MBD4 methyl-CpG binding domain 4, DNA glycosylase [Homo sapiens (human)] - Gene

Summary

Official Symbol: MBD4provided by HGNC
Official Full Name: methyl-CpG binding domain 4, DNA glycosylaseprovided by HGNC
Primary source: HGNC:HGNC:6919
See related: Ensembl:ENSG00000129071 MIM:603574; AllianceGenome:HGNC:6919
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MED1; UVM1; TPDS2
Summary: 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 an MBD domain at the N-terminus that functions both in binding to methylated DNA and in protein interactions and a C-terminal mismatch-specific glycosylase domain that is involved in DNA repair. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2013]
Expression: Ubiquitous expression in lymph node (RPKM 27.7), spleen (RPKM 17.6) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3q21.3

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (129430947..129439948, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (132175773..132184774, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (129149790..129158791, complement)

Chromosome 3 - NC_000003.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.
Title: Familial uveal melanoma and other tumors in 25 families with monoallelic germline MBD4 variants.
MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.
Title: MBD4 loss results in global reactivation of promoters and retroelements with low methylated CpG density.
MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.
Title: MBD4 deficiency is predictive of response to immune checkpoint inhibitors in metastatic uveal melanoma patients.
Structural Insights into the Mechanism of Base Excision by MBD4.
Title: Structural Insights into the Mechanism of Base Excision by MBD4.
Germline MBD4 Mutations and Predisposition to Uveal Melanoma.
Title: Germline MBD4 Mutations and Predisposition to Uveal Melanoma.
Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.
Title: Germline loss-of-function variants in MBD4 are rare in Finnish patients with uveal melanoma.
[Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4].
Title: [Comparative Analysis of the Activity of the Polymorphic Variants of Human Uracil-DNA-Glycosylases SMUG1 and MBD4].
MBD4 is sumoylated in vivo in a DNA damage-specific manner
Title: Modification of the base excision repair enzyme MBD4 by the small ubiquitin-like molecule SUMO1.
These findings suggest that RNF144A is epigenetically silenced in breast cancer cells by promoter hypermethylation and MBD4.
Title: Epigenetic silencing of RNF144A expression in breast cancer cells through promoter hypermethylation and MBD4.
Germ line MBD4 deficiency stimulates clonal hematopoiesis and guides the development of leukemia via recurrent mutations in DNMT3A.
Title: MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML.

Submit: New GeneRIF Correction See all GeneRIFs (45)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Melanoma, uveal, susceptibility to, 1 MedGen: C1847724 OMIM: 606660 GeneReviews: Not available	Compare labs
Tumor predisposition syndrome 2 MedGen: C5774186 OMIM: 619975 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH93317 (e-PCR)
- UniSTS:90888

RH78192 (e-PCR)
- UniSTS:21721

STS-AA010492 (e-PCR)
- UniSTS:37351

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA N-glycosylase activity	TAS Traceable Author Statement more info
enables DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables DNA endonuclease activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables pyrimidine-specific mismatch base pair DNA N-glycosylase activity	IDA Inferred from Direct Assay more info	PubMed
enables satellite DNA binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA repair	TAS Traceable Author Statement more info	PubMed
involved_in depyrimidination	TAS Traceable Author Statement more info
involved_in response to estradiol	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in nuclear speck	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: methyl-CpG-binding domain protein 4

Names: 3,N(4)-ethenocytosine glycosylase; G/5-fluorouracil mismatch glycosylase with biphasic kinetics; G/T mismatch glycosylase; G/U mismatch glycosylase; methyl-CpG binding domain protein 4; methyl-CpG-binding endonuclease 1; methyl-CpG-binding protein MBD4; mismatch-specific DNA N-glycosylase; putative methyl-CpG binding protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_033106.1 RefSeqGene

Range

5232..14233

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001276270.2 → NP_001263199.1 methyl-CpG-binding domain protein 4 isoform 2

See identical proteins and their annotated locations for NP_001263199.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

BC011752, BP370521, DB568237

Consensus CDS

CCDS63768.1

UniProtKB/Swiss-Prot

O95243

Related

ENSP00000394080.2, ENST00000429544.7

Conserved Domains (2) summary

smart00391
Location:79 → 155

MBD; Methyl-CpG binding domain

cl23768
Location:444 → 514

ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases
NM_001276271.2 → NP_001263200.1 methyl-CpG-binding domain protein 4 isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an exon and its transcription extends past a splice site that is used in variant 1, resulting in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 3 which is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL449212

Consensus CDS

CCDS63766.1

UniProtKB/Swiss-Prot

O95243

Related

ENSP00000422327.1, ENST00000507208.1

Conserved Domains (2) summary

smart00391
Location:79 → 155

MBD; Methyl-CpG binding domain

COG0177
Location:453 → 518

Nth; Endonuclease III [Replication, recombination and repair]
NM_001276272.2 → NP_001263201.1 methyl-CpG-binding domain protein 4 isoform 4

See identical proteins and their annotated locations for NP_001263201.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1. This results in a shorter protein (isoform 4), compared to isoform 1.

Source sequence(s)

AF532602, DB568237

Consensus CDS

CCDS63767.1

UniProtKB/Swiss-Prot

O95243

Related

ENSP00000424873.1, ENST00000503197.5

Conserved Domains (2) summary

smart00391
Location:79 → 155

MBD; Methyl-CpG binding domain

cl23768
Location:450 → 520

ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases
NM_001276273.2 → NP_001263202.1 methyl-CpG-binding domain protein 4 isoform 5

See identical proteins and their annotated locations for NP_001263202.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) uses an alternate in-frame splice site and lacks an exon in the 5' coding region, compared to variant 1. The encoded isoform (5) is shorter, compared to isoform 1.

Source sequence(s)

AM180876, BP370521, CD678412, DB568237

Consensus CDS

CCDS63769.1

UniProtKB/Swiss-Prot

O95243

Related

ENSP00000376959.2, ENST00000393278.6

Conserved Domains (1) summary

cl23768
Location:132 → 202

ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases
NM_003925.3 → NP_003916.1 methyl-CpG-binding domain protein 4 isoform 1

See identical proteins and their annotated locations for NP_003916.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

AF072250, BY997577, DB568237

Consensus CDS

CCDS3058.1

UniProtKB/Swiss-Prot

B4DZN2, D3DNC3, D3DNC4, E9PEE4, O95243, Q2MD36, Q7Z4T3, Q96F09

Related

ENSP00000249910.1, ENST00000249910.5

Conserved Domains (2) summary

smart00391
Location:79 → 155

MBD; Methyl-CpG binding domain

cl23768
Location:450 → 520

ENDO3c; endonuclease III; includes endonuclease III (DNA-(apurinic or apyrimidinic site) lyase), alkylbase DNA glycosidases (Alka-family) and other DNA glycosidases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

129430947..129439948 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047449153.1 → XP_047305109.1 methyl-CpG-binding domain protein 4 isoform X2
XM_024453810.2 → XP_024309578.1 methyl-CpG-binding domain protein 4 isoform X1

Conserved Domains (2) summary

smart00391
Location:79 → 155

MBD; Methyl-CpG binding domain

cl27658
Location:447 → 512

HHH; Helix-hairpin-helix motif