TIMP1

TIMP metallopeptidase inhibitor 1, the group of Tissue inhibitor of metallopeptidases

Basic information

Region (hg38): X:47582408-47586789

Previous symbols: [ "TIMP", "CLGI" ]

Links

ENSG00000102265

∙ NCBI:7076 ∙ OMIM:305370 ∙ HGNC:11820 ∙ Uniprot:P01033 ∙ 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 TIMP1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TIMP1 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 clinvar	1
missense			7 clinvar	4 clinvar	1 clinvar	12
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	7	4	2

Variants in TIMP1

This is a list of pathogenic ClinVar variants found in the TIMP1 region.

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

Position	Phenotype	Significance	ClinVar
X-47583437-G-A	not specified	Uncertain significance (Nov 26, 2024)	2240922
X-47583500-C-A	not specified	Uncertain significance (Nov 07, 2024)	3456646
X-47583513-C-T	not specified	Likely benign (Sep 06, 2022)	3177573
X-47584992-C-T		Likely benign (Oct 01, 2024)	3389193
X-47585009-G-T		Likely benign (Dec 01, 2022)	2660430
X-47585227-T-C	not specified	Uncertain significance (Aug 19, 2024)	3456645
X-47585586-T-C	Epilepsy, X-linked 1, with variable learning disabilities and behavior disorders	Benign (Jan 29, 2024)	1165693
X-47585602-A-C	not specified	Uncertain significance (Mar 28, 2024)	3326195
X-47586621-G-A	not specified	Uncertain significance (Aug 19, 2024)	3456644
X-47586641-C-T		Likely benign (Jul 12, 2018)	732080
X-47586642-G-A		Benign (Jul 05, 2018)	720215
X-47586660-C-T	not specified	Uncertain significance (Nov 24, 2024)	3456648
X-47586675-G-A	not specified	Uncertain significance (Jan 20, 2023)	2466164

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TIMP1	protein_coding	protein_coding	ENST00000218388	5	4477

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.499	0.483	125699	2	3	125704	0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.03	58	84.6	0.686	0.00000712	1336
Missense in Polyphen		16	29.265	0.54673		469
Synonymous	1.17	24	32.5	0.739	0.00000253	401
Loss of Function	1.90	1	6.05	0.165	3.82e-7	117

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000786	0.0000440
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling. Mediates erythropoiesis in vitro; but, unlike IL3, it is species-specific, stimulating the growth and differentiation of only human and murine erythroid progenitors. {ECO:0000269|PubMed:1420137, ECO:0000269|PubMed:16917503, ECO:0000269|PubMed:17050530, ECO:0000269|PubMed:1730286, ECO:0000269|PubMed:20545310, ECO:0000269|PubMed:22427646, ECO:0000269|PubMed:24635319, ECO:0000269|PubMed:3839290, ECO:0000269|PubMed:3903517, ECO:0000269|PubMed:8541540, ECO:0000269|PubMed:8576151, ECO:0000269|PubMed:9065415}.;
Pathway: HIF-1 signaling pathway - Homo sapiens (human);Matrix Metalloproteinases;JAK-STAT;IL1 and megakaryocytes in obesity;Lung fibrosis;IL-6 signaling pathway;Protein alkylation leading to liver fibrosis;Interleukin-10 signaling;Interleukin-4 and 13 signaling;inhibition of matrix metalloproteinases;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Extracellular matrix organization;Activation of Matrix Metalloproteinases;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Hemostasis;Degradation of the extracellular matrix;AP-1 transcription factor network;IL6-mediated signaling events (Consensus)

Recessive Scores

pRec: 0.898

Intolerance Scores

loftool: 0.204
rvis_EVS: 0.06
rvis_percentile_EVS: 58.26

Haploinsufficiency Scores

pHI: 0.478
hipred: Y
hipred_score: 0.624
ghis: 0.445

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.539

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Timp1
Phenotype: growth/size/body region phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; skeleton phenotype; respiratory system phenotype; reproductive system 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); hematopoietic system 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); limbs/digits/tail phenotype; immune system phenotype;

Gene ontology

Biological process: cell activation;connective tissue replacement involved in inflammatory response wound healing;platelet degranulation;aging;positive regulation of cell population proliferation;response to hormone;response to organic substance;regulation of signaling receptor activity;negative regulation of endopeptidase activity;cytokine-mediated signaling pathway;extracellular matrix disassembly;response to cytokine;negative regulation of apoptotic process;negative regulation of catalytic activity;response to peptide hormone;post-translational protein modification;cellular protein metabolic process;negative regulation of membrane protein ectodomain proteolysis;cartilage development;negative regulation of trophoblast cell migration;negative regulation of metallopeptidase activity;regulation of integrin-mediated signaling pathway
Cellular component: extracellular region;basement membrane;extracellular space;endoplasmic reticulum lumen;extracellular matrix;platelet alpha granule lumen;extracellular exosome
Molecular function: protease binding;cytokine activity;protein binding;growth factor activity;metalloendopeptidase inhibitor activity;zinc ion binding;peptidase inhibitor activity