MBTD1

Summary

MBTD1 (mbt domain containing 1, HGNC:19866) is a protein-coding gene on chromosome 17q21.33, encoding MBT domain-containing protein 1 (Q05BQ5). Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. It is a selective cancer dependency (DepMap: 18.2% of cell lines).

Enables NuA4 histone acetyltransferase complex binding activity and methylated histone binding activity. Involved in double-strand break repair via homologous recombination; positive regulation of double-strand break repair via homologous recombination; and regulation of cell cycle. Part of NuA4 histone acetyltransferase complex and nucleosome. Is active in site of double-strand break.

Source: NCBI Gene 54799 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 80 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 18.2% of screened cell lines
• MANE Select transcript: NM_017643

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19866
Approved symbol	MBTD1
Name	mbt domain containing 1
Location	17q21.33
Locus type	gene with protein product
Status	Approved
Aliases	SA49P01, FLJ20055
Ensembl gene	ENSG00000011258
Ensembl biotype	protein_coding
OMIM	618705
Entrez	54799

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 16 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000376381, ENST00000405860, ENST00000415868, ENST00000586178, ENST00000586898, ENST00000591270, ENST00000593259, ENST00000874452, ENST00000932336, ENST00000932337, ENST00000932338, ENST00000932339, ENST00000932340, ENST00000932341, ENST00000932342, ENST00000932343, ENST00000932344, ENST00000932345, ENST00000932346, ENST00000932347

RefSeq mRNA: 1 — MANE Select: NM_017643 NM_017643

CCDS: CCDS11581

Canonical transcript exons

ENST00000586178 — 17 exons

Exon	Start	End
ENSE00001506036	51192203	51192280
ENSE00001514401	51259143	51259206
ENSE00001548058	51177425	51180694
ENSE00002790469	51259835	51260049
ENSE00003472664	51220330	51220463
ENSE00003481497	51203140	51203228
ENSE00003483308	51201592	51201696
ENSE00003488718	51218930	51219044
ENSE00003503087	51202701	51202935
ENSE00003553045	51217334	51217416
ENSE00003566242	51203791	51203925
ENSE00003570430	51195214	51195361
ENSE00003583580	51192782	51193016
ENSE00003656960	51202022	51202077
ENSE00003658048	51225008	51225209
ENSE00003727026	51206888	51207005
ENSE00003733442	51193428	51193510

Expression profiles

Bgee: expression breadth ubiquitous, 265 present calls, max score 94.46.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.6366 / max 123.7550, expressed in 1620 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
167031	7.4451	1603
167032	0.1914	81

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper leg skin	UBERON:0004262	94.46	gold quality
tibia	UBERON:0000979	93.05	gold quality
germinal epithelium of ovary	UBERON:0001304	92.96	gold quality
buccal mucosa cell	CL:0002336	92.92	gold quality
parietal pleura	UBERON:0002400	90.89	gold quality
cortical plate	UBERON:0005343	90.43	gold quality
visceral pleura	UBERON:0002401	90.32	gold quality
ganglionic eminence	UBERON:0004023	90.30	gold quality
amniotic fluid	UBERON:0000173	90.23	gold quality
adult organism	UBERON:0007023	89.71	gold quality
skin of hip	UBERON:0001554	89.58	gold quality
palpebral conjunctiva	UBERON:0001812	89.55	gold quality
sperm	CL:0000019	89.43	gold quality
esophagus squamous epithelium	UBERON:0006920	89.25	gold quality
epithelium of nasopharynx	UBERON:0001951	89.02	gold quality
ventricular zone	UBERON:0003053	89.00	gold quality
pleura	UBERON:0000977	88.82	gold quality
jejunal mucosa	UBERON:0000399	88.61	gold quality
pigmented layer of retina	UBERON:0001782	87.62	gold quality
gingival epithelium	UBERON:0001949	87.57	gold quality
corpus epididymis	UBERON:0004359	87.49	gold quality
male germ cell	CL:0000015	87.46	gold quality
trabecular bone tissue	UBERON:0002483	87.31	gold quality
penis	UBERON:0000989	87.24	gold quality
endometrium	UBERON:0001295	87.21	gold quality
caput epididymis	UBERON:0004358	87.14	gold quality
seminal vesicle	UBERON:0000998	87.04	gold quality
monocyte	CL:0000576	87.03	gold quality
oral cavity	UBERON:0000167	86.93	gold quality
mononuclear cell	CL:0000842	86.84	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	5.08

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

311 targeting MBTD1, 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-3646	100.00	73.56	5283
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 18.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 8)

• structural analysis of a four-MBT repeat protein MBTD1 (PMID:19841675)
• The chimeric MBTD1-CXorf67 fusion identifies yet another cytogenetically distinct subgroup of low-grade Endometrial stromal sarcomas and offers the opportunity to shed light on the functions of two poorly characterized genes. (PMID:23959973)
• In this study, we show that this translocation results in an in-frame translocation fusing exon 12 of the tumor suppressor gene ZMYND11 to exon 3 of the chromatin protein MBTD1, encoding a protein of 1,054 amino acids (PMID:26608508)
• Structural Basis for EPC1-Mediated Recruitment of MBTD1 into the NuA4/TIP60 Acetyltransferase Complex. (PMID:32209463)
• A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review. (PMID:32237188)
• ZMYND11-MBTD1 induces leukemogenesis through hijacking NuA4/TIP60 acetyltransferase complex and a PWWP-mediated chromatin association mechanism. (PMID:33594072)
• Oncogenic ZMYND11-MBTD1 fusion protein anchors the NuA4/TIP60 histone acetyltransferase complex to the coding region of active genes. (PMID:35705031)
• Long Non-coding RNA H19 Recruits NFYB to Activate MBTD1 and Regulate Doxorubicin Resistance in Lymphoma Cells. (PMID:36434485)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mbtd1	ENSDARG00000060868
mus_musculus	Mbtd1	ENSMUSG00000059474
rattus_norvegicus	Mbtd1	ENSRNOG00000049988

Paralogs (18): SCMH1 (ENSG00000010803), SCML1 (ENSG00000047634), L3MBTL2 (ENSG00000100395), SCML2 (ENSG00000102098), PHC1 (ENSG00000111752), THAP10 (ENSG00000129028), PHC2 (ENSG00000134686), SAMD1 (ENSG00000141858), SCML4 (ENSG00000146285), L3MBTL4 (ENSG00000154655), SFMBT1 (ENSG00000163935), PHC3 (ENSG00000173889), L3MBTL1 (ENSG00000185513), SAMD7 (ENSG00000187033), SAMD11 (ENSG00000187634), SFMBT2 (ENSG00000198879), L3MBTL3 (ENSG00000198945), SAMD13 (ENSG00000203943)

Protein

Protein identifiers

MBT domain-containing protein 1 — Q05BQ5 (reviewed: Q05BQ5)

All UniProt accessions (2): Q05BQ5, K7EQ11

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR). MBTD1 specifically recognizes and binds monomethylated and dimethylated ‘Lys-20’ on histone H4 (H4K20me1 and H4K20me2, respectively). In the NuA4 complex, MBTD1 promotes recruitment of the complex to H4K20me marks by competing with TP53BP1 for binding to H4K20me. Following recruitment to H4K20me at DNA breaks, the NuA4 complex catalyzes acetylation of ‘Lys-15’ on histone H2A (H2AK15), blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks, thereby promoting homologous recombination (HR).

Subunit / interactions. Monomer. Component of the NuA4 histone acetyltransferase complex. Interacts with EPC1; interaction is direct and promotes recruitment of MBTD1 into the NuA4 histone acetyltransferase complex.

Subcellular location. Nucleus. Chromosome.

Disease relevance. A chromosomal aberration involving MBTD1 is a cause of acute poorly differentiated myeloid leukemia. Translocation (10;17)(p15;q21) with ZMYND11.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (3)

UniProt ID	Names	Canonical?
Q05BQ5-1	1	yes
Q05BQ5-2	2
Q05BQ5-3	3

RefSeq proteins (1): NP_060113* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004092	Mbt	Domain
IPR012313	Znf_FCS	Domain
IPR038603	Znf_FCS_sf	Homologous_superfamily
IPR050548	PcG_chromatin_remod_factors	Family

Pfam: PF02820, PF21319

UniProt features (62 total): strand 20, helix 15, repeat 4, binding site 4, splice variant 4, mutagenesis site 4, compositionally biased region 3, region of interest 3, chain 1, modified residue 1, sequence conflict 1, turn 1, zinc finger region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6NFX	X-RAY DIFFRACTION	1.95
3FEO	X-RAY DIFFRACTION	2.5
4C5I	X-RAY DIFFRACTION	2.59

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05BQ5-F1	79.76	0.63

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (4): 54; 57; 74; 78

Post-translational modifications (1): 115

Mutagenesis-validated functional residues (4):

Position	Phenotype
236	impaired interaction with epc1; when associated with 259-d–d-263.
236	impaired interaction with epc1. abolished interaction with epc1; when associated with 259-g–g-263.
259–263	impaired interaction with epc1; when associated with d-236.
259–263	impaired interaction with epc1. abolished interaction with epc1; when associated with g-236.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 301 (showing top): GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR, GOBP_REGULATION_OF_DNA_RECOMBINATION, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_REGULATION_OF_DOUBLE_STRAND_BREAK_REPAIR_VIA_HOMOLOGOUS_RECOMBINATION, GOBP_REGULATION_OF_DNA_REPAIR, YAO_TEMPORAL_RESPONSE_TO_PROGESTERONE_CLUSTER_3, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, GOBP_DNA_DAMAGE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_DNA_REPAIR, DODD_NASOPHARYNGEAL_CARCINOMA_UP, HOOI_ST7_TARGETS_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_STRESS

GO Biological Process (11): double-strand break repair via homologous recombination (GO:0000724), regulation of apoptotic process (GO:0042981), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), embryonic skeletal system development (GO:0048706), regulation of cell cycle (GO:0051726), positive regulation of double-strand break repair via homologous recombination (GO:1905168), regulation of double-strand break repair (GO:2000779), double-strand break repair via nonhomologous end joining (GO:0006303), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (7): chromatin binding (GO:0003682), zinc ion binding (GO:0008270), NuA4 histone acetyltransferase complex binding (GO:0062060), histone H4K20me2 reader activity (GO:0140005), histone H4K20me1 reader activity (GO:0140117), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleosome (GO:0000786), nucleus (GO:0005634), NuA4 histone acetyltransferase complex (GO:0035267), site of double-strand break (GO:0035861), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
double-strand break repair	3
DNA-templated transcription	3
regulation of DNA-templated transcription	2
binding	2
histone H4 reader activity	2
recombinational repair	1
apoptotic process	1
regulation of programmed cell death	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
skeletal system development	1
chordate embryonic development	1
cell cycle	1
regulation of cellular process	1
double-strand break repair via homologous recombination	1
regulation of double-strand break repair via homologous recombination	1
positive regulation of DNA recombination	1
positive regulation of double-strand break repair	1
regulation of DNA repair	1
cellular component organization	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transition metal ion binding	1
protein-containing complex binding	1
cation binding	1
chromatin	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
H4/H2A histone acetyltransferase complex	1
site of DNA damage	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MBTD1	MEAF6	Q9HAF1	817
MBTD1	EZHIP	Q86X51	772
MBTD1	PHF1	O43189	729
MBTD1	JAZF1	Q86VZ6	701
MBTD1	KAT5	Q92993	659
MBTD1	BRD8	Q9H0E9	656
MBTD1	EPC2	Q52LR7	633
MBTD1	SUZ12	Q15022	594
MBTD1	ZC3H7B	Q9UGR2	575
MBTD1	YY1	P25490	553
MBTD1	MORF4L1	Q9UBU8	543
MBTD1	NUTM2A	Q8IVF1	510
MBTD1	ING3	Q9NXR8	503
MBTD1	DMAP1	Q9NPF5	494
MBTD1	E2F6	O75461	476

IntAct

98 interactions, top by confidence:

A	B	Type	Score
RUVBL1	ZNHIT1	psi-mi:“MI:0914”(association)	0.860
YEATS4	ZNHIT1	psi-mi:“MI:0914”(association)	0.790
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
MBTD1	YEATS4	psi-mi:“MI:0914”(association)	0.730
MBTD1	MORF4L2	psi-mi:“MI:0914”(association)	0.730
MORF4L1	SIN3B	psi-mi:“MI:0914”(association)	0.730
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
RUVBL2	POLR3A	psi-mi:“MI:0914”(association)	0.640
RUVBL1	POLR3A	psi-mi:“MI:0914”(association)	0.640
MORF4L2	YEATS4	psi-mi:“MI:0914”(association)	0.640
FOXR1	YEATS4	psi-mi:“MI:0914”(association)	0.640
EPC2	YEATS4	psi-mi:“MI:0914”(association)	0.640
H4C16	MBTD1	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (152): MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), MBTD1 (Affinity Capture-MS), TRRAP (Affinity Capture-MS)

ESM2 similar proteins: A0JM98, A1L1H3, A6NAF9, A6QLE1, A9CPT4, B5MCY1, D2H0H6, D2H3M0, E1BPH3, E1C3S7, E2QTD3, E2RDV1, E7FDW8, F1R237, O60522, P59178, P61407, Q05BQ5, Q1JQD9, Q1L981, Q32N90, Q3MIF2, Q3U3W5, Q4R3G4, Q58EK5, Q5DTW2, Q5M7P8, Q5R737, Q5RAH6, Q5VZ19, Q6DIN3, Q6NU04, Q6P5G3, Q8BGG7, Q8CAS9, Q8IXQ6, Q8K1H1, Q8NAT2, Q8NHU6, Q90WE3

Diamond homologs: A2A5N8, B1B1A0, D3YUG0, D3YXK1, D3ZWK4, E1C2V1, O02274, O60284, O95251, P39769, P59178, P70047, P70475, P78364, P97500, Q01538, Q05BQ5, Q1JQD9, Q1RNF8, Q29L50, Q32N90, Q3MIF2, Q4V7W5, Q5DTW2, Q5R737, Q5SVQ0, Q5VUG0, Q5VXD3, Q64028, Q6DIN3, Q6P5G3, Q6SPE9, Q6SPF0, Q7Z3H4, Q80TY4, Q810T5, Q8BLB7, Q8C8Y5, Q8CFC2, Q8CHP6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
MBTD1	“form complex”	“NuA4 complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 81 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
HATs acetylate histones	17	25.4×	1e-17
Chromatin organization	13	20.0×	7e-12
Chromatin modifying enzymes	13	17.7×	2e-11
Deposition of new CENPA-containing nucleosomes at the centromere	5	15.0×	8e-04
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks	5	13.8×	1e-03
Formation of the beta-catenin:TCF transactivating complex	6	13.6×	3e-04
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function	5	11.3×	2e-03
NoRC negatively regulates rRNA expression	5	9.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of double-strand break repair	13	102.1×	2e-21
positive regulation of double-strand break repair via homologous recombination	13	67.3×	8e-19
regulation of DNA replication	6	29.7×	3e-06
regulation of apoptotic process	14	15.8×	2e-11
regulation of cell cycle	15	15.1×	5e-12
chromatin organization	10	13.4×	2e-07
chromatin remodeling	10	9.9×	3e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	68
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3529 predictions. Top by Δscore:

Variant	Effect	Δscore
17:51180693:CA:C	acceptor_gain	1.0000
17:51180695:C:CC	acceptor_gain	1.0000
17:51180699:A:AC	acceptor_gain	1.0000
17:51180699:A:C	acceptor_gain	1.0000
17:51192192:TGGTG:T	donor_gain	1.0000
17:51192201:A:AC	donor_gain	1.0000
17:51192202:C:CC	donor_gain	1.0000
17:51192202:CTTTT:C	donor_gain	1.0000
17:51192210:ATGT:A	donor_gain	1.0000
17:51192234:AG:A	donor_gain	1.0000
17:51192234:AGC:A	donor_gain	1.0000
17:51192235:G:C	donor_gain	1.0000
17:51192866:A:AC	donor_gain	1.0000
17:51192867:C:CC	donor_gain	1.0000
17:51193013:CATC:C	acceptor_gain	1.0000
17:51202016:TCTTA:T	donor_loss	1.0000
17:51202017:CTTA:C	donor_loss	1.0000
17:51202018:TTAC:T	donor_loss	1.0000
17:51202019:TA:T	donor_loss	1.0000
17:51202020:ACC:A	donor_loss	1.0000
17:51202021:C:CG	donor_loss	1.0000
17:51203226:TAG:T	acceptor_gain	1.0000
17:51203228:GCTAA:G	acceptor_loss	1.0000
17:51203229:C:CC	acceptor_gain	1.0000
17:51203786:CTTA:C	donor_gain	1.0000
17:51203787:TTAC:T	donor_loss	1.0000
17:51203788:TACT:T	donor_loss	1.0000
17:51203789:A:AC	donor_gain	1.0000
17:51203789:ACTT:A	donor_gain	1.0000
17:51203790:C:CA	donor_gain	1.0000

AlphaMissense

4146 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:51192827:A:G	W549R	1.000
17:51192827:A:T	W549R	1.000
17:51192866:A:G	W536R	1.000
17:51192866:A:T	W536R	1.000
17:51192885:C:A	W529C	1.000
17:51192885:C:G	W529C	1.000
17:51192887:A:G	W529R	1.000
17:51192887:A:T	W529R	1.000
17:51192895:A:G	F526S	1.000
17:51192937:G:T	A512D	1.000
17:51192967:T:C	D502G	1.000
17:51192974:C:G	A500P	1.000
17:51192997:A:G	F492S	1.000
17:51201642:C:G	A392P	1.000
17:51202733:G:A	S344F	1.000
17:51202737:A:G	W343R	1.000
17:51202737:A:T	W343R	1.000
17:51202776:A:G	W330R	1.000
17:51202776:A:T	W330R	1.000
17:51202814:A:G	L317P	1.000
17:51202822:T:A	R314S	1.000
17:51202822:T:G	R314S	1.000
17:51202850:G:T	A305E	1.000
17:51202856:C:G	R303P	1.000
17:51203180:A:G	L263P	1.000
17:51203205:A:G	W255R	1.000
17:51203205:A:T	W255R	1.000
17:51203796:G:T	P245H	1.000
17:51206915:A:G	W193R	1.000
17:51206915:A:T	W193R	1.000

dbSNP variants (sampled 300 via entrez): RS1000009118 (17:51237454 T>A), RS1000021075 (17:51199683 G>GC), RS1000060508 (17:51188657 G>A,C), RS1000107154 (17:51237104 C>T), RS1000115295 (17:51222980 T>G), RS1000162508 (17:51213039 T>C), RS1000215968 (17:51216609 T>A), RS1000240467 (17:51259316 A>G), RS1000259360 (17:51219842 C>T), RS1000268470 (17:51216825 C>T), RS1000323128 (17:51212883 A>T), RS1000348169 (17:51188903 C>T), RS1000349094 (17:51219384 C>G), RS1000365036 (17:51225579 A>G), RS1000399524 (17:51182489 A>G)

Disease associations

OMIM: gene MIM:618705 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST008103_55	Bipolar disorder	4.000000e-07
GCST010866_154	Coronary artery disease	4.000000e-08
GCST90020028_1425	Hip circumference adjusted for BMI	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1287625 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 40,315 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL505	CHLORPHENIRAMINE	4	40,315

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

ChEMBL bioactivities

21 potent at pChembl≥5 of 38 total, top 20 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.52	IC50	3000	nM	CHEMBL2426474
5.46	IC50	3500	nM	CHEMBL2426376
5.40	IC50	4000	nM	CHEMBL2426472
5.31	IC50	4900	nM	CHEMBL2426474
5.29	IC50	5100	nM	CHEMBL2424677
5.27	IC50	5400	nM	CHEMBL2426481
5.26	IC50	5500	nM	CHEMBL2426490
5.24	IC50	5700	nM	CHEMBL2426360
5.22	IC50	6000	nM	CHEMBL2426364
5.17	IC50	6800	nM	CHEMBL2426366
5.11	IC50	7800	nM	CHEMBL2426476
5.09	IC50	8100	nM	CHEMBL2426487
5.09	IC50	8100	nM	CHEMBL2426483
5.09	IC50	8200	nM	CHEMBL2426482
5.05	IC50	9000	nM	CHEMBL2426364
5.05	IC50	9000	nM	CHEMBL3220203
5.04	IC50	9200	nM	CHEMBL2426372
5.03	IC50	9300	nM	CHEMBL2426367
5.01	IC50	9700	nM	CHEMBL2426485
5.00	IC50	1e+04	nM	CHEMBL2426484

PubChem BioAssay actives

18 with measured affinity, of 130 total; 16 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
[4-(4-piperidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-piperidin-1-ylpiperidin-1-yl)methanone	2189734: Inhibition of MBT domain containing MBTD1 (unknown origin) using H4K20me2 peptide by Alpha-Screen methylated histone peptide competition assay	ic50	3.0000	uM
2-anilino-N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(4-pyrrolidin-2-ylpiperidine-1-carbonyl)benzamide	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	3.5000	uM
[4-(4-pyrrolidin-2-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-2-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	4.0000	uM
3-anilino-N-(2-ethyl-1,3-dihydroisoindol-5-yl)-4-(4-pyrrolidin-2-ylpiperidine-1-carbonyl)benzamide	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.1000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)sulfonylphenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.4000	uM
[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-2-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.5000	uM
[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)naphthalen-1-yl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	5.7000	uM
[3-anilino-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	2189734: Inhibition of MBT domain containing MBTD1 (unknown origin) using H4K20me2 peptide by Alpha-Screen methylated histone peptide competition assay	ic50	6.0000	uM
[3-benzyl-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	6.8000	uM
[3-bromo-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	7.8000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-[(4-pyrrolidin-1-ylpiperidin-1-yl)methyl]phenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.1000	uM
(4-cyclohexylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.1000	uM
(4-pyrrolidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidin-1-yl)phenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	8.2000	uM
[3-phenoxy-4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]-(4-pyrrolidin-1-ylpiperidin-1-yl)methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	9.3000	uM
[4-(azepan-1-yl)piperidin-1-yl]-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	9.7000	uM
(4-piperidin-1-ylpiperidin-1-yl)-[4-(4-pyrrolidin-1-ylpiperidine-1-carbonyl)phenyl]methanone	771615: Inhibition of MBTD1 (unknown origin) after 30 mins by AlphaScreen assay	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, decreases methylation	5
trichostatin A	decreases expression, affects cotreatment	3
sodium arsenite	decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
geldanamycin	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
butyraldehyde	decreases expression	1
rofecoxib	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Cytarabine	increases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	decreases expression	1
Silicon Dioxide	increases methylation	1
Tretinoin	decreases expression	1
Vincristine	increases expression	1
Zinc	increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases methylation	1
Lactic Acid	decreases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1286366	Binding	Inhibition of MBTD1 by alpha-screening	Identification of non-peptide malignant brain tumor (MBT) repeat antagonists by virtual screening of commercially available compounds. — J Med Chem

Clinical trials (associated diseases)

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