MBNL3

Summary

MBNL3 (muscleblind like splicing regulator 3, HGNC:20564) is a protein-coding gene on chromosome Xq26.2, encoding Muscleblind-like protein 3 (Q9NUK0). Mediates pre-mRNA alternative splicing regulation.

This gene encodes a member of the muscleblind-like family of proteins. The encoded protein may function in regulation of alternative splicing and may play a role in the pathophysiology of myotonic dystrophy. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 55796 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001386889

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20564
Approved symbol	MBNL3
Name	muscleblind like splicing regulator 3
Location	Xq26.2
Locus type	gene with protein product
Status	Approved
Aliases	CHCR, FLJ11316, MBLX39, MBXL
Ensembl gene	ENSG00000076770
Ensembl biotype	protein_coding
OMIM	300413
Entrez	55796

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 19 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000370839, ENST00000370844, ENST00000370849, ENST00000370853, ENST00000370857, ENST00000394311, ENST00000421707, ENST00000436215, ENST00000442191, ENST00000473364, ENST00000538204, ENST00000698663, ENST00000698664, ENST00000698665, ENST00000852882, ENST00000852883, ENST00000852884, ENST00000852885, ENST00000852886, ENST00000852887

RefSeq mRNA: 28 — MANE Select: NM_001386889 NM_001170701, NM_001170702, NM_001170703, NM_001170704, NM_001386889, NM_001386891, NM_001386892, NM_001386894, NM_001386896, NM_001386897, NM_001386898, NM_001386899, NM_001386900, NM_001386901, NM_001386902, NM_001386907, NM_001386909, NM_001386910, NM_001386911, NM_001386912, NM_001386913, NM_001386914, NM_001386915, NM_001386916, NM_001386917, NM_001386918, NM_018388, NM_133486

CCDS: CCDS14633, CCDS14634, CCDS55492

Canonical transcript exons

ENST00000370853 — 9 exons

Exon	Start	End
ENSE00000407164	132390847	132391083
ENSE00001390603	132386661	132386811
ENSE00002203352	132369320	132379677
ENSE00003515301	132392143	132392334
ENSE00003634732	132382178	132382272
ENSE00003648811	132406228	132406392
ENSE00003787267	132384663	132384698
ENSE00003916999	132488851	132489038
ENSE00003920558	132439435	132440314

Expression profiles

Bgee: expression breadth ubiquitous, 241 present calls, max score 99.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.1330 / max 6055.2543, expressed in 1446 samples.

FANTOM5 promoters (19 alternative TSS)

Promoter ID	TPM avg	Samples expressed
200525	18.5273	1158
200522	2.3361	286
200524	2.1237	122
200531	1.6236	483
200523	1.3326	99
200529	1.0366	432
200520	0.8960	145
200527	0.8349	394
200530	0.5371	243
200519	0.2313	37

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cauda epididymis	UBERON:0004360	99.43	gold quality
germinal epithelium of ovary	UBERON:0001304	98.91	gold quality
corpus epididymis	UBERON:0004359	98.84	gold quality
trabecular bone tissue	UBERON:0002483	97.70	gold quality
placenta	UBERON:0001987	96.67	gold quality
gingival epithelium	UBERON:0001949	95.86	gold quality
caput epididymis	UBERON:0004358	95.11	gold quality
gingiva	UBERON:0001828	95.00	gold quality
adrenal tissue	UBERON:0018303	94.07	gold quality
seminal vesicle	UBERON:0000998	93.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.40	gold quality
esophagus squamous epithelium	UBERON:0006920	93.40	gold quality
parietal pleura	UBERON:0002400	92.91	gold quality
colonic mucosa	UBERON:0000317	92.82	gold quality
epithelium of nasopharynx	UBERON:0001951	92.66	gold quality
palpebral conjunctiva	UBERON:0001812	92.46	gold quality
blood	UBERON:0000178	91.89	gold quality
superficial temporal artery	UBERON:0001614	91.18	gold quality
oral cavity	UBERON:0000167	90.58	gold quality
parotid gland	UBERON:0001831	90.36	gold quality
pleura	UBERON:0000977	89.22	gold quality
jejunal mucosa	UBERON:0000399	89.00	gold quality
monocyte	CL:0000576	88.99	gold quality
liver	UBERON:0002107	88.82	gold quality
mononuclear cell	CL:0000842	88.63	gold quality
upper leg skin	UBERON:0004262	88.57	gold quality
leukocyte	CL:0000738	88.26	gold quality
bone marrow	UBERON:0002371	87.49	gold quality
sperm	CL:0000019	87.40	gold quality
visceral pleura	UBERON:0002401	87.38	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	130.14
E-MTAB-9221	yes	11.58
E-ANND-3	yes	4.59
E-MTAB-9467	no	0.65

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

531 targeting MBNL3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4262	100.00	73.26	3931

Literature-anchored findings (GeneRIF, showing 6)

• results suggest that CHCR is an inhibitor of myogenesis (PMID:12297108)
• MBNL proteins promote opposite splicing patterns for cardiac troponin T and insulin receptor alternative exons (PMID:15257297)
• We exclude MBNL3 as the causative gene in this family. (PMID:17102799)
• MBNL3 was not found in human samples. (PMID:19095965)
• The MBNL3 splicing factor promotes hepatocellular carcinoma by increasing pacillin expression through the alternative splicing of lncRNA-PXN-AS1. (PMID:28553938)
• KANSL2 and MBNL3 are regulators of pancreatic ductal adenocarcinoma invasion. (PMID:32001790)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbnl3	ENSDARG00000016085
mus_musculus	Mbnl3	ENSMUSG00000036109
rattus_norvegicus	Mbnl3	ENSRNOG00000002487
drosophila_melanogaster	mbl	FBGN0265487
caenorhabditis_elegans		WBGENE00019347

Paralogs (3): ZC3H10 (ENSG00000135482), MBNL2 (ENSG00000139793), MBNL1 (ENSG00000152601)

Protein

Protein identifiers

Muscleblind-like protein 3 — Q9NUK0 (reviewed: Q9NUK0)

Alternative names: Cys3His CCG1-required protein, Muscleblind-like X-linked protein, Protein HCHCR

All UniProt accessions (7): Q9NUK0, A0A8V8TM16, A0A8V8TNS0, B1AKI2, B1AKI4, B1AKI5, B1AKI6

UniProt curated annotations — full annotation on UniProt →

Function. Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. May play a role in myotonic dystrophy pathophysiology (DM). Could inhibit terminal muscle differentiation, acting at approximately the time of myogenin induction.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in the placenta.

Similarity. Belongs to the muscleblind family.

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NUK0-1	1, HCHCR-G, G	yes
Q9NUK0-2	2, HCHCR-R, R
Q9NUK0-3	3
Q9NUK0-4	4
Q9NUK0-5	5

RefSeq proteins (28): NP_001164172, NP_001164173, NP_001164174, NP_001164175, NP_001373818, NP_001373820, NP_001373821, NP_001373823, NP_001373825, NP_001373826, NP_001373827, NP_001373828, NP_001373829, NP_001373830, NP_001373831, NP_001373836, NP_001373838, NP_001373839, NP_001373840, NP_001373841, NP_001373842, NP_001373843, NP_001373844, NP_001373845, NP_001373846, NP_001373847, NP_060858, NP_597846 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000571	Znf_CCCH	Domain
IPR054429	Znf-CCCH_Muscleblind-like	Domain

Pfam: PF00642, PF14608, PF22628

UniProt features (13 total): splice variant 6, zinc finger region 4, sequence conflict 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NUK0-F1	68.64	0.27

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 365 (showing top): GOZGIT_ESR1_TARGETS_DN, PATIL_LIVER_CANCER, GOBP_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, CHARAFE_BREAST_CANCER_BASAL_VS_MESENCHYMAL_UP, GOBP_NEGATIVE_REGULATION_OF_MYOBLAST_DIFFERENTIATION, GOBP_RNA_SPLICING, GOBP_MYOBLAST_DIFFERENTIATION, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, ZHANG_BREAST_CANCER_PROGENITORS_UP, CUI_TCF21_TARGETS_2_DN, MODULE_397, MARIADASON_RESPONSE_TO_BUTYRATE_SULINDAC_6, GOBP_REGULATION_OF_RNA_SPLICING

GO Biological Process (4): mRNA processing (GO:0006397), RNA splicing (GO:0008380), regulation of RNA splicing (GO:0043484), negative regulation of myoblast differentiation (GO:0045662)

GO Molecular Function (4): RNA binding (GO:0003723), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
mRNA metabolic process	1
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
myoblast differentiation	1
negative regulation of cell differentiation	1
regulation of myoblast differentiation	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1044 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBNL3	CNBP	P20694	971
MBNL3	CELF1	Q92879	900
MBNL3	CLCN1	P35523	897
MBNL3	QKI	Q96PU8	890
MBNL3	DMPK	Q09013	845
MBNL3	MBNL2	Q5VZF2	646
MBNL3	CELF2	O95319	609
MBNL3	MBNL1	Q9NR56	604
MBNL3	ADAR	P55265	604
MBNL3	ZNF609	O15014	599
MBNL3	CELF3	Q5SZQ8	589
MBNL3	CEBPD	P49716	583
MBNL3	SRY	Q05066	580
MBNL3	FMR1	Q06787	575
MBNL3	CELF4	Q9BZC1	573

IntAct

10 interactions, top by confidence:

A	B	Type	Score
IGF2BP1	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
DAB1	MBNL3	psi-mi:“MI:0915”(physical association)	0.560
MBNL3	DAB1	psi-mi:“MI:0915”(physical association)	0.560
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
CPNE5	RAD21	psi-mi:“MI:0914”(association)	0.530
SRPK1	MBNL3	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
BMI1	MEIS3P1	psi-mi:“MI:0914”(association)	0.350
MBNL1	MBNL2	psi-mi:“MI:0914”(association)	0.350

BioGRID (22): MBNL3 (Two-hybrid), MBNL3 (Affinity Capture-RNA), MBNL3 (Affinity Capture-RNA), MBNL3 (Affinity Capture-RNA), MBNL3 (Affinity Capture-MS), MBNL3 (Affinity Capture-MS), MBNL3 (Affinity Capture-MS), PRR20B (Two-hybrid), PRR20A (Two-hybrid), PRR20D (Two-hybrid), PRR20C (Two-hybrid), PRR20E (Two-hybrid), MBNL3 (Affinity Capture-MS), MBNL3 (Affinity Capture-MS), MBNL3 (Affinity Capture-MS)

ESM2 similar proteins: A0A8I6B1J2, A0AV96, A8XND8, B3M3R5, B3NGA1, B4HUE4, B4IX08, B4KX02, B4LFQ9, B4MM23, B4PIS2, B4QRJ0, F2Z3T4, G5EFF1, O01367, P16914, P31367, Q0V9L3, Q24312, Q32NN2, Q56V19, Q5R4F5, Q5R5P4, Q5VZF2, Q5W9D5, Q5W9D6, Q5W9D7, Q5ZKW9, Q66H68, Q6IRN2, Q6P0D0, Q6P104, Q6Q2B2, Q7JJZ8, Q7TSY6, Q8C181, Q8MSV2, Q8R003, Q8R205, Q91WT8

Diamond homologs: A0A8I6B1J2, A8XND8, F2Z3T4, O16011, Q0JD07, Q56V19, Q5R4F5, Q5VZF2, Q5ZKW9, Q6Q2B2, Q8C181, Q8R003, Q94250, Q9JKP5, Q9NR56, Q9NUK0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1272 predictions. Top by Δscore:

Variant	Effect	Δscore
X:132382288:C:CT	acceptor_gain	1.0000
X:132384719:CG:C	acceptor_gain	1.0000
X:132384720:G:GC	acceptor_gain	1.0000
X:132390842:CTTAC:C	donor_loss	1.0000
X:132390844:TACC:T	donor_loss	1.0000
X:132390845:A:T	donor_loss	1.0000
X:132391083:CCT:C	acceptor_gain	1.0000
X:132391085:T:C	acceptor_gain	1.0000
X:132391085:T:TC	acceptor_gain	1.0000
X:132392144:T:TA	donor_gain	1.0000
X:132406220:CGACT:C	donor_loss	1.0000
X:132406221:GACTT:G	donor_loss	1.0000
X:132406222:ACTTA:A	donor_loss	1.0000
X:132406223:CTTA:C	donor_loss	1.0000
X:132406224:TT:T	donor_loss	1.0000
X:132406225:TACAA:T	donor_loss	1.0000
X:132406226:A:AC	donor_gain	1.0000
X:132406226:ACAAG:A	donor_loss	1.0000
X:132406227:C:CT	donor_gain	1.0000
X:132406227:CA:C	donor_gain	1.0000
X:132406227:CAA:C	donor_gain	1.0000
X:132406227:CAAG:C	donor_gain	1.0000
X:132406227:CAAGT:C	donor_gain	1.0000
X:132406391:CC:C	acceptor_gain	1.0000
X:132406392:CC:C	acceptor_gain	1.0000
X:132406393:C:T	acceptor_gain	1.0000
X:132439430:CTCA:C	donor_loss	1.0000
X:132439431:TCAC:T	donor_loss	1.0000
X:132439432:CACCT:C	donor_loss	1.0000
X:132439433:A:AT	donor_loss	1.0000

AlphaMissense

2307 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:132390921:G:C	H233D	1.000
X:132390926:T:C	Y231C	1.000
X:132390927:A:G	Y231H	1.000
X:132390932:C:G	C229S	1.000
X:132390933:A:G	C229R	1.000
X:132390933:A:T	C229S	1.000
X:132390946:G:C	C224W	1.000
X:132390947:C:G	C224S	1.000
X:132390948:A:G	C224R	1.000
X:132390948:A:T	C224S	1.000
X:132390965:T:A	D218V	1.000
X:132390970:G:C	C216W	1.000
X:132390971:C:A	C216F	1.000
X:132390971:C:G	C216S	1.000
X:132390971:C:T	C216Y	1.000
X:132390972:A:G	C216R	1.000
X:132390972:A:T	C216S	1.000
X:132391023:G:C	H199D	1.000
X:132391033:G:C	C195W	1.000
X:132391034:C:G	C195S	1.000
X:132391034:C:T	C195Y	1.000
X:132391035:A:G	C195R	1.000
X:132391035:A:T	C195S	1.000
X:132391054:A:C	C188W	1.000
X:132391055:C:G	C188S	1.000
X:132391055:C:T	C188Y	1.000
X:132391056:A:G	C188R	1.000
X:132391056:A:T	C188S	1.000
X:132391078:G:C	C180W	1.000
X:132391079:C:G	C180S	1.000

dbSNP variants (sampled 300 via entrez): RS1000002499 (X:132473640 C>A,T), RS1000095416 (X:132473156 T>C), RS1000138006 (X:132380540 G>A), RS1000224097 (X:132431610 G>A), RS1000287573 (X:132443129 A>G), RS1000371540 (X:132450721 G>A,C), RS1000380194 (X:132429156 A>G), RS1000382348 (X:132463277 C>A), RS1000432603 (X:132428578 GAA>G,GA,GAAA), RS1000466017 (X:132407255 A>G), RS1000470760 (X:132409198 G>A), RS1000529941 (X:132467619 A>G), RS1000541338 (X:132400128 T>C), RS1000542662 (X:132408549 T>C), RS1000618377 (X:132418989 G>A,C)

Disease associations

OMIM: gene MIM:300413 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006442_459	Educational attainment (years of education)	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

45 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases methylation	9
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	5
trichostatin A	affects cotreatment, increases expression	3
Vorinostat	affects cotreatment, increases expression, decreases expression	3
Cyclosporine	decreases expression	3
bisphenol A	affects expression, affects cotreatment, decreases methylation	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Panobinostat	increases expression, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Cisplatin	affects expression, decreases expression	2
Phenylmercuric Acetate	increases expression, affects cotreatment	2
Tretinoin	decreases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	increases expression	1
hydroquinone	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	affects cotreatment, increases expression	1
Copper	decreases expression, affects binding	1

Clinical trials (associated diseases)

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