MME

membrane metalloendopeptidase, the group of CD molecules|M13 metallopeptidases

Basic information

Region (hg38): 3:155024123-155183704

Links

ENSG00000196549 ∙ NCBI:4311 ∙ OMIM:120520 ∙ HGNC:7154 ∙ Uniprot:P08473 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Charcot-Marie-Tooth disease axonal type 2T (Moderate), mode of inheritance: AR
• spinocerebellar ataxia 43 (Limited), mode of inheritance: AD
• congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization (Supportive), mode of inheritance: AR
• Charcot-Marie-Tooth disease type 2T (Supportive), mode of inheritance: AR
• MME-related autosomal dominant Charcot Marie Tooth disease type 2 (Supportive), mode of inheritance: AD
• spinocerebellar ataxia 43 (Supportive), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2T (Strong), mode of inheritance: AR
• Charcot-Marie-Tooth disease axonal type 2T (Definitive), mode of inheritance: Semidominant
• Charcot-Marie-Tooth disease axonal type 2T (Limited), mode of inheritance: AD
• spinocerebellar ataxia 43 (Limited), mode of inheritance: AD
• Charcot-Marie-Tooth disease axonal type 2T (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Spinocerebellar ataxia 43; Charcot-Marie-Tooth disease, axonal, type 2T	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	26991897; 27583304

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MME gene.

• not provided (519 variants)
• Charcot-Marie-Tooth disease axonal type 2T (29 variants)
• Inborn genetic diseases (29 variants)
• Spinocerebellar ataxia 43 (8 variants)
• not specified (5 variants)
• Peripheral neuropathy (3 variants)
• MME-related condition (3 variants)
• Spinocerebellar ataxia 43;Charcot-Marie-Tooth disease axonal type 2T (2 variants)
• See cases (2 variants)
• Charcot-Marie-Tooth disease type 2 (2 variants)
• Congenital membranous nephropathy due to maternal anti-neutral endopeptidase alloimmunization (1 variants)
• Autosomal recessive axonal hereditary motor and sensory neuropathy (1 variants)
• Charcot-Marie-Tooth disease type 2;Charcot-Marie-Tooth disease axonal type 2T;MME-related autosomal dominant Charcot Marie Tooth disease type 2 (1 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)
• Early-onset dementia of unclear type (1 variants)
• Charcot-Marie-Tooth disease axonal type 2T;Spinocerebellar ataxia 43 (1 variants)
• MME-related autosomal dominant Charcot Marie Tooth disease type 2 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MME 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	73	5	79
missense		6	214	7	1	228
nonsense	12	7	1			20
start loss						0
frameshift	16	5	1			22
inframe indel			1			1
splice donor/acceptor (+/-2bp)		15	2			17
splice region			25	13	6	44
non coding			4	81	47	132
Total	28	33	224	161	53

Highest pathogenic variant AF is 0.0000658

Variants in MME

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

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

Position	Type	Phenotype	Significance	ClinVar
3-155083846-C-T			Likely benign (Oct 16, 2018)
3-155083948-A-G			Benign (Aug 06, 2019)
3-155084043-G-A			Benign (Jul 15, 2018)
3-155084141-A-G			Likely benign (Oct 18, 2020)
3-155084157-G-T			Uncertain significance (Jun 09, 2020)
3-155084178-C-G			Pathogenic (Jan 26, 2024)
3-155084185-T-TC			Pathogenic (Aug 10, 2023)
3-155084189-A-G		MME-related disorder	Benign (Feb 01, 2024)
3-155084192-G-A			Uncertain significance (Oct 18, 2022)
3-155084192-G-C			Uncertain significance (Oct 29, 2021)
3-155084193-A-G			Uncertain significance (Mar 14, 2022)
3-155084205-T-C			Uncertain significance (Feb 19, 2022)
3-155084209-C-T			Likely benign (Nov 13, 2023)
3-155084214-C-A		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
3-155084220-C-T			Uncertain significance (Feb 28, 2022)
3-155084222-A-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2024)
3-155084223-A-G			Uncertain significance (Dec 23, 2021)
3-155084233-G-A			Likely benign (Dec 19, 2023)
3-155084233-G-C			Uncertain significance (Jun 12, 2022)
3-155084234-C-T			Pathogenic (Oct 11, 2023)
3-155084235-G-A			Uncertain significance (Jul 22, 2022)
3-155084238-G-A		Charcot-Marie-Tooth disease axonal type 2T	Pathogenic (Nov 01, 2023)
3-155084239-G-T			Uncertain significance (May 21, 2022)
3-155084245-A-G			Likely benign (Jun 15, 2023)
3-155084263-G-A		MME-related disorder	Likely benign (Jan 15, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
MME	protein_coding	protein_coding	ENST00000460393	22	159585

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.46e-18	0.682	125565	0	183	125748	0.000728

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.358	374	394	0.949	0.0000205	4975
Missense in Polyphen		143	159.04	0.89916		2073
Synonymous	0.672	129	139	0.927	0.00000772	1312
Loss of Function	2.00	36	51.5	0.699	0.00000285	580

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00156	0.00156
Ashkenazi Jewish	0.000596	0.000595
East Asian	0.00121	0.00120
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000866	0.000862
Middle Eastern	0.00121	0.00120
South Asian	0.000262	0.000261
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:15283675, PubMed:8168535). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:17101991). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:15283675). Involved in the degradation of atrial natriuretic factor (ANF) (PubMed:2531377, PubMed:2972276). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573). {ECO:0000269|PubMed:15283675, ECO:0000269|PubMed:17101991, ECO:0000269|PubMed:20876573, ECO:0000269|PubMed:2531377, ECO:0000269|PubMed:27588448, ECO:0000269|PubMed:2972276}.
• Disease: DISEASE: Charcot-Marie-Tooth disease 2T (CMT2T) [MIM:617017]: An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. {ECO:0000269|PubMed:26991897, ECO:0000269|PubMed:27588448}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Spinocerebellar ataxia 43 (SCA43) [MIM:617018]: A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCA43 is a slowly progressive, autosomal dominant form. {ECO:0000269|PubMed:27583304}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Agents Acting on the Renin-Angiotensin System Pathway, Pharmacodynamics;Renin-angiotensin system - Homo sapiens (human);Protein digestion and absorption - Homo sapiens (human);Alzheimer,s disease - Homo sapiens (human);Hematopoietic cell lineage - Homo sapiens (human);ACE Inhibitor Pathway, Pharmacodynamics;Alzheimers Disease;Primary Focal Segmental Glomerulosclerosis FSGS;Neutrophil degranulation;Peptide hormone metabolism;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins;Innate Immune System;Immune System (Consensus)

Recessive Scores

• pRec: 0.696

Intolerance Scores

• loftool: 0.0163
• rvis_EVS: -0.69
• rvis_percentile_EVS: 15.32

Haploinsufficiency Scores

• pHI: 0.804
• hipred: Y
• hipred_score: 0.744
• ghis: 0.458

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.751

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mme
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); homeostasis/metabolism phenotype; liver/biliary system phenotype; immune system phenotype

Gene ontology

• Biological process: kidney development;angiotensin maturation;proteolysis;peptide metabolic process;sensory perception of pain;neutrophil degranulation;creatinine metabolic process;amyloid-beta metabolic process;cellular response to cytokine stimulus;cellular response to UV-A;cellular response to UV-B;replicative senescence;amyloid-beta clearance
• Cellular component: cytoplasm;plasma membrane;integral component of plasma membrane;brush border;focal adhesion;synaptic vesicle;integral component of membrane;axon;dendrite;secretory granule membrane;neuron projection terminus;synapse;extracellular exosome
• Molecular function: endopeptidase activity;metalloendopeptidase activity;protein binding;metallopeptidase activity;exopeptidase activity;zinc ion binding;peptide binding