MME

Chr 3ADAR

membrane metalloendopeptidase

Also known as: CALLA, CD10, CMT2T, NEP, SCA43, SFE

NCBI Gene: 4311ENSG00000196549UniProt: P08473

The protein encoded by this gene is a type II transmembrane glycoprotein and a common acute lymphocytic leukemia antigen that is an important cell surface marker in the diagnosis of human acute lymphocytic leukemia (ALL). The encoded protein is present on leukemic cells of pre-B phenotype, which represent 85% of cases of ALL. This protein is not restricted to leukemic cells, however, and is found on a variety of normal tissues. The protein is a neutral endopeptidase that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. [provided by RefSeq, Aug 2017]

Primary Disease Associations & Inheritance

?Spinocerebellar ataxia 43MIM #617018
AD
Charcot-Marie-Tooth disease, axonal, type 2TMIM #617017
ADAR
489
ClinVar variants
67
Pathogenic / LP
0.00
pLI score
5
Active trials
Clinical Summary— MME
🧬
Gene-Disease Validity (ClinGen)
Charcot-Marie-Tooth disease axonal type 2T · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 182 VUS of 489 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.92LOEUF
pLI 0.000
Z-score 2.00
OE 0.70 (0.54–0.92)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.36Z-score
OE missense 0.95 (0.87–1.03)
374 obs / 394.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.70 (0.54–0.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.95 (0.87–1.03)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.93
0≤1.21.6
LoF obs/exp: 36 / 51.5Missense obs/exp: 374 / 394.0Syn Z: 0.67

ClinVar Variant Classifications

489 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic38
Likely Pathogenic29
VUS182
Likely Benign222
Benign14
Conflicting4
38
Pathogenic
29
Likely Pathogenic
182
VUS
222
Likely Benign
14
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
0
25
0
38
Likely Pathogenic
18
2
9
0
29
VUS
1
158
21
2
182
Likely Benign
0
3
119
100
222
Benign
0
0
13
1
14
Conflicting
—4
Total32163187103489

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

MME · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Spinocerebellar ataxia 43

MIM #617018

Molecular basis of disorder known

Autosomal dominant

Charcot-Marie-Tooth disease, axonal, type 2T

MIM #617017

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
📖
GeneReview available — MME
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Opioid-free anesthesia: A systematic review and meta-analysis.
Feenstra ML et al.·J Clin Anesth
2023Meta-analysis
Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.
Qiu W et al.·J Adv Res
2025
Aspartame increases the risk of liver cancer through CASP1 protein: A comprehensive network analysis insights.
Li NR et al.·Ecotoxicol Environ Saf
2025
The genetic landscape of axonal neuropathies in the middle-aged and elderly: Focus on MME.
Senderek J et al.·Neurology
2020
An overview of BAP1 biological functions and current therapeutics.
Elsayed AM et al.·Biochim Biophys Acta Rev Cancer
2025Review
Matchmaker Exchange.
Sobreira NLM et al.·Curr Protoc Hum Genet
2017
Ketamine for acute pain after trauma: A pragmatic, randomized clinical trial.
Klugh JM et al.·J Trauma Acute Care Surg
2024
Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study.
Kharasch ED et al.·Anesthesiology
2023
Effectiveness of a Therapeutic Tai Ji Quan Intervention vs a Multimodal Exercise Intervention to Prevent Falls Among Older Adults at High Risk of Falling: A Randomized Clinical Trial.
Li F et al.·JAMA Intern Med
2018
Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).
Manchikanti L et al.·Pain Physician
2023Guideline
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Integrated network pharmacology and bioinformatics analysis reveals MME as key target of Notoginsenoside R1 in diabetic nephropathy.
Gan X et al.·BMC Complement Med Ther
2026🔓 Open Access
Cell type- and neuronal differentiation-dependent MME 5'UTR splice variants with distinct translational outputs in human cells.
Iwamoto S et al.·J Biochem
2026
Navigating treatment transitions: Enhancing outpatient recovery with morphine milligram equivalent (MME) dosing in methadone to bu-prenorphine transition-Case reports.
Yousufzai W et al.·J Opioid Manag
2025Case report
A Self-Powered Double U-Finger MME Resonator Capable of Wirelessly Capturing Abnormal Message in Smart Grid Networks.
Zheng X et al.·Adv Sci (Weinh)
2025🔓 Open Access
Assessing a dose-response relationship: Preoperative opioid daily MME and duration on lumbar spine surgery patient-reported outcomes.
Tingen J et al.·Clin Neurol Neurosurg
2025
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Metastatic Triple Negative Breast Cancer

To Assess Safety and Efficacy of Agents Targeting DNA Damage Repair With Olaparib Versus Olaparib Monotherapy.

ACTIVE NOT RECRUITING
NCT03330847Phase PHASE2AstraZenecaStarted 2018-03-07
Olaparib Continuous (28-Day cycle) 300 mg BD.Ceralasertib 160 mg OD + olaparib continuous 300 mg BD (28-day cycle).Adavosertib 150 mg BD + olaparib 200 mg BD (21-day cycle).
Radiation-induced Oral Mucositis

Traditional Chinese Medicine Oral Liquids and Mouthwashes for Radiation-induced Oral Mucositis in Head and Neck Cancer Patients

NOT YET RECRUITING
NCT07282483Phase PHASE2West China HospitalStarted 2025-12-15
Qingying oral liquid and modified Da Huang-Huang Lian Xiexin mouthwashPlacebo oral solution and mouthwashradiotherapy
Transthyretin AmyloidosisATTR-CMATTRv-PN

Non-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis

RECRUITING
NCT06465810AstraZenecaStarted 2024-06-25
Treatment of transthyretin (ATTR) amyloidosis in observational study setting
Pancreas NeoplasmsPancreatic NeoplasmsPancreatic Cancer Metastatic

Predictive Value of Transcriptome-based OncoTreat/Oncotarget and Organoid Testing in Metastatic Pancreatic Cancer.

NOT YET RECRUITING
NCT06615830Prof. Dr. med. Dres. h.c. Jan Schmidt, MMEStarted 2026-06-01
Angio-Oedema Caused by Angiotensin-Converting-Enzyme Inhibitor

Bradykinin-degradating Enzymes Activities in Angiotensin-Converting Enzyme Inhibitors-associated Angioedema

RECRUITING
NCT04763577University Hospital, GrenobleStarted 2021-10-27
Assay of Bradykinin-degradating enzymes.

External Resources

Links to major genomics databases and tools