TGFBI

Chr 5AD

transforming growth factor beta induced

Also known as: BIGH3, CDB1, CDG2, CDGG1, CSD, CSD1, CSD2, CSD3

NCBI Gene: 7045 ENSG00000120708 UniProt: Q15582

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]

Primary Disease Associations & Inheritance

Corneal dystrophy, Avellino typeMIM #607541

Corneal dystrophy, epithelial basement membraneMIM #121820

Corneal dystrophy, Groenouw type IMIM #121900

Corneal dystrophy, lattice type IMIM #122200

Corneal dystrophy, lattice type IIIAMIM #608471

Corneal dystrophy, Reis-Bucklers typeMIM #608470

Corneal dystrophy, Thiel-Behnke typeMIM #602082

233

ClinVar variants

Pathogenic / LP

0.00

pLI score

Active trials

Clinical Summary— TGFBI

⚡

Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 Pathogenic / Likely Pathogenic· 144 VUS of 233 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.80LOEUF

pLI 0.000

Z-score 2.46

OE 0.53 (0.36–0.80)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

0.10Z-score

OE missense 0.99 (0.91–1.07)

393 obs / 398.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.53 (0.36–0.80)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.99 (0.91–1.07)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.91

0≤1.21.6

LoF obs/exp: 17 / 32.1Missense obs/exp: 393 / 398.7Syn Z: 0.97

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25

Likely Pathogenic9

VUS144

Likely Benign27

Benign15

Conflicting13

Pathogenic

Likely Pathogenic

144

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	12	13	0	25
Likely Pathogenic	0	7	2	0	9
VUS	0	117	18	9	144
Likely Benign	0	4	7	16	27
Benign	0	4	5	6	15
Conflicting	—				13
Total	0	144	45	31	233

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TGFBI · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

TGFBI-related lattice corneal dystrophy, type I

definitive

ADUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

TGFBI-related granular corneal dystrophy, type II

definitive

ADUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

TGFBI-related Thiel-Behnke corneal dystrophy

definitive

ADUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

TGFBI-related Reis-Bucklers corneal dystrophy

definitive

ADUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

TGFBI-related granular corneal dystrophy, type I

definitive

ADUndeterminedAltered Gene Product Structure

Eye

G2P ↗

missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

TRANSFORMING GROWTH FACTOR, BETA-INDUCED, 68-KD; TGFBI

MIM #601692 · *

Corneal dystrophy, Avellino type

MIM #607541