THBS2

protein-coding

thrombospondin 2, the group of Thrombospondin family

Gene summary

The protein encoded by this gene belongs to the thrombospondin family. It is a disulfide-linked homotrimeric glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. This protein has been shown to function as a potent inhibitor of tumor growth and angiogenesis. Studies of the mouse counterpart suggest that this protein may modulate the cell surface properties of mesenchymal cells and be involved in cell adhesion and migration. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003247.5

Inheritance

ClinVar variants

P:1U:164B:46

Top phenotype

THBS2-related disorder

gnomAD constraint

pLI —, LoF o/e 0.22

Max pathogenic AF

—

Genomic locus

chr6:169,215,780-169,254,050

External References & Databases

Ensembl (ENSG00000186340)

Transcript & Mutation Effects

hg38 • Region Span ~38.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Ehlers-Danlos syndrome, classic-like, 3LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0971044

Submitter: Ambry Genetics

Ehlers-Danlos syndrome, classic-like, 3MODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0971044

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THBS2 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 158

not providedTotal: 26

THBS2-related disorderTotal: 16

Ehlers-Danlos syndrome, classic-like, 3Total: 4

Ehlers-Danlos syndromeTotal: 2

CardiomyopathyTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003247.5. 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			7 clinvar	8 clinvar	11 clinvar	26
missense	1 clinvar		153 clinvar	19 clinvar	8 clinvar	181
nonsense			2 clinvar			2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	164	27	19	211

Highest pathogenic variant AF is 6.841143e-7

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003247.5	RefSeq	NP_003238.2	21	MANE Select
ENST00000617924.6	Ensembl	ENSP00000482784.1	21	MANE Select
NM_001381939.1	RefSeq	NP_001368868.1	20	Standard
NM_001381940.1	RefSeq	NP_001368869.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

PI3K-Akt signaling pathway - Homo sapiens (human)
ECM-receptor interaction - Homo sapiens (human)
Focal adhesion - Homo sapiens (human)
Phagosome - Homo sapiens (human)
Malaria - Homo sapiens (human)

Biological Process

cell adhesion
negative regulation of angiogenesis
positive regulation of synapse assembly

Molecular Function

extracellular matrix structural constituent
calcium ion binding
protein binding
heparin binding

Cellular Component

extracellular region
basement membrane
platelet alpha granule
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000366787
Coding exons: 21
Length: 38265
Individuals with no LoFs: 125725
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125748
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.21	587	759	0.774	0.0000501	7796
Missense (PolyPhen)		214	351.14	0.60945		3565
Synonymous	-0.248	334	328	1.02	0.0000263	2159
Loss of Function	5.58	13	59.5	0.219	0.00000283	625

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.00030	0.00030	rare
East Asian	0.00016	0.00016	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000098	0.000097	rare
South Asian	0.000065	0.000065	rare
Other	0.00017	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties. {ECO:0000269|PubMed:20714802}.;

Recessive Scores

pRec: 0.521

Intolerance Scores

LoFtool: 0.108
RVIS EVS: -0.47
RVIS percentile EVS: 23.05

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.883

Gene Damage Prediction

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