THBS3

protein-coding

thrombospondin 3, the group of Thrombospondin family

Gene summary

The protein encoded by this gene belongs to the thrombospondin family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentameric molecule linked by a single disulfide bond. This gene shares a common promoter with metaxin 1. Alternate splicing results in coding and non-coding transcript variants. [provided by RefSeq, Nov 2011]

MANE transcript

NM_007112.5

Inheritance

—

ClinVar variants

U:136B:1

Top phenotype

Prostate cancer

gnomAD constraint

pLI —, LoF o/e 0.71

Max pathogenic AF

—

Genomic locus

chr1:155,195,588-155,209,051

External References & Databases

Ensembl (ENSG00000169231)

Transcript & Mutation Effects

hg38 • Region Span ~13.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Tourette syndromeNO_KNOWN

Inheritance Pattern: Unknown

Disease ID:MONDO:0007661

Submitter: Labcorp Genetics (formerly Invitae)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to THBS3 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 121

not providedTotal: 2

Prostate cancerTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_007112.5. 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			2 clinvar	1 clinvar		3
missense			126 clinvar			126
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	136	1	0	137

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 63 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_007112.5	RefSeq	NP_009043.1	23	MANE Select
ENST00000368378.7	Ensembl	ENSP00000357362.3	23	MANE Select
NM_001252607.2	RefSeq	NP_001239536.1	22	Standard
NM_001252608.2	RefSeq	NP_001239537.1	21	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-matrix adhesion
ossification involved in bone maturation
bone trabecula formation

Molecular Function

extracellular matrix structural constituent
calcium ion binding
heparin binding

Cellular Component

extracellular region
perinuclear region of cytoplasm
collagen-containing extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000368378
Coding exons: 23
Length: 13464
Individuals with no LoFs: 125573
Homozygous LoFs: 0
Heterozygous LoFs: 175
Defined: 125748
p: 0.000696

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.78	455	575	0.791	0.0000337	6341
Missense (PolyPhen)		175	235.92	0.74178		2688
Synonymous	1.60	196	227	0.865	0.0000136	1864
Loss of Function	2.00	41	57.4	0.715	0.00000351	528

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00055	0.00055	rare
Latino/Admixed American	0.00035	0.00035	rare
Ashkenazi Jewish	0.00070	0.00069	rare
East Asian	0.00092	0.00092	rare
Finnish	0.00014	0.00014	rare
European (Non-Finnish)	0.00078	0.00077	rare
South Asian	0.0011	0.0011	notable
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Can bind to fibrinogen, fibronectin, laminin and type V collagen.;

Recessive Scores

pRec: 0.233

Intolerance Scores

LoFtool: 0.337
RVIS EVS: -1.48
RVIS percentile EVS: 3.66

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.324

Gene Damage Prediction

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