GeneBe

TGFBI

protein-coding

transforming growth factor beta induced

Gene summary

This gene encodes an RGD-containing protein that binds to type I, II and IV collagens. The RGD motif is found in many extracellular matrix proteins modulating cell adhesion and serves as a ligand recognition sequence for several integrins. This protein plays a role in cell-collagen interactions and may be involved in endochondrial bone formation in cartilage. The protein is induced by transforming growth factor-beta and acts to inhibit cell adhesion. Mutations in this gene are associated with multiple types of corneal dystrophy. [provided by RefSeq, Jul 2008]

Previous symbols:
  • CSD3
  • LCD1
  • CSD1
  • CSD2

MANE transcript

NM_000358.3

Inheritance

AD

ClinVar variants

P:20U:150B:38

Top phenotype

Corneal dystrophy, lattice type I; Corneal dystrophy, lattice type IIIA; Corneal dystrophy of Bowman layer, type I; Corneal dystrophy, Avellino type; Corneal dystrophy, Reis-Bucklers type; Corneal dystrophy, Thiel-Behnke type; Corneal dystrophy, Groenouw type I; Corneal dystrophy, epithelial basement membrane

gnomAD constraint

pLI —, LoF o/e 0.53

Max pathogenic AF

—

Genomic locus

chr5:136,028,988-136,063,818

External References & Databases

Ensembl (ENSG00000120708)NCBI Gene (7045)OMIM (601692)HGNC:11771GenCCUniProt (Q15582)AlphaFoldClinVar (TGFBI)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~34.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

epithelial basement membrane dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007375

Submitter: Orphanet

granular corneal dystrophy type ISUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007377

Submitter: Orphanet

granular corneal dystrophy type IDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007377

Submitter: G2P

granular corneal dystrophy type ISTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007377

Submitter: Labcorp Genetics (formerly Invitae)

epithelial-stromal TGFBI dystrophySTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0000764

Submitter: PanelApp Australia

epithelial-stromal TGFBI dystrophyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0000764

Submitter: Ambry Genetics

granular corneal dystrophy type IISUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011855

Submitter: Orphanet

lattice corneal dystrophy type ISUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007380

Submitter: Orphanet

granular corneal dystrophy type IIDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011855

Submitter: G2P

Reis-Bucklers corneal dystrophyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012043

Submitter: G2P

lattice corneal dystrophy type IDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007380

Submitter: G2P

Reis-Bucklers corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0012043

Submitter: Orphanet

Thiel-Behnke corneal dystrophyDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011185

Submitter: G2P

Thiel-Behnke corneal dystrophySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0011185

Submitter: Orphanet

Clinical Genomic Database (CGD)

Corneal dystrophy, lattice type I; Corneal dystrophy, lattice type IIIA; Corneal dystrophy of Bowman layer, type I; Corneal dystrophy, Avellino type; Corneal dystrophy, Reis-Bucklers type; Corneal dystrophy, Thiel-Behnke type; Corneal dystrophy, Groenouw type I; Corneal dystrophy, epithelial basement membraneAD

Manifestation: Ophthalmologic

Intervention: General

Rationale: It has been reported that in affected individuals with CDA, LASIK can increase the deposition of visually significant corneal opacities; Corneal epithelial debridement and fibronectin eye drops has been described as potentially delaying the need for keratoplasty or phototherapeutic keratoplasty; Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 9780098; 9727509; 9497262; 10442892; 11867580; 11923233; 15531312; 15019320; 15885785; 15111592; 15790870; 16652336; 16606891; 22080335; 22155582; 22194646; 22355247; 22575726Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TGFBI variants in ClinVar

14 Conditions Cataloged
Inborn genetic diseasesTotal: 94
not providedTotal: 72
Corneal dystrophyTotal: 61
Groenouw corneal dystrophy type ITotal: 10
TGFBI-related disorderTotal: 10
Reis-Bucklers' corneal dystrophyTotal: 10
Avellino corneal dystrophyTotal: 9
Thiel-Behnke corneal dystrophyTotal: 8

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_000358.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
10
clinvar
20
clinvar
2
clinvar
 32
missense
11
clinvar
9
clinvar
131
clinvar
12
clinvar
4
clinvar
 167
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
8
clinvar
 8
Total119150326208

Highest pathogenic variant AF is 0.00026354333

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 19 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_000358.3RefSeqNP_000349.117MANE Select
ENST00000442011.7EnsemblENSP00000416330.217MANE Select
ENST00000503087.1EnsemblENSP00000427137.14Standard
ENST00000507018.5EnsemblENSP00000421540.14Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
tgfbiDanio rerio

Structure: fast muscle cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Beta3 integrin cell surface interactions
  • Beta1 integrin cell surface interactions
  • Beta2 integrin cell surface interactions

Biological Process

  • angiogenesis
  • chondrocyte differentiation
  • cell adhesion
  • negative regulation of cell adhesion
  • visual perception

Molecular Function

  • integrin binding
  • extracellular matrix structural constituent
  • protein binding
  • collagen binding
  • cell adhesion molecule binding

Cellular Component

  • extracellular region
  • basement membrane
  • extracellular space
  • trans-Golgi network
  • plasma membrane

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000442011
Coding exons
17
Length
34924
Individuals with no LoFs
124640
Homozygous LoFs
0
Heterozygous LoFs
29
Defined
124669
p
0.000116
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense0.1023933990.9860.00002324410
Missense (PolyPhen)204220.940.923332399
Synonymous0.9741551710.9050.00001081411
Loss of Function2.461732.10.5300.00000167372

Population LoF Frequency

PopulationCAFp-valueStatus
African0.0000650.000065rare
Latino/Admixed American0.000150.00014rare
Ashkenazi Jewish0.000100.000099rare
East Asian0.0000560.000056rare
Finnish0.000190.00019rare
European (Non-Finnish)0.000130.00013rare
South Asian0.0000650.000065rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Plays a role in cell adhesion (PubMed:8024701). May play a role in cell-collagen interactions (By similarity). {ECO:0000250|UniProtKB:O11780, ECO:0000269|PubMed:8024701}.;
Disease
DISEASE: Corneal dystrophy, epithelial basement membrane (EBMD) [MIM:121820]: A bilateral anterior corneal dystrophy characterized by grayish epithelial fingerprint lines, geographic map-like lines, and dots (or microcysts) on slit-lamp examination. Pathologic studies show abnormal, redundant basement membrane and intraepithelial lacunae filled with cellular debris. {ECO:0000269|PubMed:16652336}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, Groenouw type 1 (CDGG1) [MIM:121900]: A rare form of stromal corneal dystrophy characterized by multiple small deposits in the superficial central corneal stroma, and progressive visual impairment. {ECO:0000269|PubMed:15623763}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, lattice type 1 (CDL1) [MIM:122200]: A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. CDL1 is characterized by progressive visual impairment, and the presence of delicate, double-contoured, interdigitating, elongated deposits that form a reticular pattern in the corneal stroma. Systemic amyloidosis is absent. Recurrent corneal ulceration sometimes occurs. {ECO:0000269|PubMed:10837380, ECO:0000269|PubMed:11413411, ECO:0000269|PubMed:14597039, ECO:0000269|PubMed:15531312, ECO:0000269|PubMed:15623763, ECO:0000269|PubMed:15838722, ECO:0000269|PubMed:16541014, ECO:0000269|PubMed:17013691, ECO:0000269|PubMed:9799082}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, Thiel-Behnke type (CDTB) [MIM:602082]: A bilateral disorder of the cornea characterized by progressive honeycomb-like, subepithelial corneal opacities with recurrent erosions. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, Reis-Bucklers type (CDRB) [MIM:608470]: A bilateral disorder of the cornea characterized by intermittent attacks of ocular irritation, recurrent painful corneal erosions starting in childhood, corneal opacities in a geographic pattern at the level of the Bowman layer, and a progressive decrease of visual acuity. The lesions are primarily in Bowman membrane with secondary involvement of the epithelium and superficial part of the stroma. Bowman membrane is almost completely replaced by pathologic materials including disoriented collagen fibrils. {ECO:0000269|PubMed:10660331, ECO:0000269|PubMed:15623763, ECO:0000269|PubMed:9780098}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, lattice type 3A (CDL3A) [MIM:608471]: A form of lattice corneal dystrophy, a class of inherited stromal amyloidoses characterized by pathognomonic branching lattice figures in the cornea. CDL3A is characterized by decreased visual acuity, and the presence of thick, ropy branching lattice lines and accumulations of amyloid deposits in the corneal stroma. Systemic amyloidosis is absent. CDL3A clinically resembles to lattice corneal dystrophy type 3, but differs in that its age of onset is 70 to 90 years. It has an autosomal dominant inheritance pattern. {ECO:0000269|PubMed:15790870, ECO:0000269|PubMed:9497262}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Corneal dystrophy, Avellino type (CDA) [MIM:607541]: A corneal disease resulting in reduced visual acuity and characterized by gray, crumb-like granular deposits in the anterior third of the stroma in each corneal button. Fusiform amyloid deposits, histochemically and morphologically identical to those of lattice corneal dystrophy, are found in the deeper stroma. Additional features include recurrent corneal erosions, and glare and decreased night vision. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec
0.707

Intolerance Scores

LoFtool
0.132
RVIS EVS
-0.66
RVIS percentile EVS
16.02

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.740

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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