YEATS2

Summary

YEATS2 (YEATS domain containing 2, HGNC:25489) is a protein-coding gene on chromosome 3q27.1, encoding YEATS domain-containing protein 2 (Q9ULM3). Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. It is a selective cancer dependency (DepMap: 61.5% of cell lines).

Summary: The protein encoded by this gene is a scaffolding subunit of the ATAC complex, which is a complex with acetyltransferase activity on histones H3 and H4. Alternative splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 55689 — RefSeq curated summary.

At a glance

• Gene–disease (curated): benign adult familial myoclonic epilepsy (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 242 total — 1 pathogenic
• Phenotypes (HPO): 18
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 61.5% of screened cell lines
• MANE Select transcript: NM_018023

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25489
Approved symbol	YEATS2
Name	YEATS domain containing 2
Location	3q27.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10201, FLJ12841, FLJ13308, KIAA1197
Ensembl gene	ENSG00000163872
Ensembl biotype	protein_coding
OMIM	613373
Entrez	55689

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 18 protein_coding, 4 retained_intron

ENST00000305135, ENST00000432781, ENST00000468850, ENST00000472593, ENST00000481343, ENST00000497765, ENST00000884732, ENST00000884733, ENST00000884734, ENST00000884735, ENST00000884736, ENST00000884737, ENST00000884738, ENST00000927061, ENST00000927062, ENST00000927063, ENST00000927064, ENST00000927065, ENST00000927066, ENST00000927067, ENST00000927068, ENST00000941369

RefSeq mRNA: 4 — MANE Select: NM_018023 NM_001351369, NM_001351370, NM_001351371, NM_018023

CCDS: CCDS43175

Canonical transcript exons

ENST00000305135 — 31 exons

Exon	Start	End
ENSE00000968683	183718500	183718592
ENSE00000968684	183721891	183722136
ENSE00000968685	183724419	183724531
ENSE00000968686	183728690	183728851
ENSE00000968687	183736718	183736829
ENSE00001180941	183786125	183786301
ENSE00001180951	183775915	183776123
ENSE00001180955	183773633	183773794
ENSE00001180957	183772305	183772563
ENSE00001180960	183762097	183762279
ENSE00001180964	183761507	183761614
ENSE00001180968	183758862	183758965
ENSE00001180973	183756528	183756689
ENSE00001180977	183754126	183754365
ENSE00001180983	183752073	183752253
ENSE00001180988	183747672	183747716
ENSE00001293401	183790797	183790980
ENSE00001297158	183777542	183777700
ENSE00001360363	183797923	183798051
ENSE00001529916	183697797	183697993
ENSE00001598579	183810475	183812624
ENSE00002209993	183715144	183715262
ENSE00002316709	183801455	183801528
ENSE00002326128	183803987	183804188
ENSE00002333247	183803256	183803335
ENSE00002402640	183717651	183717748
ENSE00003481240	183809097	183809170
ENSE00003548226	183798891	183798989
ENSE00003585182	183806866	183807092
ENSE00003600485	183808030	183808104
ENSE00003630379	183800466	183800568

Expression profiles

Bgee: expression breadth ubiquitous, 283 present calls, max score 93.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.4172 / max 499.6035, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40113	31.0236	1818
40115	2.8360	1348
40114	0.5576	306

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	93.82	gold quality
endothelial cell	CL:0000115	92.68	gold quality
ganglionic eminence	UBERON:0004023	92.40	gold quality
ventricular zone	UBERON:0003053	92.35	gold quality
cortical plate	UBERON:0005343	92.33	gold quality
embryo	UBERON:0000922	91.50	gold quality
middle temporal gyrus	UBERON:0002771	90.29	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.62	gold quality
cerebellar vermis	UBERON:0004720	89.46	gold quality
corpus callosum	UBERON:0002336	89.26	gold quality
cerebellar hemisphere	UBERON:0002245	88.81	gold quality
cerebellar cortex	UBERON:0002129	88.78	gold quality
secondary oocyte	CL:0000655	88.70	gold quality
cerebellum	UBERON:0002037	88.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.50	gold quality
trigeminal ganglion	UBERON:0001675	88.08	gold quality
stromal cell of endometrium	CL:0002255	87.99	gold quality
orbitofrontal cortex	UBERON:0004167	87.83	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.64	gold quality
oocyte	CL:0000023	87.33	gold quality
subthalamic nucleus	UBERON:0001906	87.23	gold quality
substantia nigra pars compacta	UBERON:0001965	87.11	gold quality
superior frontal gyrus	UBERON:0002661	87.03	gold quality
parotid gland	UBERON:0001831	86.95	silver quality
substantia nigra pars reticulata	UBERON:0001966	86.91	gold quality
lateral globus pallidus	UBERON:0002476	86.80	gold quality
parietal lobe	UBERON:0001872	86.72	gold quality
pericardium	UBERON:0002407	86.67	gold quality
saphenous vein	UBERON:0007318	86.63	gold quality
inferior vagus X ganglion	UBERON:0005363	86.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.68
E-MTAB-7303	no	354.82

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

66 targeting YEATS2, 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-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-548G-3P	99.48	68.67	2159
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4722-3P	99.35	65.22	1099

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 61.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 7)

• YEATS2 is a selective histone crotonylation reader. (PMID:27103431)
• YEATS2 gene is highly amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell growth and survival (PMID:29057918)
• our findings suggest that benign adult familial myoclonic epilepsy type 4 is caused by the insertions of the intronic TTTCA repeats in YEATS2 (PMID:31539032)
• YEATS2 is a target of HIF1alpha and promotes pancreatic cancer cell proliferation and migration. (PMID:32749678)
• YEATS domain-containing 2 (YEATS2), targeted by microRNA miR-378a-5p, regulates growth and metastasis in head and neck squamous cell carcinoma. (PMID:34587874)
• YEATS2 regulates the activation of TAK1/NF-kappaB pathway and is critical for pancreatic ductal adenocarcinoma cell survival. (PMID:34686948)
• Repression of YEATS2 induces cellular senescence in hepatocellular carcinoma and inhibits tumor growth. (PMID:38619971)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	yeats2	ENSDARG00000078767
danio_rerio		ENSDARG00000097253
mus_musculus	Yeats2	ENSMUSG00000041215
rattus_norvegicus	Yeats2	ENSRNOG00000023107
drosophila_melanogaster	D12	FBGN0027490

Paralogs (2): MLLT1 (ENSG00000130382), MLLT3 (ENSG00000171843)

Protein

Protein identifiers

YEATS domain-containing protein 2 — Q9ULM3 (reviewed: Q9ULM3)

All UniProt accessions (2): H0Y6M6, Q9ULM3

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. YEATS2 specifically recognizes and binds histone H3 crotonylated at ‘Lys-27’ (H3K27cr). Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors.

Subunit / interactions. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, SGF29 and DR1.

Subcellular location. Nucleus.

Disease relevance. Epilepsy, familial adult myoclonic, 4 (FAME4) [MIM:615127] A form of familial myoclonic epilepsy, a neurologic disorder characterized by cortical hand tremors, myoclonic jerks and occasional generalized or focal seizures with a non-progressive or very slowly progressive disease course. Usually, myoclonic tremor is the presenting symptom, characterized by tremulous finger movements and myoclonic jerks of the limbs increased by action and posture. In a minority of patients, seizures are the presenting symptom. Some patients exhibit mild cognitive impairment. FAME4 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The YEATS domain specifically recognizes and binds crotonylated histones.

RefSeq proteins (4): NP_001338298, NP_001338299, NP_001338300, NP_060493* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005033	YEATS	Family
IPR038704	YEAST_sf	Homologous_superfamily
IPR055127	YEATS2_3HBD	Domain
IPR055129	YEATS_dom	Domain

Pfam: PF03366, PF22951

UniProt features (67 total): cross-link 15, modified residue 14, strand 9, mutagenesis site 8, compositionally biased region 6, region of interest 6, sequence variant 3, helix 2, chain 1, domain 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7EIE	X-RAY DIFFRACTION	1.67
6LSD	X-RAY DIFFRACTION	2.05
5IQL	X-RAY DIFFRACTION	2.1
5XNV	X-RAY DIFFRACTION	2.7
9PKU	X-RAY DIFFRACTION	2.88

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9ULM3-F1	51.50	0.16

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 (29): 118, 120, 157, 407, 447, 463, 465, 471, 473, 478, 536, 575, 627, 1219, 9, 113, 189, 370, 487, 552 …

Mutagenesis-validated functional residues (8):

Position	Phenotype
259	strongly reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
261	strongly reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
262	strongly reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
282	strongly reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
283	abolished binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
284	abolished binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
285	strongly reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).
313	reduced binding to histone h3 crotonylated at ’lys-27’ (h3k27cr).

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes

MSigDB gene sets: 178 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_REGULATION_OF_PROTEIN_DEACETYLATION, GOBP_MACROMOLECULE_DEACYLATION, GTGCCTT_MIR506, MODULE_205, ATF1_Q6, MYCMAX_01, YANG_BREAST_CANCER_ESR1_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_REGULATION_OF_CELL_DIVISION, HIF1_Q3, BENPORATH_ES_CORE_NINE_CORRELATED, DODD_NASOPHARYNGEAL_CARCINOMA_UP, TAATGTG_MIR323, GOBP_EMBRYO_DEVELOPMENT

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), regulation of embryonic development (GO:0045995), regulation of cell division (GO:0051302), regulation of cell cycle (GO:0051726)

GO Molecular Function (6): transcription corepressor activity (GO:0003714), TBP-class protein binding (GO:0017025), histone binding (GO:0042393), modification-dependent protein binding (GO:0140030), histone reader activity (GO:0140566), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), NuA4 histone acetyltransferase complex (GO:0035267), mitotic spindle (GO:0072686), ATAC complex (GO:0140672)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of cellular process	2
protein binding	2
regulation of transcription by RNA polymerase II	1
chromatin organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
regulation of DNA-templated transcription	1
embryo development	1
regulation of multicellular organismal development	1
cell division	1
cell cycle	1
transcription coregulator activity	1
general transcription initiation factor binding	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
H4/H2A histone acetyltransferase complex	1
spindle	1
SAGA-type complex	1

Protein interactions and networks

STRING

2120 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
YEATS2	DR1	Q01658	858
YEATS2	SGF29	Q96ES7	855
YEATS2	MBIP	Q9NS73	854
YEATS2	KAT14	Q9H8E8	821
YEATS2	TADA2B	Q86TJ2	794
YEATS2	WDR5	P61964	784
YEATS2	TADA2A	O75478	773
YEATS2	TADA3	O75528	763
YEATS2	KAT2A	Q92830	758
YEATS2	ZZZ3	Q8IYH5	738
YEATS2	KAT2B	Q92831	736
YEATS2	H3-3A	P06351	713
YEATS2	H3C1	P02295	709
YEATS2	H3-4	Q16695	709
YEATS2	H3-7	Q5TEC6	709
YEATS2	H3-5	Q6NXT2	709
YEATS2	H3C14	Q71DI3	709

IntAct

139 interactions, top by confidence:

A	B	Type	Score
PSMC3	PSMD9	psi-mi:“MI:0914”(association)	0.940
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
WDR5	SETD1A	psi-mi:“MI:0914”(association)	0.880
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
HSPB2	BAG3	psi-mi:“MI:0914”(association)	0.670
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
HYPK	NAA10	psi-mi:“MI:0914”(association)	0.640
MAGEA10	POTEF	psi-mi:“MI:0914”(association)	0.530
BCAT1	ARNT	psi-mi:“MI:0914”(association)	0.530
EIPR1	LDHC	psi-mi:“MI:0914”(association)	0.530
FHL2	CNOT1	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
MBIP	TADA2A	psi-mi:“MI:0914”(association)	0.530
POLE4	POLE	psi-mi:“MI:0914”(association)	0.530
EIPR1	TCP1	psi-mi:“MI:0914”(association)	0.530

BioGRID (289): YEATS2 (Affinity Capture-RNA), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), YEATS2 (Affinity Capture-MS), KAT2B (Affinity Capture-Western)

ESM2 similar proteins: A0JME2, A2AUY4, D3ZKB9, D4A666, E1B7L7, F1QZ88, F6NSX9, F8VPJ6, P59759, P78364, Q08CM4, Q0IHV2, Q15723, Q2IBE6, Q2IBF7, Q2QLB3, Q3TUF7, Q4G0F8, Q5DTH5, Q5U4Q0, Q5ZIE8, Q5ZM88, Q63HK5, Q641Z1, Q6P4L9, Q6P4R8, Q6PIJ4, Q6ZPK0, Q6ZSZ6, Q6ZU65, Q76L83, Q7ZUK7, Q7ZUV7, Q80WC1, Q8AYC1, Q8BZ32, Q8C966, Q8CGV9, Q8CHP6, Q8NDX5

Diamond homologs: A2AM29, F4IPK2, O94436, O95619, P0CM08, P0CM09, P35189, P42568, P53930, Q03111, Q10319, Q3TUF7, Q4I7S1, Q4PFI5, Q4WPM8, Q59LC9, Q5BC71, Q6CF24, Q6CIV8, Q6FXM4, Q755P0, Q7RZK7, Q9CR11, Q9FH40, Q9ULM3, Q99314

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 175 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
Formation of WDR5-containing histone-modifying complexes	11	25.0×	2e-10
Epigenetic regulation by WDR5-containing histone modifying complexes	10	13.2×	1e-06
Epigenetic regulation of gene expression	12	7.3×	1e-05
Chromatin organization	10	7.0×	2e-04
HATs acetylate histones	10	6.8×	2e-04
Chromatin modifying enzymes	10	6.2×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell division	7	33.5×	5e-07
regulation of embryonic development	9	18.6×	5e-07
regulation of DNA repair	6	10.4×	3e-03
regulation of G1/S transition of mitotic cell cycle	5	9.6×	1e-02
G1/S transition of mitotic cell cycle	6	7.5×	1e-02
regulation of cell cycle	13	6.1×	6e-05
chromatin remodeling	10	4.6×	7e-03
protein stabilization	10	4.2×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	183
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
694503	NG_054747.1:g.(19392_19426)TTTTA[(7_?)]TTTCA[(n)]	Pathogenic

SpliceAI

6048 predictions. Top by Δscore:

Variant	Effect	Δscore
3:183697991:AGGG:A	donor_loss	1.0000
3:183697992:GG:G	donor_gain	1.0000
3:183697993:GG:G	donor_gain	1.0000
3:183697993:GGTG:G	donor_loss	1.0000
3:183697994:G:GG	donor_gain	1.0000
3:183697994:GTGA:G	donor_loss	1.0000
3:183697995:T:G	donor_loss	1.0000
3:183715132:A:AG	acceptor_gain	1.0000
3:183715132:ATT:A	acceptor_gain	1.0000
3:183715133:T:G	acceptor_gain	1.0000
3:183715134:T:A	acceptor_gain	1.0000
3:183715140:A:AG	acceptor_gain	1.0000
3:183715141:C:G	acceptor_gain	1.0000
3:183715141:CAGT:C	acceptor_loss	1.0000
3:183715142:A:AG	acceptor_gain	1.0000
3:183715142:AGT:A	acceptor_gain	1.0000
3:183715143:G:GT	acceptor_gain	1.0000
3:183715143:GT:G	acceptor_gain	1.0000
3:183715143:GTG:G	acceptor_gain	1.0000
3:183715143:GTGA:G	acceptor_gain	1.0000
3:183715143:GTGAA:G	acceptor_gain	1.0000
3:183715211:G:GT	donor_gain	1.0000
3:183715259:TCAG:T	donor_loss	1.0000
3:183715260:CAG:C	donor_loss	1.0000
3:183715261:AG:A	donor_loss	1.0000
3:183715262:GG:G	donor_loss	1.0000
3:183715263:G:GA	donor_loss	1.0000
3:183715264:T:G	donor_loss	1.0000
3:183717637:T:G	acceptor_gain	1.0000
3:183717644:T:TA	acceptor_gain	1.0000

AlphaMissense

9181 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:183718534:T:C	L78P	1.000
3:183724510:T:A	I210K	1.000
3:183724510:T:G	I210R	1.000
3:183724516:T:A	V212E	1.000
3:183724518:G:C	G213R	1.000
3:183724518:G:T	G213C	1.000
3:183724519:G:A	G213D	1.000
3:183724519:G:T	G213V	1.000
3:183724521:A:G	N214D	1.000
3:183724523:T:A	N214K	1.000
3:183724523:T:G	N214K	1.000
3:183724527:T:C	S216P	1.000
3:183724528:C:A	S216Y	1.000
3:183724528:C:T	S216F	1.000
3:183728691:T:C	Y218H	1.000
3:183728691:T:G	Y218D	1.000
3:183728692:A:C	Y218S	1.000
3:183728692:A:G	Y218C	1.000
3:183728695:T:A	I219K	1.000
3:183728711:G:C	R224S	1.000
3:183728711:G:T	R224S	1.000
3:183728733:C:A	H232N	1.000
3:183728733:C:G	H232D	1.000
3:183728734:A:G	H232R	1.000
3:183728735:T:A	H232Q	1.000
3:183728735:T:G	H232Q	1.000
3:183728736:A:G	K233E	1.000
3:183728738:G:C	K233N	1.000
3:183728738:G:T	K233N	1.000
3:183728739:T:A	W234R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001408 (3:183756320 G>T), RS1000023804 (3:183696417 C>A,T), RS1000032770 (3:183734643 G>A,T), RS1000051857 (3:183696807 G>A), RS1000077461 (3:183743006 G>T), RS1000090629 (3:183741860 C>G), RS1000125478 (3:183779925 T>G), RS1000128551 (3:183702865 T>A), RS1000144560 (3:183742209 T>A,G), RS1000160059 (3:183800846 C>G), RS1000183048 (3:183788120 G>A), RS1000198130 (3:183717378 T>C), RS1000202305 (3:183714454 C>G), RS1000208041 (3:183797309 A>G,T), RS1000208775 (3:183759197 T>C)

Disease associations

OMIM: gene MIM:613373 | disease phenotypes: MIM:615127

GenCC curated gene-disease

Disease	Classification	Inheritance
benign adult familial myoclonic epilepsy	Supportive	Autosomal dominant
epilepsy, familial adult myoclonic, 4	Limited	Autosomal dominant

Mondo (3): epilepsy, familial adult myoclonic, 4 (MONDO:0014055), breast ductal adenocarcinoma (MONDO:0005590), benign adult familial myoclonic epilepsy (MONDO:0019448)

Orphanet (1): Familial adult myoclonic epilepsy (Orphanet:86814)

HPO phenotypes

18 total (18 of 18 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001336	Myoclonus
HP:0001337	Tremor
HP:0001340	Enhancement of the C-reflex
HP:0001351	Jerk-locked premyoclonus spikes
HP:0002069	Bilateral tonic-clonic seizure
HP:0002197	Generalized-onset seizure
HP:0002315	Headache
HP:0002353	EEG abnormality
HP:0002378	Hand tremor
HP:0002392	EEG with polyspike wave complexes
HP:0003621	Juvenile onset
HP:0003680	Nonprogressive
HP:0007359	Focal-onset seizure
HP:0011462	Young adult onset
HP:0100576	Amaurosis fugax

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST006628_16	Systolic blood pressure	8.000000e-15
GCST008473_20	Visceral fat	4.000000e-06
GCST010988_210	Adult body size	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4296261 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.22	Ki	6000	nM	CHEMBL5439514

PubChem BioAssay actives

1 with measured affinity, of 22 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
1-[1-[(2S)-2-(4-chlorophenyl)-2-hydroxyethyl]piperidin-4-yl]-N-ethyl-2-oxo-3H-benzimidazole-5-carboxamide	1964936: Binding affinity to human his-tagged recombinant YEATS2 expressed in Escherichia coli assessed as inhibition constant using biotin tagged lysine 27-crotonylated histone H3 peptide as substrate preincubated for 20 mins followed by substrate addition measured after 30 mins by FRET analysis	ki	6.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	increases expression, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
kojic acid	increases expression	1
arsenite	affects binding, decreases reaction	1
zinc chloride	decreases reaction, increases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
ICG 001	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Cidofovir	affects expression	1
Caffeine	decreases phosphorylation	1
Cisplatin	affects expression	1
Clodronic Acid	affects expression	1
Dimethyl Sulfoxide	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Ifosfamide	affects expression	1
Methapyrilene	decreases methylation	1
Oxygen	increases expression	1

ChEMBL screening assays

11 unique, capped per target: 11 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4810343	Binding	Inhibition of human His-YEATS2 YEATS domain and biotinylated H3K27ar peptide interaction by AlphaScreen assay	Discovery of Selective Small-Molecule Inhibitors for the ENL YEATS Domain. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery