MBD3L4

Summary

MBD3L4 (methyl-CpG binding domain protein 3 like 4, HGNC:37206) is a protein-coding gene on chromosome 19p13.2, encoding Methyl-CpG-binding domain protein 3-like 4 (A6NDZ8).

This gene encodes a member of a family of proteins that are related to methyl-CpG-binding proteins but lack the methyl-CpG binding domain. There is no definitive support for transcription of this locus, and the transcript structure is inferred from other family members.

Source: NCBI Gene 653656 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001164419

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37206
Approved symbol	MBD3L4
Name	methyl-CpG binding domain protein 3 like 4
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205718
Ensembl biotype	protein_coding
Entrez	653656

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000381394

RefSeq mRNA: 1 — MANE Select: NM_001164419 NM_001164419

CCDS: CCDS54205

Canonical transcript exons

ENST00000381394 — 2 exons

Exon	Start	End
ENSE00001613202	7037749	7038442
ENSE00002271722	7040100	7040179

Expression profiles

Bgee: expression breadth not_expressed, 0 present calls, max score 37.20.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	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
bone marrow cell	CL:0002092	36.16	gold quality
skeletal muscle tissue	UBERON:0001134	35.53	gold quality
granulocyte	CL:0000094	33.91	gold quality
bone marrow	UBERON:0002371	32.79	gold quality
muscle tissue	UBERON:0002385	32.64	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	30.29	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	28.53	gold quality
duodenum	UBERON:0002114	28.14	gold quality
monocyte	CL:0000576	28.11	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	27.70	silver quality
lymph node	UBERON:0000029	27.57	gold quality
primary visual cortex	UBERON:0002436	27.30	gold quality
tonsil	UBERON:0002372	27.05	gold quality
islet of Langerhans	UBERON:0000006	26.88	gold quality
urinary bladder	UBERON:0001255	26.61	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
frontal cortex	UBERON:0001870	26.01	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
blood	UBERON:0000178	25.85	gold quality
placenta	UBERON:0001987	25.81	gold quality
muscle of leg	UBERON:0001383	25.17	gold quality
calcaneal tendon	UBERON:0003701	25.02	gold quality
pancreas	UBERON:0001264	24.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.49

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MBD3L4, 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), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3-like 4 — A6NDZ8 (reviewed: A6NDZ8)

All UniProt accessions (1): A6NDZ8

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_001157891* (*=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-A6NDZ8-F1	67.60	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 (1): methyl-CpG binding (GO:0008327)

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
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

158 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3L4	OR4F17	Q8NGA8	610
MBD3L4	ZNF557	Q8N988	528
MBD3L4	MIER2	Q8N344	507
MBD3L4	RFESD	Q8TAC1	351
MBD3L4	PLPP2	O43688	300
MBD3L4	ADGRE1	Q14246	257
MBD3L4	DUX4L2	P0CJ85	248
MBD3L4	TMEM130	Q8N3G9	232
MBD3L4	SIN3B	O75182	205
MBD3L4	GATAD2B	Q8WXI9	201
MBD3L4	TRIM43	Q96BQ3	199
MBD3L4	CHAF1A	Q13111	199
MBD3L4	MTA3	Q9BTC8	196
MBD3L4	DIP2C	Q9Y2E4	189
MBD3L4	SAP18	O00422	186

IntAct

0 interactions, top by confidence:

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

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

73 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7038438:TTCCC:T	acceptor_gain	1.0000
19:7038440:CCC:C	acceptor_gain	1.0000
19:7038440:CCCC:C	acceptor_loss	1.0000
19:7038441:CC:C	acceptor_gain	1.0000
19:7038441:CCC:C	acceptor_gain	1.0000
19:7038442:CC:C	acceptor_gain	1.0000
19:7038443:C:A	acceptor_loss	1.0000
19:7038443:C:CC	acceptor_gain	1.0000
19:7038444:T:C	acceptor_gain	1.0000
19:7038444:T:G	acceptor_loss	1.0000
19:7038447:C:CT	acceptor_gain	1.0000
19:7038448:A:T	acceptor_gain	1.0000
19:7040096:TCA:T	donor_loss	1.0000
19:7040097:CA:C	donor_loss	1.0000
19:7040098:A:AC	donor_gain	1.0000
19:7040098:ACCAG:A	donor_loss	1.0000
19:7040099:C:CC	donor_gain	1.0000
19:7038440:CCCCT:C	acceptor_gain	0.9900
19:7038443:C:T	acceptor_gain	0.9900
19:7038444:T:TC	acceptor_gain	0.9900
19:7040094:A:AC	donor_gain	0.9900
19:7040095:C:CC	donor_gain	0.9900
19:7040095:CTCA:C	donor_gain	0.9900
19:7040098:AC:A	donor_gain	0.9900
19:7040099:CC:C	donor_gain	0.9900
19:7040099:CCAG:C	donor_gain	0.9900
19:7040099:CCAGA:C	donor_gain	0.9900
19:7038439:TCCC:T	acceptor_gain	0.9800
19:7040095:CT:C	donor_gain	0.9700
19:7040099:CCA:C	donor_gain	0.9700

AlphaMissense

1335 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7038317:G:C	F57L	0.961
19:7038317:G:T	F57L	0.961
19:7038319:A:G	F57L	0.961
19:7037930:C:A	R186S	0.915
19:7037930:C:G	R186S	0.915
19:7038326:G:C	S54R	0.905
19:7038326:G:T	S54R	0.905
19:7038328:T:G	S54R	0.905
19:7038330:G:A	T53I	0.900
19:7037954:C:A	Q178H	0.889
19:7037954:C:G	Q178H	0.889
19:7037931:C:A	R186M	0.877
19:7038318:A:G	F57S	0.873
19:7038297:A:G	I64T	0.862
19:7038303:G:A	T62I	0.861
19:7037914:C:G	A192P	0.853
19:7038318:A:C	F57C	0.844
19:7038321:A:G	I56T	0.836
19:7037935:C:G	A185P	0.834
19:7038335:T:A	R51S	0.830
19:7038335:T:G	R51S	0.830
19:7037931:C:G	R186T	0.814
19:7038420:A:G	M23T	0.808
19:7037964:A:G	I175T	0.807
19:7037910:A:G	L193S	0.796
19:7038327:C:A	S54I	0.796
19:7038230:T:A	Q86H	0.793
19:7038230:T:G	Q86H	0.793
19:7038297:A:C	I64S	0.788
19:7038319:A:T	F57I	0.782

dbSNP variants (sampled 300 via entrez): RS1006243984 (19:7039961 A>C,G), RS1006502342 (19:7037358 C>A,T), RS1008031456 (19:7037307 C>A,G), RS1013806536 (19:7040253 G>A,C), RS1014905723 (19:7040014 A>G), RS1015165849 (19:7037415 C>T), RS1025188015 (19:7040291 C>A,T), RS1029033692 (19:7037345 T>A), RS1040824968 (19:7037320 A>C,G), RS1040857694 (19:7037798 C>A,T), RS1052298171 (19:7037280 G>C), RS1052328223 (19:7037747 T>C), RS1157858679 (19:7042060 G>T), RS1158378333 (19:7037611 C>G), RS1159066526 (19:7037547 G>C)

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

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases methylation	1
Cyclosporine	increases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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