TGFBR3

protein-coding

transforming growth factor beta receptor 3, the group of Proteoglycans

Gene summary

This locus encodes the transforming growth factor (TGF)-beta type III receptor. The encoded receptor is a membrane proteoglycan that often functions as a co-receptor with other TGF-beta receptor superfamily members. Ectodomain shedding produces soluble TGFBR3, which may inhibit TGFB signaling. Decreased expression of this receptor has been observed in various cancers. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[provided by RefSeq, Sep 2010]

MANE transcript

NM_003243.5

Inheritance

—

ClinVar variants

U:100B:25

Top phenotype

TGFBR3-related disorder

gnomAD constraint

pLI —, LoF o/e 0.31

Max pathogenic AF

—

Genomic locus

chr1:91,680,343-91,906,335

External References & Databases

Ensembl (ENSG00000069702)

Transcript & Mutation Effects

hg38 • Region Span ~226.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TGFBR3 variants in ClinVar

7 Conditions Cataloged

not specifiedTotal: 98

TGFBR3-related disorderTotal: 16

not providedTotal: 10

Familial thoracic aortic aneurysm and aortic dissectionTotal: 6

Connective tissue disorderTotal: 5

Prostate cancerTotal: 1

Infertility disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003243.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	7 clinvar	4 clinvar	14
missense			97 clinvar	13 clinvar	1 clinvar	111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	100	20	5	125

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 65 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003243.5	RefSeq	NP_003234.2	16	MANE Select
ENST00000212355.9	Ensembl	ENSP00000212355.4	16	MANE Select
NM_001195683.2	RefSeq	NP_001182612.1	16	Standard
NM_001195684.1	RefSeq	NP_001182613.1	16	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tgfbr3	Danio rerio	Structure: dorsal longitudinal anastomotic vessel Quality: aplastic abnormal

Gene / Model

Organism

Observed Phenotype

tgfbr3

Danio rerio

Structure: dorsal longitudinal anastomotic vessel

Quality: aplastic

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Extracellular vesicle-mediated signaling in recipient cells
Glucocorticoid Receptor Pathway
Nuclear Receptors Meta-Pathway
TGF-beta Signaling Pathway
Hypothesized Pathways in Pathogenesis of Cardiovascular Disease

Biological Process

response to hypoxia
epithelial to mesenchymal transition
liver development
heart morphogenesis
muscular septum morphogenesis

Molecular Function

transforming growth factor beta-activated receptor activity
type II transforming growth factor beta receptor binding
transforming growth factor beta receptor binding
protein binding
glycosaminoglycan binding

Cellular Component

extracellular space
cytoplasm
integral component of plasma membrane
external side of plasma membrane
cell surface

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000212355
Coding exons: 16
Length: 225991
Individuals with no LoFs: 125724
Homozygous LoFs: 1
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.21	381	453	0.840	0.0000245	5582
Missense (PolyPhen)		90	143.3	0.62807		1864
Synonymous	-0.523	188	179	1.05	0.0000107	1677
Loss of Function	4.01	12	39.0	0.308	0.00000217	452

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000090	0.000088	rare
South Asian	0.00016	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors.;

Recessive Scores

pRec: 0.359

Intolerance Scores

LoFtool: 0.283
RVIS EVS: 0.18
RVIS percentile EVS: 66.24

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.643

Gene Damage Prediction

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