MYBBP1A

Summary

MYBBP1A (MYB binding protein 1a, HGNC:7546) is a protein-coding gene on chromosome 17p13.2, encoding Myb-binding protein 1A (Q9BQG0). May activate or repress transcription via interactions with sequence specific DNA-binding proteins. It is a selective cancer dependency (DepMap: 69.5% of cell lines).

This gene encodes a nucleolar transcriptional regulator that was first identified by its ability to bind specifically to the Myb proto-oncogene protein. The encoded protein is thought to play a role in many cellular processes including response to nucleolar stress, tumor suppression and synthesis of ribosomal DNA. Alternate splicing results in multiple transcript variants.

Source: NCBI Gene 10514 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hydrops fetalis (Strong, GenCC)
• Clinical variants (ClinVar): 423 total
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 69.5% of screened cell lines
• MANE Select transcript: NM_014520

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7546
Approved symbol	MYBBP1A
Name	MYB binding protein 1a
Location	17p13.2
Locus type	gene with protein product
Status	Approved
Aliases	P160, PAP2, FLJ37886, Pol5
Ensembl gene	ENSG00000132382
Ensembl biotype	protein_coding
OMIM	604885
Entrez	10514

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 16 protein_coding, 8 retained_intron

ENST00000254718, ENST00000381556, ENST00000570986, ENST00000571354, ENST00000571368, ENST00000572759, ENST00000573116, ENST00000573175, ENST00000573723, ENST00000574167, ENST00000574547, ENST00000574934, ENST00000575662, ENST00000896003, ENST00000896004, ENST00000896005, ENST00000932210, ENST00000932211, ENST00000932212, ENST00000932213, ENST00000932214, ENST00000932215, ENST00000932216, ENST00000932217

RefSeq mRNA: 2 — MANE Select: NM_014520 NM_001105538, NM_014520

CCDS: CCDS11046, CCDS42238

Canonical transcript exons

ENST00000254718 — 26 exons

Exon	Start	End
ENSE00000671172	4544489	4544646
ENSE00000671173	4544751	4544921
ENSE00000671174	4545026	4545175
ENSE00000671175	4545259	4545345
ENSE00000671179	4547958	4548057
ENSE00000671190	4550058	4550353
ENSE00000671191	4551880	4551997
ENSE00000671192	4552125	4552292
ENSE00000671194	4553810	4553917
ENSE00000671195	4554019	4554093
ENSE00000875859	4545846	4545942
ENSE00002658727	4555127	4555384
ENSE00003467646	4540348	4540484
ENSE00003469151	4548524	4548649
ENSE00003476760	4542464	4542532
ENSE00003492560	4541463	4541564
ENSE00003496841	4542913	4543165
ENSE00003505922	4548143	4548310
ENSE00003556221	4542616	4542741
ENSE00003592193	4549332	4549442
ENSE00003602028	4545610	4545761
ENSE00003604015	4554861	4554956
ENSE00003615213	4554195	4554278
ENSE00003648030	4538904	4539967
ENSE00003657939	4541784	4541891
ENSE00003688422	4552451	4552626

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 96.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.8272 / max 276.5269, expressed in 1804 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
163920	29.5189	1804
163917	0.2015	102
163918	0.0478	29
163916	0.0387	18
163919	0.0204	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	96.52	gold quality
buccal mucosa cell	CL:0002336	95.38	gold quality
lower esophagus mucosa	UBERON:0035834	93.89	gold quality
right frontal lobe	UBERON:0002810	93.29	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.26	gold quality
right uterine tube	UBERON:0001302	93.24	gold quality
body of pancreas	UBERON:0001150	92.89	gold quality
cerebellar hemisphere	UBERON:0002245	92.58	gold quality
skin of abdomen	UBERON:0001416	92.54	gold quality
gastrocnemius	UBERON:0001388	92.52	gold quality
skin of leg	UBERON:0001511	92.42	gold quality
cerebellar cortex	UBERON:0002129	92.37	gold quality
apex of heart	UBERON:0002098	92.29	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.16	gold quality
left uterine tube	UBERON:0001303	92.10	gold quality
muscle of leg	UBERON:0001383	92.04	gold quality
esophagus mucosa	UBERON:0002469	90.90	gold quality
adenohypophysis	UBERON:0002196	90.83	gold quality
minor salivary gland	UBERON:0001830	90.56	gold quality
mucosa of transverse colon	UBERON:0004991	90.54	gold quality
ectocervix	UBERON:0012249	90.43	gold quality
endocervix	UBERON:0000458	90.41	gold quality
body of stomach	UBERON:0001161	90.41	gold quality
tendon of biceps brachii	UBERON:0008188	90.37	gold quality
tibial nerve	UBERON:0001323	90.24	gold quality
cerebellum	UBERON:0002037	90.16	gold quality
anterior cingulate cortex	UBERON:0009835	90.14	gold quality
right ovary	UBERON:0002118	90.12	gold quality
esophagus	UBERON:0001043	90.03	gold quality
right lobe of thyroid gland	UBERON:0001119	89.99	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SFTPB	Unknown

miRNA regulators (miRDB)

15 targeting MYBBP1A, 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-4692	100.00	67.32	2066
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-671-5P	99.52	67.11	1277
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4786-3P	99.36	68.35	1390
HSA-MIR-877-3P	99.09	68.10	1637
HSA-MIR-2681-3P	98.18	65.28	577
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-924	97.78	66.21	681
HSA-MIR-558	97.50	67.16	977
HSA-MIR-10398-5P	97.12	64.94	1051
HSA-MIR-4448	97.04	66.22	752
HSA-MIR-3186-5P	87.11	67.29	51

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 69.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 23)

• These results indicate that MYBBP1a is a novel NF-kappaB co-repressor of transcription that competes with p300 and may function to regulate cell type specific genes. (PMID:17196614)
• Expression of Ets-2, SRC-1 and c-Myc individually are all associated with reduced disease-free survival in breast cancer (PMID:18059336)
• SRC-1 is a strong independent predictor of reduced disease free survival, whereas the interactions of the p160 proteins with estrogen receptor alpha can predict the response of patients to endocrine treatment. (PMID:19276281)
• Myb-binding protein 1a was identified in anti-SMN pulldowns as interacting with SMN proteins. (PMID:19928837)
• identified MYBBP1A as a novel Aurora B substrate and serine 1303 as the major phosphorylation site (PMID:20177074)
• When rRNA transcription was suppressed by nucleolar stress, MYBBP1A translocated to the nucleoplasm and facilitated p53-p300 interaction to enhance p53 acetylation. (PMID:21297583)
• We provide experimental evidence that MYBBP1A is an important molecular switch in the regulation of tumor cell proliferation versus migration in head and neck squamous cell carcinoma cells. (PMID:22339894)
• Mybbp1a may play a dual role in the rRNA metabolism, potentially linking and coordinating ribosomal DNA transcription and pre-rRNA processing to allow for the efficient synthesis of ribosomes. (PMID:22645127)
• Results from our present work reveal a previously unrecognized co-repressor role of Mybbp1a in rRNA expression. (PMID:22686419)
• Data show that down-regulation of MYBBP1A decreases the growth rate of wild type mouse embryonic stem cells, embryo fibroblasts (MEFs) and of human HeLa cells, where it also promotes apoptosis. (PMID:23056166)
• Study suggests that a combination of SP110 and MYBBP1A gene polymorphisms may serve as a novel marker for identifying the risk of developing TB in the Chinese Han population. (PMID:23129390)
• Regulators, including BCL11A, MYB, and KLF1, hold great promise to develop targeted and more effective approaches for HbF induction. (PMID:23209159)
• Suggest that MYBBP1A is required for p53 activation during anoikis; therefore, it is involved in suppressing colony formation and the tumorigenesis of breast cancer cells. (PMID:23388179)
• MYBBP1A-p53 binding property can account for efficient p53-activation by MYBBP1A under nucleolar stress. Our results support the idea that MYBBP1A plays catalytic roles in p53 acetylation and activation (PMID:23583237)
• Mybbp1a is a novel negative regulator of Sirt7. (PMID:24134843)
• MYBBP1A functions to enhance p53 tetramerization that is necessary for p53 activation. (PMID:24375404)
• TPPII, MYBBP1A and CDK2 form a protein-protein interaction network. (PMID:25303791)
• MYBBP1A(low)AKT(Ser473)(high) staining pattern serves not only as a marker for the pre-senescent stage but also as an indicator of OPSCC patients at high risk for treatment failure. (PMID:25543088)
• The results indicated that both the heterozygous genotype GC and homozygous genotype CC in rs3809849 in MYBBP1A had significant effects on the risk of pulmonary tuberculosis, and heterozygous genotype CT in rs9061 in SP110 also had similar effects. (PMID:25612917)
• We propose that the nucleolus functions as a stress sensor to modulate p53 protein levels and its acetylation status, determining cell fate between cell cycle arrest and apoptosis by regulating MYBBP1A translocation. (PMID:26044764)
• This study shows the capability of MYBBP1A to regulate glucose metabolism through c-MYB and PGC1alpha in human tumors. (PMID:31066170)
• Characterization of the impact of the MYBBP1A gene and rs3809849 on asparaginase sensitivity and cellular functions. (PMID:35485735)
• Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer. (PMID:37298588)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	mybbp1a	ENSDARG00000078214
mus_musculus	Mybbp1a	ENSMUSG00000040463
rattus_norvegicus	Mybbp1a	ENSRNOG00000015236

Protein

Protein identifiers

Myb-binding protein 1A — Q9BQG0 (reviewed: Q9BQG0)

All UniProt accessions (4): Q9BQG0, I3L1L3, I3L2H8, I3L311

UniProt curated annotations — full annotation on UniProt →

Function. May activate or repress transcription via interactions with sequence specific DNA-binding proteins. Repression may be mediated at least in part by histone deacetylase activity (HDAC activity). Acts as a corepressor and in concert with CRY1, represses the transcription of the core circadian clock component PER2. Preferentially binds to dimethylated histone H3 ‘Lys-9’ (H3K9me2) on the PER2 promoter. Has a role in rRNA biogenesis together with PWP1.

Subunit / interactions. Binds to and represses JUN and MYB via the leucine zipper regions present in these proteins. Also binds to and represses PPARGC1A: this interaction is abrogated when PPARGC1A is phosphorylated by MAPK1/ERK. Binds to and stimulates transcription by AHR. Binds to KPNA2. Interacts with CLOCK and CRY1. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21.

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Post-translational modifications. Citrullinated by PADI4.

Miscellaneous. May be due to competing donor and acceptor splice sites.

Similarity. Belongs to the MYBBP1A family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BQG0-1	1	yes
Q9BQG0-2	2

RefSeq proteins (2): NP_001099008, NP_055335* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007015	DNA_pol_V/MYBBP1A	Family
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily

Pfam: PF04931

Enzyme classification (BRENDA):

• EC 2.3.1.48 — histone acetyltransferase (BRENDA: 41 organisms, 681 substrates, 1134 inhibitors, 140 Km, 96 kcat entries)

Substrate kinetics (BRENDA)

27 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ACETYL-COA	0.0002–0.046	51
HISTONE H3	0.007–2.09	23
HISTONE H4	—	11
HISTONE H4 PEPTIDE	0.0208–0.197	7
HISTONE	0.075–1.4	6
HISTONE H3 TAIL PEPTIDE	0.044–0.112	4
PICCOLONUA4 PEPTIDE	0.135–0.372	4
3-AZIDOPROPIONYL-COA	0.0002–0.0086	3
4-PENTYNOYL-COA	0.0009–0.0859	3
SPERMIDINE	0.18–0.27	3
5-HEXYNOYL-COA	0.0006–0.0117	2
6-HEPTYNOYL-COA	0.0003–0.0237	2
HISTONE H3-PEPTIDE	0.05–0.49	2
PROTEIN P53	1.28–4.63	2
3-AZIDOPROPANOYL-COA	0.0103	1

UniProt features (48 total): modified residue 23, region of interest 6, compositionally biased region 6, sequence variant 4, sequence conflict 4, short sequence motif 2, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BQG0-F1	74.69	0.34

Functional residue map

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

Post-translational modifications (24): 11, 71, 158, 775, 1159, 1163, 1186, 1190, 1196, 1207, 1232, 1239, 1241, 1244, 1248, 1267, 1269, 1290, 1303, 1307 …

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-5250913	Positive epigenetic regulation of rRNA expression
R-HSA-74160	Gene expression (Transcription)

MSigDB gene sets: 172 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_CIRCADIAN_RHYTHM, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RIBOSOME_BIOGENESIS, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSCRIPTION_BY_RNA_POLYMERASE_III, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, MUELLER_PLURINET, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (15): osteoblast differentiation (GO:0001649), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), respiratory electron transport chain (GO:0022904), circadian regulation of gene expression (GO:0032922), cellular response to glucose starvation (GO:0042149), ribosome biogenesis (GO:0042254), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase I (GO:0045943), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of transcription by RNA polymerase III (GO:0045945), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), regulation of G1 to G0 transition (GO:1903450), positive regulation of anoikis (GO:2000210), rhythmic process (GO:0048511)

GO Molecular Function (6): transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), sequence-specific DNA binding (GO:0043565), E-box binding (GO:0070888), DNA binding (GO:0003677), transcription factor binding (GO:0008134)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), membrane (GO:0016020), NLS-dependent protein nuclear import complex (GO:0042564), B-WICH complex (GO:0110016)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Positive epigenetic regulation of rRNA expression	1
Gene expression (Transcription)	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	3
cellular anatomical structure	3
DNA-templated transcription	2
regulation of gene expression	2
nucleic acid binding	2
nuclear lumen	2
ossification	1
cell differentiation	1
chromatin organization	1
regulation of RNA biosynthetic process	1
electron transport chain	1
cellular respiration	1
circadian rhythm	1
cellular response to starvation	1
ribonucleoprotein complex biogenesis	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase I	1
transcription by RNA polymerase I	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
regulation of transcription by RNA polymerase III	1
transcription by RNA polymerase III	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
regulation of cell cycle process	1
G1 to G0 transition	1
positive regulation of apoptotic process	1
anoikis	1
regulation of anoikis	1
biological_process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
DNA binding	1
RNA polymerase II cis-regulatory region sequence-specific DNA binding	1
protein binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nucleocytoplasmic transport complex	1

Protein interactions and networks

STRING

2871 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MYBBP1A	MYB	P10242	923
MYBBP1A	SIRT7	Q9NRC8	784
MYBBP1A	DDX21	Q9NR30	732
MYBBP1A	TP53	P04637	710
MYBBP1A	WDR43	Q15061	699
MYBBP1A	DEK	P35659	668
MYBBP1A	DDX56	Q9NY93	647
MYBBP1A	BAZ1B	Q9UIG0	647
MYBBP1A	POLI	Q9UNA4	635
MYBBP1A	HEATR1	Q9H583	626
MYBBP1A	UTP4	Q969X6	599
MYBBP1A	SMARCA4	P51532	591
MYBBP1A	UTP15	Q8TED0	577
MYBBP1A	SMARCA5	O60264	571
MYBBP1A	UBTF	P17480	567

IntAct

246 interactions, top by confidence:

A	B	Type	Score
EP300	TP53	psi-mi:“MI:0914”(association)	0.980
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
NOP10	DKC1	psi-mi:“MI:0914”(association)	0.890
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
H1-1	RRP8	psi-mi:“MI:0914”(association)	0.640
RBM34	RRP8	psi-mi:“MI:0914”(association)	0.640
AURKB	SEC16A	psi-mi:“MI:2364”(proximity)	0.570
CHEK2	PPM1G	psi-mi:“MI:0914”(association)	0.560
RPS6	IPO7	psi-mi:“MI:0914”(association)	0.530
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
DDX31	IGLL5	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
ZC3HAV1	KHNYN	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
RRP8	NVL	psi-mi:“MI:0914”(association)	0.530
HP1BP3	IPO8	psi-mi:“MI:0914”(association)	0.530
PUM3	RRP8	psi-mi:“MI:0914”(association)	0.530
CFTR	PLEKHG3	psi-mi:“MI:0914”(association)	0.480
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
ESR1		psi-mi:“MI:0914”(association)	0.460

BioGRID (602): MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Biochemical Activity), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Reconstituted Complex), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS), MYBBP1A (Affinity Capture-MS)

ESM2 similar proteins: A0JN53, A1L3T7, C9JE40, D2I4M3, G3HQ82, O43299, O75800, O94812, P58660, Q0P5G1, Q15572, Q1RMI8, Q1W1Y5, Q3T1I9, Q3U829, Q56B11, Q571B6, Q58CQ5, Q5ND34, Q5R8S0, Q66H85, Q6NZL6, Q6ZNJ1, Q6ZQA0, Q76MJ5, Q80TE0, Q80UU1, Q80UW5, Q8BGI5, Q8BMG1, Q8C3R1, Q8C3S2, Q8C7B8, Q8CE13, Q8IZL8, Q8N163, Q8VDP4, Q8WXE1, Q96HA7, Q9BQG0

Diamond homologs: O35821, Q6DRL5, Q7TPV4, Q9BQG0, Q9W5E4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
AURKB	unknown	MYBBP1A	phosphorylation
MYBBP1A	“form complex”	“B-WICH complex”	binding
MN1	“up-regulates activity”	MYBBP1A	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 223 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
Peptide chain elongation	23	21.9×	5e-23
Viral mRNA Translation	23	21.9×	5e-23
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	23	21.7×	5e-23
Selenocysteine synthesis	23	20.8×	1e-22
Eukaryotic Translation Termination	23	20.8×	1e-22
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	23	20.4×	2e-22
ZNF598 and the Ribosome-associated Quality Trigger (RQT) complex dissociate a ribosome stalled on a no-go mRNA	23	20.4×	2e-22
Formation of a pool of free 40S subunits	24	20.2×	5e-23

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	25	23.9×	7e-25
ribosomal large subunit biogenesis	8	18.3×	2e-06
rRNA processing	21	15.3×	1e-16
regulation of signal transduction by p53 class mediator	7	13.8×	1e-04
translation	26	13.8×	1e-19
ribosomal small subunit biogenesis	11	12.9×	2e-07
negative regulation of translation	7	7.1×	6e-03
nucleosome assembly	8	5.8×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	324
Likely benign	38
Benign	18

Top pathogenic / likely-pathogenic (0)

SpliceAI

3772 predictions. Top by Δscore:

Variant	Effect	Δscore
17:4539963:GGCGC:G	acceptor_gain	1.0000
17:4539964:GCGC:G	acceptor_gain	1.0000
17:4539965:CGC:C	acceptor_gain	1.0000
17:4539965:CGCC:C	acceptor_gain	1.0000
17:4539966:GC:G	acceptor_gain	1.0000
17:4539966:GCCTG:G	acceptor_loss	1.0000
17:4539967:CC:C	acceptor_gain	1.0000
17:4539968:C:CC	acceptor_gain	1.0000
17:4539968:C:T	acceptor_gain	1.0000
17:4539969:T:G	acceptor_loss	1.0000
17:4540346:A:AC	donor_gain	1.0000
17:4540347:C:CC	donor_gain	1.0000
17:4540347:CTGGA:C	donor_gain	1.0000
17:4540354:C:CA	donor_gain	1.0000
17:4540366:ATGG:A	donor_gain	1.0000
17:4540485:C:CC	acceptor_gain	1.0000
17:4541457:CCTCA:C	donor_loss	1.0000
17:4541458:CTCA:C	donor_loss	1.0000
17:4541459:TCA:T	donor_loss	1.0000
17:4541460:CA:C	donor_loss	1.0000
17:4541461:ACC:A	donor_loss	1.0000
17:4541462:C:CT	donor_loss	1.0000
17:4541887:CAGGC:C	acceptor_gain	1.0000
17:4541892:C:CC	acceptor_gain	1.0000
17:4541892:CTGT:C	acceptor_loss	1.0000
17:4542458:TCTCA:T	donor_loss	1.0000
17:4542459:CTCAC:C	donor_loss	1.0000
17:4542460:TCA:T	donor_loss	1.0000
17:4542461:CACCT:C	donor_loss	1.0000
17:4542462:ACC:A	donor_loss	1.0000

AlphaMissense

8645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:4544841:A:C	F797L	0.995
17:4544841:A:T	F797L	0.995
17:4544843:A:G	F797L	0.995
17:4554876:A:C	S93R	0.994
17:4554876:A:T	S93R	0.994
17:4554878:T:G	S93R	0.994
17:4554925:A:G	L77P	0.994
17:4544842:A:G	F797S	0.993
17:4545069:A:G	F756S	0.993
17:4545057:A:G	L760P	0.992
17:4555155:A:G	L57P	0.992
17:4544506:C:A	K874N	0.991
17:4544506:C:G	K874N	0.991
17:4544842:A:C	F797C	0.991
17:4554929:G:T	R76S	0.991
17:4554928:C:G	R76P	0.990
17:4544642:A:G	L829P	0.989
17:4545069:A:C	F756C	0.989
17:4544863:T:G	D790A	0.988
17:4554047:G:T	A142D	0.988
17:4554868:A:G	L96P	0.988
17:4554871:G:T	A95D	0.988
17:4555205:C:A	W40C	0.988
17:4555205:C:G	W40C	0.988
17:4544854:A:T	L793H	0.987
17:4544863:T:A	D790V	0.987
17:4545068:G:C	F756L	0.987
17:4545068:G:T	F756L	0.987
17:4545070:A:G	F756L	0.987
17:4554056:C:T	G139E	0.987

dbSNP variants (sampled 300 via entrez): RS1000256995 (17:4551715 A>G), RS1000317236 (17:4544235 G>A), RS1000493473 (17:4555624 A>C,G), RS1000797393 (17:4553814 G>A,C), RS1000905317 (17:4550714 T>C), RS1001213326 (17:4548194 T>C), RS1001333345 (17:4554951 G>A), RS1001450481 (17:4556616 G>A), RS1001497685 (17:4548397 G>A), RS1001571665 (17:4548870 G>A), RS1001620445 (17:4548698 T>C), RS1001679379 (17:4538845 T>C), RS1001734713 (17:4556807 G>A,C), RS1001793855 (17:4538743 A>G), RS1001957694 (17:4549551 C>A)

Disease associations

OMIM: gene MIM:604885 | disease phenotypes: MIM:209850, MIM:156000

GenCC curated gene-disease

Disease	Classification	Inheritance
hydrops fetalis	Strong	Autosomal recessive

Mondo (3): autism (MONDO:0005260), Meniere disease (MONDO:0007972), hydrops fetalis (MONDO:0015193)

Orphanet (1): NON RARE IN EUROPE: Menière disease (Orphanet:45360)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D015160	Hydrops Fetalis	C12.050.703.277.060.480; C15.378.295.480; C15.378.420.826.100.350; C16.300.060.480; C16.320.365.826.100.350; C20.306.480; C23.888.277.395
D008575	Meniere Disease	C09.218.568.217.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067389 (SINGLE PROTEIN)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs3809849	MYBBP1A		0.00	0

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.71	Kd	1972	nM	CHEMBL5653589
5.71	ED50	1972	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148802: Binding affinity to human MYBBP1A incubated for 45 mins by Kinobead based pull down assay	kd	1.9723	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	4
bisphenol A	decreases expression	3
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Doxorubicin	decreases expression, affects phosphorylation, affects response to substance	2
Estradiol	increases expression	2
Ozone	increases abundance, affects cotreatment, increases oxidation	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
deoxynivalenol	increases expression	1
titanium dioxide	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression, decreases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	affects expression	1
beta-lapachone	decreases expression	1
methylparaben	increases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
cupric oxide	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651844	Binding	Binding affinity to human MYBBP1A incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms