MPZ

Summary

MPZ (myelin protein zero, HGNC:7225) is a protein-coding gene on chromosome 1q23.3, encoding Myelin protein P0 (P25189). Is an adhesion molecule necessary for normal myelination in the peripheral nervous system.

This gene is specifically expressed in Schwann cells of the peripheral nervous system and encodes a type I transmembrane glycoprotein that is a major structural protein of the peripheral myelin sheath. The encoded protein contains a large hydrophobic extracellular domain and a smaller basic intracellular domain, which are essential for the formation and stabilization of the multilamellar structure of the compact myelin. Mutations in this gene are associated with autosomal dominant form of Charcot-Marie-Tooth disease type 1 (CMT1B) and other polyneuropathies, such as Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). A recent study showed that two isoforms are produced from the same mRNA by use of alternative in-frame translation termination codons via a stop codon readthrough mechanism.

Source: NCBI Gene 4359 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Charcot-Marie-Tooth disease (Definitive, ClinGen) — +7 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 728 total — 105 pathogenic, 59 likely-pathogenic (top 5% of genes corpus-wide)
• Expression (HPA): Tissue enhanced — highest in spinal cord, dorsal spinal cord, ventral spinal cord
• GTEx eGene: eQTL in 17 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 93
• Dosage sensitivity (ClinGen): haploinsufficiency emerging evidence, triplosensitivity little evidence
• Constraint (gnomAD): pLI 0.11 (intermediate), LOEUF 0.71 (unconstrained)
• MANE Select transcript: NM_000530

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7225
Approved symbol	MPZ
Name	myelin protein zero
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	HMSNIB, CMT2I, CMT2J, P0
Ensembl gene	ENSG00000158887
Ensembl biotype	protein_coding
OMIM	159440
Entrez	4359

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000533357

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 1, TSL 3: 2

ENST00000533357, ENST00000463290, ENST00000476410, ENST00000488271, ENST00000526189, ENST00000672287, ENST00000672602, ENST00001144307

RefSeq mRNA: 2 — MANE Select: NM_000530 NM_000530, NM_001315491

CCDS: CCDS1229, CCDS91087

Canonical transcript exons

ENST00000533357 — 6 exons

Exon	Start	End
ENSE00001041809	161307258	161307424
ENSE00001313871	161309839	161309968
ENSE00001414908	161304735	161305977
ENSE00003615032	161306329	161306464
ENSE00003629276	161306108	161306168
ENSE00003643873	161306708	161306921

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 99.74.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8498 / max 2128.2039, expressed in 1219 samples.

Highest expression (Bgee): tibial nerve, sural nerve, olfactory bulb, trigeminal ganglion, dorsal root ganglion.

Genetic regulation across tissues (GTEx eQTL / sQTL)

MPZ is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 17 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 23 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Nucleus accumbens basal ganglia	eqtl	4.4e-16	+0.87	1:161307811:C:T
Brain Hippocampus	eqtl	1.3e-14	+0.83	1:161307811:C:T
Esophagus Muscularis	eqtl	1.6e-08	+0.18	1:161308772:C:G
Colon Sigmoid	eqtl	8.3e-08	+0.20	1:161308772:C:G
Brain Caudate basal ganglia	eqtl	1.1e-07	+0.60	1:161307811:C:T
Whole Blood	eqtl	2.4e-07	-0.56	1:161306153:C:T
Brain Amygdala	eqtl	2.5e-07	+0.74	1:161307811:C:T
Esophagus Gastroesophageal Junction	eqtl	5.0e-07	+0.24	1:161310092:A:G
Testis	sqtl	9.1e-06	+0.45	1:161274783:T:C
Brain Nucleus accumbens basal ganglia	sqtl	3.2e-05	+0.62	1:161310092:A:G
Whole Blood	sqtl	9.3e-05	+0.33	1:161286727:C:T
Testis	eqtl	9.8e-05	-0.46	1:161308988:C:T
Brain Putamen basal ganglia	eqtl	2.2e-04	+0.55	1:161307811:C:T
Colon Transverse	eqtl	2.8e-03	+0.13	1:161310092:A:G
Skin Sun Exposed Lower leg	eqtl	1.1e-02	-0.93	1:162028365:A:G
Muscle Skeletal	eqtl	1.1e-02	-0.68	1:162062065:T:C
Brain Spinal cord cervical c-1	eqtl	1.7e-02	+0.35	1:161309440:G:C
Heart Atrial Appendage	eqtl	1.9e-02	+0.14	1:161309440:G:C
Breast Mammary Tissue	sqtl	2.1e-02	-1.45	1:162197392:G:A
Thyroid	eqtl	2.6e-02	+0.43	1:161538654:A:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
15636	5.5921	234
15631	1.5161	678
15635	1.5068	679
15632	0.1909	75
15633	0.0439	11

Top tissues by expression

showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibial nerve	UBERON:0001323	99.74	gold quality
sural nerve	UBERON:0015488	99.51	gold quality
olfactory bulb	UBERON:0002264	99.30	gold quality
trigeminal ganglion	UBERON:0001675	98.33	gold quality
dorsal root ganglion	UBERON:0000044	97.66	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.36	gold quality
lower esophagus	UBERON:0013473	85.32	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	85.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	84.35	gold quality
left coronary artery	UBERON:0001626	83.28	gold quality
right atrium auricular region	UBERON:0006631	82.19	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.06	silver quality
coronary artery	UBERON:0001621	81.96	gold quality
cardiac atrium	UBERON:0002081	80.98	gold quality
seminal vesicle	UBERON:0000998	80.00	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	79.48	gold quality
sigmoid colon	UBERON:0001159	79.43	gold quality
colonic epithelium	UBERON:0000397	79.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	78.84	gold quality
minor salivary gland	UBERON:0001830	78.41	gold quality
monocyte	CL:0000576	78.13	gold quality
skin of abdomen	UBERON:0001416	78.06	gold quality
left ventricle myocardium	UBERON:0006566	77.65	gold quality
esophagus	UBERON:0001043	77.64	gold quality
mononuclear cell	CL:0000842	77.63	gold quality
leukocyte	CL:0000738	77.30	gold quality
transverse colon	UBERON:0001157	76.80	gold quality
stromal cell of endometrium	CL:0002255	76.76	gold quality
left uterine tube	UBERON:0001303	76.73	gold quality
heart	UBERON:0000948	76.58	gold quality
endocervix	UBERON:0000458	76.50	gold quality
vagina	UBERON:0000996	76.43	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	76.33	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.29	silver quality
adenohypophysis	UBERON:0002196	76.22	gold quality
heart left ventricle	UBERON:0002084	76.21	gold quality
omental fat pad	UBERON:0010414	76.01	gold quality
skin of leg	UBERON:0001511	75.98	gold quality
peritoneum	UBERON:0002358	75.92	gold quality
mucosa of transverse colon	UBERON:0004991	75.87	gold quality
right hemisphere of cerebellum	UBERON:0014890	75.70	gold quality
granulocyte	CL:0000094	75.64	gold quality
colon	UBERON:0001155	75.55	gold quality
saliva-secreting gland	UBERON:0001044	75.54	gold quality
cardiac ventricle	UBERON:0002082	75.54	gold quality
subcutaneous adipose tissue	UBERON:0002190	75.45	gold quality
small intestine Peyer’s patch	UBERON:0003454	75.41	gold quality
lower esophagus mucosa	UBERON:0035834	75.32	gold quality
pituitary gland	UBERON:0000007	75.30	gold quality
blood	UBERON:0000178	75.20	gold quality
spinal cord	UBERON:0002240	74.90	gold quality
cerebellar hemisphere	UBERON:0002245	74.87	gold quality
adipose tissue of abdominal region	UBERON:0007808	74.87	gold quality
apex of heart	UBERON:0002098	74.70	gold quality
body of stomach	UBERON:0001161	74.65	gold quality
zone of skin	UBERON:0000014	74.58	gold quality
cerebellar cortex	UBERON:0002129	74.57	gold quality
large intestine	UBERON:0000059	74.40	gold quality
calcaneal tendon	UBERON:0003701	74.39	gold quality
prostate gland	UBERON:0002367	74.18	gold quality
intestine	UBERON:0000160	73.99	gold quality
mouth mucosa	UBERON:0003729	73.89	gold quality
tibial artery	UBERON:0007610	73.89	gold quality
popliteal artery	UBERON:0002250	73.88	gold quality
gastrocnemius	UBERON:0001388	73.71	gold quality
ectocervix	UBERON:0012249	73.66	gold quality
right lobe of liver	UBERON:0001114	73.58	gold quality
right lung	UBERON:0002167	73.47	gold quality
spleen	UBERON:0002106	73.32	gold quality
muscle of leg	UBERON:0001383	73.29	gold quality
right coronary artery	UBERON:0001625	73.27	gold quality
left adrenal gland	UBERON:0001234	73.25	gold quality
small intestine	UBERON:0002108	73.09	gold quality
right lobe of thyroid gland	UBERON:0001119	73.08	gold quality
stomach	UBERON:0000945	72.97	gold quality
diaphragm	UBERON:0001103	72.71	gold quality
metanephros cortex	UBERON:0010533	72.71	gold quality
vermiform appendix	UBERON:0001154	72.48	gold quality
aorta	UBERON:0000947	72.29	gold quality
left lobe of thyroid gland	UBERON:0001120	72.29	gold quality
left adrenal gland cortex	UBERON:0035825	72.24	gold quality
right adrenal gland	UBERON:0001233	72.15	gold quality
rectum	UBERON:0001052	72.14	gold quality
cerebellum	UBERON:0002037	71.76	gold quality
adrenal gland	UBERON:0002369	71.72	gold quality
mucosa of stomach	UBERON:0001199	71.41	gold quality
adipose tissue	UBERON:0001013	71.28	gold quality
thyroid gland	UBERON:0002046	71.28	gold quality
esophagus mucosa	UBERON:0002469	71.21	gold quality
ascending aorta	UBERON:0001496	71.02	gold quality
right ovary	UBERON:0002118	71.02	gold quality
hair follicle	UBERON:0002073	70.93	gold quality
thoracic aorta	UBERON:0001515	70.60	gold quality
right adrenal gland cortex	UBERON:0035827	70.55	gold quality
connective tissue	UBERON:0002384	70.49	gold quality
gall bladder	UBERON:0002110	70.36	gold quality
anatomical system	UBERON:0000467	70.05	gold quality
fundus of stomach	UBERON:0001160	69.97	gold quality
body of uterus	UBERON:0009853	69.89	gold quality
left ovary	UBERON:0002119	69.88	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-MTAB-8221	yes	1319.56
E-HCAD-56	yes	487.87
E-MTAB-10485	yes	405.93
E-HCAD-11	yes	34.93
E-MTAB-8410	yes	17.53
E-CURD-46	yes	13.61
E-ANND-3	no	1.73

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spinal cord	tissue	2820.7
Substantia nigra	tissue	292.0
Superior colliculi	tissue	33.9
Tongue	tissue	17.2
Adipose tissue	tissue	9.7	not detected
Vagina	tissue	9.1	not detected
Seminal vesicle	tissue	7.6	not detected
Adrenal gland	tissue	6.5	not detected
Pituitary gland	tissue	5.4
Nucleus accumbens	tissue	4.9
Medulla oblongata	tissue	4.9
Heart muscle	tissue	4.1	not detected
Locus coeruleus	tissue	3.6
Salivary gland	tissue	3.4	not detected
Esophagus	tissue	3.3	low
Small intestine	tissue	3.3	low
Colon	tissue	3.2	not detected
Prostate	tissue	2.9	not detected
Rectum	tissue	2.5	not detected
Urinary bladder	tissue	2.4	not detected
Hippocampus	tissue	2.4	not detected
Postcentral gyrus	tissue	2.4
Gallbladder	tissue	2.2	not detected
Cervix	tissue	2.0	not detected
Appendix	tissue	2.0	not detected
Epididymis	tissue	1.9	not detected
Olfactory bulb	tissue	1.8
Putamen	tissue	1.5
Choroid plexus	tissue	1.5
Duodenum	tissue	1.5	not detected
Cerebral cortex	tissue	1.4	not detected
Amygdala	tissue	1.4
Cerebellum	tissue	1.4	not detected
Retrosplenial and cingulate cortex	tissue	1.4
Pons	tissue	1.3
Pancreas	tissue	1.3	not detected
Thymus	tissue	1.3
Hippocampal formation	tissue	1.3
Septum	tissue	1.3
Skin 1	tissue	1.2	not detected
Basal ganglia	tissue	1.2	not detected
Corpus callosum	tissue	1.2
Entorhinal cortex	tissue	1.2
Retrosplenial cortex	tissue	1.2
Temporal cortex	tissue	1.2
Breast	tissue	1.1	not detected
Stomach 1	tissue	1.1	low
Retina	tissue	1.1
Skeletal muscle	tissue	1.1	not detected
Thalamus	tissue	1.1
Spleen	tissue	1.1	not detected
Bone marrow	tissue	1.1	not detected
Ventral forebrain	tissue	1.1
Insular cortex	tissue	1.1
Lymph node	tissue	1.0	not detected
Prefrontal cortex	tissue	1.0
Ovary	tissue	1.0	not detected
Motor cortex	tissue	1.0
Midbrain	tissue	1.0
Liver	tissue	1.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Dorsal spinal cord (2820.7), Ventral spinal cord (446.9), Blood vessel (20.2), Dorsal cochlear nucleus (19.9), Supraoptic nucleus (7.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTCF, EGR2, ID1, JUN, MYC, PAX6, POU3F1, SOX10, ZNF699

miRNA regulators (miRDB)

Targeting MPZ by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 132 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-223-3P	99.99	70.14	1140
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-4525	99.94	64.38	675
HSA-MIR-5010-5P	99.94	64.11	705
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354

Functional genomics

gnomAD constraint: pLI 0.112, LOEUF 0.708, missense Z 1.48 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000533357 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:161,305,879–161,306,385	101 / 93.6	1.08	no
1:161,306,386–161,309,905	155 / 223.9	0.69	no

ClinGen dosage: haploinsufficiency 2 (emerging evidence), triplosensitivity 1 (little evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• SSCP analysis for this gene in Croatian patients (PMID:12211648)
• We suggest that axonal and demyelinating forms of CMT are not two distinct classes, but rather parts of a spectrum of genotypically related conditions, particularly with some MPZ mutations (PMID:12911457)
• DNA sequencing analysis shows the Asn131Lys mutation in the myelin protein zero gene in three members of an affected family. (PMID:12940837)
• A novel mutation, Thr65Ala, in the MPZ gene in a patient with Charcot-Marie-Tooth type 1B disease with focally folded myelin. (PMID:15036333)
• Four missense mutations and one 4-base pair (bp) deletion, respectively, were identified in five patients, of which one mutation, c.173 T>A, has never been previously reported (PMID:15050444)
• MPZ gene screening should be performed for wide phenotype spectrum of Charcot-Marie-Tooth disease. (PMID:15094849)
• Chronic cough was associated with a Thr124 Met mutation. MPZ must be critical for maintenance of axonal function in addition to its role in myelin. All MPZ mutations associated with tonic pupils affect the same region of the extracellular domain. (PMID:15159512)
• A novel Thr124Lys mutation in the MPZ gene is associated with congenital neuropathy with hypomyelination. (PMID:15184631)
• Within 94 MPZ gene mutations reported up to now, only a few were identified in the exon 4 of the MPZ gene. In this study we have identified a novel Leu190fs mutation in the MPZ gene. (PMID:15261887)
• A novel mutation, 290 A–>T (Glu97Val), in the myelin protein zero gene (P0) is reported in a family with late-onset Charcot-Marie-Tooth disease type 2. (PMID:15326256)
• PMP22 and P0 are involved in both trans-homophilic and trans-heterophilic interactions. Disease-related point mutations of P0 resulted in a decreased adhesion capability correlating with the severity of the respective disease phenotype. (PMID:15555916)
• 4 patients had a Val102/fs null mutation (306delA at codon 102), age-dependent variability of clinical & electrophysiologic phenotype, segmental conduction abnormalities mainly in ulnar nerves at the elbow, & excessive myelin foldings & thickenings. (PMID:15596778)
• There was concordance between median MNCV and specific MPZ mutations. (PMID:15729519)
• P0, the major myelin protein, is also expressed during nephrogenesis and in mature kidney, mostly in podocytes. (PMID:16162811)
• family in which five members of three consecutive generations had a heterozygous mutation in nucleotide position 143 with a T-C transition in exon 2 of the MPZ gene. The resulting substitution of Leu48 with proline has not been previously described. (PMID:16198109)
• Charcot-Marie-Tooth disease due to the Thr124Met mutation in the myelin protein zero gene associated with multiple sclerosis. (PMID:16279991)
• Polymorphic short tandem repeats for PCR-based diagnosis of the Charcot-Marie-Tooth 1A duplication in Ukraine was performed. (PMID:16398147)
• Peripheral neuropathies caused by mutations in the myelin protein zero. (PMID:16414078)
• Two patients of Charcot-Marie-Tooth disease type 1B from subsequent generations were homozygous for an Asp195Tyr mutation in the intracellular domain of P0 (P0ic). (PMID:16488608)
• MPZ gene showed a novel point mutation in the extracellular domain in two families with axonal CMT. (PMID:16543539)
• Data confirm that a mutation in myelin protein zero can cause axonal neuropathy, in the absence of segmental demyelination, thus uncoupling the two pathological processes. (PMID:16856127)
• Intronic mutations cause CMT1B by disrupting splicing and certain MPZ mutations may cause neuropathy by interacting with the wild type MPZ in the extracellular space of compact myelin. (PMID:17030746)
• the cytoplasmic apposition (major dense line) in compact myelin may be stabilized via the hydrogen-bonding of beta-strands formed as a result of local P0-P0 aggregation. (PMID:17142269)
• a new myelin protein zero gene mutation (c.89T>C,Ile30Thr) was detected in a family with the Dejerine-Sottas disease phenotype (PMID:17143884)
• A patient with Charcot Marie Tooth Disease, Type Ib had a MPZ mutation with A-C transversion (nucleotide: 116, codon: 10, histidine-to-proline). (PMID:17602703)
• a novel Pro105Thr mutation in the MPZ gene (PMID:17663472)
• Congenital hypomyelinating neuropathy is a rare condition characterized by prenatal, neonatal or early infantile onset of hypotonia, paresis and areflexia.Here we describe a family with a heterozygous mutation in MPZ, confirmed in two generations. (PMID:17825553)
• In all patients, molecular analysis demonstrated a novel heterozygous missense mutation (208C>T) in MPZ exon 2, causing the Pro70Ser substitution in the extracellular domain. The diagnosis of CMT2 associated with MPZ (PMID:17940173)
• The novel mutation causes a late-onset demyelinating polyneuropathy, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells. (PMID:18209201)
• Results suggest that at least some late-onset MPZ mutations cause a partial loss of function in the transfected cells, whereas multiple abnormal gain of function pathways can result in early-onset neuropathy. (PMID:18337304)
• Our study provides further evidence that phenotypic features of MPZ mutations can vary within and among different families with CMT Ib (PMID:18422810)
• A heterozygous nonsense mutation (Tyr145Stop) corresponding to a T-to-A transition at nucleotide position 435 in exon 3 of the MPZ gene was identified in Charcot-Marie-Tooth disease type 1B patients. (PMID:18663734)
• Data show that the CMT1Adup, GJB1, MPZ and PMP22 mutation frequencies were in the range of those described in other CMT patient collectives with different ethnical backgrounds. (PMID:19259128)
• Findings suggest that the clinical features associated with MPZ mutations depend partly on the nature of amino acid change. (PMID:19293842)
• mutations in MPZ may have a role in Charcot-Marie-Tooth disease type 1B [case report] (PMID:19475438)
• The index patient of this family with unusual Charcot-Marie-Tooth phenotype is found to have a missense mutation within the intracellular domain of myelin protein zero. (PMID:19882637)
• Here we describe an unusual presentation of the Val102fs mutation characterized by symptoms of spinal root hypertrophy with no overt peroneal muscular atrophy. This report adds new data concerning the clinical presentations of MPZ mutations. (PMID:19906531)
• A genetic test disclosed a heterozygous mutation of myelin protein zero (MPZ); p.Thr124Met. (PMID:19928689)
• novel mutation in vocal cord paralysis (PMID:19950375)
• The results of this study concluded that ARG98HIS MPZ mutation may cause hereditary and relatively mild and asymmetric demyelinating sensorimotor polyneuropathy (PMID:20215982)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mpz	ENSDARG00000038609
mus_musculus	Mpz	ENSMUSG00000056569
rattus_norvegicus	Mpz	ENSRNOG00000003171

Paralogs (6): MPZL2 (ENSG00000149573), SCN2B (ENSG00000149575), MPZL3 (ENSG00000160588), JAML (ENSG00000160593), SCN4B (ENSG00000177098), MPZL1 (ENSG00000197965)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:103177) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 53 distinct phenotype terms.

Mouse phenotype (MP)	Records
tremors	8
abnormal gait	6
abnormal myelin sheath morphology	5
dysmyelination	5
demyelination	4
decreased nerve conduction velocity	4
abnormal myelination	3
ataxia	3
impaired coordination	3
limb grasping	3
muscular atrophy	3
decreased myelin sheath thickness	3
weakness	2
abnormal Schwann cell morphology	2
infertility	2
premature death	2
abnormal nervous system physiology	2
abnormal action potential	2
abnormal nerve conduction	2
axon degeneration	2
decreased grip strength	2
abnormal axon radial sorting	2
increased monocyte cell number	1
muscle weakness	1
paralysis	1

+28 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R804	98.6%	Diamond
Equus caballus	Q6WEB5	97.6%	Diamond
Bos taurus	P10522	94.0%	Diamond
Xenopus tropicalis	A0JM41	91.8%	Diamond
Xenopus laevis	A2VD98	91.8%	Diamond
Gallus gallus	P37301	75.6%	Diamond
Heterodontus francisci	P20938	52.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
PCP4L1	protein-coding	654790
TOMM40L	protein-coding	84134
NR1I3	protein-coding	9970
SDHC	protein-coding	6391
CFAP126	protein-coding	257177

Protein

Protein identifiers

Myelin protein P0 — P25189 (reviewed: P25189)

Alternative names: Myelin peripheral protein, Myelin protein zero

All UniProt accessions (4): A0A0J9YWT2, A0A5F9ZI26, E9PL80, P25189

UniProt curated annotations — full annotation on UniProt →

Function. Is an adhesion molecule necessary for normal myelination in the peripheral nervous system. It mediates adhesion between adjacent myelin wraps and ultimately drives myelin compaction.

Subunit / interactions. Homodimer and homotetramer.

Subcellular location. Cell membrane Myelin membrane.

Tissue specificity. Found only in peripheral nervous system Schwann cells.

Post-translational modifications. N-glycosylated; contains sulfate-substituted glycan.

Disease relevance. Charcot-Marie-Tooth disease, demyelinating, type 1B (CMT1B) [MIM:118200] A dominant demyelinating 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). Demyelinating neuropathies are characterized by severely reduced nerve conduction velocities (less than 38 m/sec), segmental demyelination and remyelination with onion bulb formations on nerve biopsy, slowly progressive distal muscle atrophy and weakness, absent deep tendon reflexes, and hollow feet. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2I (CMT2I) [MIM:607677] A dominant 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. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, axonal, type 2J (CMT2J) [MIM:607736] A dominant 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. Charcot-Marie-Tooth disease type 2J is characterized by the association of axonal peripheral neuropathy with hearing loss and pupillary abnormalities such as Adie pupil. The disease is caused by variants affecting the gene represented in this entry. Adie pupil (ADIEP) [MIM:103100] A stationary, benign disorder characterized by tonic, sluggishly reacting pupil and hypoactive or absent tendon reflexes. Adie pupil is a characteristic of Charcot-Marie-Tooth disease type 2J. The disease is caused by variants affecting the gene represented in this entry. Charcot-Marie-Tooth disease, dominant intermediate D (CMTDID) [MIM:607791] A 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. The dominant intermediate type D is characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec. The disease may be caused by variants affecting the gene represented in this entry. Dejerine-Sottas syndrome (DSS) [MIM:145900] A severe degenerating neuropathy of the demyelinating Charcot-Marie-Tooth disease category, with onset by age 2 years. Characterized by motor and sensory neuropathy with very slow nerve conduction velocities, increased cerebrospinal fluid protein concentrations, hypertrophic nerve changes, delayed age of walking as well as areflexia. There are both autosomal dominant and autosomal recessive forms of Dejerine-Sottas syndrome. The disease is caused by variants affecting the gene represented in this entry. Roussy-Levy syndrome (ROULS) [MIM:180800] Autosomal dominant disorder that resembles Charcot-Marie-Tooth disease type 1 in that it presents with foot deformity, weakness and atrophy of distal limb muscles, especially the peronei, and absent tendon reflexes. The phenotype differs, however, in that it includes static tremor of the upper limbs and gait ataxia. The disease is caused by variants affecting the gene represented in this entry. Neuropathy, congenital hypomyelinating, 2 (CHN2) [MIM:618184] A form of congenital hypomyelinating neuropathy, a neurologic disorder characterized by early-onset hypotonia, areflexia, distal muscle weakness, and very slow nerve conduction velocities (NCV) resulting from improper myelination of axons. In its extreme form, it may present with severe joint contractures or arthrogryposis multiplex congenita and respiratory insufficiency. In less severe cases patients may achieve walking. Patients lack both active myelin breakdown and well-organized onion bulbs on sural nerve biopsies, have absence of inflammation, and show hypomyelination of most or all fibers. CHN2 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. Based on a naturally occurring readthrough transcript. Highly antigenic.

Similarity. Belongs to the myelin P0 protein family.

Isoforms (2)

UniProt ID	Names	Canonical?
P25189-1	1	yes
P25189-2	L-MPZ

RefSeq proteins (2): NP_000521, NP_001302420 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000920	Myelin_P0-rel	Family
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR019566	MYP0_C	Domain
IPR019738	Myelin_P0_CS	Conserved_site
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR047014	Myelin_P0_Ig-like	Domain

Pfam: PF07686, PF10570

UniProt features (121 total): sequence variant 91, strand 12, modified residue 5, helix 2, topological domain 2, signal peptide 1, chain 1, turn 1, glycosylation site 1, disulfide bond 1, splice variant 1, transmembrane region 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures by resolution:

PDB	Title	Method	Resolution (Å)
8IIA	Crystal structure of the oligomeric state of the extracellular domain of human myelin …	X-RAY DIFFRACTION	2.09
3OAI	Crystal structure of the extra-cellular domain of human myelin protein zero	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25189-F1	82.38	0.57

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted intracellular proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (5)

Type	Positions
Phosphoserine	233, 243, 210, 226, 228

Disulfide bonds (1)

Type	Positions
Disulfide bond	50–127

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) (complex) asparagine	122

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 3; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

3 pathways:

ID	Pathway	Evidence
R-HSA-9619665	EGR2 and SOX10-mediated initiation of Schwann cell myelination	curated
R-HSA-1266738	Developmental Biology	—
R-HSA-9675108	Nervous system development	—

MSigDB gene sets: 283 (showing top): RNGTGGGC_UNKNOWN, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_CELL_CELL_SIGNALING, GOBP_CELL_CELL_ADHESION, MCBRYAN_PUBERTAL_BREAST_4_5WK_DN, GOBP_ENSHEATHMENT_OF_NEURONS, GOBP_CELL_AGGREGATION, MODULE_157, GOBP_SYNAPTIC_SIGNALING, LE_EGR2_TARGETS_DN, CTCAAGA_MIR526B, CAGCCTC_MIR4855P, KEGG_CELL_ADHESION_MOLECULES_CAMS, MODULE_104, GOCC_MYELIN_SHEATH

GO Biological Process (4): chemical synaptic transmission (GO:0007268), myelination (GO:0042552), cell-cell adhesion (GO:0098609), cell aggregation (GO:0098743)

GO Molecular Function (2): structural molecule activity (GO:0005198), protein binding (GO:0005515)

GO Cellular Component (4): plasma membrane (GO:0005886), myelin sheath (GO:0043209), synapse (GO:0045202), membrane (GO:0016020)

Reactome top-level categories

2 top-level categories:

Category	Pathways
Nervous system development	1
Developmental Biology	1

GO top-level categories

10 GO namespaces:

Category	Terms
cellular anatomical structure	2
anterograde trans-synaptic signaling	1
axon ensheathment	1
cell adhesion	1
cellular process	1
molecular_function	1
binding	1
membrane	1
cell periphery	1
cell junction	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
cell aggregation	BP	mutant phenotype
cell-cell adhesion	BP	mutant phenotype
myelination	BP	mutant phenotype
plasma membrane	CC	direct assay

Protein interactions and networks

IntAct

Human interaction partners of MPZ in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
IL6R	physical association	0.400	2
FCGR2A	physical association	0.400	1
ISLR2	physical association	0.400	1
KIR2DL5A	physical association	0.400	1
LILRA5	physical association	0.400	1
LILRA6	physical association	0.400	1
LILRB3	physical association	0.400	1
LILRB5	physical association	0.400	1
SIGLEC6	physical association	0.400	1
CCP110	physical association	0.370	1
PSMB3	physical association	0.370	1
PINX1	physical association	0.000	1

BioGRID (10 interactions; top human partners by supporting records): PMP22 (Affinity Capture-Western; 3 records), CSK (Synthetic Lethality), MBD3 (Cross-Linking-MS (XL-MS)), MCAM (Proximity Label-MS), NRAS (Proximity Label-MS), PSMB3 (Two-hybrid), SRGN (Affinity Capture-MS), ZRANB1 (Affinity Capture-MS)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
PMP22	“up-regulates activity”	MPZ	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 12 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
immune response-regulating signaling pathway	5	189.8×	2e-09
cytokine-mediated signaling pathway	5	54.4×	6e-07

Disease & clinical

Genetic variants

Variant evidence for MPZ: 728 ClinVar records (164 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

728 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	105
Likely pathogenic	59
Uncertain significance	328
Likely benign	101
Benign	12

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 164 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
14181	NM_000530.8(MPZ):c.371C>T (p.Thr124Met)	Pathogenic	criteria provided, multiple submitters, no conflicts	16
14175	NM_000530.8(MPZ):c.292C>T (p.Arg98Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	14
14185	NM_000530.8(MPZ):c.131C>T (p.Ser44Phe)	Pathogenic	criteria provided, multiple submitters, no conflicts	10
14191	NM_000530.8(MPZ):c.434A>C (p.Tyr145Ser)	Pathogenic	criteria provided, multiple submitters, no conflicts	9
14170	NM_000530.8(MPZ):c.499G>C (p.Gly167Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
14179	NM_000530.8(MPZ):c.242A>G (p.His81Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
586153	NM_000530.8(MPZ):c.303G>A (p.Trp101Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	6
14169	NM_000530.8(MPZ):c.188C>G (p.Ser63Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
549681	NM_000530.8(MPZ):c.245A>G (p.Tyr82Cys)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
14167	NM_000530.8(MPZ):c.270C>A (p.Asp90Glu)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
14172	NM_000530.8(MPZ):c.404T>C (p.Ile135Thr)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
14186	NM_000530.8(MPZ):c.393C>A (p.Asn131Lys)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
208146	NM_000530.8(MPZ):c.181G>A (p.Asp61Asn)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
208148	NM_000530.8(MPZ):c.487G>A (p.Gly163Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
208149	NM_000530.8(MPZ):c.499G>A (p.Gly167Arg)	Pathogenic	criteria provided, multiple submitters, no conflicts	4

Per-variant reference — Sugi Variant

Explore MPZ’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 40 predictions of 466):

Position(s)	Effect	Δscore	Sites
1:161306327–161306328	donor_loss	1.0000	5
1:161306465–161306466	acceptor_loss	1.0000	6
1:161306474	acceptor_gain	1.0000
1:161307256–161307257	donor_loss	1.0000	4
1:161307425–161307426	acceptor_loss	1.0000	6
1:161306106–161306107	donor_loss	0.9900	5
1:161306110	donor_gain	0.9900
1:161306169–161306170	acceptor_loss	0.9900	6
1:161306745	donor_gain	0.9900
1:161306922–161306923	acceptor_loss	0.9900	5

AlphaMissense

663 missense substitutions predicted likely pathogenic (of 1,598 scored), across 181 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D134	8	0.995	0.998
N131	8	0.994	1.000
D121	8	0.993	0.999
F95	8	0.982	1.000
D128	8	0.982	0.997
H81	8	0.976	0.999
F80	8	0.972	0.998
F52	8	0.971	0.999
D109	8	0.940	0.989
D90	8	0.868	0.967
D224	8	0.789	0.944
C127	7	1.000	1.000
C50	7	0.999	1.000
W66	7	0.999	1.000
F125	7	0.997	1.000
W101	7	0.992	0.999
N122	7	0.955	0.989
K130	7	0.945	0.999
F147	7	0.895	0.965
G123	6	0.997	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enriched (Skin Cutaneous Melanoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Lung Adenocarcinoma (validation)	unfavorable	0.000445

Disease associations

OMIM: gene MIM:159440 | disease phenotypes: MIM:118200 (Charcot-Marie-Tooth disease, type 1B), MIM:145900 (Hypertrophic neuropathy of dejerine-sottas), MIM:180800 (Roussy-Levy hereditary areflexic dystasia), MIM:605253 (Neuropathy, congenital hypomyelinating, 1, autosomal recessive), MIM:607677 (Charcot-Marie-Tooth disease, axonal, type 2I), MIM:607736 (Charcot-Marie-Tooth disease, type 2J), MIM:607791 (Charcot-Marie-Tooth disease, dominant intermediate D), MIM:118220 (Charcot-Marie-Tooth disease, demyelinating, type 1A), MIM:618184 (Neuropathy, congenital hypomyelinating, 2)

GenCC curated gene-disease

8 curated gene-disease records:

Disease	Classification	Inheritance	Records
Charcot-Marie-Tooth disease	Definitive	Autosomal dominant	2
Charcot-Marie-Tooth disease type 1B	Definitive	Autosomal dominant	3
neuropathy, congenital hypomyelinating, 2	Definitive	Autosomal dominant
Charcot-Marie-Tooth disease dominant intermediate D	Supportive	Autosomal dominant
autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain	Supportive	Autosomal dominant
Charcot-Marie-Tooth disease type 3	Supportive	Autosomal dominant
Charcot-Marie-Tooth disease type 2I	Supportive	Autosomal dominant
Charcot-Marie-Tooth disease type 2J	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
Charcot-Marie-Tooth disease	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 4 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
DDG2P	green
Hereditary neuropathy	green
Hereditary neuropathy or pain disorder	green
Paediatric disorders	green
Fetal anomalies	amber

Mondo (12): Charcot-Marie-Tooth disease (MONDO:0015626), Charcot-Marie-Tooth disease type 1B (MONDO:0007307), neuropathy, congenital hypomyelinating, 2 (MONDO:0020765), Charcot-Marie-Tooth disease dominant intermediate D (MONDO:0011909), Charcot-Marie-Tooth disease type 3 (MONDO:0007790), Charcot-Marie-Tooth disease type 2I (MONDO:0011889), Charcot-Marie-Tooth disease type 2J (MONDO:0011903), autosomal dominant intermediate Charcot-Marie-Tooth disease with neuropathic pain (MONDO:0017937), Charcot-Marie-Tooth disease type 1 (MONDO:0019011), Roussy-Levy syndrome (MONDO:0008392), Charcot-Marie-Tooth disease type 4E (MONDO:0011527), peripheral neuropathy (MONDO:0005244)

Orphanet (9): Charcot-Marie-Tooth disease type 1B (Orphanet:101082), Dejerine-Sottas syndrome (Orphanet:64748), Roussy-Lévy syndrome (Orphanet:3115), Charcot-Marie-Tooth disease type 4E (Orphanet:99951), Autosomal dominant Charcot-Marie-Tooth disease type 2I (Orphanet:99942), Autosomal dominant Charcot-Marie-Tooth disease type 2J (Orphanet:99943), Autosomal dominant intermediate Charcot-Marie-Tooth disease type D (Orphanet:100046), Charcot-Marie-Tooth disease/Hereditary motor and sensory neuropathy (Orphanet:166), Charcot-Marie-Tooth disease type 1 (Orphanet:65753)

HPO phenotypes

showing 60 of 93 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000408	Progressive sensorineural hearing impairment
HP:0000615	Abnormal pupil morphology
HP:0000639	Nystagmus
HP:0000762	Decreased nerve conduction velocity
HP:0001171	Split hand
HP:0001178	Ulnar claw
HP:0001252	Hypotonia
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001284	Areflexia
HP:0001288	Gait disturbance
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001349	Facial diplegia
HP:0001558	Decreased fetal movement
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001763	Pes planus
HP:0001765	Hammertoe
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002070	Limb ataxia
HP:0002136	Broad-based gait
HP:0002174	Postural tremor
HP:0002312	Clumsiness
HP:0002317	Unsteady gait
HP:0002345	Action tremor
HP:0002359	Frequent falls
HP:0002375	Hypokinesia
HP:0002421	Poor head control
HP:0002460	Distal muscle weakness
HP:0002495	Impaired vibratory sensation
HP:0002540	Inability to walk
HP:0002650	Scoliosis
HP:0002715	Abnormality of the immune system
HP:0002747	Respiratory insufficiency due to muscle weakness
HP:0002751	Kyphoscoliosis
HP:0002839	Urinary bladder sphincter dysfunction
HP:0002857	Genu valgum
HP:0002922	Increased CSF protein concentration
HP:0002936	Distal sensory impairment
HP:0003202	Skeletal muscle atrophy
HP:0003236	Elevated circulating creatine kinase activity
HP:0003376	Steppage gait
HP:0003378	Axonal degeneration/regeneration
HP:0003380	Decreased number of peripheral myelinated nerve fibers
HP:0003382	Hypertrophic nerve changes
HP:0003383	Onion bulb formation
HP:0003431	Decreased motor nerve conduction velocity
HP:0003448	Decreased sensory nerve conduction velocity
HP:0003449	Cold-induced muscle cramps
HP:0003469	Peripheral dysmyelination
HP:0003474	Somatic sensory dysfunction
HP:0003477	Peripheral axonal neuropathy
HP:0003481	Segmental peripheral demyelination/remyelination
HP:0003484	Upper limb muscle weakness

GWAS associations

2 associations:

Study	Trait	p-value
GCST008156_98	Hip circumference adjusted for BMI	4e-7
GCST001523_16	Visceral adipose tissue adjusted for BMI	8e-6

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D002607	Charcot-Marie-Tooth Disease	C10.500.300.200; C10.574.500.495.200; C10.668.829.800.300.200; C16.131.666.300.200; C16.320.400.375.200
C564333	Charcot-Marie-Tooth Disease, Dominant Intermediate D *(supp.)*
C535417	Charcot-Marie-Tooth disease, Type 2J *(supp.)*
C535301	Charcot-Marie-Tooth disease, Type 4E *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
trichostatin A	affects cotreatment, increases expression	3
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Nickel	decreases expression	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	increases expression	1
Copper	increases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
N-Nitrosopyrrolidine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Quercetin	increases expression	1
Thiram	increases expression	1

Cellosaurus cell lines

12 cell lines: 8 induced pluripotent stem cell, 3 transformed cell line, 1 finite cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_1K24	GM05148	Finite cell line	Male
CVCL_1K25	GM05149	Transformed cell line	Male
CVCL_B0IG	GM28252	Induced pluripotent stem cell	Male
CVCL_JW96	NYSCF-AG0003-01-MR	Induced pluripotent stem cell	Female
CVCL_JW98	NYSCF-AG0007-01-MR	Induced pluripotent stem cell	Male
CVCL_JX00	NYSCF-AG0009-02-MR	Induced pluripotent stem cell	Male
CVCL_JX10	NYSCF-AG0019-01-MR	Induced pluripotent stem cell	Male
CVCL_M916	GM23721	Transformed cell line	Female
CVCL_QX72	KUCFRi002-A	Induced pluripotent stem cell	Female
CVCL_RZ99	NYSCF-AG0001-01-MR	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 299 trials:

NCT	Phase	Status	Title
NCT00380965	Phase 4	COMPLETED	Evaluation of the Efficacy of Cesamet™ for the Treatment of Pain in Patients With Chemotherapy-Induced Neuropathy
NCT00487981	Phase 4	TERMINATED	Spinal Cord Stimulation for Painful Diabetic Neuropathy
NCT00904202	Phase 4	COMPLETED	A Study Of Lidocaine Patch 5% Alone, Gabapentin Alone, And Lidocaine Patch 5% And Gabapentin In Combination For The Relief Of Pain In Patients With Diverse Peripheral Neuropathic Pain Conditions
NCT01192113	Phase 4	COMPLETED	Safety and Efficacy of Mecobalamin Injection in Peripheral Neuropathies Patients (Study JGAZSY091109)
NCT01373983	Phase 4	COMPLETED	Intrathecal Bolus Doses of Ziconotide
NCT01458015	Phase 4	TERMINATED	Tapentadol Versus Oxycodone - a Mechanism-based Treatment Approach in Neuropathic Pain
NCT02074267	Phase 4	COMPLETED	Clinical Study for Assessment of the Efficacy of Gabapentin (Carbatin and Neurontin) in Patients With Neuropathy Pain
NCT02372149	Phase 4	UNKNOWN	IVIg for Demyelination in Diabetes Mellitus
NCT02670161	Phase 4	ENROLLING_BY_INVITATION	Quality Improvement and Practice Based Research in Neurology Using the EMR
NCT07022938	Phase 4	COMPLETED	Nutritional Supplement for Treating Chemotherapy Induced Neuropathy
NCT07025005	Phase 4	RECRUITING	Fenofibrate Role in the Prophylaxis From Peripheral Neuropathy Induced by Bortezomib, Lenalidomide and Dexamethasone (VRd) Protocol in the Treatment of Patients With Multiple Myeloma (MM)
NCT04762758	Phase 3	UNKNOWN	Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
NCT00058071	Phase 3	COMPLETED	Amifostine in Treating Peripheral Neuropathy in Patients Who Have Received Chemotherapy for Cancer
NCT00125268	Phase 3	TERMINATED	Near Infrared Light for the Treatment of Painful Peripheral Neuropathy
NCT00195013	Phase 3	COMPLETED	Randomized Placebo-Controlled Trial of Glutamine for Breast Cancer Patients With Peripheral Neuropathy
NCT00232141	Phase 3	COMPLETED	Study of Pregabalin Versus Placebo in the Treatment of Nerve Pain Associated With HIV Neuropathy
NCT00264875	Phase 3	COMPLETED	Open Label Safety And Efficacy Study Of Pregabalin In Subjects With Nerve Pain Asociated With Human Immunodeficiency Virus (HIV) Neuropathy
NCT00369564	Phase 3	COMPLETED	Glutamic Acid in Reducing Nerve Damage Caused by Vincristine in Young Patients With Cancer
NCT00471445	Phase 3	COMPLETED	Topical Amitriptyline and Ketamine Cream in Treating Peripheral Neuropathy Caused by Chemotherapy in Cancer Patients
NCT00489411	Phase 3	COMPLETED	Duloxetine in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer
NCT00710554	Phase 3	COMPLETED	A Study of Sativex® for Pain Relief of Peripheral Neuropathic Pain, Associated With Allodynia
NCT00711880	Phase 3	COMPLETED	A Study of Sativex® for Relief of Peripheral Neuropathic Pain Associated With Allodynia.
NCT00713323	Phase 3	COMPLETED	A Study to Compare the Safety and Tolerability of Sativex® in Patients With Neuropathic Pain.
NCT00713817	Phase 3	COMPLETED	A Study to Determine the Maintenance of Effect After Long-term Treatment of Sativex® in Subjects With Neuropathic Pain
NCT00775645	Phase 3	COMPLETED	S0715: Acetyl-L-Carnitine in Preventing Neuropathy in Women With Stage I, II, or IIIA Breast Cancer Undergoing Chemo
NCT00872352	Phase 3	UNKNOWN	Evaluation of Bortezomib Induced Peripheral Neuropathy of Multiple Myeloma (MM) Patients
NCT00998738	Phase 3	TERMINATED	Calcium and Magnesium in Preventing Peripheral Neuropathy Caused by Ixabepilone in Patients With Breast Cancer
NCT01049217	Phase 3	TERMINATED	Pregabalin Versus Placebo In The Treatment Of Neuropathic Pain Associated With HIV Neuropathy
NCT01099449	Phase 3	COMPLETED	Calcium Gluconate and Magnesium Sulfate in Preventing Neurotoxicity in Patients With Colon Cancer or Rectal Cancer Receiving Oxaliplatin-Based Combination Chemotherapy
NCT01288937	Phase 3	TERMINATED	A Placebo Controlled, Randomized, Double Blind Trial of Milnacipran for the Treatment of Idiopathic Neuropathy Pain
NCT01492920	Phase 3	WITHDRAWN	Acetyl-L-Carnitine Hydrochloride in Preventing Peripheral Neuropathy in Patients With Recurrent Ovarian Epithelial Cancer, Primary Peritoneal Cavity Cancer, or Fallopian Tube Cancer Undergoing Chemotherapy
NCT01775449	Phase 3	COMPLETED	Prevention of Oxaliplatin-induced Neuropathic Pain by a Specific Diet
NCT02024191	Phase 3	UNKNOWN	The Role of Glutamine for Preventing Oxaliplatin-Induced Peripheral Neuropathy
NCT02217267	Phase 3	COMPLETED	Long Term Outcome After Serial Lidocaine Infusion in Peripheral Neuropathic Pain
NCT02294149	Phase 3	UNKNOWN	Vit D3 and Omega 3 in Chemo Induced Neuropathy
NCT02311907	Phase 3	COMPLETED	Glutathione in Preventing Peripheral Neuropathy Caused by Paclitaxel and Carboplatin in Patients With Ovarian Cancer, Fallopian Tube Cancer, and/or Primary Peritoneal Cancer
NCT06071936	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06071975	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT06071988	Phase 3	UNKNOWN	Long Term Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Traumatic or Post-operative Peripheral Neuropathy
NCT06072573	Phase 3	UNKNOWN	Efficacy and Tolerability of AP707 in Patients With Chronic Pain Due to Diabetic Polyneuropathy
NCT07287592	Phase 3	NOT_YET_RECRUITING	Glutamine for the Prophylaxis of Vincristine-induced Neuropathy in Children and Adolescents With Cancer.
NCT00271635	Phase 2	COMPLETED	Ascorbic Acid Treatment in CMT1A Trial (AATIC)
NCT01401257	Phase 2	COMPLETED	Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
NCT02561702	Phase 2	COMPLETED	Mexiletine for Muscle Cramps in Charcot Marie Tooth Disease
NCT02967679	Phase 2	COMPLETED	SERENDEM : MD1003 in Patients Suffering From Demyelinating Neuropathies, an Open Label Pilot Study
NCT03124459	Phase 2	TERMINATED	Study of ACE-083 in Patients With Charcot-Marie-Tooth Disease
NCT03254199	Phase 2	TERMINATED	A Study to Assess the Safety and Effectiveness of FLX-787 in Subjects With Charcot-Marie-Tooth Disease Experiencing Muscle Cramps.
NCT03943290	Phase 2	TERMINATED	Extension Study to Evaluate the Long-Term Effects of ACE-083 in Patients With Facioscapulohumeral Muscular Dystrophy (FSHD) and Charcot-Marie Tooth (CMT) Disease Types 1 and X (CMT1 and CMTX)
NCT05777226	Phase 2	UNKNOWN	Research of SORD-CMT Natural History and Epalrestat Treatment
NCT06482437	Phase 2	COMPLETED	Safety and Efficacy of NMD670 in Adult Patients With Type 1 and Type 2 Charcot-Marie-Tooth Disease
NCT00006072	Phase 2	UNKNOWN	A Study of Rituxan in the Treatment of Polyneuropathies Associated With Serum IgM Autoantibodies
NCT00365768	Phase 2	COMPLETED	Glutamine in Treating Neuropathy Caused by Vincristine in Young Patients With Lymphoma, Leukemia, or Solid Tumors
NCT00475904	Phase 2	COMPLETED	A Comparison of EpiCept™ NP-1 Topical Cream vs. Oral Gabapentin in Postherpetic Neuralgia (PHN)
NCT00528593	Phase 2	WITHDRAWN	Epoetin Alfa for HIV-Associated Neuropathy Trial
NCT00603265	Phase 2	COMPLETED	Safety and Efficacy Study of ADL5859 in Participants With Neuropathic Pain Associated With Diabetic Peripheral Neuropathy
NCT00665652	Phase 2	TERMINATED	Study of Lenalidomide as a Treatment for Neuropathy Associated With Monoclonal Gammopathy of Undetermined Significance
NCT00863057	Phase 2	TERMINATED	Combination Pain Therapy in HIV Neuropathy
NCT00891618	Phase 2	COMPLETED	Acupuncture for Chemo-Induced Peripheral Neuropathy
NCT00952848	Phase 2	COMPLETED	Electrical Stimulation Therapy Using the MC5-A Scrambler in Reducing Peripheral Neuropathy Caused by Chemotherapy
NCT01135251	Phase 2	COMPLETED	Safety and Preliminary Evidence of Efficacy of Escalating Doses of Dimiracetam in AIDS Patients With Painful Neuropathy