TIMP2

TIMP metallopeptidase inhibitor 2, the group of Tissue inhibitor of metallopeptidases

Basic information

Region (hg38): 17:78852976-78925387

Links

ENSG00000035862 ∙ NCBI:7077 ∙ OMIM:188825 ∙ HGNC:11821 ∙ Uniprot:P16035 ∙ 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 TIMP2 gene.

• Inborn genetic diseases (7 variants)
• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIMP2 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						0
missense			7			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	0	7	1	0

Variants in TIMP2

This is a list of pathogenic ClinVar variants found in the TIMP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-78855707-G-A		not specified	Uncertain significance (Oct 06, 2021)
17-78855712-G-A		TIMP2-related disorder	Likely benign (May 09, 2022)
17-78855756-C-T		not specified	Uncertain significance (Feb 27, 2024)
17-78855812-A-G		not specified	Uncertain significance (Apr 08, 2022)
17-78857541-T-A		not specified	Uncertain significance (May 24, 2023)
17-78857596-C-T		not specified	Uncertain significance (Jan 31, 2023)
17-78857625-T-C		not specified	Uncertain significance (Dec 20, 2023)
17-78857629-C-T		not specified	Uncertain significance (Feb 06, 2023)
17-78857638-C-T		not specified	Uncertain significance (Jun 03, 2022)
17-78870935-C-T		TIMP2-related disorder	Benign (Jun 11, 2019)
17-78873811-A-G		TIMP2-related disorder	Benign (Feb 18, 2019)
17-78873857-G-C		not specified	Uncertain significance (Oct 13, 2023)
17-78873903-C-T		TIMP2-related disorder	Likely benign (Sep 06, 2019)
17-78892237-G-A			Likely benign (Mar 01, 2023)
17-78925022-G-A		not specified	Uncertain significance (Feb 01, 2023)
17-78925053-G-A		TIMP2-related disorder	Benign (Oct 21, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMP2	protein_coding	protein_coding	ENST00000262768	5	72411

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.789	0.210	125545	0	2	125547	0.00000797

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.61	71	121	0.589	0.00000747	1444
Missense in Polyphen		20	51.63	0.38737		594
Synonymous	-0.0323	54	53.7	1.01	0.00000436	408
Loss of Function	2.56	1	9.50	0.105	4.04e-7	123

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.000109	0.000109
South Asian	0.00	0.00
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, MMP-8, MMP-9, MMP-10, MMP-13, MMP-14, MMP-15, MMP-16 and MMP-19. {ECO:0000269|PubMed:11710594, ECO:0000269|PubMed:2554304, ECO:0000269|PubMed:2793861}.
• Pathway: Matrix Metalloproteinases;Angiogenesis;Angiogenesis overview;IL1 and megakaryocytes in obesity;Vitamin D Receptor Pathway;Protein alkylation leading to liver fibrosis;Neutrophil degranulation;inhibition of matrix metalloproteinases;Extracellular matrix organization;Innate Immune System;Immune System;Activation of Matrix Metalloproteinases;Degradation of the extracellular matrix (Consensus)

Intolerance Scores

• loftool: 0.197
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.46

Haploinsufficiency Scores

• pHI: 0.299
• hipred: N
• hipred_score: 0.472
• ghis: 0.657

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.760

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Timp2
• Phenotype: immune system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: timp2a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: decreased length

Gene ontology

• Biological process: central nervous system development;aging;negative regulation of cell population proliferation;response to hormone;response to organic substance;negative regulation of endopeptidase activity;extracellular matrix disassembly;regulation of Rap protein signal transduction;response to cytokine;response to drug;neutrophil degranulation;positive regulation of MAPK cascade;positive regulation of neuron differentiation;positive regulation of adenylate cyclase activity;negative regulation of mitotic cell cycle;negative regulation of Ras protein signal transduction;negative regulation of membrane protein ectodomain proteolysis;negative regulation of metallopeptidase activity
• Cellular component: extracellular region;extracellular space;cell surface;growth cone;extracellular matrix;specific granule lumen;neuronal cell body;collagen-containing extracellular matrix;tertiary granule lumen;ficolin-1-rich granule lumen
• Molecular function: protease binding;integrin binding;protein binding;metalloendopeptidase inhibitor activity;zinc ion binding;peptidase inhibitor activity