MBD3L3

Summary

MBD3L3 (methyl-CpG binding domain protein 3 like 3, HGNC:37205) is a protein-coding gene on chromosome 19p13.2, encoding Methyl-CpG-binding domain protein 3-like 3 (A6NE82).

Predicted to enable methyl-CpG binding activity. Predicted to be involved in DNA methylation-dependent constitutive heterochromatin formation and negative regulation of transcription by RNA polymerase II. Predicted to be active in nucleus.

Source: NCBI Gene 653657 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001164425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37205
Approved symbol	MBD3L3
Name	methyl-CpG binding domain protein 3 like 3
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182315
Ensembl biotype	protein_coding
Entrez	653657

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000333843, ENST00000689071, ENST00000693237

RefSeq mRNA: 1 — MANE Select: NM_001164425 NM_001164425

CCDS: CCDS45944

Canonical transcript exons

ENST00000333843 — 2 exons

Exon	Start	End
ENSE00001592667	7056207	7056903
ENSE00001694235	7058561	7058676

Expression profiles

Bgee: expression breadth tissue_specific, 10 present calls, max score 93.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.22	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.38	gold quality
left testis	UBERON:0004533	38.81	gold quality
granulocyte	CL:0000094	38.37	gold quality
bone marrow cell	CL:0002092	38.30	gold quality
testis	UBERON:0000473	38.08	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ganglionic eminence	UBERON:0004023	37.14	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
right testis	UBERON:0004534	35.95	gold quality
bone marrow	UBERON:0002371	34.16	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.24	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
liver	UBERON:0002107	28.53	gold quality
duodenum	UBERON:0002114	28.14	gold quality
leukocyte	CL:0000738	27.95	gold quality
lymph node	UBERON:0000029	27.57	gold quality
monocyte	CL:0000576	27.31	gold quality
primary visual cortex	UBERON:0002436	27.30	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.28	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.99	gold quality
frontal cortex	UBERON:0001870	26.81	gold quality
urinary bladder	UBERON:0001255	26.61	gold quality
endocervix	UBERON:0000458	26.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	4618.75
E-ANND-3	no	0.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MBD3L3, 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

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), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3-like 3 — A6NE82 (reviewed: A6NE82)

All UniProt accessions (1): A6NE82

UniProt curated annotations — full annotation on UniProt →

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_001157897* (*=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 (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NE82-F1	66.82	0.17

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 15 (showing top): GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_DNA_METHYLATION_DEPENDENT_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, 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, MIR92A_2_5P, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION, GOBP_CONSTITUTIVE_HETEROCHROMATIN_FORMATION, GOBP_CHROMATIN_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_RNA_BIOSYNTHETIC_PROCESS

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA methylation-dependent constitutive heterochromatin formation (GO:0006346)

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
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
nucleotide binding	1
sequence-specific DNA binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

258 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3L3	LEUTX	A8MZ59	580
MBD3L3	PRAMEF15	P0DUQ1	571
MBD3L3	PRAMEF25	A6NGN4	540
MBD3L3	TRIM49	P0CI25	513
MBD3L3	A0A096LNW4	A0A096LNW4	507
MBD3L3	DUXA	A6NLW8	507
MBD3L3	OR4F17	Q8NGA8	507
MBD3L3	DUXB	A0A1W2PPF3	503
MBD3L3	H3Y1	P0DPK2	496
MBD3L3	TRIM43	Q96BQ3	480
MBD3L3	ZSCAN4	Q8NAM6	480
MBD3L3	TRIM43B	A6NCK2	447
MBD3L3	RFPL4B	Q6ZWI9	446
MBD3L3	H3Y2	P0DPK5	437
MBD3L3	ZNF566	Q969W8	431

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MBD3L3	TRIML2	psi-mi:“MI:0915”(physical association)	0.560
MBD3L3	TRIML2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (1): MBD3L3 (Two-hybrid)

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

80 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7056899:TTCCC:T	acceptor_gain	1.0000
19:7056901:CCC:C	acceptor_gain	1.0000
19:7056902:CCC:C	acceptor_gain	1.0000
19:7056903:CCT:C	acceptor_gain	1.0000
19:7056904:C:CC	acceptor_gain	1.0000
19:7056905:T:C	acceptor_gain	1.0000
19:7056908:C:CT	acceptor_gain	1.0000
19:7056909:A:T	acceptor_gain	1.0000
19:7058557:TCA:T	donor_loss	1.0000
19:7058558:CACCA:C	donor_loss	1.0000
19:7058559:A:AC	donor_gain	1.0000
19:7058559:ACCAG:A	donor_loss	1.0000
19:7058560:C:CG	donor_loss	1.0000
19:7058560:C:CT	donor_gain	1.0000
19:7056901:CCCCT:C	acceptor_gain	0.9900
19:7056902:CC:C	acceptor_gain	0.9900
19:7056904:C:T	acceptor_gain	0.9900
19:7056905:T:TC	acceptor_gain	0.9900
19:7058555:A:AC	donor_gain	0.9900
19:7058556:C:CC	donor_gain	0.9900
19:7058556:CTCA:C	donor_gain	0.9900
19:7058559:AC:A	donor_gain	0.9900
19:7058560:CC:C	donor_gain	0.9900
19:7058560:CCAG:C	donor_gain	0.9900
19:7058560:CCAGA:C	donor_gain	0.9900
19:7056900:TCCC:T	acceptor_gain	0.9800
19:7058556:CT:C	donor_gain	0.9700
19:7058560:CCA:C	donor_gain	0.9700
19:7056900:TCCCC:T	acceptor_gain	0.9500
19:7056906:T:TC	acceptor_gain	0.9500

AlphaMissense

1337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7056778:G:C	F57L	0.947
19:7056778:G:T	F57L	0.947
19:7056780:A:G	F57L	0.947
19:7056787:G:C	S54R	0.916
19:7056787:G:T	S54R	0.916
19:7056789:T:G	S54R	0.916
19:7056391:C:A	R186S	0.898
19:7056391:C:G	R186S	0.898
19:7056791:G:A	T53I	0.887
19:7056415:C:A	Q178H	0.874
19:7056415:C:G	Q178H	0.874
19:7056779:A:G	F57S	0.866
19:7056764:G:A	T62I	0.855
19:7056392:C:A	R186M	0.843
19:7056758:A:G	I64T	0.842
19:7056782:A:G	I56T	0.832
19:7056796:T:A	R51S	0.824
19:7056796:T:G	R51S	0.824
19:7056375:C:G	A192P	0.809
19:7056779:A:C	F57C	0.808
19:7056881:A:G	M23T	0.806
19:7056396:C:G	A185P	0.803
19:7056788:C:A	S54I	0.797
19:7056425:A:G	I175T	0.791
19:7056371:A:G	L193S	0.781
19:7056392:C:G	R186T	0.777
19:7056440:A:T	V170E	0.775
19:7056691:T:A	Q86H	0.769
19:7056691:T:G	Q86H	0.769
19:7056786:A:G	C55R	0.765

dbSNP variants (sampled 300 via entrez): RS1002081621 (19:7056684 C>T), RS1002711986 (19:7055876 C>T), RS1002733154 (19:7055737 C>G,T), RS1003469872 (19:7058474 A>G), RS1005935452 (19:7060454 T>A), RS1006970306 (19:7056022 G>A,C,T), RS1010686627 (19:7056654 A>G), RS1011072542 (19:7056270 A>G), RS1012042347 (19:7055716 G>A), RS1014511248 (19:7056770 G>A,C), RS1014543743 (19:7060343 T>A), RS1017025852 (19:7060457 A>G,T), RS1017978500 (19:7056030 A>G,T), RS1018448564 (19:7055920 C>A), RS1021282934 (19:7059836 C>G)

Disease associations

OMIM: gene `` | 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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression, increases abundance	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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