THBS4

thrombospondin 4, the group of Thrombospondin family

Basic information

Region (hg38): 5:79991310-80083287

Links

ENSG00000113296 ∙ NCBI:7060 ∙ OMIM:600715 ∙ HGNC:11788 ∙ Uniprot:P35443 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the THBS4 gene.

• Inborn genetic diseases (42 variants)
• not provided (5 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the THBS4 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				1	1	2
missense			42	1	2	45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	42	2	3

Variants in THBS4

This is a list of pathogenic ClinVar variants found in the THBS4 region.

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

Position	Type	Phenotype	Significance	ClinVar
5-80035620-C-G		not specified	Uncertain significance (Feb 11, 2022)
5-80040079-T-C		not specified	Uncertain significance (Jun 24, 2022)
5-80040121-G-A		not specified	Uncertain significance (Mar 06, 2023)
5-80040134-T-C		not specified	Uncertain significance (Apr 05, 2023)
5-80040146-C-T		not specified	Uncertain significance (Dec 21, 2022)
5-80040167-T-G		not specified	Uncertain significance (Dec 21, 2023)
5-80040188-A-G		not specified	Uncertain significance (Apr 07, 2022)
5-80055787-A-G		not specified	Uncertain significance (Feb 01, 2023)
5-80055793-C-T		not specified	Uncertain significance (Jan 26, 2022)
5-80055880-A-G		not specified	Uncertain significance (Dec 06, 2022)
5-80055915-A-G			Benign (Mar 29, 2018)
5-80055967-G-A		not specified	Uncertain significance (Jul 25, 2023)
5-80056031-A-G		not specified	Uncertain significance (Apr 11, 2023)
5-80058209-T-C		not specified	Uncertain significance (Dec 08, 2023)
5-80058287-A-T		not specified	Uncertain significance (Sep 14, 2022)
5-80058299-G-A		not specified	Uncertain significance (Nov 01, 2022)
5-80058737-A-G		not specified	Uncertain significance (Nov 10, 2022)
5-80058776-C-T		not specified	Uncertain significance (Mar 02, 2023)
5-80059700-T-G			Benign (Dec 01, 2023)
5-80059724-C-T		not specified	Uncertain significance (Apr 07, 2023)
5-80059771-C-T		not specified	Uncertain significance (Dec 22, 2023)
5-80059783-C-T		not specified	Uncertain significance (Dec 27, 2023)
5-80059799-C-T		not specified	Uncertain significance (Nov 10, 2021)
5-80059813-G-T		not specified	Uncertain significance (Mar 11, 2022)
5-80059825-G-A		not specified	Uncertain significance (Oct 28, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
THBS4	protein_coding	protein_coding	ENST00000350881	22	91977

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.51e-18	0.689	125521	2	225	125748	0.000903

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.21	474	554	0.856	0.0000310	6377
Missense in Polyphen		216	264.8	0.81571		3120
Synonymous	-0.0513	229	228	1.00	0.0000143	1819
Loss of Function	2.01	36	51.6	0.698	0.00000275	549

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00310	0.00309
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.00169	0.00163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000877	0.000871
Middle Eastern	0.00169	0.00163
South Asian	0.000198	0.000196
Other	0.00147	0.00147

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner (By similarity). {ECO:0000250, ECO:0000269|PubMed:19441079}.
• Pathway: 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);Human papillomavirus infection - Homo sapiens (human);Focal Adhesion;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;PI3K-Akt Signaling Pathway;Signal Transduction;Signaling by PDGF;Signaling by Receptor Tyrosine Kinases (Consensus)

Recessive Scores

• pRec: 0.340

Intolerance Scores

• loftool: 0.180
• rvis_EVS: -0.24
• rvis_percentile_EVS: 36.32

Haploinsufficiency Scores

• pHI: 0.190
• hipred: N
• hipred_score: 0.488
• ghis: 0.441

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.170

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Thbs4
• Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; muscle phenotype

Zebrafish Information Network

• Gene name: thbs4b
• Affected structure: muscle
• Phenotype tag: abnormal
• Phenotype quality: detached from

Gene ontology

• Biological process: positive regulation of endothelial cell proliferation;response to unfolded protein;regulation of signaling receptor activity;negative regulation of angiogenesis;regulation of tissue remodeling;response to endoplasmic reticulum stress;behavioral response to pain;tissue remodeling;positive regulation of peptidyl-tyrosine phosphorylation;myoblast migration;positive regulation of cell division;endothelial cell-cell adhesion;positive regulation of neutrophil chemotaxis
• Cellular component: extracellular region;basement membrane;extracellular space;endoplasmic reticulum;sarcoplasmic reticulum;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: integrin binding;calcium ion binding;protein binding;growth factor activity;heparin binding