ABTB1

Summary

ABTB1 (ankyrin repeat and BTB domain containing 1, HGNC:18275) is a protein-coding gene on chromosome 3q21.3, encoding Ankyrin repeat and BTB/POZ domain-containing protein 1 (Q969K4). May act as a mediator of the PTEN growth-suppressive signaling pathway.

This gene encodes a protein with an ankyrin repeat region and two BTB/POZ domains, which are thought to be involved in protein-protein interactions. Expression of this gene is activated by the phosphatase and tensin homolog, a tumor suppressor. Alternate splicing results in three transcript variants.

Source: NCBI Gene 80325 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 131 total — 2 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_172027

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18275
Approved symbol	ABTB1
Name	ankyrin repeat and BTB domain containing 1
Location	3q21.3
Locus type	gene with protein product
Status	Approved
Aliases	BPOZ, EF1ABP, Btb3, BTBD21, BPOZ-2
Ensembl gene	ENSG00000114626
Ensembl biotype	protein_coding
OMIM	608308
Entrez	80325

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 13 protein_coding, 6 retained_intron, 3 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000232744, ENST00000453791, ENST00000464431, ENST00000466612, ENST00000467179, ENST00000468137, ENST00000474129, ENST00000475042, ENST00000475265, ENST00000478298, ENST00000479280, ENST00000483857, ENST00000491633, ENST00000493365, ENST00000497162, ENST00000858995, ENST00000858996, ENST00000858997, ENST00000858998, ENST00000858999, ENST00000929315, ENST00000929316, ENST00000929317, ENST00000970417, ENST00000970418

RefSeq mRNA: 2 — MANE Select: NM_172027 NM_032548, NM_172027

CCDS: CCDS3045, CCDS46901

Canonical transcript exons

ENST00000232744 — 12 exons

Exon	Start	End
ENSE00001854830	127672952	127673081
ENSE00001910872	127680269	127680926
ENSE00003493512	127679985	127680185
ENSE00003493630	127677676	127677843
ENSE00003501777	127676536	127676581
ENSE00003520141	127674391	127674453
ENSE00003593173	127674545	127674600
ENSE00003616869	127676272	127676431
ENSE00003637134	127676967	127677083
ENSE00003652497	127677465	127677563
ENSE00003656359	127677168	127677286
ENSE00003690003	127675970	127676114

Expression profiles

Bgee: expression breadth ubiquitous, 240 present calls, max score 98.49.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.6996 / max 877.9400, expressed in 1749 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38389	16.5516	1748
38390	0.1480	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	98.49	gold quality
cerebellar hemisphere	UBERON:0002245	98.34	gold quality
cerebellar cortex	UBERON:0002129	98.31	gold quality
granulocyte	CL:0000094	98.01	gold quality
cerebellum	UBERON:0002037	97.50	gold quality
blood	UBERON:0000178	97.19	gold quality
spleen	UBERON:0002106	97.15	gold quality
apex of heart	UBERON:0002098	96.75	gold quality
nerve	UBERON:0001021	96.46	gold quality
tibial nerve	UBERON:0001323	96.46	gold quality
right lung	UBERON:0002167	96.42	gold quality
mucosa of stomach	UBERON:0001199	96.38	gold quality
endocervix	UBERON:0000458	96.15	gold quality
leukocyte	CL:0000738	96.10	gold quality
monocyte	CL:0000576	96.01	gold quality
right frontal lobe	UBERON:0002810	95.97	gold quality
descending thoracic aorta	UBERON:0002345	95.96	gold quality
popliteal artery	UBERON:0002250	95.81	gold quality
tibial artery	UBERON:0007610	95.81	gold quality
right coronary artery	UBERON:0001625	95.78	gold quality
aorta	UBERON:0000947	95.62	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.56	gold quality
ascending aorta	UBERON:0001496	95.55	gold quality
thoracic aorta	UBERON:0001515	95.52	gold quality
left coronary artery	UBERON:0001626	95.47	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.38	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.35	gold quality
coronary artery	UBERON:0001621	95.31	gold quality
lower esophagus	UBERON:0013473	95.31	gold quality
body of uterus	UBERON:0009853	95.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.05
E-GEOD-70580	no	261.35

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PTEN

miRNA regulators (miRDB)

28 targeting ABTB1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3913-5P	99.78	67.26	968
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3122	99.50	66.33	821
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-4687-5P	99.14	66.26	488
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-3127-5P	97.52	65.24	786
HSA-MIR-1226-3P	97.51	66.32	1063
HSA-MIR-558	97.50	67.16	977
HSA-MIR-4732-3P	97.15	65.45	881
HSA-MIR-6515-5P	97.08	65.48	1219
HSA-MIR-4515	95.70	65.73	716

Literature-anchored findings (GeneRIF, showing 3)

• Study showed that BPOZ-2 is a human counterpart of yeast Btb3p, which is a putative adaptor for Pcu3p-based ubiquitin ligase; BPOZ-2 bound to E3 ligase CUL3 in vitro and in vivo. (PMID:18429817)
• BPOZ-2 promoted eEF1A1 ubiquitylation and degradation, suggesting that eEF1A1 is a substrate of BPOZ-2. (PMID:18459963)
• Study demonstrates that miR-4319 is expressed at a low level in colorectal cancer (CRC) tissues, which predicts the poor clinical outcome of CRC. MiR-4319 regulates the proliferation, cell cycle, invasion and migration of CRC cells. Mechanically, miR-4319 is found to be transcriptionally regulated by PLZF, and acts as a tumour suppressor in CRC by targeting ABTB1. (PMID:31065369)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	abtb1	ENSDARG00000063354
mus_musculus	Abtb1	ENSMUSG00000030083
rattus_norvegicus	Abtb1	ENSRNOG00000015762

Paralogs (11): BTBD1 (ENSG00000064726), SPOP (ENSG00000121067), KBTBD4 (ENSG00000123444), BTBD3 (ENSG00000132640), BTBD2 (ENSG00000133243), SPOPL (ENSG00000144228), ABTB3 (ENSG00000151136), ABTB2 (ENSG00000166016), KLHL11 (ENSG00000178502), BTBD9 (ENSG00000183826), BTBD6 (ENSG00000184887)

Protein

Protein identifiers

Ankyrin repeat and BTB/POZ domain-containing protein 1 — Q969K4 (reviewed: Q969K4)

Alternative names: Elongation factor 1A-binding protein

All UniProt accessions (3): Q969K4, F2Z3F5, H7C4W8

UniProt curated annotations — full annotation on UniProt →

Function. May act as a mediator of the PTEN growth-suppressive signaling pathway. May play a role in developmental processes.

Subcellular location. Cytoplasm.

Tissue specificity. Ubiquitously expressed in all fetal tissues examined including heart, brain, liver, and kidney. Also expressed at lower levels in both adult heart and hypertrophic heart.

Isoforms (4)

UniProt ID	Names	Canonical?
Q969K4-1	2, BPOZ-2	yes
Q969K4-2	1, BPOZ-1
Q969K4-3	3, BPOZ-3
Q969K4-4	4

RefSeq proteins (2): NP_115937, NP_742024* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR002110	Ankyrin_rpt	Repeat
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR036770	Ankyrin_rpt-contain_sf	Homologous_superfamily
IPR044515	ABTB1	Family

Pfam: PF00651, PF12796

UniProt features (12 total): splice variant 6, repeat 2, domain 2, chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q969K4-F1	86.59	0.58

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 101 (showing top): FREAC2_01, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_TRANSLATION, MODULE_171, GOBP_TRANSLATIONAL_ELONGATION, chr3q21, GOCC_TRANSFERASE_COMPLEX, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_UP, GOMF_TRANSLATION_ELONGATION_FACTOR_ACTIVITY, GOCC_UBIQUITIN_LIGASE_COMPLEX, MODULE_292, FOXO3_01

GO Biological Process (2): translation (GO:0006412), translational elongation (GO:0006414)

GO Molecular Function (2): translation elongation factor activity (GO:0003746), protein binding (GO:0005515)

GO Cellular Component (5): ubiquitin ligase complex (GO:0000151), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational elongation	2
macromolecule biosynthetic process	2
cellular anatomical structure	2
peptidyltransferase activity	1
translational initiation	1
translational termination	1
protein metabolic process	1
protein biosynthetic process	1
translation	1
translation factor activity	1
binding	1
intracellular protein-containing complex	1
transferase complex	1
nuclear lumen	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1548 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABTB1	CUL3	Q13618	719
ABTB1	ANK1	P16157	550
ABTB1	ANK2	Q01484	547
ABTB1	ANK3	Q12955	522
ABTB1	ADPRHL1	Q8NDY3	491
ABTB1	CARD19	Q96LW7	474
ABTB1	PTEN	P60484	456
ABTB1	LRCOL1	A6NCL2	448
ABTB1	FAF2	Q96CS3	438
ABTB1	OGDHL	Q9ULD0	418
ABTB1	ASB5	Q8WWX0	412
ABTB1	TRIM72	Q6ZMU5	409
ABTB1	EGR2	P11161	408
ABTB1	DPEP1	P16444	407
ABTB1	PARK7	Q99497	405

IntAct

39 interactions, top by confidence:

A	B	Type	Score
ABTB1	EEF1A2	psi-mi:“MI:0915”(physical association)	0.910
EEF1A2	ABTB1	psi-mi:“MI:0915”(physical association)	0.910
CUL3	ABTB1	psi-mi:“MI:0915”(physical association)	0.740
ABTB1	CUL3	psi-mi:“MI:0915”(physical association)	0.740
FBXL17	BACH1	psi-mi:“MI:0914”(association)	0.730
EEF1D	ABTB1	psi-mi:“MI:0915”(physical association)	0.670
ABTB1	ZBTB21	psi-mi:“MI:0915”(physical association)	0.620
	ABTB1	psi-mi:“MI:0915”(physical association)	0.560
ATXN1	ABTB1	psi-mi:“MI:0915”(physical association)	0.560
TARDBP	ABTB1	psi-mi:“MI:0915”(physical association)	0.560
EEF1D	ABTB1	psi-mi:“MI:0915”(physical association)	0.550
ABTB1	VARS1	psi-mi:“MI:0914”(association)	0.530
CAPRIN1	ABTB1	psi-mi:“MI:0915”(physical association)	0.400
SMAD2	ABTB1	psi-mi:“MI:0915”(physical association)	0.370
ABTB1	SMAD9	psi-mi:“MI:0915”(physical association)	0.370
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
NTRK3	ILVBL	psi-mi:“MI:0914”(association)	0.350

BioGRID (34): ABTB1 (Two-hybrid), ABTB1 (Two-hybrid), ABTB1 (Two-hybrid), ZBTB21 (Affinity Capture-MS), EEF1A2 (Affinity Capture-MS), CARS (Affinity Capture-MS), EEF1D (Affinity Capture-MS), VARS (Affinity Capture-MS), ABTB1 (Two-hybrid), ABTB1 (Protein-RNA), ABTB1 (Affinity Capture-RNA), ABTB1 (Two-hybrid), ABTB1 (Two-hybrid), ABTB1 (Proximity Label-MS), ABTB1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A0B4J1F4, A0A0G2JXN2, A4FV98, A6QPA3, C9J798, C9JJ37, D3YWP0, D3ZVU9, D4A2K4, O43374, O70277, O75382, O95294, P0C6S8, P22674, P57775, Q08DS0, Q0GA42, Q3U410, Q3UGX3, Q4G0W2, Q4V892, Q5SUV1, Q5XIU1, Q6GQU6, Q6IA17, Q6PF15, Q6TDP3, Q6TDP4, Q7TNM2, Q7Z4K8, Q86WI3, Q8CIW5, Q8IZ69, Q8K430, Q8N531, Q8N8L6, Q8NE01, Q8WXI3, Q969K4

Diamond homologs: P40560, Q10225, Q5XIU1, Q969K4, Q99LJ2, O95271, Q10728, Q1RJ94, Q3UES3, Q4JHE0, Q55FM5, Q5H9F3, Q5TYM7, Q6P1S6, Q6PFX9, Q8N9B4, Q9DBR7, Q9H2K2, Q9P2R3, Q9VBP3, Q9XZC0, Q0P5B9, Q4I8B6, Q4X251, Q53RE8, Q54KH3, Q5I1X5, Q5M9H0, Q7S3M5, Q7XUW4, Q7Z8U2, Q86WC6, Q8N7Z5, Q8WUF5, Q9CZK6, Q9D119, Q9D2X0, A0A072VIM5, A2VDR2, A9JRD8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
ABTB1	down-regulates	Proliferation
PTEN	“up-regulates quantity by expression”	ABTB1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	103
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
148370	GRCh38/hg38 3q21.3(chr3:126797420-128946623)x1	Pathogenic
150138	GRCh38/hg38 3q13.2-21.3(chr3:112620977-128734134)x1	Pathogenic
154720	GRCh38/hg38 3q21.3-22.1(chr3:127607945-133566661)x1	Likely pathogenic

SpliceAI

2255 predictions. Top by Δscore:

Variant	Effect	Δscore
3:127673058:G:GT	donor_gain	1.0000
3:127673059:A:T	donor_gain	1.0000
3:127673065:G:T	donor_gain	1.0000
3:127673077:GTGCG:G	donor_gain	1.0000
3:127674449:CCCTT:C	donor_gain	1.0000
3:127674451:CTT:C	donor_gain	1.0000
3:127674452:TT:T	donor_gain	1.0000
3:127674453:TGT:T	donor_loss	1.0000
3:127674454:G:GG	donor_gain	1.0000
3:127674456:GAGT:G	donor_loss	1.0000
3:127674539:CTTCA:C	acceptor_loss	1.0000
3:127674540:TTCA:T	acceptor_loss	1.0000
3:127674541:TCA:T	acceptor_loss	1.0000
3:127674542:CAG:C	acceptor_loss	1.0000
3:127674543:A:T	acceptor_loss	1.0000
3:127674611:G:GT	donor_gain	1.0000
3:127675968:A:AG	acceptor_gain	1.0000
3:127675968:AG:A	acceptor_gain	1.0000
3:127675969:G:GG	acceptor_gain	1.0000
3:127675969:GG:G	acceptor_gain	1.0000
3:127675969:GGA:G	acceptor_gain	1.0000
3:127676082:G:GT	donor_gain	1.0000
3:127676112:GCG:G	donor_gain	1.0000
3:127676113:CGGTG:C	donor_loss	1.0000
3:127676115:G:GA	donor_loss	1.0000
3:127676115:G:GG	donor_gain	1.0000
3:127676116:T:A	donor_loss	1.0000
3:127676527:T:A	acceptor_gain	1.0000
3:127676530:CCACA:C	acceptor_loss	1.0000
3:127676531:CACA:C	acceptor_loss	1.0000

AlphaMissense

3111 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:127675993:T:C	F67L	1.000
3:127675995:C:A	F67L	1.000
3:127675995:C:G	F67L	1.000
3:127674437:T:A	W35R	0.998
3:127674437:T:C	W35R	0.998
3:127674439:G:C	W35C	0.998
3:127674439:G:T	W35C	0.998
3:127674431:G:C	D33H	0.997
3:127674432:A:T	D33V	0.997
3:127674450:C:A	P39H	0.997
3:127674553:C:A	A43D	0.997
3:127674556:G:A	C44Y	0.997
3:127674557:C:G	C44W	0.997
3:127674589:T:C	L55P	0.997
3:127675994:T:G	F67C	0.997
3:127676005:C:A	R71S	0.997
3:127673054:G:A	C10Y	0.996
3:127674432:A:C	D33A	0.996
3:127674443:A:C	S37R	0.996
3:127674445:C:A	S37R	0.996
3:127674445:C:G	S37R	0.996
3:127674453:T:G	L40W	0.996
3:127674555:T:C	C44R	0.996
3:127675994:T:C	F67S	0.996
3:127676000:G:A	G69D	0.996
3:127673055:C:G	C10W	0.995
3:127674450:C:G	P39R	0.995
3:127674453:T:C	L40S	0.995
3:127674431:G:T	D33Y	0.994
3:127674433:C:A	D33E	0.994

dbSNP variants (sampled 300 via entrez): RS1000328890 (3:127672812 T>A,C), RS1000365043 (3:127680872 A>C), RS1000427026 (3:127672939 G>A,T), RS1000872292 (3:127675645 A>G), RS1001179093 (3:127672030 T>C,G), RS1001293921 (3:127671761 G>A,C), RS1002175060 (3:127673190 G>A,C,T), RS1002701464 (3:127672727 C>T), RS1003298993 (3:127674099 G>A,T), RS1003401002 (3:127679324 A>G), RS1003788344 (3:127671068 C>CT), RS1003840725 (3:127673227 A>C), RS1004129833 (3:127672701 C>G,T), RS1004222517 (3:127672657 C>T), RS1004594267 (3:127672574 C>T)

Disease associations

OMIM: gene MIM:608308 | disease phenotypes: MIM:614038, MIM:614172

GenCC curated gene-disease

Mondo (2): deafness-lymphedema-leukemia syndrome (MONDO:0013540), monocytopenia with susceptibility to infections (MONDO:0013607)

Orphanet (2): GATA2 deficiency spectrum (Orphanet:228423), Deafness-lymphedema-leukemia syndrome (Orphanet:3226)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_438	Refractive error	9.000000e-21

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
Cisplatin	affects expression, affects cotreatment, increases expression	2
afuresertib	increases expression	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
perfluorooctane sulfonic acid	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Calcitriol	increases expression, affects cotreatment	1
Estradiol	decreases expression	1
Ozone	affects expression, increases abundance	1
Phthalic Acids	increases methylation	1
Smoke	decreases expression	1
Testosterone	affects cotreatment, increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Toluene	increases methylation, decreases expression	1
Tunicamycin	increases expression	1
Urethane	increases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	decreases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition