MBD3L5

Summary

MBD3L5 (methyl-CpG binding domain protein 3 like 5, HGNC:37204) is a protein-coding gene on chromosome 19p13.2, encoding Methyl-CpG-binding domain protein 3-like 5 (A6NJ08).

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 284428 — RefSeq curated summary.

At a glance

• MANE Select transcript: NM_001136507

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37204
Approved symbol	MBD3L5
Name	methyl-CpG binding domain protein 3 like 5
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000237247
Ensembl biotype	protein_coding
Entrez	284428

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329753

RefSeq mRNA: 1 — MANE Select: NM_001136507 NM_001136507

CCDS: CCDS45942

Canonical transcript exons

ENST00000329753 — 2 exons

Exon	Start	End
ENSE00001594518	7032313	7033011
ENSE00002301436	7030578	7030656

Expression profiles

Bgee: expression breadth tissue_specific, 3 present calls, max score 72.10.

Top tissues by expression

131 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	72.10	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	67.39	silver quality
sural nerve	UBERON:0015488	37.36	gold 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
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
bone marrow	UBERON:0002371	32.78	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
smooth muscle tissue	UBERON:0001135	30.27	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
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
leukocyte	CL:0000738	26.38	gold quality
monocyte	CL:0000576	26.26	gold quality
blood	UBERON:0000178	25.98	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	24.86	gold quality
primary visual cortex	UBERON:0002436	24.61	gold quality
superior frontal gyrus	UBERON:0002661	24.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

16 targeting MBD3L5, 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), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3-like 5 — A6NJ08 (reviewed: A6NJ08)

All UniProt accessions (1): A6NJ08

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_001129979* (*=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-A6NJ08-F1	66.45	0.18

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

264 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3L5	TRIM43	Q96BQ3	580
MBD3L5	ZSCAN4	Q8NAM6	506
MBD3L5	PRAMEF25	A6NGN4	506
MBD3L5	OR4F17	Q8NGA8	475
MBD3L5	A0A096LNW4	A0A096LNW4	474
MBD3L5	DUXB	A0A1W2PPF3	471
MBD3L5	LEUTX	A8MZ59	448
MBD3L5	DUX4L2	P0CJ85	447
MBD3L5	PRAMEF15	P0DUQ1	447
MBD3L5	TRIM43B	A6NCK2	418
MBD3L5	RFPL4B	Q6ZWI9	415
MBD3L5	GOLGA8O	A6NCC3	400
MBD3L5	ZNF557	Q8N988	375
MBD3L5	MIER2	Q8N344	370
MBD3L5	KHDC1L	Q5JSQ8	370

IntAct

0 interactions, top by confidence:

BioGRID (1): MBD3L5 (Synthetic Lethality)

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

74 predictions. Top by Δscore:

Variant	Effect	Δscore
19:7030657:G:GG	donor_gain	1.0000
19:7032307:T:TA	acceptor_gain	1.0000
19:7032310:AAG:A	acceptor_gain	1.0000
19:7032310:AAGG:A	acceptor_gain	1.0000
19:7032311:A:AG	acceptor_gain	1.0000
19:7032311:A:T	acceptor_loss	1.0000
19:7032312:G:GA	acceptor_loss	1.0000
19:7032312:G:GG	acceptor_gain	1.0000
19:7032312:GGGGA:G	acceptor_gain	1.0000
19:7030652:TTCTG:T	donor_gain	0.9900
19:7030653:TCTG:T	donor_gain	0.9900
19:7030655:TG:T	donor_gain	0.9900
19:7030656:GG:G	donor_gain	0.9900
19:7030661:G:GG	donor_gain	0.9900
19:7032310:A:AG	acceptor_gain	0.9900
19:7032310:AAGGG:A	acceptor_gain	0.9900
19:7032311:AG:A	acceptor_gain	0.9900
19:7032311:AGG:A	acceptor_gain	0.9900
19:7032312:GG:G	acceptor_gain	0.9900
19:7032312:GGG:G	acceptor_gain	0.9900
19:7030660:A:AG	donor_gain	0.9800
19:7032311:AGGG:A	acceptor_gain	0.9800
19:7032312:GGGG:G	acceptor_gain	0.9800
19:7030654:CTG:C	donor_gain	0.9700
19:7030659:GA:G	donor_gain	0.9700
19:7032309:AAAG:A	acceptor_gain	0.9600
19:7032309:AAAGG:A	acceptor_gain	0.9600
19:7032311:AGGGG:A	acceptor_gain	0.9600
19:7032309:A:AG	acceptor_gain	0.9500
19:7030657:G:A	donor_gain	0.9400

AlphaMissense

1334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:7032436:T:C	F57L	0.957
19:7032438:C:A	F57L	0.957
19:7032438:C:G	F57L	0.957
19:7032825:G:C	R186S	0.914
19:7032825:G:T	R186S	0.914
19:7032425:C:T	T53I	0.897
19:7032427:A:C	S54R	0.897
19:7032429:C:A	S54R	0.897
19:7032429:C:G	S54R	0.897
19:7032801:G:C	Q178H	0.885
19:7032801:G:T	Q178H	0.885
19:7032437:T:C	F57S	0.880
19:7032824:G:T	R186M	0.870
19:7032452:C:T	T62I	0.865
19:7032458:T:C	I64T	0.857
19:7032841:G:C	A192P	0.851
19:7032437:T:G	F57C	0.845
19:7032820:G:C	A185P	0.829
19:7032434:T:C	I56T	0.824
19:7032420:A:C	R51S	0.813
19:7032420:A:T	R51S	0.813
19:7032824:G:C	R186T	0.812
19:7032791:T:C	I175T	0.805
19:7032845:T:C	L193S	0.804
19:7032335:T:C	M23T	0.803
19:7032458:T:G	I64S	0.782
19:7032436:T:A	F57I	0.781
19:7032436:T:G	F57V	0.781
19:7032776:T:A	V170E	0.781
19:7032428:G:T	S54I	0.780

dbSNP variants (sampled 300 via entrez): RS1007329409 (19:7032295 TTTC>T), RS1016487589 (19:7032989 A>C,G), RS1025648351 (19:7033124 TTG>T), RS1035933855 (19:7033310 T>A,G), RS1037547858 (19:7033478 G>C), RS1041397479 (19:7028987 G>C), RS1051622331 (19:7032212 G>A), RS1051655284 (19:7033417 A>G), RS111314830 (19:7032155 C>A), RS1156356488 (19:7030813 A>T), RS1157616389 (19:7032288 ATTTTC>A,ATTTTCTTTTC), RS1158380392 (19:7030232 G>A), RS1158431009 (19:7033338 C>A,T), RS1159705093 (19:7033148 G>C), RS1160014927 (19:7030618 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
Tretinoin	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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