TADA3

Summary

TADA3 (transcriptional adaptor 3, HGNC:19422) is a protein-coding gene on chromosome 3p25.3, encoding Transcriptional adapter 3 (O75528). Functions as a component of the PCAF complex. It is a selective cancer dependency (DepMap: 31.2% of cell lines).

DNA-binding transcriptional activator proteins increase the rate of transcription by interacting with the transcriptional machinery bound to the basal promoter in conjunction with adaptor proteins, possibly by acetylation and destabilization of nucleosomes. The protein encoded by this gene is a transcriptional activator adaptor and a component of the histone acetyl transferase (HAT) coactivator complex which plays a crucial role in chromatin modulation and cell cycle progression. Along with the other components of the complex, this protein links transcriptional activators bound to specific promoters, to histone acetylation and the transcriptional machinery. The protein is also involved in the stabilization and activation of the p53 tumor suppressor protein that plays a role in the cellular response to DNA damage. Alternate splicing results in multiple transcript variants of this gene.

Source: NCBI Gene 10474 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 7 total
• Cancer dependency (DepMap): dependent in 31.2% of screened cell lines
• MANE Select transcript: NM_006354

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19422
Approved symbol	TADA3
Name	transcriptional adaptor 3
Location	3p25.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20221, FLJ21329, ADA3, hADA3, NGG1
Ensembl gene	ENSG00000171148
Ensembl biotype	protein_coding
OMIM	602945
Entrez	10474

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 19 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000301964, ENST00000343450, ENST00000439043, ENST00000440161, ENST00000492103, ENST00000492635, ENST00000906008, ENST00000906009, ENST00000906010, ENST00000906011, ENST00000906012, ENST00000906013, ENST00000906014, ENST00000906015, ENST00000906016, ENST00000906017, ENST00000906018, ENST00000906019, ENST00000918904, ENST00000957666, ENST00000957667

RefSeq mRNA: 3 — MANE Select: NM_006354 NM_001278270, NM_006354, NM_133480

CCDS: CCDS2583, CCDS2584

Canonical transcript exons

ENST00000301964 — 9 exons

Exon	Start	End
ENSE00001164965	9787199	9787340
ENSE00001164974	9789509	9789614
ENSE00001164982	9789713	9789963
ENSE00001302575	9791260	9791493
ENSE00001857028	9779967	9780549
ENSE00001868702	9792216	9792473
ENSE00003525306	9784028	9784213
ENSE00003526576	9785316	9785425
ENSE00003540455	9787006	9787109

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 95.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 54.8370 / max 231.4070, expressed in 1823 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40980	28.0003	1817
40983	25.8257	1814
40984	0.6448	334
40982	0.2832	120
40981	0.0830	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	95.71	gold quality
granulocyte	CL:0000094	95.68	gold quality
right adrenal gland cortex	UBERON:0035827	95.63	gold quality
left adrenal gland	UBERON:0001234	95.35	gold quality
left adrenal gland cortex	UBERON:0035825	95.34	gold quality
apex of heart	UBERON:0002098	95.25	gold quality
adrenal cortex	UBERON:0001235	95.04	gold quality
right testis	UBERON:0004534	94.92	gold quality
left testis	UBERON:0004533	94.90	gold quality
stromal cell of endometrium	CL:0002255	94.82	gold quality
prefrontal cortex	UBERON:0000451	94.81	gold quality
endometrium epithelium	UBERON:0004811	94.56	gold quality
adrenal gland	UBERON:0002369	94.42	gold quality
right coronary artery	UBERON:0001625	94.39	gold quality
right frontal lobe	UBERON:0002810	94.38	gold quality
amygdala	UBERON:0001876	94.35	gold quality
adenohypophysis	UBERON:0002196	94.32	gold quality
left ovary	UBERON:0002119	94.22	gold quality
cingulate cortex	UBERON:0003027	94.17	gold quality
right ovary	UBERON:0002118	94.15	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.13	gold quality
anterior cingulate cortex	UBERON:0009835	94.10	gold quality
thoracic aorta	UBERON:0001515	94.06	gold quality
ascending aorta	UBERON:0001496	94.01	gold quality
left uterine tube	UBERON:0001303	94.00	gold quality
descending thoracic aorta	UBERON:0002345	94.00	gold quality
body of uterus	UBERON:0009853	93.99	gold quality
pituitary gland	UBERON:0000007	93.91	gold quality
caudate nucleus	UBERON:0001873	93.81	gold quality
mucosa of transverse colon	UBERON:0004991	93.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-6142	no	501.23
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): KAT7, TADA2A, TP53, TP63

miRNA regulators (miRDB)

16 targeting TADA3, 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-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-497-3P	99.61	69.71	1990
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-3179	98.22	65.90	1445
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-1972	97.67	67.38	1172
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-3162-5P	95.67	67.53	794

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 31.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 24)

• Data identify hADA3, human homologue of the yeast transcriptional coactivator yADA3, as a novel human papillomavirus oncoprotein E6-interacting protein and a target of E6-induced degradation. (PMID:12138191)
• Results demonstrate that human papilloma virus 16 E6 oncoprotein inhibits the RXR(alpha)-mediated transactivation of target genes, implying that perturbation of RXR-mediated transactivation by E6 could contribute to HPV oncogenesis. (PMID:12235159)
• results demonstrate that transcriptional adaptor ADA3 protein directly binds to human estrogen receptor alpha and beta and enhances the transcription of estrogen receptor-responsive genes (PMID:15496419)
• human Ada3 has an essential role in p53 acetylation (PMID:17272277)
• p14ARF signals through hAda3 to stimulate p53 acetylation and the induction of cell senescence (PMID:17452980)
• hADA2a and hADA3 as crucial cofactors of beta-catenin that are likely involved in the assembly of transactivation-competent beta-catenin complexes at Wnt target genes. (PMID:18059173)
• Role of Ada3 in histone acetyltransferase recruitment to estrogen-responsive target gene promoters and for estrogen-dependent proliferation of breast cancer cells. (PMID:18089809)
• The findings strongly imply that the inactivation of the p14ARF-p53 pathway, either by the E6-mediated degradation of p53 or hAda3 or by cellular adaptation, is required for MEC immortalization. (PMID:18256148)
• ADA3 is a newly identified target of the ANCO proteins, which may modulate co-activator function in a transcription-factor-specific manner (PMID:18377363)
• oncoprotein E6 inhibits hADA3 in cervical cancer cells and this process is E6AP-dependent. (PMID:19194825)
• hADA3 interacts directly with RARalpha in a hormone-dependent manner and this interaction contributes to RARalpha transactivation (PMID:20413580)
• a critical role of Ada3 in embryogenesis and cell cycle progression as an essential component of HAT complex. (PMID:22736770)
• Expression of the interacting proteins altered expression of an hADA3-regulated reporter gene, suggesting functional consequences for the interactions. (PMID:23167988)
• Cytoplasmic localization of alteration/deficiency in activation 3 (ADA3) predicts poor clinical outcome in breast cancer patients. (PMID:23288344)
• PCAF and ADA3 regulate Bid processing via PACS2, to modulate the mitochondrial cell death pathway in response to hGrzB. (PMID:24464226)
• results thus demonstrate that the catalytic activity of GCN5 is stimulated by subunits of the ADA2a- or ADA2b-containing HAT modules and is further increased by incorporation of the distinct HAT modules in the ATAC or SAGA holo-complexes (PMID:26468280)
• Findings demonstrate that acetylation of ADA3 by its associated histone acetyltransferases is essential for its key role in histone acetylation and cell cycle progression. (PMID:27402865)
• review on hADA3 with a comprehensive outlook on the molecular and functional roles of hADA3 (PMID:27605378)
• ADA3 overexpression enhances cell proliferation that is associated with increased expression of c-MYC. Expression patterns with respect to ADA3/c-MYC can divide patients into four significantly different subgroups, with c-MYC High and ADA3 Low status independently predicting poor survival in patients. (PMID:27852327)
• PCAF and ADA3 transcriptionally regulate PACS1 and PACS1 is a key regulator of BAX/BAK oligomerization and the intrinsic (mitochondrial) pathway to apoptosis. (PMID:28060382)
• These results reveal a novel RTK-AKT-p300-ADA3 signaling pathway involved in growth factor-induced cell cycle progression. (PMID:28759294)
• a pro-apoptotic mechanism centered on the intrinsic (mitochondrial) pathway and regulated by PCAF/ADA3 can influence the progression from premalignant to malignant change, and thus act as a tumor suppression mechanism in gastric cancer. (PMID:29670108)
• ADA3 expression level elevates in non-small cell lung cancer and correlates with poor overall survival in non-small cell lung cancer patients (PMID:30954347)
• Transcriptional adaptor 3 influences the proliferative and invasive phenotypes of non-small cell lung cancer cells via regulating EMT. (PMID:37005955)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	tada3l	ENSDARG00000058220
mus_musculus	Tada3	ENSMUSG00000048930
rattus_norvegicus	Tada3	ENSRNOG00000008597
drosophila_melanogaster	Ada3	FBGN0030891

Protein

Protein identifiers

Transcriptional adapter 3 — O75528 (reviewed: O75528)

Alternative names: ADA3 homolog, STAF54, Transcriptional adapter 3-like

All UniProt accessions (3): A0A024R2D7, C9JMS0, O75528

UniProt curated annotations — full annotation on UniProt →

Function. Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context. The PCAF complex could be considered as the human version of the yeast SAGA complex. Also known as a coactivator for p53/TP53-dependent transcriptional activation. Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4.

Subunit / interactions. The PCAF complex is composed of a number of TBP-associated factors (TAFS), such as TAF5, TAF5L, TAF6, TAF6L, TAF9, TAF10 and TAF12, PCAF, and also PCAF-associated factors (PAFs), such as TADA2L/ADA2, TADA3L/ADA3 and SPT3. Interacts directly with TADA2L and PCAF and also with the high-risk HPV oncoprotein E6. Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9. Component of the TFTC-HAT complex. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitously expressed.

Similarity. Belongs to the NGG1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75528-1	1	yes
O75528-2	2

RefSeq proteins (3): NP_001265199, NP_006345, NP_597814 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019340	Histone_AcTrfase_su3	Family

Pfam: PF10198

UniProt features (13 total): modified residue 3, region of interest 2, cross-link 2, coiled-coil region 2, chain 1, splice variant 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75528-F1	76.21	0.38

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 (5): 129, 280, 298, 418, 21

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3214847	HATs acetylate histones
R-HSA-5689880	Ub-specific processing proteases
R-HSA-9772755	Formation of WDR5-containing histone-modifying complexes
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-392499	Metabolism of proteins
R-HSA-4839726	Chromatin organization
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-74160	Gene expression (Transcription)
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes

MSigDB gene sets: 215 (showing top): NAGY_STAGA_COMPONENTS_HUMAN, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_PROTEIN_DEACETYLATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_DEACYLATION, MORF_HDAC1, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_REGULATION_OF_DNA_REPAIR, SP1_Q2_01, SRF_Q5_01, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, SRF_C, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, MORF_CTBP1, GOBP_REGULATION_OF_CELL_CYCLE

GO Biological Process (14): negative regulation of transcription by RNA polymerase II (GO:0000122), mitotic cell cycle (GO:0000278), regulation of DNA repair (GO:0006282), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of gene expression (GO:0010628), estrogen receptor signaling pathway (GO:0030520), regulation of protein stability (GO:0031647), regulation of RNA splicing (GO:0043484), positive regulation of DNA-templated transcription (GO:0045893), regulation of embryonic development (GO:0045995), regulation of cell division (GO:0051302), regulation of cell cycle (GO:0051726)

GO Molecular Function (4): transcription coactivator activity (GO:0003713), nuclear receptor binding (GO:0016922), protein domain specific binding (GO:0019904), protein binding (GO:0005515)

GO Cellular Component (6): SAGA complex (GO:0000124), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription factor TFTC complex (GO:0033276), mitotic spindle (GO:0072686), ATAC complex (GO:0140672)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Chromatin modifying enzymes	1
Deubiquitination	1
Epigenetic regulation by WDR5-containing histone modifying complexes	1
Gene expression (Transcription)	1
Chromatin organization	1
Post-translational protein modification	1
Metabolism of proteins	1
Epigenetic regulation of gene expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of gene expression	3
SAGA-type complex	3
transcription by RNA polymerase II	2
cell cycle	2
DNA-templated transcription	2
regulation of DNA-templated transcription	2
regulation of cellular process	2
regulation of transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
mitotic nuclear division	1
DNA repair	1
regulation of DNA metabolic process	1
regulation of cellular response to stress	1
cellular component organization	1
regulation of RNA biosynthetic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
nuclear receptor-mediated steroid hormone signaling pathway	1
regulation of biological quality	1
RNA splicing	1
regulation of primary metabolic process	1
positive regulation of RNA biosynthetic process	1
embryo development	1
regulation of multicellular organismal development	1
cell division	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
protein binding	1
binding	1
DUBm complex	1
peptidase complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
RNA polymerase II, holoenzyme	1
RNA polymerase II transcription regulator complex	1
spindle	1

Protein interactions and networks

STRING

1720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TADA3	KAT2A	Q92830	999
TADA3	KAT2B	Q92831	998
TADA3	SGF29	Q96ES7	998
TADA3	TADA2A	O75478	997
TADA3	TADA2B	Q86TJ2	989
TADA3	TAF9	Q16594	908
TADA3	TRRAP	Q9Y4A5	908
TADA3	ATXN7	O15265	887
TADA3	TAF10	Q12962	859
TADA3	ENY2	Q9NPA8	850
TADA3	SUPT20H	Q8NEM7	837
TADA3	TAF5	Q15542	829
TADA3	TAF5L	O75529	792
TADA3	TAF6L	Q9Y6J9	792
TADA3	TAF12	Q16514	790

IntAct

169 interactions, top by confidence:

A	B	Type	Score
TADA3	SGF29	psi-mi:“MI:0915”(physical association)	0.940
SGF29	TADA3	psi-mi:“MI:0915”(physical association)	0.940
WDR5	KMT2D	psi-mi:“MI:0914”(association)	0.910
CDK8	MED19	psi-mi:“MI:2364”(proximity)	0.850
SGF29	NDC80	psi-mi:“MI:0914”(association)	0.840
TAF12	TAF4	psi-mi:“MI:0914”(association)	0.760
TADA3	TADA2A	psi-mi:“MI:0914”(association)	0.740
TRRAP	ATXN7	psi-mi:“MI:0914”(association)	0.740
TADA2A	TADA3	psi-mi:“MI:0915”(physical association)	0.740
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
KAT2B	TADA2A	psi-mi:“MI:0914”(association)	0.640
ATXN7L3	USP27X	psi-mi:“MI:0914”(association)	0.640
PSMC3	PSMD12	psi-mi:“MI:0914”(association)	0.640
TADA1	TADA3	psi-mi:“MI:0914”(association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
TADA3	PIAS4	psi-mi:“MI:0915”(physical association)	0.630

BioGRID (346): TP53 (Affinity Capture-Western), TADA3 (Affinity Capture-Western), TADA3 (Two-hybrid), CCDC101 (Two-hybrid), HEXIM2 (Two-hybrid), TADA3 (Protein-peptide), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), TADA3 (Affinity Capture-MS), CSRP2BP (Affinity Capture-MS), YEATS2 (Affinity Capture-MS)

ESM2 similar proteins: A4RMA9, A6QPH1, A8B976, B0WII7, B1WB17, B4NSP6, B5XDD3, B5XG19, B8BDW1, C5DMI3, O74517, O75528, P0CO36, P0CO37, P0CP34, P0CP35, P82804, Q09556, Q0II91, Q13442, Q16LW2, Q2F5J3, Q2H6A9, Q3UHX2, Q4IB50, Q4PEZ0, Q4V8F5, Q5ASA5, Q5EAE2, Q5R5V0, Q62785, Q640E9, Q65W23, Q69JZ7, Q6C0K9, Q6C3L4, Q6C5V7, Q6CBW0, Q6PH11, Q6ZBF6

Diamond homologs: O75528, Q4V8F5, Q5EAE2, Q5R5V0, Q66IZ5, Q66JG5, Q6PGT0, Q7SY21, Q8R0L9

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
TADA3	“form complex”	“SAGA complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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	34.0×	2e-12
Signaling by NOTCH1 PEST Domain Mutants in Cancer	5	23.7×	8e-05
Signaling by NOTCH1 in Cancer	5	23.7×	8e-05
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	5	23.7×	8e-05
Epigenetic regulation by WDR5-containing histone modifying complexes	12	21.5×	2e-11
Signaling by NOTCH1	5	20.8×	1e-04
Positive epigenetic regulation of rRNA expression	5	20.1×	1e-04
Chromatin organization	21	19.9×	3e-19

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell division	7	45.1×	1e-08
regulation of DNA repair	18	41.8×	4e-22
regulation of RNA splicing	16	29.4×	3e-17
regulation of embryonic development	8	22.2×	2e-07
transcription initiation-coupled chromatin remodeling	5	16.1×	8e-04
RNA polymerase II preinitiation complex assembly	7	16.0×	2e-05
mRNA transcription by RNA polymerase II	5	13.9×	1e-03
positive regulation of transcription initiation by RNA polymerase II	6	13.7×	3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	0
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1549 predictions. Top by Δscore:

Variant	Effect	Δscore
3:9780545:CCAGC:C	acceptor_gain	1.0000
3:9780546:CAGC:C	acceptor_gain	1.0000
3:9780546:CAGCC:C	acceptor_gain	1.0000
3:9780548:GC:G	acceptor_gain	1.0000
3:9780549:CC:C	acceptor_gain	1.0000
3:9780550:C:CC	acceptor_gain	1.0000
3:9780550:C:CG	acceptor_loss	1.0000
3:9780551:T:G	acceptor_loss	1.0000
3:9780560:C:CT	acceptor_gain	1.0000
3:9780561:A:T	acceptor_gain	1.0000
3:9784022:GCTCA:G	donor_loss	1.0000
3:9784023:CTCA:C	donor_loss	1.0000
3:9784024:TCA:T	donor_loss	1.0000
3:9784025:CA:C	donor_loss	1.0000
3:9784026:A:AC	donor_gain	1.0000
3:9784027:C:CA	donor_loss	1.0000
3:9784027:C:CC	donor_gain	1.0000
3:9784027:CCT:C	donor_gain	1.0000
3:9784210:CACA:C	acceptor_gain	1.0000
3:9784211:ACA:A	acceptor_gain	1.0000
3:9784212:CA:C	acceptor_gain	1.0000
3:9784212:CAC:C	acceptor_gain	1.0000
3:9784214:C:CC	acceptor_gain	1.0000
3:9787000:GCTCA:G	donor_loss	1.0000
3:9787001:CTCAC:C	donor_loss	1.0000
3:9787002:TCACC:T	donor_loss	1.0000
3:9787004:A:C	donor_loss	1.0000
3:9787105:CACAT:C	acceptor_gain	1.0000
3:9787107:CAT:C	acceptor_gain	1.0000
3:9787109:TC:T	acceptor_loss	1.0000

AlphaMissense

2827 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:9780388:C:G	R423P	1.000
3:9780389:G:T	R423S	1.000
3:9780397:A:G	L420P	1.000
3:9780409:G:T	A416D	1.000
3:9780410:C:G	A416P	1.000
3:9780433:G:C	P408R	1.000
3:9780433:G:T	P408H	1.000
3:9780454:G:T	A401D	1.000
3:9780469:C:G	R396P	1.000
3:9784034:A:G	L367P	1.000
3:9784076:A:G	L353P	1.000
3:9784097:A:G	L346P	1.000
3:9784169:A:G	L322P	1.000
3:9787013:A:G	L268P	1.000
3:9787025:A:G	L264P	1.000
3:9787305:C:A	W200C	1.000
3:9787305:C:G	W200C	1.000
3:9787306:C:G	W200S	1.000
3:9787307:A:G	W200R	1.000
3:9787307:A:T	W200R	1.000
3:9787327:C:T	G193E	1.000
3:9789592:A:C	Y161D	1.000
3:9789608:C:A	W155C	1.000
3:9789608:C:G	W155C	1.000
3:9789610:A:G	W155R	1.000
3:9789610:A:T	W155R	1.000
3:9789611:G:C	F154L	1.000
3:9789611:G:T	F154L	1.000
3:9789612:A:C	F154C	1.000
3:9789612:A:G	F154S	1.000

dbSNP variants (sampled 300 via entrez): RS1000111939 (3:9781199 G>A), RS1000142713 (3:9780889 A>G), RS1000246456 (3:9786647 C>T), RS1000304726 (3:9792329 G>A), RS1000723900 (3:9786445 C>G), RS1000833333 (3:9792547 G>A,C), RS1000987391 (3:9785659 T>C), RS1001193476 (3:9794674 C>T), RS1001442171 (3:9782206 C>G), RS1001815116 (3:9779699 T>C), RS1002499252 (3:9788985 A>G), RS1002712828 (3:9788201 T>C), RS1002733375 (3:9794003 C>T), RS1003110645 (3:9793680 G>A,C), RS1003273664 (3:9793483 C>A,G,T)

Disease associations

OMIM: gene MIM:602945 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
naringenin	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
bisphenol A	decreases expression, affects cotreatment	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
4-hydroxy-2-nonenal	decreases expression	1
methacrylaldehyde	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	increases expression	1
Temozolomide	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Ozone	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
Quercetin	decreases expression	1
Selenium	increases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1
tert-Butylhydroperoxide	decreases expression	1
Volatile Organic Compounds	affects cotreatment, decreases expression, increases oxidation	1

Clinical trials (associated diseases)

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