MECP2

Summary

MECP2 (methyl-CpG binding protein 2, HGNC:6990) is a protein-coding gene on chromosome Xq28, encoding Methyl-CpG-binding protein 2 (P51608). Chromosomal protein that binds to methylated DNA. It is haploinsufficient (ClinGen: sufficient evidence).

DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. In contrast to other MBD family members, MECP2 is X-linked and subject to X inactivation. MECP2 is dispensible in stem cells, but is essential for embryonic development. MECP2 gene mutations are the cause of most cases of Rett syndrome, a progressive neurologic developmental disorder and one of the most common causes of cognitive disability in females. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 4204 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Rett syndrome (Definitive, ClinGen) — +6 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 2,151 total — 585 pathogenic, 239 likely-pathogenic
• Phenotypes (HPO): 255
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 35 downstream targets (CollecTRI)
• MANE Select transcript: NM_001110792

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6990
Approved symbol	MECP2
Name	methyl-CpG binding protein 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000169057
Ensembl biotype	protein_coding
OMIM	300005
Entrez	4204

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 15 protein_coding_CDS_not_defined, 7 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron

ENST00000303391, ENST00000369957, ENST00000407218, ENST00000415944, ENST00000453960, ENST00000460227, ENST00000463644, ENST00000481807, ENST00000486506, ENST00000488293, ENST00000496908, ENST00000611468, ENST00000625300, ENST00000626422, ENST00000627864, ENST00000628176, ENST00000629277, ENST00000630151, ENST00000631210, ENST00000637467, ENST00000637533, ENST00000637791, ENST00000637917, ENST00000638041, ENST00000674996, ENST00000675526, ENST00000675841, ENST00000676382, ENST00000700484, ENST00000713611

RefSeq mRNA: 10 — MANE Select: NM_001110792 NM_001110792, NM_001316337, NM_001369391, NM_001369392, NM_001369393, NM_001369394, NM_001386137, NM_001386138, NM_001386139, NM_004992

CCDS: CCDS14741, CCDS48193

Canonical transcript exons

ENST00000453960 — 3 exons

Exon	Start	End
ENSE00001877797	154097604	154097717
ENSE00003772050	154032207	154032557
ENSE00004020471	154021573	154031450

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.5136 / max 910.2235, expressed in 1817 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200964	26.9334	1816
200965	1.2980	884
200958	0.9373	145
200956	0.4253	65
200961	0.1980	49
200954	0.1752	20
200959	0.1483	47
200957	0.1351	44
200955	0.1329	15
200953	0.0711	26

Top tissues by expression

299 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
paraflocculus	UBERON:0005351	97.92	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.01	gold quality
sural nerve	UBERON:0015488	96.30	gold quality
frontal pole	UBERON:0002795	95.89	gold quality
colonic epithelium	UBERON:0000397	95.84	gold quality
middle frontal gyrus	UBERON:0002702	95.66	gold quality
cerebellar vermis	UBERON:0004720	95.09	gold quality
calcaneal tendon	UBERON:0003701	94.44	gold quality
postcentral gyrus	UBERON:0002581	92.41	gold quality
tendon	UBERON:0000043	91.59	gold quality
parietal lobe	UBERON:0001872	91.22	gold quality
blood	UBERON:0000178	91.07	gold quality
corpus callosum	UBERON:0002336	90.35	gold quality
mucosa of stomach	UBERON:0001199	90.32	gold quality
bone marrow cell	CL:0002092	90.24	gold quality
adrenal tissue	UBERON:0018303	90.22	gold quality
granulocyte	CL:0000094	90.17	gold quality
gastrocnemius	UBERON:0001388	89.95	gold quality
muscle of leg	UBERON:0001383	89.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.82	gold quality
monocyte	CL:0000576	89.49	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	89.38	gold quality
right lung	UBERON:0002167	89.22	gold quality
mononuclear cell	CL:0000842	89.00	gold quality
leukocyte	CL:0000738	88.98	gold quality
cerebellum	UBERON:0002037	88.88	gold quality
parotid gland	UBERON:0001831	88.87	silver quality
left ovary	UBERON:0002119	88.84	gold quality
popliteal artery	UBERON:0002250	88.73	gold quality
tibial artery	UBERON:0007610	88.73	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.38
E-MTAB-7381	no	587.84
E-MTAB-7606	no	174.62

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

35 targets.

Target	Regulation
ABCB1	Unknown
ALOX5	Unknown
BDNF	Unknown
CCND1	Repression
CDKL5	Unknown
CRH	Repression
DLL1	Repression
DLX5	Unknown
EHMT2	Repression
ESR1	Repression
FKBP5	Repression
FOXP3
FXYD1	Repression
GAD1	Repression
GRIA2	Repression
GRIN2B	Repression
HDAC7	Repression
IGFBP3	Repression
MEF2C	Repression
MGMT	Unknown
MYOCD	Repression
NOTCH1	Repression
NOX4	Repression
PCDH7	Repression
PCDHB1	Repression
PLA2G7	Repression
PTPN1	Unknown
RBFOX1	Repression
RELN	Repression
SGK1	Repression

Upstream regulators (CollecTRI, top): EGR2, ESR1, GATA2, HOXB13, MBD2, MEF2C, PITX2, SP1, TFCP2

miRNA regulators (miRDB)

647 targeting MECP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4776-3P	100.00	68.73	1340

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• mutation and role in Rett syndrome (PMID:11432961)
• mutation analysis in Italian Rett patients (PMID:11462237)
• Reported five novel frameshift mutations (named 345delC, 895del202, 989ins18del8, 996insAG and 1124del53) in exon 3 and 4 of the MECP2 gene. (PMID:11524737)
• Mutations in MECP2 were identified from most of the patients with classical and variant RTT (25 of 27 cases). (PMID:11524741)
• represses LINE-1 expression and retrotransposition but not Alu transcription (PMID:11691937)
• somatic mosaicism for a MECP2 mutation in females with Rett syndrome (PMID:11768391)
• A neurologic disorder associated with A140V MECP2 mutation affects males more severely than females of the same family. (PMID:11805248)
• MeCP2 may become abundant once a neuron has reached a certain degree of maturity, and this may explain some aspects of the RTT phenotype. (PMID:11809720)
• MeCP2 mutations have been functionally characterized in male patients with X linked mental retardation. (PMID:11836365)
• mutation hot spot for nonspecific X-linked mental retardation in the MECP2 gene causes the PPM-X syndrome (PMID:11885030)
• a MECP2 mutation associated with Rett syndrome in females could lead to a similar phenotype in males as a result of somatic mosaicism. (PMID:11896459)
• Some mutations found in mentally disabled boys are also found in normal relatives. (PMID:11896461)
• MECP2 gene mutations in six Chinese females with Rett syndrome. reduction in N-acetylaspartate/total creatine ratio may not be related to the MECP2 mutation. (PMID:11955928)
• screening of MECP2 gene mutations in Swedish Rett Syndrome clusters (PMID:12081725)
• MECP2 mutations in Rett syndrome adversely affect lymphocyte growth, but do not affect imprinted gene expression in blood or brain. Results do not support an essential role for either MeCP2 or HDAC in the silencing of several imprinted genes. (PMID:12107440)
• the spectrum of MECP2 mutations in Chinese patients with Rett syndrome (PMID:12111643)
• low frequency of mutations in mentally retarded males (PMID:12111644)
• MECP2 gene nucleotide changes affect pathology in males: at c.1282 G>A (G428S) severe encephalopathy, at C.1030 C>T (R344W) a Rett-like phenotype, at c.590 C>T (T197M) (congenital encephalopathy, microcephaly, and severe developmental delay). (PMID:12161600)
• Mutations in MECP2 gene were found over 50% of patients with Rett syndrome in China. (PMID:12170461)
• High degree of genetic heterogeneity in Rett patients (PMID:12180070)
• Review–Rett syndrome and MeCP2: linking epigenetics and neuronal function (PMID:12442230)
• MECP2 gene mutation is implicated in Rett’s syndrome. (PMID:12449561)
• Methyl-CpG-binding protein 2 but not Sin3 is found in both nuclear and postsynaptic compartments of neurons in normal brain. (PMID:12535940)
• Elevated expression of MECP2 is acquired during postnatal brain development and is correlated with alternative polyadenylation. (PMID:12545250)
• Results show that methyl-CpG binding domain protein 1 (MBD1) is expressed in tumor cells, but methyl-CpG binding domain protein 2 (MBD2) and methyl CpG binding protein 2 (MeCP2) are not. (PMID:12646234)
• conclude that MECP2 mutations (missense or late truncating) can be found in girls with an IQ close to 45 and a history of Preserved Speech Variant of Rett syndrome. MECP2 mutations are not found in patients in which autism remains stable over the years. (PMID:12707946)
• genotype-phenotype relationship of the R133C mutation (PMID:12746406)
• MECP2 mutations in mentally retarded males are far more rare than initially thought (PMID:14529314)
• MECP2 gene mutations are correlated with non-syndromic X-linked mental retardation phenotypes. (PMID:14598336)
• Strong association seen between estrogen receptor (ER) status and MeCP2 mRNA expression; MeCP2, regulated by ER, may play key role in breast tissue differentiation (PMID:14612906)
• This case deserves attention in order, among other things, to provide important clues to better understand the puzzling battery of neuroimpairments and behavioural abnormalities met in classical Rett phenotypes and Rett variants defined thus far. (PMID:14623222)
• MeCP2 acts as a corepressor of PU.1 probably due to facilitating complex formation with mSin3A and HDACs. (PMID:14647463)
• Our data provide compelling evidence for the existence of a novel MeCP2 molecular form, most likely the result of post-translational modification. This novel form of MeCP2 is present in both brain and lymphoid cells. (PMID:14649548)
• The regulation of MeCP2 abundance is related to human brain development, being expressed in neurons when they appear mature. In the Rett syndrome brain, fewer neurons express MeCP2 than in the normal brain. (PMID:14649549)
• Fifteen large deletions found in a deletion prone region in MECP2 in 130 female Rett syndrome patients. (PMID:14974082)
• We screened 24 of the sporadic AS angelman syndrome) cases without detectable UBE3A mutations for mutations of MECP2, but found none. (PMID:14981718)
• description of a previously unknown MeCP2 isoform (PMID:15034579)
• Phenotypic manifestations of mutations in MECP2 were evaluated in classical and atypical Rett syndrome. (PMID:15057977)
• higher frequency of missense and 3’-UTR variants was found in autism (PMID:15211631)
• The average mRNA level of Dnmt1 gene from cancerous tissue was higher and that of mbd2 gene from cancerous tissue was lower than that from non-cancerous tissue (PMID:15526354)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mecp2	ENSDARG00000014218
mus_musculus	Mecp2	ENSMUSG00000031393
rattus_norvegicus	Mecp2	ENSRNOG00000056659

Paralogs (1): MBD4 (ENSG00000129071)

Protein

Protein identifiers

Methyl-CpG-binding protein 2 — P51608 (reviewed: P51608)

All UniProt accessions (11): P51608, A0A0D9SEX1, A0A0S2Z401, A0A140VKC4, A0A6Q8PF93, A0A6Q8PHQ3, A0AAQ5BGE7, B5MCB4, C9JH89, D3YJ43, H7BY72

UniProt curated annotations — full annotation on UniProt →

Function. Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).

Subunit / interactions. Interacts with FNBP3. Interacts with CDKL5. Interacts with ATRX; MECP2 recruits ATRX to pericentric heterochromatin in neuronal cells. Interacts with NCOR2. Interacts with TBL1XR1; bridges interaction between MECP2 and NCOR1. Interacts with TBL1X; recruits TBL1X to the heterochromatin foci.

Subcellular location. Nucleus.

Tissue specificity. Present in all adult somatic tissues tested.

Post-translational modifications. Phosphorylated on Ser-423 in brain upon synaptic activity, which attenuates its repressor activity and seems to regulate dendritic growth and spine maturation.

Disease relevance. Angelman syndrome (AS) [MIM:105830] A neurodevelopmental disorder characterized by severe motor and intellectual retardation, ataxia, frequent jerky limb movements and flapping of the arms and hands, hypotonia, seizures, absence of speech, frequent smiling and episodes of paroxysmal laughter, open-mouthed expression revealing the tongue. The disease may be caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, X-linked, syndromic 13 (MRXS13) [MIM:300055] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXS13 patients manifest intellectual disability associated with other variable features such as spasticity, episodes of manic depressive psychosis, increased tone and macroorchidism. The disease is caused by variants affecting the gene represented in this entry. Rett syndrome (RTT) [MIM:312750] An X-linked dominant neurodevelopmental disorder, and one of the most common causes of intellectual disability in females. Patients appear to develop normally until 6 to 18 months of age, then gradually lose speech and purposeful hand movements, and develop microcephaly, seizures, autism, ataxia, intellectual disability and stereotypic hand movements. After initial regression, the condition stabilizes and patients usually survive into adulthood. The disease is caused by variants affecting the gene represented in this entry. Autism, X-linked 3 (AUTSX3) [MIM:300496] A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate intellectual disability. The disease may be caused by variants affecting the gene represented in this entry. Encephalopathy, neonatal severe, due to MECP2 mutations (ENS-MECP2) [MIM:300673] A neurodevelopmental disorder characterized by severe neonatal encephalopathy, developmental delay, intellectual disability, microcephaly, seizures. Additional features include respiratory insufficiency and central hypoventilation, gastroesophageal reflux, axial hypotonia, hyperreflexia and dyskinetic movements. The disease is caused by variants affecting the gene represented in this entry. The MECP2 gene is mutated in Rett syndrome, a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Additional reports have confirmed a severe phenotype in males with Rett syndrome-associated MECP2 mutations. Intellectual developmental disorder, X-linked, syndromic, Lubs type (MRXSL) [MIM:300260] A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSL patients manifest intellectual disability associated with variable features. They include swallowing dysfunction and gastroesophageal reflux with secondary recurrent respiratory infections, hypotonia, mild myopathy and characteristic facies such as downslanting palpebral fissures, hypertelorism and a short nose with a low nasal bridge. The disease is caused by variants affecting the gene represented in this entry. Increased dosage of MECP2 due to gene duplication appears to be responsible for the intellectual disability phenotype.

Miscellaneous. Ten times higher expression levels than isoform A in brain.

Isoforms (2)

UniProt ID	Names	Canonical?
P51608-1	A, Beta	yes
P51608-2	B, Alpha

RefSeq proteins (10): NP_001104262, NP_001303266, NP_001356320, NP_001356321, NP_001356322, NP_001356323, NP_001373066, NP_001373067, NP_001373068, NP_004983 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001739	Methyl_CpG_DNA-bd	Domain
IPR016177	DNA-bd_dom_sf	Homologous_superfamily
IPR017353	Me_CpG-bd_MeCP2	Family
IPR045138	MeCP2/MBD4	Family

Pfam: PF01429

UniProt features (116 total): sequence variant 74, modified residue 10, strand 7, compositionally biased region 6, region of interest 5, sequence conflict 3, turn 3, helix 3, DNA-binding region 2, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
6OGK	X-RAY DIFFRACTION	1.65
6OGJ	X-RAY DIFFRACTION	1.8
6YWW	X-RAY DIFFRACTION	2.1
5BT2	X-RAY DIFFRACTION	2.2
6C1Y	X-RAY DIFFRACTION	2.3
3C2I	X-RAY DIFFRACTION	2.5
1QK9	SOLUTION NMR
8AJR	SOLUTION NMR
8ALQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51608-F1	57.25	0.09

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 (10): 13, 80, 116, 162, 216, 229, 321, 423, 426, 449

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-8986944	Transcriptional Regulation by MECP2
R-HSA-9022534	Loss of MECP2 binding ability to 5hmC-DNA
R-HSA-9022535	Loss of phosphorylation of MECP2 at T308
R-HSA-9022537	Loss of MECP2 binding ability to the NCoR/SMRT complex
R-HSA-9022538	Loss of MECP2 binding ability to 5mC-DNA
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9022699	MECP2 regulates neuronal receptors and channels
R-HSA-9022702	MECP2 regulates transcription of neuronal ligands
R-HSA-9022707	MECP2 regulates transcription factors
R-HSA-9022927	MECP2 regulates transcription of genes involved in GABA signaling
R-HSA-9725371	Nuclear events stimulated by ALK signaling in cancer

MSigDB gene sets: 1020 (showing top): GOBP_DENDRITE_DEVELOPMENT, GOBP_MEMORY, GOBP_HINDBRAIN_DEVELOPMENT, AP1_01, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_METENCEPHALON_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_RESPIRATORY_GASEOUS_EXCHANGE_BY_RESPIRATORY_SYSTEM, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_BLOOD_PRESSURE

GO Biological Process (65): negative regulation of transcription by RNA polymerase II (GO:0000122), behavioral fear response (GO:0001662), response to hypoxia (GO:0001666), startle response (GO:0001964), nervous system process involved in regulation of systemic arterial blood pressure (GO:0001976), regulation of respiratory gaseous exchange by nervous system process (GO:0002087), inositol metabolic process (GO:0006020), L-glutamine metabolic process (GO:0006541), biogenic amine metabolic process (GO:0006576), Notch signaling pathway (GO:0007219), synapse assembly (GO:0007416), respiratory gaseous exchange by respiratory system (GO:0007585), long-term memory (GO:0007616), intracellular protein localization (GO:0008104), glucocorticoid metabolic process (GO:0008211), adult locomotory behavior (GO:0008344), visual learning (GO:0008542), post-embryonic development (GO:0009791), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), glial cell proliferation (GO:0014009), dendrite development (GO:0016358), negative regulation of angiogenesis (GO:0016525), proprioception (GO:0019230), sensory perception of pain (GO:0019233), cerebellum development (GO:0021549), ventricular system development (GO:0021591), heterochromatin formation (GO:0031507), cardiolipin metabolic process (GO:0032048), social behavior (GO:0035176), neuron maturation (GO:0042551), negative regulation of neuron apoptotic process (GO:0043524), negative regulation of blood vessel endothelial cell migration (GO:0043537), negative regulation of gene expression via chromosomal CpG island methylation (GO:0044027), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), phosphatidylcholine metabolic process (GO:0046470), catecholamine secretion (GO:0050432), negative regulation of smooth muscle cell differentiation (GO:0051151), response to other organism (GO:0051707)

GO Molecular Function (14): nucleic acid binding (GO:0003676), DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), mRNA binding (GO:0003729), methyl-CpG binding (GO:0008327), double-stranded methylated DNA binding (GO:0010385), siRNA binding (GO:0035197), molecular adaptor activity (GO:0060090), histone reader activity (GO:0140566), molecular condensate scaffold activity (GO:0140693), promoter-specific chromatin binding (GO:1990841), protein binding (GO:0005515)

GO Cellular Component (10): heterochromatin (GO:0000792), obsolete extracellular space (GO:0005615), nucleus (GO:0005634), nucleoplasm (GO:0005654), centrosome (GO:0005813), cytosol (GO:0005829), postsynapse (GO:0098794), chromatin (GO:0000785), cytoplasm (GO:0005737), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional Regulation by MECP2	5
Loss of function of MECP2 in Rett syndrome	4
Generic Transcription Pathway	1
Signaling by ALK fusions and activated point mutants	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
binding	4
negative regulation of DNA-templated transcription	2
nervous system process	2
multicellular organismal process	2
nucleic acid binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
behavioral defense response	1
fear response	1
response to stress	1
response to decreased oxygen levels	1
response to external stimulus	1
neuromuscular process	1
regulation of systemic arterial blood pressure	1
respiratory gaseous exchange by respiratory system	1
regulation of respiratory system process	1
polyol metabolic process	1
L-amino acid metabolic process	1
proteinogenic amino acid metabolic process	1
amine metabolic process	1
cell surface receptor signaling pathway	1
nervous system development	1
cell junction assembly	1
synapse organization	1
memory	1
macromolecule localization	1
steroid metabolic process	1
locomotory behavior	1
adult behavior	1
visual behavior	1
associative learning	1
multicellular organism development	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
transcription coregulator activity	1
RNA binding	1
nucleotide binding	1

Protein interactions and networks

STRING

3950 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MECP2	DNMT1	P26358	997
MECP2	SIN3A	Q96ST3	997
MECP2	HDAC1	Q13547	996
MECP2	HDAC2	Q92769	994
MECP2	RCOR1	Q9UKL0	992
MECP2	NCOR1	O75376	992
MECP2	SUV39H1	O43463	991
MECP2	CREB1	P16220	988
MECP2	ATRX	P46100	970
MECP2	CDKL5	O76039	963
MECP2	YBX1	P16990	958
MECP2	DNMT3A	Q9Y6K1	945
MECP2	FMR1	Q06787	912
MECP2	LBR	Q14739	896
MECP2	DGCR8	Q8WYQ5	892

IntAct

239 interactions, top by confidence:

A	B	Type	Score
PPIE	AQR	psi-mi:“MI:0914”(association)	0.810
KLHL20	MECP2	psi-mi:“MI:0915”(physical association)	0.670
MECP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
MECP2	Ncor1	psi-mi:“MI:0915”(physical association)	0.590
MECP2	Ncor1	psi-mi:“MI:0407”(direct interaction)	0.590
MECP2	Tbl1x	psi-mi:“MI:0407”(direct interaction)	0.590
MECP2	Tbl1x	psi-mi:“MI:0915”(physical association)	0.590
DEAF1	MECP2	psi-mi:“MI:0915”(physical association)	0.590
MECP2		psi-mi:“MI:0915”(physical association)	0.560
MECP2	HSPB1	psi-mi:“MI:0915”(physical association)	0.560
AP2B1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
CTNNB1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
EYA3	MECP2	psi-mi:“MI:0915”(physical association)	0.560
LYN	MECP2	psi-mi:“MI:0915”(physical association)	0.560
MSH5	MECP2	psi-mi:“MI:0915”(physical association)	0.560
NAP1L3	MECP2	psi-mi:“MI:0915”(physical association)	0.560
SMARCB1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
SMN1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
TXN	MECP2	psi-mi:“MI:0915”(physical association)	0.560
BRK1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
RNF112	MECP2	psi-mi:“MI:0915”(physical association)	0.560
COPS3	MECP2	psi-mi:“MI:0915”(physical association)	0.560
PIAS1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
STX11	MECP2	psi-mi:“MI:0915”(physical association)	0.560
IQSEC1	MECP2	psi-mi:“MI:0915”(physical association)	0.560
KAT5	MECP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1499): MECP2 (Biochemical Activity), MECP2 (Affinity Capture-RNA), MECP2 (Proximity Label-MS), MECP2 (Proximity Label-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS), MECP2 (Affinity Capture-MS)

ESM2 similar proteins: A4D2P6, A6NNA2, A7MD48, A8IHN8, C9JLR9, G3V9M2, O00287, O95644, P04198, P12755, P18444, P49796, P49797, P51608, P55199, Q00566, Q08DA0, Q0PHV7, Q13387, Q1W6H9, Q29RS4, Q3UPL5, Q3YEC7, Q4QQU1, Q4VA45, Q5XKK7, Q61976, Q6NV74, Q6R891, Q7Z6J2, Q80WV7, Q80YR4, Q86UK7, Q8BKA3, Q8N554, Q8R149, Q8R4T5, Q8TF61, Q8VCG9, Q95LG8

Diamond homologs: O95243, O95983, P51608, Q00566, Q0IGK1, Q95LG8, Q9UBB5, Q9YDP0, Q9Z2D6, Q9Z2D7, Q9Z2D8, Q9Z2E1, A0A1B0GVZ6, A6NDZ8, A6NE82, A6NJ08, Q8NHZ7, Q8WWY6, Q9D9H3, Q9UIS9, Q9Z2E2, Q9VGA4, Q9FZP6, Q9LTJ1, Q9LYB9, O08550, Q27746, Q5EA28, Q9CWW7, Q9P0U4, Q9UMN6, Q7LX22, A0A1L8GSA2, A0JP82

SIGNOR signaling

49 interactions.

A	Effect	B	Mechanism
MECP2	“down-regulates quantity by repression”	ESR1	“transcriptional regulation”
MEF2C	“up-regulates quantity by expression”	MECP2	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	MGMT	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	CCND1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	TFF1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	RELN	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	GAD1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	IGFBP3	“transcriptional regulation”
MECP2	“up-regulates quantity by expression”	miR-199a	“post transcriptional regulation”
MECP2	“up-regulates activity”	DNMT1	binding
MECP2	“down-regulates quantity by repression”	PTPN1	“transcriptional regulation”
HIPK2	“up-regulates activity”	MECP2	phosphorylation
MECP2	up-regulates	Apoptosis
MECP2	“down-regulates quantity by repression”	MET	“post transcriptional regulation”
CHUK	“up-regulates activity”	MECP2	phosphorylation
MECP2	“down-regulates quantity by repression”	BDNF	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	DLX5	“transcriptional regulation”
miR-132	“down-regulates quantity by repression”	MECP2	“post transcriptional regulation”
MECP2	“down-regulates quantity by repression”	FKBP5	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	SGK1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	CRH	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	DLL1	“transcriptional regulation”
MECP2	“down-regulates quantity by repression”	NOTCH1	“transcriptional regulation”
MECP2	“up-regulates quantity by expression”	SST	“post transcriptional regulation”
MECP2	“up-regulates quantity by expression”	OPRK1	“post transcriptional regulation”
MECP2	“up-regulates quantity by expression”	GAMT	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of transcription cofactors	5	17.9×	7e-04
Leishmania infection	6	14.4×	6e-04
Parasitic Infection Pathways	6	14.4×	6e-04
SUMO E3 ligases SUMOylate target proteins	5	13.1×	2e-03
SUMOylation of DNA damage response and repair proteins	6	12.9×	7e-04
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	6	12.9×	7e-04
SUMOylation	5	12.0×	2e-03
Transcriptional regulation by RUNX1	5	10.8×	3e-03

GO biological processes:

GO term	Partners	Fold	FDR
double-strand break repair	5	11.3×	8e-03
nucleosome assembly	6	9.4×	6e-03
in utero embryonic development	10	8.0×	2e-04
angiogenesis	8	5.5×	8e-03
negative regulation of apoptotic process	11	4.2×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

2151 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	585
Likely pathogenic	239
Uncertain significance	525
Likely benign	402
Benign	167

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1006548	NM_001110792.2(MECP2):c.933_968del (p.Leu313_Val324del)	Pathogenic
1069856	NC_000023.10:g.(?_153296154)_153302832del	Pathogenic
1071768	NM_001110792.2(MECP2):c.74C>G (p.Ser25Ter)	Pathogenic
1071811	NM_001110792.2(MECP2):c.674dup (p.Glu226fs)	Pathogenic
1073280	NM_001110792.2(MECP2):c.984_1023del (p.Lys329fs)	Pathogenic
1075736	NC_000023.10:g.(?153292375)(153296122_?)del	Pathogenic
1075737	NC_000023.10:g.(?153357622)(153363142_?)del	Pathogenic
1076185	NM_001110792.2(MECP2):c.231del (p.Glu78fs)	Pathogenic
1076937	NM_001110792.2(MECP2):c.954_962del (p.Lys319_Arg321del)	Pathogenic
11809	NM_001110792.2(MECP2):c.433C>T (p.Arg145Cys)	Pathogenic
11815	NM_001110792.2(MECP2):c.844C>T (p.Arg282Ter)	Pathogenic
11817	NM_001110792.2(MECP2):c.1216G>T (p.Glu406Ter)	Pathogenic
11818	NM_001110792.2(MECP2):c.203_204del (p.Pro68fs)	Pathogenic
11819	NM_001110792.2(MECP2):c.916C>T (p.Arg306Ter)	Pathogenic
11824	NM_001110792.2(MECP2):c.952C>T (p.Arg318Cys)	Pathogenic
11828	NM_001110792.2(MECP2):c.538C>T (p.Arg180Ter)	Pathogenic
11833	NM_001110792.2(MECP2):c.459C>G (p.Tyr153Ter)	Pathogenic
11834	NM_001110792.2(MECP2):c.1399G>T (p.Glu467Ter)	Pathogenic
11835	NM_001110792.2(MECP2):c.334C>G (p.Leu112Val)	Pathogenic
11842	NM_001110792.2(MECP2):c.1192_1224del (p.Leu398_Ser408del)	Pathogenic
11846	NM_001110792.2(MECP2):c.746del (p.Gly249fs)	Pathogenic
1206780	NM_001110792.2(MECP2):c.62+2T>A	Pathogenic
1301354	NM_001110792.2(MECP2):c.1209_1243del (p.Pro403_Glu404insTer)	Pathogenic
1308657	NM_001110792.2(MECP2):c.1209_*6del (p.Glu404fs)	Pathogenic
1354117	NM_001110792.2(MECP2):c.140_144del (p.Lys47fs)	Pathogenic
1386387	NC_000023.10:g.(?153296109)(153297633_?)del	Pathogenic
1389127	NM_001110792.2(MECP2):c.1201_1237del (p.Pro401fs)	Pathogenic
1401512	NM_001110792.2(MECP2):c.1199del (p.Pro400fs)	Pathogenic
1402665	NM_001110792.2(MECP2):c.573_574insT (p.Lys192Ter)	Pathogenic
1403027	NM_001110792.2(MECP2):c.798_837del (p.Lys266fs)	Pathogenic

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154031446:GGGGA:G	acceptor_gain	1.0000
X:154031448:GGA:G	acceptor_gain	1.0000
X:154031449:GA:G	acceptor_gain	1.0000
X:154031451:C:CC	acceptor_gain	1.0000
X:154031453:G:C	acceptor_gain	1.0000
X:154031460:C:CT	acceptor_gain	1.0000
X:154032201:A:AC	donor_gain	1.0000
X:154032202:C:CC	donor_gain	1.0000
X:154032202:CTTA:C	donor_gain	1.0000
X:154032205:A:AC	donor_gain	1.0000
X:154032206:C:CC	donor_gain	1.0000
X:154032229:T:TA	donor_gain	1.0000
X:154032230:C:A	donor_gain	1.0000
X:154032558:C:CC	acceptor_gain	1.0000
X:154092179:CTTA:C	donor_loss	1.0000
X:154092180:TTACC:T	donor_loss	1.0000
X:154092181:TACCT:T	donor_loss	1.0000
X:154092183:C:A	donor_loss	1.0000
X:154097600:TCA:T	donor_loss	1.0000
X:154097601:CA:C	donor_loss	1.0000
X:154097602:A:AC	donor_gain	1.0000
X:154097603:C:CG	donor_gain	1.0000
X:154097603:CA:C	donor_gain	1.0000
X:154097603:CAGT:C	donor_gain	1.0000
X:154097613:T:TA	donor_gain	1.0000
X:154031447:GGGA:G	acceptor_gain	0.9900
X:154031447:GGGAC:G	acceptor_gain	0.9900
X:154031448:GGAC:G	acceptor_gain	0.9900
X:154031449:GACT:G	acceptor_gain	0.9900
X:154031450:ACTG:A	acceptor_gain	0.9900

AlphaMissense

3201 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154030912:G:T	R306S	1.000
X:154030916:C:A	K304N	1.000
X:154030916:C:G	K304N	1.000
X:154030920:A:G	I303T	1.000
X:154031163:A:T	V222D	1.000
X:154031340:C:T	G163E	1.000
X:154031346:C:A	G161V	1.000
X:154031346:C:T	G161E	1.000
X:154031347:C:A	G161W	1.000
X:154031347:C:G	G161R	1.000
X:154031347:C:T	G161R	1.000
X:154031352:A:G	V159A	1.000
X:154031352:A:T	V159E	1.000
X:154031355:G:T	T158K	1.000
X:154031357:G:C	F157L	1.000
X:154031357:G:T	F157L	1.000
X:154031358:A:C	F157C	1.000
X:154031358:A:G	F157S	1.000
X:154031359:A:C	F157V	1.000
X:154031359:A:G	F157L	1.000
X:154031359:A:T	F157I	1.000
X:154031360:G:C	D156E	1.000
X:154031360:G:T	D156E	1.000
X:154031361:T:A	D156V	1.000
X:154031361:T:C	D156G	1.000
X:154031361:T:G	D156A	1.000
X:154031362:C:A	D156Y	1.000
X:154031362:C:G	D156H	1.000
X:154031363:A:C	F155L	1.000
X:154031363:A:T	F155L	1.000

dbSNP variants (sampled 300 via entrez): RS1000013864 (X:154053259 T>A), RS1000022743 (X:154069273 G>A), RS1000138878 (X:154088158 A>C,G), RS1000186351 (X:154023655 G>A), RS1000282882 (X:154045001 C>T), RS1000288577 (X:154073870 G>T), RS1000415623 (X:154074125 A>G), RS1000509245 (X:154027334 C>A,G), RS1000625371 (X:154027541 G>A), RS1000674861 (X:154038646 C>T), RS1000691569 (X:154065087 C>T), RS1000775571 (X:154093335 C>T), RS1000813490 (X:154083933 C>A,T), RS1000886373 (X:154046903 C>G,T), RS1000892768 (X:154038280 G>C,T)

Disease associations

OMIM: gene MIM:300005 | disease phenotypes: MIM:300673, MIM:312750, MIM:300055, MIM:300260, MIM:300496, MIM:105830, MIM:209850, MIM:181500, MIM:309530, MIM:120970, MIM:150280, MIM:300672

GenCC curated gene-disease

Disease	Classification	Inheritance
Rett syndrome	Definitive	X-linked
severe neonatal-onset encephalopathy with microcephaly	Definitive	X-linked
syndromic X-linked intellectual disability Lubs type	Definitive	X-linked
X-linked intellectual disability-psychosis-macroorchidism syndrome	Supportive	X-linked
atypical Rett syndrome	Supportive	Autosomal dominant
systemic lupus erythematosus	Supportive	Unknown
non-syndromic X-linked intellectual disability	Supportive	X-linked

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
Rett syndrome	Definitive	XL

Mondo (28): severe neonatal-onset encephalopathy with microcephaly (MONDO:0010397), Rett syndrome (MONDO:0010726), X-linked intellectual disability-psychosis-macroorchidism syndrome (MONDO:0010235), syndromic X-linked intellectual disability Lubs type (MONDO:0010283), autism, susceptibility to, X-linked 3 (MONDO:0010342), intellectual disability (MONDO:0001071), Angelman syndrome (MONDO:0007113), congenital nervous system disorder (MONDO:0002320), microcephaly (MONDO:0001149), hearing loss disorder (MONDO:0005365), neurodevelopmental disorder (MONDO:0700092), autism (MONDO:0005260), atypical Rett syndrome (MONDO:0017746), attention deficit-hyperactivity disorder (MONDO:0007743), schizophrenia (MONDO:0005090)

Orphanet (17): MECP2-related severe neonatal encephalopathy (Orphanet:209370), Atypical Rett syndrome (Orphanet:3095), Rett syndrome (Orphanet:778), Proximal Xq28 duplication syndrome (Orphanet:1762), X-linked intellectual disability-psychosis-macroorchidism syndrome (Orphanet:3077), Angelman syndrome (Orphanet:72), X-linked non-syndromic intellectual disability (Orphanet:777), Cone rod dystrophy (Orphanet:1872), Obesity due to melanocortin 4 receptor deficiency (Orphanet:71529), Congenital laryngomalacia (Orphanet:2373), Early infantile developmental and epileptic encephalopathy (Orphanet:1934), West syndrome (Orphanet:3451), CDKL5-deficiency disorder (Orphanet:505652), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

255 total (30 of 255 shown, HPO-id order):

HPO	Term
HP:0000026	Male hypogonadism
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000053	Macroorchidism
HP:0000093	Proteinuria
HP:0000155	Oral ulcer
HP:0000160	Narrow mouth
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000232	Everted lower lip vermilion
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000256	Macrocephaly
HP:0000272	Malar flattening
HP:0000286	Epicanthus
HP:0000297	Facial hypotonia
HP:0000347	Micrognathia
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000488	Retinopathy
HP:0000508	Ptosis
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000687	Widely spaced teeth
HP:0000709	Psychosis

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001873_1	Red blood cell traits	2.000000e-16
GCST001873_11	Red blood cell traits	4.000000e-19
GCST001873_4	Red blood cell traits	4.000000e-18
GCST002190_1	Schizophrenia	4.000000e-08
GCST003155_27	Systemic lupus erythematosus	2.000000e-15
GCST003599_17	Systemic lupus erythematosus	4.000000e-10
GCST004867_3	Systemic lupus erythematosus	8.000000e-07
GCST005990_1	Non-albumin protein levels	5.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004348	hematocrit
EFO:0004305	erythrocyte count
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (21)

Descriptor	Name	Tree numbers
D017204	Angelman Syndrome	C10.228.662.075; C16.131.077.095; C16.131.260.040; C16.320.180.040; C16.320.447.250
D001321	Autistic Disorder	F03.625.164.113.500
D002012	Bruxism	C07.793.099; F01.145.466.132; F01.470.315.500
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D020821	Dystonic Disorders	C10.228.662.300
D004828	Epilepsies, Partial	C10.228.140.490.360
D004827	Epilepsy	C10.228.140.490
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D055092	Laryngomalacia	C05.182.310; C08.360.563; C09.400.563; C16.131.621.568; C17.300.182.310
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
D015518	Rett Syndrome	C10.597.606.360.455.937; C16.320.322.500.937; C16.320.400.525.937
D012804	Sick Sinus Syndrome	C14.280.067.093.249; C14.280.067.558.536; C14.280.123.500.536; C23.550.073.093.249; C23.550.073.425.440
D019956	Stereotypic Movement Disorder	F03.625.984
C564064	CDKL5 deficiency disorder (supp.)
C566878	Encephalopathy, Neonatal Severe, Due To Mecp2 Mutations (supp.)
C531619	Happy puppet syndrome (formerly) (supp.)
C537723	Lubs X-linked mental retardation syndrome (supp.)
C564490	Mental Retardation, X-Linked Nonsyndromic (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3638346 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17435	MECP2		0.00	0
rs1734787	MECP2		0.00	0
rs1734791	MECP2		0.00	0

Binding affinities (BindingDB)

9 measured of 11 human assays (12 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-(5-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)phenol	IC50	11 nM	US-9034574: Agents for reversing epigenetic silencing of genes
2-(4-chlorophenyl)-5-phenyl-2,3-dihydro-1,3,4-thiadiazole	IC50	210 nM	US-9034574: Agents for reversing epigenetic silencing of genes
[5-hydroxy-3-phenyl-5-(trifluoromethyl)-4H-pyrazol-1-yl]-phenylmethanethione	IC50	470 nM	US-9034574: Agents for reversing epigenetic silencing of genes
1-(5-phenyl-2,3-dihydro-1,3,4-thiadiazol-2-yl)naphthalen-2-ol	IC50	670 nM	US-9034574: Agents for reversing epigenetic silencing of genes
3-[(4-pyridin-2-yl-1,3-thiazol-2-yl)amino]phenol	IC50	1550 nM	US-9034574: Agents for reversing epigenetic silencing of genes
TCMDC-124275	IC50	1550 nM	US-9034574: Agents for reversing epigenetic silencing of genes
4-methyl-2-(4-nitrophenyl)imidazo[1,2-a]benzimidazole	IC50	6140 nM	US-9034574: Agents for reversing epigenetic silencing of genes
3-(5-phenyl-1,3,4-oxadiazol-2-yl)aniline	IC50	8590 nM	US-9034574: Agents for reversing epigenetic silencing of genes
US9034574, XVIII	IC50	38000 nM	US-9034574: Agents for reversing epigenetic silencing of genes

ChEMBL bioactivities

3 potent at pChembl≥5 of 6 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.21	IC50	610	nM	CHEMBL520851
5.55	IC50	2810	nM	CHEMBL1371175
5.07	IC50	8590	nM	CHEMBL3687968

CTD chemical–gene interactions

60 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, decreases expression, affects expression	6
bisphenol A	affects binding, increases reaction, decreases expression	2
trichostatin A	affects cotreatment, decreases expression, affects binding, decreases reaction	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, affects expression	2
Benzo(a)pyrene	affects methylation	2
Butyrates	decreases reaction, decreases expression, affects binding	2
Lead	affects splicing, decreases expression	2
Ozone	decreases expression, increases oxidation, increases abundance, affects expression, affects cotreatment	2
Tobacco Smoke Pollution	decreases methylation, decreases reaction, increases expression, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
Genistein	increases expression, decreases expression	2
Particulate Matter	affects methylation, decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
Batroxase, Bothrops atrox	increases expression	1
dicrotophos	increases expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
geniposide	decreases expression, decreases reaction	1
pyrimidin-2-one beta-ribofuranoside	decreases expression	1
withaferin A	decreases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel sulfide	affects binding, increases reaction	1
sodium arsenite	affects cotreatment, decreases expression, affects expression	1
butyraldehyde	decreases expression	1
pregna-4,17-diene-3,16-dione	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3705985	Binding	Binding Assay: DNA binding assays using recombinant MBDs. To produce recombinant His6-tagged MBD polypeptides from human MBD2 (MBD2-MBD), MBD2-MBD cDNA was amplified from clone MGC-45084 (American Type Culture Collection), using PCR primers	Agents for reversing epigenetic silencing of genes

Cellosaurus cell lines

127 cell lines: 56 transformed cell line, 43 induced pluripotent stem cell, 18 finite cell line, 6 cancer cell line, 4 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_4F14	GM11272	Finite cell line	Female
CVCL_4F15	GM11273	Finite cell line	Female
CVCL_4F17	GM11299	Transformed cell line	Female
CVCL_4F18	GM11300	Transformed cell line	Female
CVCL_4F19	GM11301	Transformed cell line	Female
CVCL_4F22	GM11304	Transformed cell line	Female
CVCL_4F27	GM11310	Transformed cell line	Female
CVCL_4F30	GM11313	Transformed cell line	Female
CVCL_4F33	GM16270	Transformed cell line	Female
CVCL_4F34	GM16271	Transformed cell line	Female

Clinical trials (associated diseases)

511 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
NCT02270970	PHASE4	UNKNOWN	Evaluation of Belimumab Impact on a BLyS Activity Signature Test in the Absence of Confounding Polypharmacy
NCT02477150	PHASE4	COMPLETED	Safety and Immunogenicity of a Zoster Vaccine in SLE
NCT02741960	PHASE4	COMPLETED	The Effect of Metformin on Reducing Lupus Flares
NCT02779153	PHASE4	WITHDRAWN	Acthar SLE (Systemic Lupus Erythematosus)
NCT02953821	PHASE4	COMPLETED	Acthar Gel for Active Systemic Lupus Erythematosus (SLE)
NCT03042260	PHASE4	UNKNOWN	Prophylactic Trimethoprim/Sulfamethoxazole to Prevent Severe Infections in Patients With Lupus Erythematous
NCT03098823	PHASE4	COMPLETED	A Crossover Study to Compare RAYOS to IR Prednisone to Improve Fatigue and Morning Symptoms for SLE
NCT03122431	PHASE4	COMPLETED	Relevance of Monitoring Blood and Salivar Levels of Drugs Used in Rheumatic Autoimmune Diseases
NCT03543839	PHASE4	RECRUITING	Trial of Belimumab in Early Lupus
NCT04447053	PHASE4	UNKNOWN	Sequential Belimumab and T-cell Based Therapy in SLE
NCT04515719	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in SLE Patients
NCT04893161	PHASE4	UNKNOWN	A Model About the Response of Belimumab in SLE
NCT04908865	PHASE4	COMPLETED	Open-label Study of Belimumab Plus Standard Therapy in Chinese Pediatric Participants With Active Systemic Lupus Erythematosus (SLE)
NCT04956484	PHASE4	COMPLETED	Belimumab In Early Systemic Lupus Erythematosus
NCT05559671	PHASE4	RECRUITING	Safety of the Herpes Zoster Subunit Vaccine in Lupus
NCT05666336	PHASE4	UNKNOWN	Multi-omics Studies on the Efficacy of Telitacicept in Chinese SLE Patients
NCT05748925	PHASE4	COMPLETED	Cardio Renal Effects of SGLT2 Inhibitors Among Lupus Nephritis Patients