AATF

Summary

AATF (apoptosis antagonizing transcription factor, HGNC:19235) is a protein-coding gene on chromosome 17q12, encoding Protein AATF (Q9NY61). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. It is a selective cancer dependency (DepMap: 83.4% of cell lines).

The protein encoded by this gene was identified on the basis of its interaction with MAP3K12/DLK, a protein kinase known to be involved in the induction of cell apoptosis. This gene product contains a leucine zipper, which is a characteristic motif of transcription factors, and was shown to exhibit strong transactivation activity when fused to Gal4 DNA binding domain. Overexpression of this gene interfered with MAP3K12 induced apoptosis.

Source: NCBI Gene 26574 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 231 total — 98 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 3
• Cancer dependency (DepMap): dependent in 83.4% of screened cell lines
• MANE Select transcript: NM_012138

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19235
Approved symbol	AATF
Name	apoptosis antagonizing transcription factor
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	DED, CHE-1, CHE1, BFR2
Ensembl gene	ENSG00000275700
Ensembl biotype	protein_coding
OMIM	608463
Entrez	26574

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 18 protein_coding, 8 retained_intron, 4 nonsense_mediated_decay, 3 protein_coding_CDS_not_defined

ENST00000610798, ENST00000613840, ENST00000615319, ENST00000616062, ENST00000616392, ENST00000616434, ENST00000617141, ENST00000619387, ENST00000622432, ENST00000679508, ENST00000679600, ENST00000679881, ENST00000679985, ENST00000679997, ENST00000680330, ENST00000680340, ENST00000680356, ENST00000680579, ENST00000680782, ENST00000680807, ENST00000681062, ENST00000681070, ENST00000681800, ENST00000905215, ENST00000905216, ENST00000905217, ENST00000905218, ENST00000937261, ENST00000937262, ENST00000937263, ENST00000937264, ENST00000953116, ENST00000953117

RefSeq mRNA: 2 — MANE Select: NM_012138 NM_001411094, NM_012138

CCDS: CCDS32632, CCDS92291

Canonical transcript exons

ENST00000619387 — 12 exons

Exon	Start	End
ENSE00003712094	36989247	36989411
ENSE00003719458	36990774	36990857
ENSE00003722560	36950214	36950405
ENSE00003725720	37031614	37031685
ENSE00003726718	36952886	36953296
ENSE00003730467	36953770	36953907
ENSE00003731024	36948954	36949216
ENSE00003734863	36986617	36986731
ENSE00003739876	37019005	37019072
ENSE00003747387	37020934	37021014
ENSE00003749803	37056601	37056871
ENSE00003754167	36988519	36988720

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2482 / max 288.0773, expressed in 1822 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160445	35.1153	1822
160446	0.1329	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	94.51	gold quality
leukocyte	CL:0000738	94.47	gold quality
granulocyte	CL:0000094	94.21	gold quality
corpus callosum	UBERON:0002336	93.89	gold quality
calcaneal tendon	UBERON:0003701	93.83	gold quality
popliteal artery	UBERON:0002250	93.02	gold quality
tibial artery	UBERON:0007610	93.02	gold quality
blood	UBERON:0000178	92.95	gold quality
skin of leg	UBERON:0001511	92.58	gold quality
bone marrow	UBERON:0002371	92.44	gold quality
zone of skin	UBERON:0000014	92.34	gold quality
body of pancreas	UBERON:0001150	92.22	gold quality
sural nerve	UBERON:0015488	92.12	gold quality
bone marrow cell	CL:0002092	92.09	gold quality
skin of abdomen	UBERON:0001416	92.09	gold quality
pancreas	UBERON:0001264	92.02	gold quality
islet of Langerhans	UBERON:0000006	92.00	gold quality
ganglionic eminence	UBERON:0004023	91.81	gold quality
lymph node	UBERON:0000029	91.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.70	gold quality
lower esophagus	UBERON:0013473	91.67	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	91.44	gold quality
urinary bladder	UBERON:0001255	91.39	gold quality
right coronary artery	UBERON:0001625	91.36	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.24	gold quality
nucleus accumbens	UBERON:0001882	91.23	gold quality
descending thoracic aorta	UBERON:0002345	91.21	gold quality
placenta	UBERON:0001987	91.14	gold quality
subcutaneous adipose tissue	UBERON:0002190	91.11	gold quality
ascending aorta	UBERON:0001496	91.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.63

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
BAX	Repression
CDKN1A	Unknown
KLK3	Unknown
MYC	Activation
TP53	Unknown

Upstream regulators (CollecTRI, top): AR, CTNNB1, ESR1, STAT3, ZNF362

miRNA regulators (miRDB)

5 targeting AATF, 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-5582-5P	99.27	71.42	1879
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-3189-5P	97.55	66.71	655
HSA-MIR-663A	94.99	63.54	378
HSA-MIR-6789-3P	83.91	59.77	58

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 83.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 34)

• Che-1 affects cell growth by interfering with the recruitment of HDAC1 by retinoblastoma protein. Che-1 overexpression activates DNA synthesis in quiescent NIH-3T3 cells through HFDAC1 displacement. (PMID:12450794)
• Che-1 can be considered a general HDAC1 competitor and its down-regulation is involved in colon carcinoma cell proliferation (PMID:12847090)
• apoptosis-antagonizing transcription factor binds to TSG101 in a process that enhances androgen receptor-mediated transcription by promoting its monoubiquitination (PMID:14761944)
• AATF gene may be of crucial importance in maintaining the leukemic state of a cell compartment through its ability to initiate cell proliferation coupled with repression of cellular apoptosis. (PMID:17006618)
• Che-1 as a new Pin1 and HDM2 target and confirm its important role in the cellular response to DNA damage. (PMID:17468107)
• Che-1 interacts with NRAGE and NRAGE overexpression downregulates endogenous Che-1 by targeting it for proteasome-dependent degradation. (PMID:17488777)
• This review explains the novel miRNA encoded exclusively by HIV-1 genome that has the ability to specifically target cellular AATF gene known to play a crucial role in the maintenance of adaptive immunity at nucleic acid level against HIV-1 invasion. (PMID:18341201)
• No evidence for the association of mutations with breast cancer was observed. (PMID:20025740)
• found that Che-1 is required for sustaining mutant p53 expression in several cancer cell lines, and that Che-1 depletion by siRNA induces apoptosis both in vitro and in vivo (PMID:20708154)
• Nuclear AATF enrichment is selected for in p53-proficient endometrial cancers. Focal copy number AATF gains correlate with reduced overall survival in neuroblastoma. AATF is a critical repressor of p53-driven apoptosis. (PMID:22909821)
• These results identify AATF as a nucleolar-confined c-Jun cofactor whose expression levels and spatial distribution determine the stress-induced activity of c-Jun and the levels of c-Jun-mediated apoptosis. (PMID:22933572)
• Che-1 depletion abolishes the ability of Chk1 to bind pericentrin and to localize at centrosomes, which, in its turn, deregulates the activation of centrosomal cyclin B-Cdk1 and advances entry into mitosis. (PMID:23798705)
• Cell proliferation decreased by 41% which was accompanied by apoptosis induction in 30% MCF-7 cells after AATF gene knockdown. (PMID:23801113)
• HIPK2 depletion strongly decreases Che-1 ubiquitylation and degradation. (PMID:25210797)
• This mutant AATF along with its interactome consisting of SP1, DNMT3B and Par-4 ensures cancer cell DNA methylation required for down-regulation of tumor suppressor genes. (PMID:25231211)
• Che-1 expression correlates with the progression of multiple myeloma and is required for cell growth and survival.Che-1 controls mTOR through the induction of Redd1 and Deptor, two important repressors of mTOR. (PMID:25770584)
• In the face of high glucose threat, mitochondrial UCP2 gene expression is regulated by miR-2909 and AATF. (PMID:25976474)
• These results confirm Che-1 as an important regulator of p53 activity and suggest Che-1 to be a promising yet attractive drug target for cancer therapy. (PMID:25996291)
• It was concluded that PARP-1 was involved in the DNA damage repair induced by HQ via increasing the accumulation of apoptosis antagonizing transcription factor through PARylation. (PMID:26822515)
• loss of Che-1 inhibits proliferation and promotes apoptosis in MG-63 cells by decreasing the level of mutant p53 (PMID:27012205)
• we identified the ANN complex as a novel functional module supporting the nucleolar maturation of 40S ribosomal subunits. Our data help to explain the described role of AATF in cell proliferation during mouse development as well as its requirement for malignant tumor growth. (PMID:27599843)
• the effect of APOBEC3G over-expression upon AATF gene expression, was examined. (PMID:27611213)
• Results show that eEF1Bgamma binds to the Che-1 promoter region and its transcript, and describe a novel mitochondrial localization for the Che-1 protein which needs mitochondrial integrity for correct localization. (PMID:27639846)
• Results show that Che-1 protects colon cancer cells from apoptosis induced by hypoxia through its ability to regulate HIF1-alpha stabilization in colorectal cancer cells. (PMID:28214471)
• Identification of the transcriptional regulator AATF/CHE-1 as a key molecule to sustain proliferative tissues and tumor progression in parts by inhibiting p53-driven apoptosis in vivo. (PMID:29321668)
• Genomewide ChIP-seq experiments suggest that Che-1 acts as a downstream effector of c-Myc. These results identify the pivotal role of Che-1 in the control of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) proliferation and present the protein as a possible therapeutic target in children with relapsed BCP-ALL (PMID:29367285)
• These data individuate Che-1 as a possible novel target in the treatment of B-cell precursor acute lymphoblastic leukemia able to affect c-Myc-driven tumorigenicity. (PMID:29943642)
• drives hepatocarcinogenesis in nonalcoholic fatty liver disease (PMID:30394550)
• miR-663 may function as an ‘apoptomiR’ by inhibiting the anti-apoptotic gene AATF to induce apoptosis. These findings could have therapeutic implications for epithelial cell targeting in cancer therapy. (PMID:30610504)
• AATF and SMARCA2 are associated with thyroid volume in Hashimoto’s thyroiditis patients. (PMID:32019955)
• Che-1/AATF binds to RNA polymerase I machinery and sustains ribosomal RNA gene transcription. (PMID:32421830)
• CK2-mediated phosphorylation of Che-1/AATF is required for its pro-proliferative activity. (PMID:34266450)
• HAX1 is a novel binding partner of Che-1/AATF. Implications in oxidative stress cell response. (PMID:37742722)
• Vinblastine Resistance Is Associated with Nephronophthisis 3-Mediated Primary Cilia via Intraflagellar Transport Protein 88 and Apoptosis-Antagonizing Transcription Factor. (PMID:39408701)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	aatf	ENSDARG00000025467
mus_musculus	Aatf	ENSMUSG00000018697
rattus_norvegicus	Aatf	ENSRNOG00000002778

Protein

Protein identifiers

Protein AATF — Q9NY61 (reviewed: Q9NY61)

Alternative names: Apoptosis-antagonizing transcription factor, Rb-binding protein Che-1

All UniProt accessions (11): Q9NY61, A0A087WTH8, A0A087WW41, A0A087WWS8, A0A7P0T868, A0A7P0TAR0, A0A7P0TBG4, A0A7P0TBI0, A0A7P0Z434, A0A7P0Z4N2, A0A7P0Z4P2

UniProt curated annotations — full annotation on UniProt →

Function. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. May function as a general inhibitor of the histone deacetylase HDAC1. Binding to the pocket region of RB1 may displace HDAC1 from RB1/E2F complexes, leading to activation of E2F target genes and cell cycle progression. Conversely, displacement of HDAC1 from SP1 bound to the CDKN1A promoter leads to increased expression of this CDK inhibitor and blocks cell cycle progression. Also antagonizes PAWR mediated induction of aberrant amyloid peptide production in Alzheimer disease (presenile and senile dementia), although the molecular basis for this phenomenon has not been described to date.

Subunit / interactions. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with POLR2J, RB1/RB, RBL1/P107 and RBL2/P130. Interacts with PAWR and SP1. May also bind MAPT.

Subcellular location. Nucleus. Nucleolus.

Tissue specificity. Ubiquitously expressed. Expressed at high levels in brain, heart, kidney, placenta and thymus.

Post-translational modifications. Hyperphosphorylated during the G1/S phase transition.

Similarity. Belongs to the AATF family.

RefSeq proteins (2): NP_001398023, NP_036270* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR012617	AATF_C	Domain
IPR025160	AATF	Domain
IPR039223	AATF/Bfr2	Family

Pfam: PF08164, PF13339

UniProt features (27 total): modified residue 10, sequence conflict 7, region of interest 5, compositionally biased region 3, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5W6A	X-RAY DIFFRACTION	1.74
7MQ8	ELECTRON MICROSCOPY	3.6
7MQ9	ELECTRON MICROSCOPY	3.87

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY61-F1	65.74	0.24

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 (10): 2, 61, 63, 150, 155, 203, 273, 316, 320, 321

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-162582	Signal Transduction
R-HSA-193704	p75 NTR receptor-mediated signalling
R-HSA-204998	Cell death signalling via NRAGE, NRIF and NADE
R-HSA-73887	Death Receptor Signaling

MSigDB gene sets: 226 (showing top): GOBP_RIBOSOME_BIOGENESIS, BENPORATH_ES_WITH_H3K27ME3, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MATURATION_OF_SSU_RRNA, MORF_UBE2I, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MORF_CDK2, REACTOME_NRAGE_SIGNALS_DEATH_THROUGH_JNK, MORF_HDAC2, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_TOPOLOGICALLY_INCORRECT_PROTEIN, PUJANA_CHEK2_PCC_NETWORK, MARTINEZ_RB1_TARGETS_UP

GO Biological Process (7): cell adhesion (GO:0007155), regulation of mitotic cell cycle (GO:0007346), embryonic cleavage (GO:0040016), ribosomal small subunit biogenesis (GO:0042274), negative regulation of amyloid precursor protein biosynthetic process (GO:0042985), negative regulation of apoptotic signaling pathway (GO:2001234), ribosome biogenesis (GO:0042254)

GO Molecular Function (3): RNA binding (GO:0003723), leucine zipper domain binding (GO:0043522), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), nucleolus (GO:0005730), cytoplasm (GO:0005737), small-subunit processome (GO:0032040)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell death signalling via NRAGE, NRIF and NADE	1
Death Receptor Signaling	1
p75 NTR receptor-mediated signalling	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ribonucleoprotein complex biogenesis	2
nuclear lumen	2
cellular anatomical structure	2
cellular process	1
mitotic cell cycle	1
regulation of cell cycle	1
embryo development	1
cell division	1
ribosome biogenesis	1
negative regulation of glycoprotein biosynthetic process	1
amyloid precursor protein biosynthetic process	1
regulation of amyloid precursor protein biosynthetic process	1
negative regulation of signal transduction	1
negative regulation of apoptotic process	1
apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
nucleic acid binding	1
LRR domain binding	1
binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nucleolus	1
preribosome	1
t-UTP complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

2565 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
AATF	DAPK3	O43293	803
AATF	NOL10	Q9BSC4	796
AATF	NGDN	Q8NEJ9	791
AATF	NAT10	Q9H0A0	718
AATF	POLR2J	P52435	698
AATF	REPS1	Q96D71	630
AATF	DDX52	Q9Y2R4	612
AATF	ABT1	Q9ULW3	609
AATF	MAGED1	Q9Y5V3	591
AATF	BYSL	Q13895	565
AATF	BMS1	Q14692	558
AATF	IRGQ	Q8WZA9	549
AATF	ADPGK	Q9BRR6	548
AATF	GGNBP2	Q9H3C7	547
AATF	DDX10	Q13206	527
AATF	DPAGT1	Q9H3H5	527

IntAct

204 interactions, top by confidence:

A	B	Type	Score
AATF	NGDN	psi-mi:“MI:0915”(physical association)	0.810
AATF	NGDN	psi-mi:“MI:0914”(association)	0.810
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.660
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
CHEK2	AATF	psi-mi:“MI:0915”(physical association)	0.600
AATF	CHEK2	psi-mi:“MI:0217”(phosphorylation reaction)	0.600
MNS1	AATF	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	AATF	psi-mi:“MI:0915”(physical association)	0.560
RAC1	AATF	psi-mi:“MI:0915”(physical association)	0.560
APP	AATF	psi-mi:“MI:0915”(physical association)	0.560
AATF	ATM	psi-mi:“MI:0915”(physical association)	0.540
ATM	AATF	psi-mi:“MI:0217”(phosphorylation reaction)	0.540
TADA2A	AATF	psi-mi:“MI:0915”(physical association)	0.540
TADA2B	AATF	psi-mi:“MI:0915”(physical association)	0.540

BioGRID (425): AATF (Affinity Capture-Western), HIPK2 (Affinity Capture-Western), AATF (Biochemical Activity), AATF (Affinity Capture-Western), AATF (Co-localization), AR (Co-localization), DAPK3 (Co-localization), TSG101 (Co-localization), AATF (Co-localization), AATF (Two-hybrid), AATF (Affinity Capture-RNA), AATF (Affinity Capture-MS), AATF (Affinity Capture-MS), AATF (Affinity Capture-MS), AATF (Affinity Capture-MS)

ESM2 similar proteins: A2AFR3, A6QLZ5, O08838, O94888, O95983, P0C6S7, P21580, P49418, P50478, Q05B58, Q08DU8, Q14161, Q14CM0, Q1RMZ1, Q32KN2, Q3KR37, Q3ZK22, Q497H0, Q5E948, Q5RD48, Q5REE1, Q5REY7, Q5RFL7, Q5U2M7, Q5UAK0, Q5ZIA0, Q5ZKA4, Q60769, Q66H91, Q6DC60, Q6ZPY2, Q7TQF7, Q7Z6G8, Q8BIZ1, Q8BR63, Q8BXK4, Q8IW50, Q8N108, Q8N128, Q8R3V6

Diamond homologs: Q4P5V5, Q55E65, Q5ACL9, Q5ZIM6, Q6BXX1, Q6C9G2, Q7S6P8, Q9NY61, Q9US05, Q06631, Q6CTS8, Q6FSD4, Q75EZ2, Q4I327, Q4WMI1, Q5AW04, Q9JKX4, Q9QYW0, Q9VM95

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
MAPKAPK2	up-regulates	AATF	phosphorylation
AATF	“down-regulates quantity”	BAX	“transcriptional regulation”
ATM	“up-regulates quantity by stabilization”	AATF	phosphorylation
CHEK2	“up-regulates quantity by stabilization”	AATF	phosphorylation
HIPK2	“down-regulates quantity”	AATF	phosphorylation
AATF	“up-regulates quantity by expression”	KLK3	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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
Eukaryotic Translation Initiation	8	23.1×	4e-08
Cap-dependent Translation Initiation	8	23.1×	4e-08
SARS-CoV-1 modulates host translation machinery	8	23.1×	4e-08
Peptide chain elongation	19	22.5×	1e-18
Viral mRNA Translation	19	22.5×	1e-18
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	19	22.3×	1e-18
Selenocysteine synthesis	19	21.4×	2e-18
Eukaryotic Translation Termination	19	21.4×	2e-18

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of DNA recombination	5	39.3×	2e-05
chromosome condensation	6	35.4×	3e-06
cytoplasmic translation	20	25.9×	4e-20
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	5	23.6×	2e-04
ribosomal small subunit biogenesis	12	19.1×	5e-10
ribosomal large subunit biogenesis	6	18.6×	1e-04
translation	19	13.7×	9e-14
regulation of alternative mRNA splicing, via spliceosome	7	12.0×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	98
Likely pathogenic	14
Uncertain significance	96
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144179	GRCh37/hg19 17q12(chr17:34450405-36248918)x1	Pathogenic
144685	GRCh37/hg19 17q12(chr17:35076189-36248926)x1	Pathogenic
148852	GRCh37/hg19 17q12(chr17:34817422-36188700)x1	Pathogenic
148853	GRCh38/hg38 17q12(chr17:36446545-38225796)x1	Pathogenic
149616	GRCh37/hg19 17q12(chr17:34817422-36248918)x1	Pathogenic
149644	GRCh38/hg38 17q12(chr17:36500465-37889304)x1	Pathogenic
151517	GRCh37/hg19 17q12(chr17:34360168-36248859)x1	Pathogenic
152579	GRCh37/hg19 17q12(chr17:34856055-36248859)x3	Pathogenic
152580	GRCh37/hg19 17q12(chr17:34856055-36248859)x1	Pathogenic
153717	GRCh37/hg19 17q12(chr17:34822466-36393628)x1	Pathogenic
153746	GRCh37/hg19 17q12(chr17:34822466-36307773)x1	Pathogenic
153855	GRCh37/hg19 17q12(chr17:34822466-36283612)x1	Pathogenic
153885	GRCh37/hg19 17q12(chr17:34822466-36316161)x1	Pathogenic
154005	GRCh37/hg19 17q12(chr17:34822465-36283807)x1	Pathogenic
160874	GRCh38/hg38 17q12(chr17:36500215-37889296)x1	Pathogenic
160929	GRCh37/hg19 17q12(chr17:34508117-36248918)x3	Pathogenic
160937	GRCh37/hg19 17q12(chr17:34856055-36248918)x3	Pathogenic
161041	GRCh38/hg38 17q12(chr17:36357258-37889296)x1	Pathogenic
1703619	GRCh37/hg19 17q12(chr17:34463923-36410559)	Pathogenic
1703620	GRCh37/hg19 17q12(chr17:34822465-36410559)	Pathogenic
1708189	GRCh37/hg19 17q12(chr17:34822465-36243781)x1	Pathogenic
1807768	GRCh37/hg19 17q12(chr17:34425363-36404555)x3	Pathogenic
1808648	GRCh37/hg19 17q12(chr17:34822466-36404136)x1	Pathogenic
236377	Single allele	Pathogenic
2499653	GRCh38/hg38 17q12(chr17:36138501-37924067)	Pathogenic
2506537	GRCh37/hg19 17q12(chr17:34842545-36293050)	Pathogenic
253472	GRCh37/hg19 17q12(chr17:34849849-36151346)x3	Pathogenic
253502	GRCh37/hg19 17q12(chr17:34849849-36151346)x1	Pathogenic
2579204	GRCh38/hg38 17q12(chr17:36486532-37745203)x1	Pathogenic
2671580	Single allele	Pathogenic

SpliceAI

2491 predictions. Top by Δscore:

Variant	Effect	Δscore
17:36949212:GGAAG:G	donor_gain	1.0000
17:36949213:G:GT	donor_gain	1.0000
17:36949214:A:T	donor_gain	1.0000
17:36949217:G:A	donor_loss	1.0000
17:36950406:G:GA	donor_loss	1.0000
17:36950406:G:GG	donor_gain	1.0000
17:36950407:T:G	donor_loss	1.0000
17:36952883:TA:T	acceptor_loss	1.0000
17:36952884:A:AC	acceptor_loss	1.0000
17:36952884:A:AG	acceptor_gain	1.0000
17:36952884:AGAT:A	acceptor_gain	1.0000
17:36952884:AGATG:A	acceptor_gain	1.0000
17:36952885:G:GG	acceptor_gain	1.0000
17:36952885:GA:G	acceptor_gain	1.0000
17:36952885:GAT:G	acceptor_gain	1.0000
17:36952885:GATG:G	acceptor_gain	1.0000
17:36953185:G:GT	donor_gain	1.0000
17:36953260:G:GT	donor_gain	1.0000
17:36953273:G:GT	donor_gain	1.0000
17:36953292:GATAG:G	donor_gain	1.0000
17:36953293:A:G	donor_gain	1.0000
17:36953293:ATAGG:A	donor_loss	1.0000
17:36953294:TAGG:T	donor_loss	1.0000
17:36953295:AGG:A	donor_loss	1.0000
17:36953296:GGTT:G	donor_loss	1.0000
17:36953297:G:GA	donor_loss	1.0000
17:36953298:T:A	donor_loss	1.0000
17:36953908:G:GG	donor_gain	1.0000
17:36988516:TAGTG:T	acceptor_gain	1.0000
17:36988517:AGTGA:A	acceptor_gain	1.0000

AlphaMissense

3740 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:37021005:G:C	R513T	0.998
17:37021006:G:C	R513S	0.998
17:37021006:G:T	R513S	0.998
17:36988679:T:A	W370R	0.997
17:36988679:T:C	W370R	0.997
17:37021005:G:T	R513M	0.997
17:37019006:T:C	L467P	0.996
17:37019009:T:C	L468P	0.996
17:37019018:T:C	L471P	0.996
17:37021000:A:C	K511N	0.996
17:37021000:A:T	K511N	0.996
17:36990837:G:C	D460H	0.995
17:37019012:G:C	R469P	0.995
17:37020995:A:C	S510R	0.995
17:37020997:C:A	S510R	0.995
17:37020997:C:G	S510R	0.995
17:37020999:A:T	K511I	0.995
17:36988671:T:C	L367P	0.994
17:37019009:T:A	L468H	0.994
17:37020938:T:A	W491R	0.994
17:37020938:T:C	W491R	0.994
17:36953836:T:C	L254P	0.993
17:36953800:T:C	I242T	0.992
17:36990838:A:T	D460V	0.992
17:37020993:C:A	A509D	0.992
17:37021004:A:G	R513G	0.992
17:36988681:G:C	W370C	0.991
17:36988681:G:T	W370C	0.991
17:37020960:G:C	R498P	0.991
17:36990831:T:C	F458L	0.990

dbSNP variants (sampled 300 via entrez): RS1000008224 (17:37050092 G>T), RS1000070395 (17:37019801 ATAT>A), RS1000077055 (17:36959272 C>T), RS1000101975 (17:37005825 T>C), RS1000171472 (17:36995364 A>G), RS1000174452 (17:36947425 G>A,T), RS1000193057 (17:37013690 T>C), RS1000244247 (17:37044078 G>A), RS1000285434 (17:36998806 G>A), RS1000335171 (17:37011663 T>C), RS1000345086 (17:37033092 T>G), RS1000352383 (17:37030692 A>C,G), RS1000396119 (17:36991514 T>C,G), RS1000419779 (17:37037497 A>G), RS1000470278 (17:36962538 T>G)

Disease associations

OMIM: gene MIM:608463 | disease phenotypes: MIM:614527, MIM:616025, MIM:192350, MIM:137920, MIM:209850, MIM:181500, MIM:614526

GenCC curated gene-disease

Mondo (12): chromosome 17q12 deletion syndrome (MONDO:0013797), diaphragmatic eventration (MONDO:0006726), primary ovarian failure (MONDO:0005387), autism spectrum disorder (MONDO:0005258), hyperphosphatasia with intellectual disability syndrome 5 (MONDO:0014457), VACTERL/vater association (MONDO:0008642), renal cysts and diabetes syndrome (MONDO:0007669), intellectual disability (MONDO:0001071), autism (MONDO:0005260), schizophrenia (MONDO:0005090), chromosome 17q12 duplication syndrome (MONDO:0013796), neurodevelopmental disorder (MONDO:0700092)

Orphanet (9): 17q12 microdeletion syndrome (Orphanet:261265), Hyperphosphatasia-intellectual disability syndrome (Orphanet:247262), VACTERL/VATER association (Orphanet:887), HNF1B-related autosomal dominant tubulointerstitial kidney disease (Orphanet:93111), 17q12 microduplication syndrome (Orphanet:261272), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140)

HPO phenotypes

3 total (3 of 3 shown, HPO-id order):

HPO	Term
HP:0009110	Diaphragmatic eventration
HP:0000717	Autism
HP:0100753	Schizophrenia

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST001762_165	Obesity-related traits	9.000000e-06
GCST001762_625	Obesity-related traits	2.000000e-06
GCST005951_15	Body mass index	3.000000e-13
GCST006956_23	Erectile dysfunction	5.000000e-06
GCST009997_1	Thyroid volume in Hashimoto’s thyroiditis	9.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005106	body composition measurement
EFO:0004340	body mass index

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D003965	Diaphragmatic Eventration	C06.198.257; C16.131.314.244
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C535520	Renal cysts and diabetes syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, affects reaction, increases expression	2
Air Pollutants	affects expression, increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
beauvericin	decreases expression	1
alpha phellandrene	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
coumarin	increases phosphorylation	1
hydroquinone	increases expression, affects reaction, increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
eprenetapopt	increases expression, affects reaction	1
bisphenol S	increases methylation	1
PF 3758309	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	decreases expression	1
Resveratrol	increases phosphorylation	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Vehicle Emissions	decreases expression, increases abundance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0A0	SEES3-1V human AATF, clone1	Embryonic stem cell	Male
CVCL_A0A1	SEES3-1V human AATF, clone2	Embryonic stem cell	Male
CVCL_A0A2	SEES3-1V human AATF, clone3	Embryonic stem cell	Male
CVCL_B7VS	Abcam Raji AATF KO	Cancer cell line	Male
CVCL_B9W7	Abcam THP-1 AATF KO	Cancer cell line	Male
CVCL_C6Y9	Abcam PC-3 AATF KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in 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
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
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
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD