TIMP4

protein-coding

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

Gene summary

This gene belongs to the TIMP gene family. The proteins encoded by this gene family are inhibitors of the matrix metalloproteinases, a group of peptidases involved in degradation of the extracellular matrix. The secreted, netrin domain-containing protein encoded by this gene is involved in regulation of platelet aggregation and recruitment and may play role in hormonal regulation and endometrial tissue remodeling. [provided by RefSeq, Jul 2008]

MANE transcript

NM_003256.4

Inheritance

—

ClinVar variants

U:55B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.59

Max pathogenic AF

—

Genomic locus

chr3:12,153,068-12,158,912

External References & Databases

Ensembl (ENSG00000157150)

Transcript & Mutation Effects

hg38 • Region Span ~5.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TIMP4 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_003256.4. 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				1 clinvar	1 clinvar	2
missense			53 clinvar	1 clinvar		54
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	55	2	1	58

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_003256.4	RefSeq	NP_003247.1	5	MANE Select
ENST00000287814.5	Ensembl	ENSP00000287814.4	5	MANE Select
ENST00000946698.1	Ensembl	ENSP00000616757.1	5	Standard
ENST00000946698.2	Ensembl	ENSP00000616757.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Matrix Metalloproteinases
Angiogenesis overview
Protein alkylation leading to liver fibrosis
inhibition of matrix metalloproteinases

Biological Process

Notch signaling pathway
central nervous system development
biological_process
response to hormone
response to organic substance

Molecular Function

protease binding
metalloendopeptidase inhibitor activity
metal ion binding

Cellular Component

extracellular space
sarcomere
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287814
Coding exons: 5
Length: 6301
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.607	147	128	1.15	0.00000673	1460
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000058	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00071	0.00071	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00011	0.00011	rare
South Asian	0.000099	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.284

Intolerance Scores

LoFtool: 0.246
RVIS EVS: -0.49
RVIS percentile EVS: 22.09

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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