ATF7IP2

Summary

ATF7IP2 (activating transcription factor 7 interacting protein 2, HGNC:20397) is a protein-coding gene on chromosome 16p13.2-p13.13, encoding Activating transcription factor 7-interacting protein 2 (Q5U623). Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation.

Predicted to enable transcription coregulator activity. Predicted to be involved in regulation of DNA-templated transcription. Predicted to be part of transcription regulator complex. Predicted to be active in nucleus.

Source: NCBI Gene 80063 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 156 total — 1 pathogenic
• MANE Select transcript: NM_001393719

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20397
Approved symbol	ATF7IP2
Name	activating transcription factor 7 interacting protein 2
Location	16p13.2-p13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12668, MCAF2
Ensembl gene	ENSG00000166669
Ensembl biotype	protein_coding
OMIM	613645
Entrez	80063

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 19 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000324570, ENST00000356427, ENST00000396559, ENST00000396560, ENST00000535850, ENST00000543967, ENST00000561932, ENST00000562102, ENST00000562396, ENST00000562527, ENST00000564797, ENST00000565450, ENST00000565616, ENST00000566316, ENST00000568027, ENST00000569900, ENST00000569939, ENST00000570163, ENST00000876243, ENST00000876244, ENST00000876245, ENST00000876246, ENST00000876247, ENST00000914621, ENST00000914622, ENST00000914623, ENST00000914624, ENST00000950976

RefSeq mRNA: 4 — MANE Select: NM_001393719 NM_001256160, NM_001352120, NM_001393719, NM_024997

CCDS: CCDS10540, CCDS58422

Canonical transcript exons

ENST00000562102 — 14 exons

Exon	Start	End
ENSE00001203767	10438101	10438235
ENSE00001286005	10433525	10433649
ENSE00001322159	10457372	10457529
ENSE00001329066	10440364	10440462
ENSE00001525464	10430611	10431455
ENSE00001525465	10428868	10429016
ENSE00001525466	10386061	10386122
ENSE00001732210	10419581	10419623
ENSE00002595942	10414574	10414612
ENSE00003475249	10473923	10473989
ENSE00003495711	10473479	10473534
ENSE00003555489	10472110	10472183
ENSE00003621488	10480879	10480964
ENSE00003693025	10481836	10483638

Expression profiles

Bgee: expression breadth ubiquitous, 254 present calls, max score 97.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.7486 / max 326.4104, expressed in 1474 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152699	15.4324	1433
152698	1.3163	589

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	97.12	gold quality
left testis	UBERON:0004533	97.02	gold quality
testis	UBERON:0000473	95.53	gold quality
left adrenal gland cortex	UBERON:0035825	94.75	gold quality
left adrenal gland	UBERON:0001234	94.74	gold quality
right adrenal gland	UBERON:0001233	94.63	gold quality
corpus epididymis	UBERON:0004359	94.15	gold quality
right lobe of liver	UBERON:0001114	94.08	gold quality
right adrenal gland cortex	UBERON:0035827	93.97	gold quality
body of pancreas	UBERON:0001150	92.97	gold quality
adrenal cortex	UBERON:0001235	92.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.71	gold quality
adrenal gland	UBERON:0002369	92.33	gold quality
sperm	CL:0000019	91.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.01	gold quality
heart left ventricle	UBERON:0002084	90.49	gold quality
male germ cell	CL:0000015	90.27	gold quality
cardiac ventricle	UBERON:0002082	90.02	gold quality
apex of heart	UBERON:0002098	89.88	gold quality
liver	UBERON:0002107	89.43	gold quality
right atrium auricular region	UBERON:0006631	88.94	gold quality
oocyte	CL:0000023	88.92	gold quality
pancreas	UBERON:0001264	88.64	gold quality
heart	UBERON:0000948	88.01	gold quality
bronchial epithelial cell	CL:0002328	87.99	gold quality
right uterine tube	UBERON:0001302	87.59	gold quality
secondary oocyte	CL:0000655	87.58	gold quality
cardiac atrium	UBERON:0002081	87.48	gold quality
epithelium of bronchus	UBERON:0002031	86.79	gold quality
body of stomach	UBERON:0001161	86.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.73
E-MTAB-6379	no	2166.60

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

63 targeting ATF7IP2, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6762-3P	99.66	66.94	1188
HSA-MIR-7152-5P	99.60	69.33	2094

Literature-anchored findings (GeneRIF, showing 1)

• These data suggest that MBD1.MCAF1.SETDB1 complex facilitates the formation of heterochromatic domains, emphasizing the role of MCAF/AM family proteins in epigenetic control, and describe a new family member, MCAF2 (ATF7IP2). (PMID:15691849)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	atf7ip2	ENSDARG00000089698
mus_musculus	Atf7ip2	ENSMUSG00000039200
rattus_norvegicus	Atf7ip2	ENSRNOG00000025522
drosophila_melanogaster	wde	FBGN0027499

Paralogs (1): ATF7IP (ENSG00000171681)

Protein

Protein identifiers

Activating transcription factor 7-interacting protein 2 — Q5U623 (reviewed: Q5U623)

Alternative names: MBD1-containing chromatin-associated factor 2

All UniProt accessions (8): B4DKH3, Q5U623, F5GY73, H3BNE6, H3BPC9, H3BR07, H3BUP1, I3L4M8

UniProt curated annotations — full annotation on UniProt →

Function. Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing SETDB1. The complex formed with MBD1 and SETDB1 represses transcription and probably couples DNA methylation and histone H3 ‘Lys-9’ trimethylation (H3K9me3) activity.

Subunit / interactions. Interacts with MBD1, SETDB1 and SP1. Probably forms a complex with SETDB1 and MBD1.

Subcellular location. Nucleus.

Similarity. Belongs to the MCAF family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5U623-1	1	yes
Q5U623-2	2

RefSeq proteins (4): NP_001243089, NP_001339049, NP_001380648, NP_079273 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003961	FN3_dom	Domain
IPR026085	ATF7-int	Family
IPR031870	ATF7IP_BD	Domain
IPR056565	Fn3_ATF7IP	Domain

Pfam: PF16788, PF16794

UniProt features (21 total): compositionally biased region 4, modified residue 3, sequence variant 3, sequence conflict 3, region of interest 3, splice variant 2, chain 1, domain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5U623-F1	56.88	0.21

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 (3): 416, 488, 521

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 141 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, MARTINEZ_RB1_TARGETS_DN, ROZANOV_MMP14_TARGETS_UP, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, GOCC_TRANSCRIPTION_REGULATOR_COMPLEX, DODD_NASOPHARYNGEAL_CARCINOMA_DN, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN, WANG_RESPONSE_TO_GSK3_INHIBITOR_SB216763_UP, LEE_DIFFERENTIATING_T_LYMPHOCYTE, SMIRNOV_RESPONSE_TO_IR_2HR_DN, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, ASH1L_TARGET_GENES, CAVIN1_TARGET_GENES, CBX5_TARGET_GENES

GO Biological Process (1): regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (2): transcription coregulator activity (GO:0003712), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

721 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ATF7IP2	SETDB1	Q15047	856
ATF7IP2	GTF2E2	P29084	640
ATF7IP2	GTF2E1	P29083	549
ATF7IP2	CDYL	Q9Y232	465
ATF7IP2	GLIPR1L2	Q4G1C9	454
ATF7IP2	TCEAL1	Q15170	451
ATF7IP2	CBX1	P23197	451
ATF7IP2	NBPF26	B4DH59	446
ATF7IP2	A0A087WTG0	A0A087WTG0	445
ATF7IP2	TMCO1	Q9UM00	442
ATF7IP2	TMEM144	Q7Z5S9	433
ATF7IP2	ATF7	P17544	433
ATF7IP2	ERCC3	P19447	428
ATF7IP2	ERCC2	P18074	426
ATF7IP2	VTA1	Q9NP79	421

IntAct

10 interactions, top by confidence:

A	B	Type	Score
SPSB2	ARHGEF10	psi-mi:“MI:0914”(association)	0.530
MAP1LC3A	ATF7IP2	psi-mi:“MI:0407”(direct interaction)	0.440
ATF7IP2	RCN1	psi-mi:“MI:0915”(physical association)	0.400
ATF7IP2	SSR3	psi-mi:“MI:0915”(physical association)	0.400
ATF7IP2	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ARL14EP	ARPC2	psi-mi:“MI:0914”(association)	0.350
ATF7IP2	SETDB1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
BIN1	ATF7IP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (24): ATF7IP2 (Affinity Capture-MS), ATF7IP2 (Two-hybrid), FSD2 (Two-hybrid), NUP62 (Two-hybrid), ATF7IP2 (Proximity Label-MS), HIST1H2BH (Proximity Label-MS), SSR3 (Proximity Label-MS), ATF7IP2 (Affinity Capture-RNA), SETDB1 (Affinity Capture-MS), ARL14EP (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), STRA6 (Affinity Capture-MS), ATF7IP2 (Affinity Capture-MS), ATF7IP2 (Affinity Capture-MS), ATF7IP2 (Protein-peptide)

ESM2 similar proteins: A2AWL7, A2RRX6, A6QNQ6, B0S6S9, B2RRE4, B2RRF6, B3NP26, B4HMH2, B4P8I0, B4QIJ9, D3Z987, E1BC15, Q14207, Q28BT7, Q2M2Z5, Q32N19, Q3U285, Q3V089, Q499M7, Q499R0, Q4R7M0, Q5DTT1, Q5DTT3, Q5EXX3, Q5HZI1, Q5R9I1, Q5RC05, Q5T3J3, Q5U623, Q5VWN6, Q5ZJK5, Q6AHZ1, Q6P0N0, Q6ZP01, Q7K4M4, Q7Z4V0, Q80WQ8, Q8BMA5, Q8BN78, Q8CDD9

Diamond homologs: A0JME2, Q3UL97, Q5U623, Q5ZIE8, Q6VMQ6, Q7TT18

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	119
Likely benign	18
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
688399	GRCh37/hg19 16p13.13(chr16:10563055-10958954)x1	Pathogenic

SpliceAI

2742 predictions. Top by Δscore:

Variant	Effect	Δscore
16:10387287:TG:T	donor_gain	1.0000
16:10387288:G:GT	donor_gain	1.0000
16:10387291:G:GG	donor_gain	1.0000
16:10431451:CAACA:C	donor_gain	1.0000
16:10431453:ACA:A	donor_gain	1.0000
16:10438232:TTTGG:T	donor_loss	1.0000
16:10438233:TTGG:T	donor_loss	1.0000
16:10438234:TGGT:T	donor_loss	1.0000
16:10438235:GGTA:G	donor_loss	1.0000
16:10438236:G:GC	donor_loss	1.0000
16:10438237:TAAGT:T	donor_loss	1.0000
16:10457478:G:GT	donor_gain	1.0000
16:10457478:G:T	donor_gain	1.0000
16:10472108:A:AG	acceptor_gain	1.0000
16:10472109:G:GA	acceptor_gain	1.0000
16:10473474:TTCA:T	acceptor_loss	1.0000
16:10473475:TCA:T	acceptor_loss	1.0000
16:10473476:CAG:C	acceptor_loss	1.0000
16:10473477:A:AG	acceptor_gain	1.0000
16:10473477:A:G	acceptor_loss	1.0000
16:10473478:G:GG	acceptor_gain	1.0000
16:10473478:G:GT	acceptor_loss	1.0000
16:10473478:GAT:G	acceptor_gain	1.0000
16:10473478:GATA:G	acceptor_gain	1.0000
16:10473530:TTATG:T	donor_gain	1.0000
16:10473531:TATG:T	donor_gain	1.0000
16:10473533:TG:T	donor_gain	1.0000
16:10473534:GG:G	donor_gain	1.0000
16:10473534:GGTG:G	donor_loss	1.0000
16:10473535:G:GA	donor_loss	1.0000

AlphaMissense

548 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:10430688:G:C	R23P	0.986
16:10430668:G:C	K16N	0.984
16:10430668:G:T	K16N	0.984
16:10430661:C:A	A14D	0.982
16:10430673:T:C	M18T	0.976
16:10430665:A:C	K15N	0.972
16:10430665:A:T	K15N	0.972
16:10430659:A:C	K13N	0.969
16:10430659:A:T	K13N	0.969
16:10430666:A:G	K16E	0.969
16:10430655:T:C	L12S	0.964
16:10430667:A:C	K16T	0.956
16:10430666:A:C	K16Q	0.954
16:10430670:C:T	T17I	0.954
16:10430674:G:A	M18I	0.951
16:10430674:G:C	M18I	0.951
16:10430674:G:T	M18I	0.951
16:10430667:A:T	K16M	0.942
16:10430673:T:G	M18R	0.941
16:10430660:G:C	A14P	0.937
16:10430673:T:A	M18K	0.933
16:10430664:A:T	K15I	0.920
16:10430661:C:T	A14V	0.916
16:10430660:G:A	A14T	0.914
16:10430669:A:C	T17P	0.904
16:10430657:A:G	K13E	0.899
16:10430687:C:G	R23G	0.899
16:10430670:C:G	T17R	0.885
16:10430658:A:T	K13I	0.884
16:10430669:A:G	T17A	0.880

dbSNP variants (sampled 300 via entrez): RS1000056533 (16:10403668 A>C,G), RS1000066195 (16:10444826 C>G,T), RS1000117486 (16:10426078 A>G), RS1000134495 (16:10441333 C>T), RS1000176411 (16:10465494 C>T), RS1000179065 (16:10472157 C>A,T), RS1000202281 (16:10440342 T>A,C), RS1000216203 (16:10422931 T>C,G), RS1000231288 (16:10472485 A>G), RS1000240659 (16:10408661 G>A), RS1000308478 (16:10389604 T>C), RS1000327443 (16:10451407 T>C), RS1000330466 (16:10435383 C>T), RS1000441672 (16:10451142 C>T), RS1000461107 (16:10399499 A>G)

Disease associations

OMIM: gene MIM:613645 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000618_27	Response to antipsychotic treatment	7.000000e-07
GCST002938_6	Copper levels	7.000000e-07
GCST003542_209	Night sleep phenotypes	9.000000e-06
GCST005358_2	Disease progression to choroidal neovascularization form in age-related macular degeneration	3.000000e-08
GCST009144_17	Disease progression in age-related macular degeneration (adjusted for baseline)	8.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008336	disease progression measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Cadmium Chloride	increases expression	2
pirinixic acid	increases activity, increases expression, affects binding	1
2-methyl-4-isothiazolin-3-one	increases expression	1
trichostatin A	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
potassium chromate(VI)	increases expression	1
ciglitazone	affects binding, increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	decreases expression	1
(+)-JQ1 compound	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Doxorubicin	decreases expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases expression	1
Vanadates	decreases expression	1
Cyclosporine	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	affects expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression	1

Clinical trials (associated diseases)

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