TGFBI

transforming growth factor beta induced

Basic information

Region (hg38): 5:136028987-136063818

Previous symbols: [ "CSD3", "LCD1", "CSD1", "CSD2" ]

Links

ENSG00000120708 ∙ NCBI:7045 ∙ OMIM:601692 ∙ HGNC:11771 ∙ Uniprot:Q15582 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epithelial basement membrane dystrophy (Supportive), mode of inheritance: AD
• Thiel-Behnke corneal dystrophy (Supportive), mode of inheritance: AD
• Reis-Bucklers corneal dystrophy (Supportive), mode of inheritance: AD
• granular corneal dystrophy type I (Supportive), mode of inheritance: AD
• granular corneal dystrophy type II (Supportive), mode of inheritance: AD
• lattice corneal dystrophy type I (Supportive), mode of inheritance: AD
• granular corneal dystrophy type I (Definitive), mode of inheritance: AD
• Reis-Bucklers corneal dystrophy (Definitive), mode of inheritance: AD
• Thiel-Behnke corneal dystrophy (Definitive), mode of inheritance: AD
• granular corneal dystrophy type II (Definitive), mode of inheritance: AD
• lattice corneal dystrophy type I (Definitive), mode of inheritance: AD
• granular corneal dystrophy type I (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
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	AD	General	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	Ophthalmologic	9780098; 9727509; 9497262; 10442892; 11867580; 11923233; 15531312; 15019320; 15885785; 15111592; 15790870; 16652336; 16606891; 22080335; 22155582; 22194646; 22355247; 22575726

ClinVar

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

• Corneal dystrophy (79 variants)
• not provided (43 variants)
• Inborn genetic diseases (24 variants)
• not specified (9 variants)
• Epithelial-stromal TGFBI dystrophy (4 variants)
• Lattice corneal dystrophy Type I (3 variants)
• Groenouw corneal dystrophy type I (3 variants)
• Reis-Bucklers' corneal dystrophy (2 variants)
• Thiel-Behnke corneal dystrophy (2 variants)
• - (2 variants)
• Avellino corneal dystrophy (2 variants)
• 7 conditions (1 variants)
• Epithelial basement membrane dystrophy (1 variants)
• Corneal dystrophy, lattice type 3A (1 variants)
• Corneal dystrophy, lattice type 3A;Groenouw corneal dystrophy type I (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TGFBI gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			10	10	5	25
missense	7	5	44	3	3	62
nonsense			3			3
start loss						0
frameshift			1			1
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region				2	2	4
non coding			12	2	4	18
Total	7	6	70	15	12

Highest pathogenic variant AF is 0.0000328

Variants in TGFBI

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

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

Position	Type	Phenotype	Significance	ClinVar
5-136029060-C-G		Inborn genetic diseases	Uncertain significance (Oct 12, 2022)
5-136029105-G-C		Inborn genetic diseases • TGFBI-related disorder	Conflicting classifications of pathogenicity (Aug 13, 2021)
5-136029122-G-T		Inborn genetic diseases	Uncertain significance (Jun 12, 2023)
5-136029132-C-T		Inborn genetic diseases	Uncertain significance (Sep 17, 2021)
5-136029169-G-C		Inborn genetic diseases	Uncertain significance (Sep 22, 2023)
5-136029203-C-A		Corneal dystrophy	Conflicting classifications of pathogenicity (Jan 18, 2024)
5-136033769-C-T		Corneal dystrophy	Uncertain significance (Jan 12, 2018)
5-136033818-A-C		Inborn genetic diseases	Uncertain significance (Apr 07, 2023)
5-136033852-G-A		Inborn genetic diseases	Uncertain significance (Dec 27, 2023)
5-136033864-G-A			Likely benign (Jan 04, 2022)
5-136044097-C-T		Corneal dystrophy	Uncertain significance (Jan 13, 2018)
5-136044107-A-G		Corneal dystrophy	Uncertain significance (Jan 12, 2018)
5-136046357-C-T		Corneal dystrophy	Uncertain significance (Jan 12, 2018)
5-136046370-G-A		Corneal dystrophy	Uncertain significance (Apr 28, 2017)
5-136046373-G-A			Uncertain significance (Nov 03, 2023)
5-136046384-C-A		Corneal dystrophy	Uncertain significance (Jan 13, 2018)
5-136046403-G-C		not specified	Benign (May 04, 2022)
5-136046406-C-A		Groenouw corneal dystrophy type I • Epithelial-stromal TGFBI dystrophy	Pathogenic (Sep 21, 2021)
5-136046406-C-T		Lattice corneal dystrophy Type I • Epithelial-stromal TGFBI dystrophy	Pathogenic (Jan 04, 2024)
5-136046407-G-A		Avellino corneal dystrophy • Lattice corneal dystrophy Type I	Pathogenic (Feb 09, 2024)
5-136046407-G-T		Reis-Bucklers' corneal dystrophy • Avellino corneal dystrophy	Pathogenic (Sep 12, 2023)
5-136046423-G-C		Corneal dystrophy	Uncertain significance (Jan 12, 2018)
5-136046429-G-T		Corneal dystrophy	Uncertain significance (Apr 28, 2017)
5-136046459-C-T			Likely benign (Nov 15, 2018)
5-136046482-C-T		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TGFBI	protein_coding	protein_coding	ENST00000442011	17	34924

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.97e-8	0.993	124640	0	29	124669	0.000116

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.102	393	399	0.986	0.0000232	4410
Missense in Polyphen		204	220.94	0.92333		2399
Synonymous	0.974	155	171	0.905	0.0000108	1411
Loss of Function	2.46	17	32.1	0.530	0.00000167	372

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000211	0.000210
Ashkenazi Jewish	0.0000999	0.0000993
East Asian	0.0000556	0.0000556
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000134	0.000133
Middle Eastern	0.0000556	0.0000556
South Asian	0.0000654	0.0000654
Other	0.00	0.00

dbNSFP

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.
• Pathway: Beta3 integrin cell surface interactions;Beta1 integrin cell surface interactions;Beta2 integrin cell surface interactions (Consensus)

Recessive Scores

• pRec: 0.707

Intolerance Scores

• loftool: 0.132
• rvis_EVS: -0.66
• rvis_percentile_EVS: 16.02

Haploinsufficiency Scores

• pHI: 0.493
• hipred: Y
• hipred_score: 0.694
• ghis: 0.505

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.740

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tgfbi
• Phenotype: vision/eye phenotype; immune system phenotype; neoplasm; hematopoietic system phenotype; growth/size/body region phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: tgfbi
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: angiogenesis;chondrocyte differentiation;cell adhesion;negative regulation of cell adhesion;visual perception;cell population proliferation;extracellular matrix organization;cellular protein metabolic process;response to stimulus
• Cellular component: extracellular region;basement membrane;extracellular space;trans-Golgi network;plasma membrane;extracellular matrix;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: integrin binding;extracellular matrix structural constituent;protein binding;collagen binding;cell adhesion molecule binding;extracellular matrix binding