MBD3L2

Summary

MBD3L2 (methyl-CpG binding domain protein 3 like 2, HGNC:18532) is a protein-coding gene on chromosome 19p13.2, encoding Methyl-CpG-binding domain protein 3-like 2 (Q8NHZ7). May displace the NuRD complex from chromatin.

This gene encodes a protein that is related to methyl-CpG-binding proteins but lacks the methyl-CpG binding domain. The protein has been found in germ cell tumors and some somatic tissues.

Source: NCBI Gene 125997 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_144614

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18532
Approved symbol	MBD3L2
Name	methyl-CpG binding domain protein 3 like 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000230522
Ensembl biotype	protein_coding
OMIM	607964
Entrez	125997

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381393

RefSeq mRNA: 1 — MANE Select: NM_144614 NM_144614

CCDS: CCDS42483

Canonical transcript exons

ENST00000381393 — 2 exons

Exon	Start	End
ENSE00001634112	7049321	7049418
ENSE00001801727	7051041	7051735

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 80.70.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.70	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	52.35	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
sural nerve	UBERON:0015488	36.17	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
monocyte	CL:0000576	27.71	gold quality
leukocyte	CL:0000738	27.70	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
blood	UBERON:0000178	26.10	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
urinary bladder	UBERON:0001255	25.72	gold quality
muscle of leg	UBERON:0001383	25.01	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
pancreas	UBERON:0001264	24.26	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD2

miRNA regulators (miRDB)

16 targeting MBD3L2, 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-607	99.97	73.62	5593
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4504	99.10	69.14	1328
HSA-MIR-3945	98.68	64.21	553
HSA-MIR-595	98.25	67.44	699
HSA-MIR-5681A	97.99	67.17	1658
HSA-MIR-4253	97.48	65.11	692
HSA-MIR-6862-5P	97.48	64.84	713

Literature-anchored findings (GeneRIF, showing 3)

• MBD3L2 interacts with MBD3 and components of the NuRD complex and can oppose MBD2-MeCP1-mediated methylation silencing (PMID:15701600)
• These factors lead to a binding affinity hierarchy of p66alpha for the different MBD2 homologues (MBD2 approximately MBD3 > MBD3L1 approximately MBD3L2). (PMID:23239876)
• MBD3L2 is more effective than MBD3 in promoting Tet2 enzymatic activity through strengthening the binding affinity between Tet2 and the methylated DNA target. (PMID:26769901)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbd3a	ENSDARG00000061774
mus_musculus	Mbd3l2	ENSMUSG00000047508
rattus_norvegicus	Mbd3l2	ENSRNOG00000026629
rattus_norvegicus	Mbd3l3	ENSRNOG00000065634
drosophila_melanogaster	MBD-like	FBGN0027950

Paralogs (8): MBD3 (ENSG00000071655), MBD2 (ENSG00000134046), MBD1 (ENSG00000141644), MBD3L1 (ENSG00000170948), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3-like 2 — Q8NHZ7 (reviewed: Q8NHZ7)

All UniProt accessions (1): Q8NHZ7

UniProt curated annotations — full annotation on UniProt →

Function. May displace the NuRD complex from chromatin.

Subunit / interactions. Interacts (via N-terminus) with MBD3; the interaction is direct. Interacts with MTA1. Interacts with HDAC1. Interacts with HDAC2. Interacts with RBBP4. Interacts with RBBP7.

Subcellular location. Nucleus.

Tissue specificity. Detected at low levels in several somatic tissues. Highly expressed in the ovarian teratocarcinoma cell line PA-1.

Miscellaneous. The MBD3L proteins are encoded by strongly repeated regions of the 19p13 chromosome. The exact number of functional copies is unclear, and some of them may represent pseudogenes.

Similarity. Belongs to the MBD3L family.

RefSeq proteins (1): NP_653215* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025884	MeCpG-bd_2/3_C_dom	Domain
IPR032343	MBD2/MBD3_p55-bd	Domain

Pfam: PF14048, PF16564

UniProt features (4 total): sequence conflict 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHZ7-F1	66.84	0.18

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9937850	NuRD complex assembly

MSigDB gene sets: 28 (showing top): PID_HDAC_CLASSI_PATHWAY, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, MARTINEZ_RB1_TARGETS_DN, GOBP_REGULATION_OF_CHROMATIN_ORGANIZATION, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, chr19p13, GOMF_METHYL_CPG_BINDING, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, GOBP_NEGATIVE_REGULATION_OF_TRANSCRIPTION_BY_RNA_POLYMERASE_II, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR92A_2_5P

GO Biological Process (4): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346), regulation of transcription by RNA polymerase II (GO:0006357), regulation of chromatin organization (GO:1902275)

GO Molecular Function (2): methyl-CpG binding (GO:0008327), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
CHD3, CHD4, CHD5 subfamily	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
constitutive heterochromatin formation	1
regulation of DNA-templated transcription	1
chromatin organization	1
regulation of cellular component organization	1
nucleotide binding	1
sequence-specific DNA binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

372 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3L2	TRIM43	Q96BQ3	812
MBD3L2	ACRV1	P26436	777
MBD3L2	DPM1	O60762	770
MBD3L2	ZSCAN4	Q8NAM6	762
MBD3L2	DUX4L2	P0CJ85	718
MBD3L2	LEUTX	A8MZ59	663
MBD3L2	PRAMEF1	O95521	656
MBD3L2	KHDC1L	Q5JSQ8	609
MBD3L2	KHDC1	Q4VXA5	603
MBD3L2	SMCHD1	A6NHR9	577
MBD3L2	PRAMEF15	P0DUQ1	570
MBD3L2	RFPL2	O75678	518
MBD3L2	RFPL1	O75677	506
MBD3L2	OR2Z1	Q8NG97	480
MBD3L2	A0A096LNW4	A0A096LNW4	479

IntAct

32 interactions, top by confidence:

A	B	Type	Score
RUNDC3A	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
MBD3L2	GPRASP2	psi-mi:“MI:0915”(physical association)	0.560
GOLGA6L9	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
KRT27	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
TRIML2	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
KRT34	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
SBK3	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
MBD3L2	MDFI	psi-mi:“MI:0915”(physical association)	0.560
	MBD3L2	psi-mi:“MI:0915”(physical association)	0.560
MBD3L2	AHCYL1	psi-mi:“MI:0914”(association)	0.350
MBD3L2	RUNDC3A	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	MDFI	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	KRT27	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	GPRASP2	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	GOLGA6L9	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2		psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	KRTAP6-3	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	TRIML2	psi-mi:“MI:0915”(physical association)	0.000
MBD3L2	KRT34	psi-mi:“MI:0915”(physical association)	0.000
SBK3	MBD3L2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (52): MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), MBD3L2 (Two-hybrid), SBK3 (Two-hybrid), CHD5 (Affinity Capture-MS), PROX1 (Affinity Capture-MS), GGPS1 (Affinity Capture-MS), AHCYL1 (Affinity Capture-MS), ZNF296 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GVZ6, A5D7I0, A6H7B4, A6NDZ8, A6NE82, A6NJ08, A6NJB7, A6NJI1, A6NL46, A6QP24, A8MUA0, A8MUI8, A8MV72, A8MX80, B2RW88, O94850, P0C6A0, P24097, P50617, Q0P5M0, Q0VD86, Q2KIL8, Q3B8N5, Q3SY00, Q3SYA9, Q3UN58, Q5BMD4, Q5JTZ5, Q5RBE4, Q5VZ46, Q66MI6, Q68US1, Q6GQV0, Q6PAC4, Q80TS7, Q80VY2, Q8BFY7, Q8BII1, Q8IXW0, Q8K2F3

Diamond homologs: A0A1B0GVZ6, A6NDZ8, A6NE82, A6NJ08, O95983, Q8NHZ7, Q8WWY6, Q9D9H3, Q9UBB5, Q9Z2D8, Q9Z2E1, O95243, P51608, Q00566, Q95LG8, Q9UIS9, Q9Z2D6, Q9Z2D7, Q9Z2E2, Q9FZP6, Q9LTJ1, Q9LYB9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	0
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

85 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7049414:TTCTG:T	donor_gain	1.0000
19:7049415:TCTG:T	donor_gain	1.0000
19:7049417:TG:T	donor_gain	1.0000
19:7049417:TGGTG:T	donor_loss	1.0000
19:7049418:GG:G	donor_gain	1.0000
19:7049418:GGT:G	donor_loss	1.0000
19:7049419:G:GG	donor_gain	1.0000
19:7051039:A:G	acceptor_gain	1.0000
19:7051040:G:GG	acceptor_gain	1.0000
19:7049416:CTG:C	donor_gain	0.9900
19:7049422:A:AG	donor_gain	0.9900
19:7049423:G:GG	donor_gain	0.9900
19:7051035:T:TA	acceptor_gain	0.9900
19:7051038:A:AG	acceptor_gain	0.9900
19:7051038:AAG:A	acceptor_gain	0.9900
19:7051038:AAGG:A	acceptor_gain	0.9900
19:7051039:A:T	acceptor_loss	0.9900
19:7051039:AG:A	acceptor_gain	0.9900
19:7051039:AGG:A	acceptor_gain	0.9900
19:7051040:G:GA	acceptor_loss	0.9900
19:7051040:GG:G	acceptor_gain	0.9900
19:7051040:GGG:G	acceptor_gain	0.9900
19:7051040:GGGGA:G	acceptor_gain	0.9900
19:7051038:AAGGG:A	acceptor_gain	0.9700
19:7051039:AGGG:A	acceptor_gain	0.9700
19:7051040:GGGG:G	acceptor_gain	0.9700
19:7049421:GA:G	donor_gain	0.9400
19:7051039:AGGGG:A	acceptor_gain	0.9300
19:7051037:AAAGG:A	acceptor_gain	0.9200
19:7051037:AAAG:A	acceptor_gain	0.9100

AlphaMissense

1332 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7051164:T:C	F57L	0.961
19:7051166:C:A	F57L	0.961
19:7051166:C:G	F57L	0.961
19:7051153:C:T	T53I	0.915
19:7051155:A:C	S54R	0.915
19:7051157:C:A	S54R	0.915
19:7051157:C:G	S54R	0.915
19:7051553:G:C	R186S	0.910
19:7051553:G:T	R186S	0.910
19:7051529:G:C	Q178H	0.895
19:7051529:G:T	Q178H	0.895
19:7051180:C:T	T62I	0.885
19:7051165:T:C	F57S	0.883
19:7051552:G:T	R186M	0.883
19:7051186:T:C	I64T	0.871
19:7051165:T:G	F57C	0.848
19:7051063:T:C	M23T	0.842
19:7051162:T:C	I56T	0.842
19:7051548:G:C	A185P	0.826
19:7051569:G:C	A192P	0.823
19:7051148:A:C	R51S	0.821
19:7051148:A:T	R51S	0.821
19:7051186:T:G	I64S	0.817
19:7051253:A:C	Q86H	0.815
19:7051253:A:T	Q86H	0.815
19:7051156:G:T	S54I	0.812
19:7051552:G:C	R186T	0.808
19:7051519:T:C	I175T	0.803
19:7051573:T:C	L193S	0.802
19:7051164:T:A	F57I	0.799

dbSNP variants (sampled 300 via entrez): RS1002417770 (19:7048007 T>A,C), RS1005912550 (19:7051749 A>G), RS1007716707 (19:7052203 T>C,G), RS1007750899 (19:7052073 G>A,C), RS1009298919 (19:7048770 G>A), RS1016583400 (19:7052167 T>C,G), RS1019594392 (19:7052078 G>A,T), RS1020641718 (19:7049950 C>G,T), RS1027955604 (19:7050181 G>C,T), RS1028084016 (19:7052069 G>A,C,T), RS1028446828 (19:7051651 C>G,T), RS1031709283 (19:7052118 G>A,C,T), RS1032348923 (19:7052219 C>T), RS1032960340 (19:7048010 G>A,C), RS1036441896 (19:7047755 A>G)

Disease associations

OMIM: gene MIM:607964 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
propionaldehyde	increases expression	1
potassium perchlorate	decreases expression	1
CGP 52608	affects binding, increases reaction	1
Decitabine	increases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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