MMP1

protein-coding

matrix metallopeptidase 1, the group of Receptor ligands|M10 matrix metallopeptidases

Gene summary

This gene encodes a member of the peptidase M10 family of matrix metalloproteinases (MMPs). Proteins in this family are involved in the breakdown of extracellular matrix in normal physiological processes, such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes, such as arthritis and metastasis. The encoded preproprotein is proteolytically processed to generate the mature protease. This secreted protease breaks down the interstitial collagens, including types I, II, and III. The gene is part of a cluster of MMP genes on chromosome 11. Mutations in this gene are associated with chronic obstructive pulmonary disease (COPD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Jan 2016]

Previous symbols:

MANE transcript

NM_002421.4

Inheritance

—

ClinVar variants

U:83B:21

Top phenotype

MMP1-related disorder

gnomAD constraint

pLI —, LoF o/e 1.09

Max pathogenic AF

—

Genomic locus

chr11:102,789,401-102,798,160

External References & Databases

Ensembl (ENSG00000196611)

Transcript & Mutation Effects

hg38 • Region Span ~8.8 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 MMP1 variants in ClinVar

6 Conditions Cataloged

not specifiedTotal: 86

not providedTotal: 13

MMP1-related disorderTotal: 9

COPD, severe early onsetTotal: 1

Recessive dystrophic epidermolysis bullosaTotal: 1

Interstitial lung disease 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002421.4. 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	7 clinvar	1 clinvar	9
missense			77 clinvar	11 clinvar	1 clinvar	89
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar		1 clinvar	2
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	83	18	3	104

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002421.4	RefSeq	NP_002412.1	10	MANE Select
ENST00000315274.7	Ensembl	ENSP00000322788.6	10	MANE Select
NM_001145938.2	RefSeq	NP_001139410.1	9	Standard
ENST00001144079.1	Ensembl	ENSP00000806847.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Relaxin signaling pathway - Homo sapiens (human)
Bladder cancer - Homo sapiens (human)
IL-17 signaling pathway - Homo sapiens (human)
PPAR signaling pathway - Homo sapiens (human)
Pathways in cancer - Homo sapiens (human)

Biological Process

proteolysis
viral process
cytokine-mediated signaling pathway
extracellular matrix disassembly
extracellular matrix organization

Molecular Function

endopeptidase activity
metalloendopeptidase activity
serine-type endopeptidase activity
zinc ion binding

Cellular Component

extracellular region
extracellular space
extracellular matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000315274
Coding exons: 10
Length: 8241
Individuals with no LoFs: 122374
Homozygous LoFs: 24
Heterozygous LoFs: 3347
Defined: 125745
p: 0.0135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-1.12	308	258	1.20	0.0000134	3131
Missense (PolyPhen)		112	95.573	1.1719		1190
Synonymous	-0.0725	92	91.1	1.01	0.00000487	860
Loss of Function	-0.413	25	22.9	1.09	0.00000107	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0031	notable
Latino/Admixed American	0.010	0.010	notable
Ashkenazi Jewish	0.0043	0.0043	notable
East Asian	0.0016	0.0016	notable
Finnish	0.013	0.013	notable
European (Non-Finnish)	0.020	0.020	notable
South Asian	0.0096	0.0095	notable
Other	0.014	0.014	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X (PubMed:2557822, PubMed:2153297, PubMed:1645757). In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity (PubMed:16807369). {ECO:0000269|PubMed:1645757, ECO:0000269|PubMed:16807369, ECO:0000269|PubMed:2153297, ECO:0000269|PubMed:2557822}.;

Recessive Scores

pRec: 0.810

Intolerance Scores

LoFtool: 0.907
RVIS EVS: 0.73
RVIS percentile EVS: 86.27

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.851

Gene Damage Prediction

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