TIMP4

TIMP metallopeptidase inhibitor 4, the group of Tissue inhibitor of metallopeptidases

Basic information

Region (hg38): 3:12153067-12158912

Links

ENSG00000157150 ∙ NCBI:7079 ∙ OMIM:601915 ∙ HGNC:11823 ∙ Uniprot:Q99727 ∙ 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 TIMP4 gene.

• Inborn genetic diseases (19 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIMP4 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			18	1		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	18	2	1

Variants in TIMP4

This is a list of pathogenic ClinVar variants found in the TIMP4 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-12153526-C-T		not specified	Likely benign (Nov 17, 2022)
3-12153588-A-G		not specified	Uncertain significance (Nov 09, 2023)
3-12153597-A-G		not specified	Uncertain significance (Feb 23, 2023)
3-12153616-C-T		not specified	Uncertain significance (May 24, 2023)
3-12153699-T-C		not specified	Uncertain significance (Mar 07, 2024)
3-12154365-T-C		not specified	Uncertain significance (Aug 20, 2023)
3-12154371-T-C		not specified	Uncertain significance (Mar 06, 2023)
3-12154401-C-T		not specified	Uncertain significance (Jun 29, 2023)
3-12154402-G-A			Likely benign (May 21, 2018)
3-12154404-T-C		not specified	Uncertain significance (Oct 12, 2022)
3-12154411-G-C		not specified	Uncertain significance (Nov 30, 2021)
3-12154421-A-C		not specified	Uncertain significance (Feb 22, 2023)
3-12156824-C-G		not specified	Uncertain significance (Jan 04, 2022)
3-12156888-G-A		not specified	Uncertain significance (Dec 21, 2023)
3-12157461-C-T		not specified	Uncertain significance (Feb 17, 2022)
3-12158710-G-A		not specified	Uncertain significance (Aug 08, 2023)
3-12158716-C-T		not specified	Uncertain significance (Dec 19, 2022)
3-12158719-A-G		not specified	Uncertain significance (Feb 13, 2023)
3-12158728-T-C		not specified	Uncertain significance (Dec 27, 2023)
3-12158744-C-T		not specified	Uncertain significance (Aug 21, 2023)
3-12158770-G-A		not specified	Uncertain significance (Mar 29, 2023)
3-12158770-G-T		not specified	Uncertain significance (Jul 25, 2023)
3-12158778-C-T			Benign (Dec 31, 2019)
3-12158788-A-G		not specified	Uncertain significance (Oct 12, 2021)
3-12158789-G-C		not specified	Uncertain significance (Dec 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMP4	protein_coding	protein_coding	ENST00000287814	5	6301

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000383	0.854	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.607	147	128	1.15	0.00000673	1460
Missense in Polyphen		54	46.21	1.1686		587
Synonymous	-2.21	74	53.4	1.39	0.00000294	429
Loss of Function	1.30	7	11.8	0.593	6.00e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000578	0.0000578
Ashkenazi Jewish	0.00	0.00
East Asian	0.000707	0.000707
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000110	0.000105
Middle Eastern	0.000707	0.000707
South Asian	0.0000988	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. Known to act on MMP-1, MMP-2, MMP-3, MMP-7 and MMP- 9.
• Pathway: Matrix Metalloproteinases;Angiogenesis overview;Protein alkylation leading to liver fibrosis;inhibition of matrix metalloproteinases (Consensus)

Recessive Scores

• pRec: 0.284

Intolerance Scores

• loftool: 0.246
• rvis_EVS: -0.49
• rvis_percentile_EVS: 22.09

Haploinsufficiency Scores

• pHI: 0.541
• hipred: N
• hipred_score: 0.383
• ghis: 0.506

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.731

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Timp4
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); 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

Gene ontology

• Biological process: Notch signaling pathway;central nervous system development;biological_process;response to hormone;response to organic substance;negative regulation of endopeptidase activity;response to lipopolysaccharide;response to cytokine;response to drug;ovulation cycle;response to peptide hormone;negative regulation of membrane protein ectodomain proteolysis
• Cellular component: extracellular space;sarcomere;extracellular matrix
• Molecular function: protease binding;metalloendopeptidase inhibitor activity;metal ion binding