MBD1

Summary

MBD1 (methyl-CpG binding domain protein 1, HGNC:6916) is a protein-coding gene on chromosome 18q21.1, encoding Methyl-CpG-binding domain protein 1 (Q9UIS9). Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides.

The protein encoded by this gene is a member of a family of nuclear proteins related by the presence of a methyl-CpG binding domain (MBD). These proteins are capable of binding specifically to methylated DNA, and some members can also repress transcription from methylated gene promoters. This protein contains multiple domains: MBD at the N-terminus that functions both in binding to methylated DNA and in protein interactions; several CXXC-type zinc finger domains that mediate binding to non-methylated CpG dinucleotides; transcriptional repression domain (TRD) at the C-terminus that is involved in transcription repression and in protein interactions. Numerous alternatively spliced transcript variants encoding different isoforms have been noted for this gene.

Source: NCBI Gene 4152 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 107 total
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 18 downstream targets (CollecTRI)
• MANE Select transcript: NM_015846

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6916
Approved symbol	MBD1
Name	methyl-CpG binding domain protein 1
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Aliases	PCM1, CXXC3
Ensembl gene	ENSG00000141644
Ensembl biotype	protein_coding
OMIM	156535
Entrez	4152

Gene structure

Transcript identifiers

Ensembl transcripts: 148 — 141 protein_coding, 6 retained_intron, 1 nonsense_mediated_decay

ENST00000269468, ENST00000269471, ENST00000339998, ENST00000347968, ENST00000353909, ENST00000382948, ENST00000398488, ENST00000398493, ENST00000398495, ENST00000457839, ENST00000585595, ENST00000585672, ENST00000586118, ENST00000586679, ENST00000586884, ENST00000587605, ENST00000588937, ENST00000589541, ENST00000589733, ENST00000589758, ENST00000589867, ENST00000590208, ENST00000590215, ENST00000591416, ENST00000591535, ENST00000591661, ENST00000592060, ENST00000705655, ENST00000865886, ENST00000865887, ENST00000865888, ENST00000865889, ENST00000865890, ENST00000865891, ENST00000865892, ENST00000865893, ENST00000865894, ENST00000865895, ENST00000865896, ENST00000865897, ENST00000865898, ENST00000865899, ENST00000865900, ENST00000865901, ENST00000865902, ENST00000865903, ENST00000865904, ENST00000865905, ENST00000865906, ENST00000865907, ENST00000865908, ENST00000865909, ENST00000865910, ENST00000865911, ENST00000865912, ENST00000865913, ENST00000865914, ENST00000865915, ENST00000865916, ENST00000865917, ENST00000865918, ENST00000865919, ENST00000865920, ENST00000865921, ENST00000865922, ENST00000865923, ENST00000865924, ENST00000865925, ENST00000865926, ENST00000865927, ENST00000865928, ENST00000865929, ENST00000865930, ENST00000865931, ENST00000865932, ENST00000919205, ENST00000919206, ENST00000919207, ENST00000919208, ENST00000919209, ENST00000919210, ENST00000919211, ENST00000919212, ENST00000919213, ENST00000919214, ENST00000919215, ENST00000919216, ENST00000919217, ENST00000919218, ENST00000919219, ENST00000919220, ENST00000919221, ENST00000919222, ENST00000919223, ENST00000919224, ENST00000919225, ENST00000919226, ENST00000919227, ENST00000919228, ENST00000919229, ENST00000919230, ENST00000919231, ENST00000919232, ENST00000919233, ENST00000919234, ENST00000919235, ENST00000919236, ENST00000919237, ENST00000919238, ENST00000919239, ENST00000919240, ENST00000950594, ENST00000950595, ENST00000950596, ENST00000950597, ENST00000950598, ENST00000950599, ENST00000950600, ENST00000950601, ENST00000950602, ENST00000950603, ENST00000950604, ENST00000950605, ENST00000950606, ENST00000950607, ENST00000950608, ENST00000950609, ENST00000950610, ENST00000950611, ENST00000950612, ENST00000950613, ENST00000950614, ENST00000950615, ENST00000950616, ENST00000950617, ENST00000950618, ENST00000950619, ENST00000950620, ENST00000950621, ENST00000950622, ENST00000950623, ENST00000950624, ENST00000950625, ENST00000950626, ENST00000950627, ENST00000950628, ENST00000950629, ENST00000950630

RefSeq mRNA: 147 — MANE Select: NM_015846 NM_001204136, NM_001204137, NM_001204138, NM_001204139, NM_001204140, NM_001204141, NM_001204142, NM_001204143, NM_001204151, NM_001323942, NM_001323947, NM_001323949, NM_001323950, NM_001323951, NM_001323952, NM_001323953, NM_001323954, NM_001388138, NM_001388139, NM_001388140, NM_001388141, NM_001388142, NM_001388143, NM_001388144, NM_001388145, NM_001388146, NM_001388147, NM_001388148, NM_001388149, NM_001388150, NM_001388151, NM_001388152, NM_001388153, NM_001388154, NM_001388155, NM_001388156, NM_001388157, NM_001388158, NM_001388159, NM_001388160, NM_001388161, NM_001388162, NM_001388163, NM_001388164, NM_001388165, NM_001388166, NM_001388167, NM_001399879, NM_001399880, NM_001399881, NM_001399882, NM_001399883, NM_001399884, NM_001399885, NM_001399886, NM_001399887, NM_001399888, NM_001399889, NM_001399890, NM_001399891, NM_001399892, NM_001399893, NM_001399894, NM_001399895, NM_001399896, NM_001399897, NM_001399898, NM_001399899, NM_001399900, NM_001399901, NM_001399902, NM_001399903, NM_001399904, NM_001399905, NM_001399906, NM_001399907, NM_001399908, NM_001399909, NM_001399910, NM_001399911, NM_001399912, NM_001399913, NM_001399914, NM_001399915, NM_001399916, NM_001399917, NM_001399918, NM_001399919, NM_001399920, NM_001399921, NM_001399922, NM_001399923, NM_001399924, NM_001399925, NM_001399926, NM_001399927, NM_001399928, NM_001399929, NM_001399930, NM_001399931, NM_001399932, NM_001399933, NM_001399934, NM_001399935, NM_001399936, NM_001399937, NM_001399938, NM_001399939, NM_001399940, NM_001399941, NM_001399942, NM_001399943, NM_001399944, NM_001399945, NM_001399946, NM_001399947, NM_001399948, NM_001399949, NM_001399950, NM_001399952, NM_001399953, NM_001399954, NM_001399955, NM_001399956, NM_001399957, NM_001399958, NM_001399959, NM_001399960, NM_001399961, NM_001399962, NM_001399963, NM_001399964, NM_001399965, NM_001399966, NM_001399967, NM_001399968, NM_001399970, NM_001399971, NM_001399973, NM_001399974, NM_001399975, NM_001399976, NM_002384, NM_015844, NM_015845, NM_015846, NM_015847

CCDS: CCDS11941, CCDS11942, CCDS11943, CCDS11944, CCDS32832, CCDS56071, CCDS56072, CCDS56073, CCDS59318, CCDS59319, CCDS59320, CCDS92462

Canonical transcript exons

ENST00000269468 — 17 exons

Exon	Start	End
ENSE00000950206	50276662	50276744
ENSE00000950210	50274977	50275045
ENSE00000950211	50274186	50274353
ENSE00000950212	50273564	50273863
ENSE00000950213	50273334	50273471
ENSE00000950214	50272824	50272955
ENSE00001640699	50272677	50272738
ENSE00001774155	50271469	50271540
ENSE00003564002	50275600	50275728
ENSE00003608558	50276832	50276998
ENSE00003620784	50279883	50280017
ENSE00003622171	50275835	50275981
ENSE00003629308	50277090	50277204
ENSE00003653570	50275129	50275245
ENSE00003688745	50276378	50276418
ENSE00003921337	50268846	50269818
ENSE00003921595	50281363	50281523

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 97.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.5323 / max 175.0210, expressed in 1802 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
171946	14.4312	1797
171948	1.9728	1041
171947	0.1284	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	97.51	gold quality
right testis	UBERON:0004534	97.27	gold quality
parotid gland	UBERON:0001831	96.48	gold quality
testis	UBERON:0000473	95.61	gold quality
pituitary gland	UBERON:0000007	95.36	gold quality
adenohypophysis	UBERON:0002196	95.31	gold quality
skin of leg	UBERON:0001511	95.24	gold quality
middle temporal gyrus	UBERON:0002771	95.23	gold quality
right lobe of thyroid gland	UBERON:0001119	95.02	gold quality
left ovary	UBERON:0002119	95.02	gold quality
right ovary	UBERON:0002118	94.99	gold quality
skin of abdomen	UBERON:0001416	94.94	gold quality
tibia	UBERON:0000979	94.79	gold quality
hair follicle	UBERON:0002073	94.73	gold quality
left lobe of thyroid gland	UBERON:0001120	94.71	gold quality
body of uterus	UBERON:0009853	94.67	gold quality
left uterine tube	UBERON:0001303	94.64	gold quality
gingival epithelium	UBERON:0001949	94.52	gold quality
granulocyte	CL:0000094	94.51	gold quality
lower esophagus	UBERON:0013473	94.46	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.46	gold quality
zone of skin	UBERON:0000014	94.45	gold quality
body of stomach	UBERON:0001161	94.40	gold quality
thyroid gland	UBERON:0002046	94.39	gold quality
left adrenal gland cortex	UBERON:0035825	94.37	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.34	gold quality
esophagus mucosa	UBERON:0002469	94.32	gold quality
right coronary artery	UBERON:0001625	94.31	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.31	gold quality
left adrenal gland	UBERON:0001234	94.25	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	155.64
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

18 targets.

Target	Regulation
ABCB1	Unknown
ACTB
ALOX5	Repression
AURKB
CCL2
CDH1
FGF2
HTR2C
IFNG
IGF2	Unknown
IRF8	Repression
MAGEA12
MBD1
MBD4
MGMT	Repression
NDRG1
SETDB1	Repression
SNRPN	Repression

Upstream regulators (CollecTRI, top): DMTF1, HDAC3, MBD1, MYC, STAT3

miRNA regulators (miRDB)

44 targeting MBD1, 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-4282	99.99	75.36	6408
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-23B-5P	99.98	66.07	587
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-1236-3P	99.94	68.04	1695
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-1251-3P	99.64	67.21	1408
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-425-5P	99.59	67.67	900
HSA-MIR-4452	99.50	68.45	1493
HSA-MIR-532-3P	99.34	65.76	1195
HSA-MIR-3614-5P	99.30	65.25	837
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-2054	99.20	68.89	1699
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-4680-3P	98.64	68.60	2093
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-5581-3P	98.55	70.31	1161
HSA-MIR-9903	98.47	66.70	748
HSA-MIR-624-3P	98.37	67.06	1067

Literature-anchored findings (GeneRIF, showing 33)

• lack of binding to mCpG and interaction with NuRD/Mi2 components HDAC1 and MTA2 (PMID:12124384)
• investigation of role of specific mutations in autism (PMID:12384770)
• 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)
• MCAF interacts with the transcriptional repression domain of MBD1 (PMID:12665582)
• Suv39h1 enhanced MBD1-mediated transcriptional repression via MBD, not the C-terminal transcriptional repression domain of MBD1. MBD1 links to histone deacetylases through Suv39h1, causing methylation and deacetylation of histones for gene inactivation (PMID:12711603)
• Additional evidence of variable expression in the Rett disorder phenotype is presented by a small mixed gender group of children with autistic disorder. (PMID:12770674)
• role in chromatin compaction (PMID:12788925)
• determination of link of p59 OASL with MBD1 transcriptional control in the context of an interferon-stimulated cell, and provision of basis for future studies to examine the functional role of this interaction (PMID:14728690)
• regulates G1-S transition and apoptosis via p53/p21(Waf1) pathway (PMID:15081425)
• These data suggest that MBD1.MCAF1.SETDB1 complex facilitates the formation of heterochromatic domains, emphasizing the role of MCAF/AM family proteins in epigenetic control, and describe a new family member, MCAF2. (PMID:15691849)
• Methyl-CpG binding protein MBD1 binds to teneurin 1. (PMID:15777793)
• PML-RARalpha functions by recruiting an HDAC3-MBD1 complex that contributes to the establishment and maintenance of the silenced chromatin state (PMID:16432238)
• MBD1- and MCAF1-mediated heterochromatin formation involves SUMO modification (PMID:16757475)
• Sex-specific time windows for concomitant upregulation of MBD1 are associated with prenatal remethylation of the human male and female germ line. (PMID:16998846)
• MBD1 and Polycomb group proteins have overlapping roles in epigenetic gene silencing and heterochromatin foci formation through their interactions. (PMID:17428788)
• These data show, for the first time, the involvement of methyl-CpG binding domain proteins in the regulation of the MAGE-A genes. (PMID:17634428)
• some insight into the functional mechanism of MBD1 in the development of pancreatic cancer (PMID:18445260)
• Silencing of MBD1 and MeCP2 in prostate-cancer-derived PC3 cells produces differential gene expression profiles and cellular phenotypes (PMID:18666890)
• Results suggest that MBD1 polymorphisms might be involved in the development of lung cancer in Chinese population. (PMID:18668384)
• This review tries to match MeCP2 structural domains, or their lack, and specific chromatin features needed for proper recruitment of MeCP2 to its functions as either activator or repressor. We specifically focused on MeCP2’s role in Rett syndrome (PMID:21326358)
• MBD1-containing chromatin associated factor 2, epithelial malignancy-related vimentin and exocytosis-related annexin A2 were changed upon exposure to airborne nanoparticle PM(0.056). (PMID:21491466)
• higher MBD1 expression correlated with lymph node metastasis and poor survival in pancreatic cancer; gain- and loss-of-function studies in vitro validated MBD1 as a potent oncogene promoting pancreatic cancer cell invasion and epithelial-mesenchymal transition (PMID:23331011)
• an important function of MBD1 in DNA repair and mediation of chemoradioresistance of cancer cells (PMID:23588667)
• We demonstrated the importance of Aire’s interaction with the ATF7ip-MBD1 protein complex in maintaining central tolerance (PMID:24464130)
• This study investigates the genetic association between methyl-CpG-binding domain (MBD) gene polymorphisms and schizophrenia. (PMID:24849540)
• Molecular dynamic simulation reveals mechanism of the recognition of dimethylated CpG sites by MBD1 protein. (PMID:25658035)
• MBD1 targets short interspersed nuclear elements, but does not exclude RNA Polymerase III. (PMID:25798578)
• c-myc plays a key role in MBD1 mediated epigenetic silencing of KEAP1. (PMID:26980696)
• Our findings imply that reduced stability and enhanced dynamics of MBD1 or MBD6 is the origin of ATP7B dysfunction in Wilson disease patients with the G85V or G591D mutation. (PMID:27744583)
• the binding of MBD1 to nucleosomes demonstrates sequence preferences depending on the position of the methyl groups on the nucleosome. (PMID:28377300)
• MBD1 regulates localization and activity of Tet1 in a CXXC3 domain-dependent manner. (PMID:28449087)
• MBD1 may be a tumor suppressor gene in advanced colorectal cancer (CRC)and affect the development and metastasis of CRC by regulating 8 tumor suppressor genes through binding with SP1. (PMID:28473981)
• ZEB1 silenced SIRT3 expression via interaction with MBD1 to promote aerobic glycolysis in pancreatic cancer. (PMID:30487699)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbd1b	ENSDARG00000025699
mus_musculus	Mbd1	ENSMUSG00000024561
rattus_norvegicus	Mbd1	ENSRNOG00000024104
drosophila_melanogaster	MBD-like	FBGN0027950

Paralogs (8): MBD3 (ENSG00000071655), MBD2 (ENSG00000134046), MBD3L1 (ENSG00000170948), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 1 — Q9UIS9 (reviewed: Q9UIS9)

Alternative names: CXXC-type zinc finger protein 3, Methyl-CpG-binding protein MBD1, Protein containing methyl-CpG-binding domain 1

All UniProt accessions (7): A0A0A0MS90, A0A994J7H0, Q9UIS9, K7EIN3, K7EMA9, K7EN65, K7EPZ6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor that binds CpG islands in promoters where the DNA is methylated at position 5 of cytosine within CpG dinucleotides. Binding is abolished by the presence of 7-mG that is produced by DNA damage by methylmethanesulfonate (MMS). Acts as transcriptional repressor and plays a role in gene silencing by recruiting ATF7IP, which in turn recruits factors such as the histone methyltransferase SETDB1. Probably forms a complex with SETDB1 and ATF7IP that represses transcription and couples DNA methylation and histone ‘Lys-9’ trimethylation. Isoform 1 and isoform 2 can also repress transcription from unmethylated promoters.

Subunit / interactions. Interacts with OASL, ATF7IP, ATF7IP2 and BAHD1. Binds CHAF1A and the SUV39H1-CBX5 complex via the MBD domain. Binds MGP via the TRD domain. May be part of the MeCP1 complex.

Subcellular location. Nucleus. Nucleus matrix. Nucleus speckle. Chromosome.

Tissue specificity. Widely expressed.

Post-translational modifications. Sumoylated, sumoylation may increase interaction with ATF7IP.

Domain organisation. The methyl-CpG-binding domain (MBD) functions both in binding to methylated DNA and in protein interactions. The third CXXC-type zinc finger mediates binding to DNA containing unmethylated CpG dinucleotides. The transcriptional repression domain (TRD) is involved in transcription repression and in protein interactions.

Induction. Up-regulated by interferon.

Isoforms (11)

UniProt ID	Names	Canonical?
Q9UIS9-1	1, MBD1v1	yes
Q9UIS9-2	2, MBD1v2
Q9UIS9-4	4, MBD1v3
Q9UIS9-5	5, PCM1
Q9UIS9-6	6, MBD1v6
Q9UIS9-7	7
Q9UIS9-8	8
Q9UIS9-9	9
Q9UIS9-10	10
Q9UIS9-11	11
Q9UIS9-12	12

RefSeq proteins (147): NP_001191065, NP_001191066, NP_001191067, NP_001191068, NP_001191069, NP_001191070, NP_001191071, NP_001191072, NP_001191080, NP_001310871, NP_001310876, NP_001310878, NP_001310879, NP_001310880, NP_001310881, NP_001310882, NP_001310883, NP_001375067, NP_001375068, NP_001375069, NP_001375070, NP_001375071, NP_001375072, NP_001375073, NP_001375074, NP_001375075, NP_001375076, NP_001375077, NP_001375078, NP_001375079, NP_001375080, NP_001375081, NP_001375082, NP_001375083, NP_001375084, NP_001375085, NP_001375086, NP_001375087, NP_001375088, NP_001375089, NP_001375090, NP_001375091, NP_001375092, NP_001375093, NP_001375094, NP_001375095, NP_001375096, NP_001386808, NP_001386809, NP_001386810, NP_001386811, NP_001386812, NP_001386813, NP_001386814, NP_001386815, NP_001386816, NP_001386817, NP_001386818, NP_001386819, NP_001386820, NP_001386821, NP_001386822, NP_001386823, NP_001386824, NP_001386825, NP_001386826, NP_001386827, NP_001386828, NP_001386829, NP_001386830, NP_001386831, NP_001386832, NP_001386833, NP_001386834, NP_001386835, NP_001386836, NP_001386837, NP_001386838, NP_001386839, NP_001386840, NP_001386841, NP_001386842, NP_001386843, NP_001386844, NP_001386845, NP_001386846, NP_001386847, NP_001386848, NP_001386849, NP_001386850, NP_001386851, NP_001386852, NP_001386853, NP_001386854, NP_001386855, NP_001386856, NP_001386857, NP_001386858, NP_001386859, NP_001386860, NP_001386861, NP_001386862, NP_001386863, NP_001386864, NP_001386865, NP_001386866, NP_001386867, NP_001386868, NP_001386869, NP_001386870, NP_001386871, NP_001386872, NP_001386873, NP_001386874, NP_001386875, NP_001386876, NP_001386877, NP_001386878, NP_001386879, NP_001386881, NP_001386882, NP_001386883, NP_001386884, NP_001386885, NP_001386886, NP_001386887, NP_001386888, NP_001386889, NP_001386890, NP_001386891, NP_001386892, NP_001386893, NP_001386894, NP_001386895, NP_001386896, NP_001386897, NP_001386899, NP_001386900, NP_001386902, NP_001386903, NP_001386904, NP_001386905, NP_002375, NP_056669, NP_056670, NP_056671, NP_056723 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001739	Methyl_CpG_DNA-bd	Domain
IPR002857	Znf_CXXC	Domain
IPR016177	DNA-bd_dom_sf	Homologous_superfamily

Pfam: PF01429, PF02008

UniProt features (100 total): binding site 24, splice variant 12, mutagenesis site 12, strand 8, helix 8, cross-link 7, compositionally biased region 5, region of interest 5, sequence conflict 5, turn 4, zinc finger region 3, modified residue 3, chain 1, domain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
5W9Q	X-RAY DIFFRACTION	1.8
6D1T	X-RAY DIFFRACTION	2.25
1D9N	SOLUTION NMR
1IG4	SOLUTION NMR
4D4W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UIS9-F1	60.41	0.18

Functional residue map

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

Ligand- & substrate-binding residues (24): 176; 179; 182; 188; 191; 194; 210; 215; 225; 228; 231; 237 …

Post-translational modifications (10): 297, 391, 399, 117, 277, 422, 440, 499, 538, 558

Mutagenesis-validated functional residues (12):

Position	Phenotype
22	abolishes binding to methylated dna.
30	strongly reduces binding to methylated dna.
30	no loss of binding to methylated dna.
32	strongly reduces binding to methylated dna.
34	strongly reduces binding to methylated dna.
44	abolishes binding to methylated dna.
45	reduces binding to methylated dna.
46	strongly reduces binding to methylated dna.
52	no loss of binding to methylated dna.
64	disrupts tertiary structure and abolishes dna binding.
65	strongly reduces binding to methylated dna.
576	abolishes interaction with atf7ip and subsequent transcription repression activity.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 445 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GOBP_PROTEIN_LOCALIZATION_TO_CYTOSKELETON, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, GOBP_BEHAVIOR, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_MICROTUBULE_ANCHORING, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GCANCTGNY_MYOD_Q6, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, SATO_SILENCED_BY_DEACETYLATION_IN_PANCREATIC_CANCER, GOBP_NEUROGENESIS

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), transcription by RNA polymerase II (GO:0006366), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): DNA binding (GO:0003677), zinc ion binding (GO:0008270), methyl-CpG binding (GO:0008327), double-stranded methylated DNA binding (GO:0010385), unmethylated CpG binding (GO:0045322), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nuclear matrix (GO:0016363), nuclear speck (GO:0016607)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	2
sequence-specific DNA binding	2
nuclear lumen	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
constitutive heterochromatin formation	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
nucleic acid binding	1
transition metal ion binding	1
nucleotide binding	1
double-stranded DNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

1659 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD1	ATF7IP	Q6VMQ6	741
MBD1	SETDB1	Q15047	665
MBD1	SUV39H1	O43463	605
MBD1	MECP2	P51608	598
MBD1	DNMT3A	Q9Y6K1	588
MBD1	CBX3	Q13185	551
MBD1	CBX5	P45973	542
MBD1	CHAF1B	Q13112	515
MBD1	CBX1	P23197	483
MBD1	SUMO2	P55855	459
MBD1	KDM2B	Q8NHM5	451
MBD1	RARA	P10276	425
MBD1	TET3	O43151	422
MBD1	MBD4	O95243	411
MBD1	SUMO1	P55856	392

IntAct

99 interactions, top by confidence:

A	B	Type	Score
CBX5	MBD1	psi-mi:“MI:0914”(association)	0.700
MBD1	CBX5	psi-mi:“MI:0915”(physical association)	0.700
CBX5	MBD1	psi-mi:“MI:0915”(physical association)	0.700
CBX5	MBD1	psi-mi:“MI:0403”(colocalization)	0.700
SETDB1	MBD1	psi-mi:“MI:0915”(physical association)	0.580
MBD1	CHAF1A	psi-mi:“MI:0915”(physical association)	0.580
MBD1	PIAS3	psi-mi:“MI:0915”(physical association)	0.580
MBD1	PIAS1	psi-mi:“MI:0915”(physical association)	0.580
CHAF1A	MBD1	psi-mi:“MI:0915”(physical association)	0.580
MBD1	SETDB1	psi-mi:“MI:0915”(physical association)	0.580
PIAS1	MBD1	psi-mi:“MI:0915”(physical association)	0.580
PIAS3	MBD1	psi-mi:“MI:0915”(physical association)	0.580
HDAC3	MBD1	psi-mi:“MI:0915”(physical association)	0.580
MBD1	HDAC3	psi-mi:“MI:0914”(association)	0.580
MBD1	HDAC3	psi-mi:“MI:0915”(physical association)	0.580
MBD1	SUV39H1	psi-mi:“MI:0915”(physical association)	0.560
SUV39H1	MBD1	psi-mi:“MI:0915”(physical association)	0.560
SUV39H1	MBD1	psi-mi:“MI:0403”(colocalization)	0.560
SUMO1	MBD1	psi-mi:“MI:0915”(physical association)	0.520
MBD1	SUMO1	psi-mi:“MI:0915”(physical association)	0.520
MBD1	HDAC1	psi-mi:“MI:0915”(physical association)	0.520

BioGRID (116): MBD1 (Affinity Capture-RNA), MBD1 (Affinity Capture-RNA), MBD1 (Affinity Capture-RNA), MBD1 (Affinity Capture-MS), MBD1 (Affinity Capture-MS), MBD1 (Affinity Capture-MS), SP1 (Reconstituted Complex), MBD1 (Affinity Capture-MS), MYC (Affinity Capture-Western), MBD1 (Negative Genetic), MBD1 (Negative Genetic), MBD1 (Affinity Capture-MS), SUV39H1 (Affinity Capture-Western), SUV39H1 (Reconstituted Complex), CBX5 (Affinity Capture-Western)

ESM2 similar proteins: A0A1L8HBI7, A0A1L8HJK9, A0A1L8HTT5, A6NP61, A7E2V4, B2RVL6, C0SPG1, C3VD30, K7SGN7, P56163, P56198, P62932, Q1XFL1, Q29RJ0, Q32L09, Q3UHH1, Q3V0J4, Q497M3, Q4R739, Q58D79, Q5EA86, Q5R8D5, Q5TKR9, Q5VWQ0, Q5XI33, Q6DMN8, Q768S4, Q7T3T8, Q7T3T9, Q7T3U0, Q80T69, Q8BV79, Q8BZ21, Q8CAK3, Q8CDN1, Q8HXK7, Q8K3Y6, Q8N2G6, Q8N9V6, Q8ND61

Diamond homologs: A0A1B0GVZ6, A6NDZ8, A6NE82, A6NJ08, O95243, O95983, P51608, Q00566, Q8NHZ7, Q8WWY6, Q95LG8, Q9D9H3, Q9UBB5, Q9UIS9, Q9Z2D6, Q9Z2D7, Q9Z2D8, Q9Z2E1, Q9Z2E2, Q9VGA4, A0A0P0VUY4, B1Q3J6, C0SQ89, D4ZX35, O23273, O33481, O34939, O49139, P13864, P23737, P25267, P25282, P26358, P31033, P34881, P34905, P45000, P50196, P59997, P94147

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
MBD1	“down-regulates quantity by repression”	ALOX5	“transcriptional regulation”
MBD1	“down-regulates quantity by repression”	MGMT	“transcriptional regulation”
DMTF1	“up-regulates quantity by expression”	MBD1	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 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
Notch-HLH transcription pathway	6	48.9×	9e-07
SUMOylation of intracellular receptors	5	33.6×	4e-05
NOTCH1 Intracellular Domain Regulates Transcription	6	28.6×	8e-06
Constitutive Signaling by NOTCH1 PEST Domain Mutants	7	27.6×	9e-07
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	7	27.6×	9e-07
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	6	17.6×	1e-04
SUMOylation of chromatin organization proteins	5	15.9×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
odontogenesis of dentin-containing tooth	5	22.8×	7e-04
heterochromatin formation	5	19.3×	1e-03
protein stabilization	7	7.1×	4e-03
positive regulation of gene expression	9	5.3×	4e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — GBM.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	11
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

9933 predictions. Top by Δscore:

Variant	Effect	Δscore
18:50272842:T:TA	donor_gain	1.0000
18:50272852:T:TA	donor_gain	1.0000
18:50272882:T:TA	donor_gain	1.0000
18:50272952:CTGC:C	acceptor_gain	1.0000
18:50272954:GCC:G	acceptor_loss	1.0000
18:50272956:C:A	acceptor_loss	1.0000
18:50272956:C:CC	acceptor_gain	1.0000
18:50272957:T:G	acceptor_loss	1.0000
18:50274194:A:AC	donor_gain	1.0000
18:50274195:C:CC	donor_gain	1.0000
18:50274214:CGACA:C	donor_gain	1.0000
18:50274221:T:TA	donor_gain	1.0000
18:50274349:GGCTG:G	acceptor_gain	1.0000
18:50274351:CTG:C	acceptor_gain	1.0000
18:50274352:TG:T	acceptor_gain	1.0000
18:50274353:GCTGG:G	acceptor_loss	1.0000
18:50274354:C:CC	acceptor_gain	1.0000
18:50274354:CTGGG:C	acceptor_loss	1.0000
18:50274355:T:C	acceptor_loss	1.0000
18:50274359:G:C	acceptor_gain	1.0000
18:50274359:G:GC	acceptor_gain	1.0000
18:50274975:A:AC	donor_gain	1.0000
18:50274976:C:CC	donor_gain	1.0000
18:50274976:CTAG:C	donor_gain	1.0000
18:50275123:CCTCA:C	donor_loss	1.0000
18:50275124:CTCA:C	donor_loss	1.0000
18:50275125:TCA:T	donor_loss	1.0000
18:50275126:CACCG:C	donor_loss	1.0000
18:50275127:ACC:A	donor_loss	1.0000
18:50275128:C:A	donor_loss	1.0000

AlphaMissense

3880 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:50274203:A:G	C377R	1.000
18:50274217:C:G	C372S	1.000
18:50274218:A:G	C372R	1.000
18:50274218:A:T	C372S	1.000
18:50274267:G:C	F355L	1.000
18:50274267:G:T	F355L	1.000
18:50274269:A:G	F355L	1.000
18:50274275:A:G	C353R	1.000
18:50277169:A:G	L49P	1.000
18:50279890:A:C	Y35D	1.000
18:50279950:A:G	W15R	1.000
18:50279950:A:T	W15R	1.000
18:50274201:G:C	C377W	0.999
18:50274202:C:G	C377S	0.999
18:50274203:A:T	C377S	0.999
18:50274209:G:T	R375S	0.999
18:50274216:A:C	C372W	0.999
18:50274222:C:A	Q370H	0.999
18:50274222:C:G	Q370H	0.999
18:50274246:G:C	F362L	0.999
18:50274246:G:T	F362L	0.999
18:50274248:A:G	F362L	0.999
18:50274264:G:C	C356W	0.999
18:50274265:C:G	C356S	0.999
18:50274265:C:T	C356Y	0.999
18:50274266:A:G	C356R	0.999
18:50274266:A:T	C356S	0.999
18:50274274:C:G	C353S	0.999
18:50274275:A:T	C353S	0.999
18:50274284:A:G	C350R	0.999

dbSNP variants (sampled 300 via entrez): RS1000043942 (18:50282078 C>A,T), RS1000124255 (18:50266475 G>A), RS1000184842 (18:50278451 T>C), RS1000447135 (18:50283204 A>G,T), RS1000480070 (18:50282834 A>C,G), RS1000522581 (18:50279717 CA>C), RS1000655873 (18:50272173 A>G), RS1000774267 (18:50277171 C>T), RS1001134332 (18:50277046 G>C), RS1001407844 (18:50279069 A>G), RS1001630894 (18:50266530 G>A,C,T), RS1001754266 (18:50278823 T>C), RS1001951292 (18:50267818 A>C), RS1002057840 (18:50281518 G>A), RS1002120995 (18:50282331 T>C)

Disease associations

OMIM: gene MIM:156535 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004146_27	Chronic lymphocytic leukemia	3.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, decreases reaction, increases expression, affects cotreatment, decreases expression	5
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation	2
Valproic Acid	decreases expression, increases methylation	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment, increases expression	1
butyraldehyde	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
abrine	increases expression	1
NSC 689534	affects binding, increases expression	1
Bortezomib	decreases expression	1
Decitabine	increases expression	1
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Arsenic	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Copper	affects binding, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases reaction, increases expression, decreases expression	1
Gallic Acid	decreases expression	1
Methotrexate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	increases oxidation, increases abundance, affects cotreatment, increases expression	1
Selenium	decreases expression	1

Cellosaurus cell lines

8 cell lines: 7 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_B1WT	Abcam HeLa MBD1 KO	Cancer cell line	Female
CVCL_B7Y7	Abcam Raji MBD1 KO	Cancer cell line	Male
CVCL_B9YX	Abcam THP-1 MBD1 KO	Cancer cell line	Male
CVCL_C7AN	Abcam PC-3 MBD1 KO	Cancer cell line	Male
CVCL_SX40	HAP1 MBD1 (-) 1	Cancer cell line	Male
CVCL_SX41	HAP1 MBD1 (-) 2	Cancer cell line	Male
CVCL_SX42	HAP1 MBD1 (-) 3	Cancer cell line	Male
CVCL_U952	ES-E14TG2a EGFP-MBD-nls	Embryonic stem cell	Male

Clinical trials (associated diseases)

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