MBD3L1

Summary

MBD3L1 (methyl-CpG binding domain protein 3 like 1, HGNC:15774) is a protein-coding gene on chromosome 19p13.2, encoding Methyl-CpG-binding domain protein 3-like 1 (Q8WWY6). Transcriptional repressor.

This gene encodes a protein that is related to methyl-CpG-binding proteins but lacks the methyl-CpG binding domain. The protein is localized to discrete areas in the nucleus, and expression appears to be restricted to round spermatids, suggesting that the protein plays a role in the postmeiotic stages of male germ cell development.

Source: NCBI Gene 85509 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_001393532

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15774
Approved symbol	MBD3L1
Name	methyl-CpG binding domain protein 3 like 1
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000170948
Ensembl biotype	protein_coding
OMIM	607963
Entrez	85509

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000305625, ENST00000595891

RefSeq mRNA: 4 — MANE Select: NM_001393532 NM_001393532, NM_001393533, NM_001393534, NM_145208

CCDS: CCDS12209

Canonical transcript exons

ENST00000595891 — 3 exons

Exon	Start	End
ENSE00002998889	8840915	8840999
ENSE00003031999	8842658	8843319
ENSE00003108041	8832377	8832522

Expression profiles

Bgee: expression breadth broad, 38 present calls, max score 92.33.

Top tissues by expression

219 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	92.33	gold quality
left testis	UBERON:0004533	86.07	gold quality
sperm	CL:0000019	85.17	gold quality
right testis	UBERON:0004534	84.73	gold quality
testis	UBERON:0000473	83.30	gold quality
buccal mucosa cell	CL:0002336	81.06	silver quality
right uterine tube	UBERON:0001302	72.35	gold quality
adult organism	UBERON:0007023	62.28	gold quality
oviduct epithelium	UBERON:0004804	61.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	59.11	gold quality
fallopian tube	UBERON:0003889	57.57	gold quality
myocardium	UBERON:0002349	55.17	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	54.59	gold quality
pericardium	UBERON:0002407	54.13	gold quality
lower lobe of lung	UBERON:0008949	52.74	silver quality
substantia nigra pars reticulata	UBERON:0001966	52.39	gold quality
lateral globus pallidus	UBERON:0002476	50.87	gold quality
oocyte	CL:0000023	50.21	gold quality
body of pancreas	UBERON:0001150	49.59	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.21	gold quality
subthalamic nucleus	UBERON:0001906	48.35	gold quality
granulocyte	CL:0000094	46.21	silver quality
upper leg skin	UBERON:0004262	45.95	silver quality
biceps brachii	UBERON:0001507	45.39	gold quality
amniotic fluid	UBERON:0000173	44.66	gold quality
synovial joint	UBERON:0002217	44.03	gold quality
dorsal plus ventral thalamus	UBERON:0001897	43.88	gold quality
inferior vagus X ganglion	UBERON:0005363	43.79	gold quality
medulla oblongata	UBERON:0001896	43.39	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.96

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• interacts with methyl-CpG-binding protein 2 (MBD2) and components of the NuRD complex (PMID:15456747)
• These factors lead to a binding affinity hierarchy of p66alpha for the different MBD2 homologues (MBD2 approximately MBD3 > MBD3L1 approximately MBD3L2). (PMID:23239876)
• These and other approaches identified the Nucleosome Remodeling Deacetylase (NuRD) and Chromatin Assembly Factor 1 (CAF-1) complexes as necessary for DUX4 repression in human skeletal muscle cells and induced pluripotent stem (iPS) cells.Furthermore, DUX4-induced expression of MBD3L proteins partly relieved this repression in FSHD muscle cells. (PMID:29533181)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbd3a	ENSDARG00000061774
mus_musculus	Mbd3l1	ENSMUSG00000038691
rattus_norvegicus	Mbd3l1	ENSRNOG00000006363
drosophila_melanogaster	MBD-like	FBGN0027950

Paralogs (8): MBD3 (ENSG00000071655), MBD2 (ENSG00000134046), MBD1 (ENSG00000141644), MBD3L3 (ENSG00000182315), MBD3L2B (ENSG00000196589), MBD3L4 (ENSG00000205718), MBD3L2 (ENSG00000230522), MBD3L5 (ENSG00000237247)

Protein

Protein identifiers

Methyl-CpG-binding domain protein 3-like 1 — Q8WWY6 (reviewed: Q8WWY6)

All UniProt accessions (1): Q8WWY6

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor.

Subcellular location. Nucleus.

Tissue specificity. Highly expressed in testis. Detected at low levels in pancreas. Not detected in the other tissues tested.

Domain organisation. The N-terminal half of the protein mediates transcription repression.

Miscellaneous. Does not bind methylated DNA. 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 (4): NP_001380461, NP_001380462, NP_001380463, NP_660209 (=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 (3 total): chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WWY6-F1	66.83	0.16

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9937850	NuRD complex assembly

MSigDB gene sets: 48 (showing top): ROVERSI_GLIOMA_COPY_NUMBER_UP, 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, SRC_UP.V1_UP, CHAF1B_TARGET_GENES, DIDO1_TARGET_GENES, ELF2_TARGET_GENES

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)

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
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

386 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBD3L1	MECP2	P51608	649
MBD3L1	OR2Z1	Q8NG97	582
MBD3L1	PRAMEF5	Q5TYX0	474
MBD3L1	ZNF558	Q96NG5	469
MBD3L1	OR1M1	Q8NGA1	468
MBD3L1	GATAD2A	Q86YP4	383
MBD3L1	PRAMEF15	P0DUQ1	370
MBD3L1	DNMT1	P26358	323
MBD3L1	GATAD2B	Q8WXI9	292
MBD3L1	MBD4	O95243	283
MBD3L1	ACCSL	Q4AC99	277
MBD3L1	SHROOM1	Q2M3G4	276
MBD3L1	ACTL9	Q8TC94	268
MBD3L1	TRDMT1	O14717	268
MBD3L1	H3Y2	P0DPK5	255

IntAct

133 interactions, top by confidence:

A	B	Type	Score
GATAD2A	MBD3L1	psi-mi:“MI:0915”(physical association)	0.670
EFHC1	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
ZNF77	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
ZNF76	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
ANKS1A	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
AIRIM	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
CLIC3	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
SNAPC5	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
TSGA10	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	NEK6	psi-mi:“MI:0915”(physical association)	0.560
MLH1	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	GTPBP3	psi-mi:“MI:0915”(physical association)	0.560
DTX2	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	NXF1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	NDUFAF3	psi-mi:“MI:0915”(physical association)	0.560
EXOC8	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
SUOX	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
BOLA2-SMG1P6	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	CTNNA3	psi-mi:“MI:0915”(physical association)	0.560
TRAPPC2	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560
MBD3L1	UBL5	psi-mi:“MI:0915”(physical association)	0.560
SNRPB	MBD3L1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (123): RBBP4 (Affinity Capture-MS), RBBP7 (Affinity Capture-MS), HDAC1 (Affinity Capture-MS), HDAC2 (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), CHD3 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), ZNF521 (Affinity Capture-MS), ZNF423 (Affinity Capture-MS), MTA2 (Affinity Capture-MS), MTA1 (Affinity Capture-MS), MTA3 (Affinity Capture-MS), CDK2AP1 (Affinity Capture-MS), BEND7 (Affinity Capture-MS)

ESM2 similar proteins: A2A7Y5, A2AFS9, A2AIW0, A6NFA0, A6NMK8, A9JRX0, B2RQL2, C3VD30, P54257, Q0VET5, Q0VG85, Q14B48, Q2M243, Q2YDE2, Q3V036, Q3V0C3, Q3V0M2, Q4R739, Q5E9L4, Q5PQS2, Q5R9L2, Q60664, Q6AYH0, Q6AYP4, Q6DF94, Q6GQV1, Q6NZK5, Q6P1D7, Q6ZRS4, Q6ZVD7, Q70YC5, Q7L3B6, Q7M6U3, Q7Z572, Q86WZ0, Q8BG89, Q8CCC3, Q8CCG1, Q8CH09, Q8IYA8

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

658 predictions. Top by Δscore:

Variant	Effect	Δscore
19:8832520:GGG:G	donor_gain	0.9800
19:8832521:GGG:G	donor_gain	0.9800
19:8832519:GGGG:G	donor_gain	0.9700
19:8832520:GGGG:G	donor_gain	0.9700
19:8832521:GG:G	donor_gain	0.9700
19:8832522:GG:G	donor_gain	0.9700
19:8832494:T:G	donor_gain	0.9500
19:8832523:GT:G	donor_loss	0.9500
19:8832524:T:A	donor_loss	0.9500
19:8832482:G:GG	donor_gain	0.9100
19:8832511:G:T	donor_gain	0.9100
19:8832462:G:GT	donor_gain	0.9000
19:8832481:A:AG	donor_gain	0.9000
19:8840911:GCA:G	acceptor_gain	0.9000
19:8840985:C:T	donor_gain	0.9000
19:8832511:G:GT	donor_gain	0.8900
19:8832523:G:GG	donor_gain	0.8900
19:8842656:A:AG	acceptor_gain	0.8900
19:8842657:G:GG	acceptor_gain	0.8900
19:8842657:GT:G	acceptor_gain	0.8800
19:8832525:A:AG	donor_loss	0.8700
19:8840911:GCAGT:G	acceptor_gain	0.8700
19:8840997:GTG:G	donor_gain	0.8700
19:8840911:GC:G	acceptor_gain	0.8000
19:8841211:T:TA	acceptor_gain	0.8000
19:8832478:C:G	donor_gain	0.7700
19:8832529:T:TA	donor_gain	0.7700
19:8832530:T:A	donor_gain	0.7700
19:8842972:TAG:T	acceptor_gain	0.7700
19:8832467:GTTCT:G	donor_gain	0.7500

AlphaMissense

1258 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:8842781:T:C	F35L	0.924
19:8842783:C:A	F35L	0.924
19:8842783:C:G	F35L	0.924
19:8843173:A:C	R165S	0.914
19:8843173:A:T	R165S	0.914
19:8842765:A:C	R29S	0.903
19:8842765:A:T	R29S	0.903
19:8843149:G:C	Q157H	0.850
19:8843149:G:T	Q157H	0.850
19:8843189:G:C	A171P	0.839
19:8842772:A:C	S32R	0.838
19:8842774:T:A	S32R	0.838
19:8842774:T:G	S32R	0.838
19:8843124:T:A	V149D	0.831
19:8842794:T:A	V39E	0.819
19:8842888:A:C	R70S	0.817
19:8842888:A:T	R70S	0.817
19:8843181:T:C	L168P	0.816
19:8842764:G:C	R29T	0.806
19:8843181:T:A	L168H	0.799
19:8842770:C:T	S31F	0.798
19:8843193:T:C	L172P	0.795
19:8843172:G:T	R165I	0.790
19:8842803:T:C	I42T	0.785
19:8842803:T:G	I42S	0.783
19:8842786:G:C	K36N	0.777
19:8842786:G:T	K36N	0.777
19:8842877:T:A	W67R	0.777
19:8842877:T:C	W67R	0.777
19:8842870:G:C	Q64H	0.776

dbSNP variants (sampled 300 via entrez): RS1000158420 (19:8835918 C>A,T), RS1000201811 (19:8838878 A>G), RS1000459045 (19:8833545 GTC>G), RS1000577804 (19:8836523 G>A), RS1000726641 (19:8830994 T>C), RS1000831242 (19:8833342 A>G,T), RS1000906547 (19:8836711 C>T), RS1001503414 (19:8838064 T>C), RS1001695950 (19:8832513 A>G), RS1001971467 (19:8843423 C>A), RS1002043287 (19:8832152 T>G), RS1002054435 (19:8843247 G>A), RS1002268923 (19:8834239 A>C,G), RS1002500572 (19:8839309 T>C), RS1002521575 (19:8836931 G>A)

Disease associations

OMIM: gene MIM:607963 | 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
perfluorooctanoic acid	decreases expression	1
Arsenic	affects methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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