3): calcium ion binding (GO:0005509), heparin binding (GO:0008201), heparan sulfate proteoglycan binding (GO:0043395)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), focal adhesion (GO:0005925), extracellular matrix (GO:0031012), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
metal ion binding	1
glycosaminoglycan binding	1
sulfur compound binding	1
proteoglycan binding	1
cell-substrate junction	1
external encapsulating structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

862 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FBLN7	DSPP	Q9NZW4	709
FBLN7	TSPAN16	Q9UKR8	644
FBLN7	TMEM87B	Q96K49	638
FBLN7	FN1	P02751	513
FBLN7	ZC3H6	P61129	513
FBLN7	TPM3	P06753	441
FBLN7	FNDC3A	Q9Y2H6	409
FBLN7	ANAPC1	Q9H1A4	408
FBLN7	DMRT3	Q9NQL9	407
FBLN7	FGFR2	P18443	398
FBLN7	ACOXL	Q9NUZ1	393
FBLN7	NTNG1	Q9Y2I2	386
FBLN7	FZD9	O00144	381
FBLN7	SLC4A4	Q9Y6R1	379
FBLN7	PBX3	P40426	372

IntAct

7 interactions, top by confidence:

A	B	Type	Score
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
FBLN7	HSPA5	psi-mi:“MI:0914”(association)	0.350
FBLN7	CIBAR1	psi-mi:“MI:0914”(association)	0.350
FBLN7	SRPX2	psi-mi:“MI:0914”(association)	0.350
LUC7L2	SAP18	psi-mi:“MI:0914”(association)	0.350
UBXN6	ENDOD1	psi-mi:“MI:0914”(association)	0.350

BioGRID (29): HSPA5 (Affinity Capture-MS), ASPH (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS), CLNS1A (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), FBLN7 (Affinity Capture-MS), ASPH (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), TXNDC11 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), FBLN7 (Affinity Capture-MS), FBLN7 (Affinity Capture-MS), FBLN7 (Reconstituted Complex), ASPH (Affinity Capture-MS), HSPA5 (Affinity Capture-MS)

ESM2 similar proteins: A0A0R4IKU3, A0A8M9PFP2, A1A5Y0, A2A863, A2VCU8, A5A6L1, B0S5G3, L7VG99, O00622, O08841, O35118, O42493, O93512, P08163, P08833, P16042, P16144, P17668, P18406, Q07663, Q0VCN6, Q13753, Q501P1, Q53RD9, Q5R9Q9, Q61220, Q61592, Q64632, Q6DDW2, Q7T3Q2, Q7ZV46, Q7ZXL5, Q8R4Y4, Q8R553, Q8VDA1, Q91166, Q91167, Q91713, Q99JH7, Q9BQT9

Diamond homologs: A0A1F4, D3ZHH1, G5EDK5, O35474, O43854, O88277, P10040, P13508, P14585, P18168, P78504, P97607, Q06561, Q19319, Q20911, Q501P1, Q53RD9, Q5R7K9, Q5ZQU0, Q63722, Q6R8J2, Q70E20, Q8TER0, Q90Y54, Q90Y57, Q9JLB4, Q9QXX0, Q9QYE5, Q9W332, Q9Y219, A0A087WV53, A1KZ92, A2AJ76, A4IFW2, A4IGL7, A6NDA9, B0BNK7, B0V2N1, D2HFT7, D3YXG0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	100
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1433 predictions. Top by Δscore:

Variant	Effect	Δscore
2:112181737:A:AG	acceptor_gain	1.0000
2:112181738:G:GG	acceptor_gain	1.0000
2:112181738:GCC:G	acceptor_gain	1.0000
2:112181875:GG:G	donor_gain	1.0000
2:112181876:GG:G	donor_gain	1.0000
2:112182790:GAC:G	acceptor_gain	1.0000
2:112182927:GG:G	donor_gain	1.0000
2:112182928:GG:G	donor_gain	1.0000
2:112185197:TCA:T	acceptor_loss	1.0000
2:112185198:CAGAT:C	acceptor_loss	1.0000
2:112185199:A:AG	acceptor_gain	1.0000
2:112185200:G:GG	acceptor_gain	1.0000
2:112185200:GAT:G	acceptor_gain	1.0000
2:112185337:ATTGT:A	donor_loss	1.0000
2:112185338:TT:T	donor_gain	1.0000
2:112185338:TTG:T	donor_loss	1.0000
2:112185339:TGT:T	donor_loss	1.0000
2:112185340:G:GG	donor_gain	1.0000
2:112185340:GTGA:G	donor_loss	1.0000
2:112187133:GCCA:G	acceptor_gain	1.0000
2:112149968:GTGCC:G	donor_gain	0.9900
2:112149969:TGCCT:T	donor_gain	0.9900
2:112159675:GAACT:G	acceptor_gain	0.9900
2:112165152:G:T	donor_gain	0.9900
2:112175835:GACTG:G	donor_gain	0.9900
2:112181734:CGCA:C	acceptor_loss	0.9900
2:112181735:GCA:G	acceptor_loss	0.9900
2:112181736:CAGCC:C	acceptor_loss	0.9900
2:112181737:A:C	acceptor_loss	0.9900
2:112181737:AGCC:A	acceptor_gain	0.9900

AlphaMissense

2873 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:112165146:G:C	W127C	0.998
2:112165146:G:T	W127C	0.998
2:112165126:T:A	C121S	0.995
2:112165127:G:C	C121S	0.995
2:112187138:T:A	C318S	0.995
2:112187139:G:C	C318S	0.995
2:112165126:T:C	C121R	0.994
2:112165144:T:A	W127R	0.993
2:112165144:T:C	W127R	0.993
2:112165085:G:A	C107Y	0.992
2:112165128:T:G	C121W	0.992
2:112187138:T:C	C318R	0.992
2:112187250:T:G	F355C	0.992
2:112181838:T:G	F211C	0.991
2:112187337:T:G	F384C	0.991
2:112187421:T:A	V412D	0.991
2:112165084:T:A	C107S	0.990
2:112165084:T:C	C107R	0.990
2:112165085:G:C	C107S	0.990
2:112165086:C:G	C107W	0.990
2:112165127:G:A	C121Y	0.990
2:112181837:T:C	F211L	0.990
2:112181839:C:A	F211L	0.990
2:112181839:C:G	F211L	0.990
2:112185293:T:C	C301R	0.990
2:112187153:T:C	C323R	0.990
2:112182802:T:A	C228S	0.989
2:112182803:G:C	C228S	0.989
2:112182922:T:A	C268S	0.989
2:112182923:G:C	C268S	0.989

dbSNP variants (sampled 300 via entrez): RS1000024939 (2:112159897 C>T), RS1000027056 (2:112150139 A>T), RS1000029067 (2:112214182 A>G), RS1000044486 (2:112189486 A>G), RS1000125122 (2:112142796 G>A), RS1000125619 (2:112199840 C>A,G), RS1000209408 (2:112194377 C>T), RS1000213601 (2:112230368 T>C), RS1000225168 (2:112243963 T>C), RS1000255428 (2:112154137 C>T), RS1000304748 (2:112237037 G>A), RS1000339991 (2:112216163 A>G), RS1000343936 (2:112223840 T>TAATC), RS1000395729 (2:112189833 A>G), RS1000411172 (2:112171505 A>T)

Disease associations

OMIM: gene MIM:611551 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST003264_76	Post bronchodilator FEV1/FVC ratio	2.000000e-06
GCST004025_15	Systemic juvenile idiopathic arthritis	3.000000e-06
GCST005097_2	Fractures (vertebral)	1.000000e-09
GCST010242_126	HDL cholesterol levels	2.000000e-08
GCST012276_22	Clostridioides difficle infection in antibiotics-users	8.000000e-06
GCST90002407_59	White blood cell count	3.000000e-14

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0009130	clostridium difficile infection

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	3
Aflatoxin B1	affects expression, decreases expression	3
entinostat	decreases expression, affects cotreatment	2
belinostat	decreases expression, affects cotreatment	2
Panobinostat	affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression	2
bisphenol A	decreases methylation	1
sodium arsenite	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	increases methylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression, affects cotreatment	1
Acetaminophen	decreases expression	1
Citrulline	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Methapyrilene	affects methylation	1
N-Nitrosopyrrolidine	decreases expression	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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