BTBD3

Summary

BTBD3 (BTB domain containing 3, HGNC:15854) is a protein-coding gene on chromosome 20p12.2, encoding BTB/POZ domain-containing protein 3 (Q9Y2F9). Acts as a key regulator of dendritic field orientation during development of sensory cortex.

Enables identical protein binding activity. Predicted to be involved in cerebral cortex development and dendrite morphogenesis. Predicted to be located in nucleus. Predicted to be active in cytosol.

Source: NCBI Gene 22903 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 54 total
• MANE Select transcript: NM_014962

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15854
Approved symbol	BTBD3
Name	BTB domain containing 3
Location	20p12.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0952, dJ742J24.1
Ensembl gene	ENSG00000132640
Ensembl biotype	protein_coding
OMIM	615566
Entrez	22903

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 10 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000254977, ENST00000378226, ENST00000399006, ENST00000405977, ENST00000422390, ENST00000430557, ENST00000449299, ENST00000450368, ENST00000455911, ENST00000471120, ENST00000473180, ENST00000473416, ENST00000488503, ENST00000618296, ENST00000618918

RefSeq mRNA: 13 — MANE Select: NM_014962 NM_001282550, NM_001282551, NM_001282552, NM_001282554, NM_001395003, NM_001395004, NM_001395005, NM_001395006, NM_001395007, NM_001395008, NM_001395009, NM_014962, NM_181443

CCDS: CCDS13113, CCDS13114

Canonical transcript exons

ENST00000378226 — 4 exons

Exon	Start	End
ENSE00001476769	11917893	11918601
ENSE00003514068	11919718	11919836
ENSE00003849570	11922634	11926595
ENSE00003893285	11919086	11919176

Expression profiles

Bgee: expression breadth ubiquitous, 298 present calls, max score 98.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4095 / max 1002.9869, expressed in 1756 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183580	19.5840	1748
183585	9.0342	639
183581	2.0860	965
208995	0.6771	247
183588	0.2640	101
183582	0.2135	65
183579	0.1746	75
183590	0.1584	48
183589	0.0772	39
183586	0.0712	33

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar vermis	UBERON:0004720	98.92	gold quality
adrenal tissue	UBERON:0018303	98.78	gold quality
paraflocculus	UBERON:0005351	98.44	gold quality
decidua	UBERON:0002450	98.39	gold quality
corpus callosum	UBERON:0002336	97.27	gold quality
endothelial cell	CL:0000115	96.21	gold quality
frontal pole	UBERON:0002795	96.18	gold quality
CA1 field of hippocampus	UBERON:0003881	96.11	gold quality
choroid plexus epithelium	UBERON:0003911	95.93	gold quality
cerebellum	UBERON:0002037	95.92	gold quality
cerebellar cortex	UBERON:0002129	95.67	gold quality
cerebellar hemisphere	UBERON:0002245	95.60	gold quality
Ammon’s horn	UBERON:0001954	95.45	gold quality
subthalamic nucleus	UBERON:0001906	95.30	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.22	gold quality
dorsal plus ventral thalamus	UBERON:0001897	95.13	gold quality
inferior vagus X ganglion	UBERON:0005363	95.09	gold quality
primary visual cortex	UBERON:0002436	95.06	gold quality
postcentral gyrus	UBERON:0002581	95.00	gold quality
occipital lobe	UBERON:0002021	94.90	gold quality
orbitofrontal cortex	UBERON:0004167	94.88	gold quality
Brodmann (1909) area 23	UBERON:0013554	94.87	gold quality
parietal lobe	UBERON:0001872	94.66	gold quality
tibia	UBERON:0000979	94.65	gold quality
medulla oblongata	UBERON:0001896	94.64	gold quality
Brodmann (1909) area 10	UBERON:0013541	94.61	gold quality
pons	UBERON:0000988	94.58	gold quality
superior vestibular nucleus	UBERON:0007227	94.52	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.51	gold quality
endometrium	UBERON:0001295	94.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.56

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
NCAM1

Upstream regulators (CollecTRI, top): LHX2

miRNA regulators (miRDB)

230 targeting BTBD3, 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-4262	100.00	73.26	3931
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788

Literature-anchored findings (GeneRIF, showing 1)

• BTBD3 is repressed by miR-9 and -181c, either alone or in combination. (PMID:21720722)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	btbd3b	ENSDARG00000087517
mus_musculus	Btbd3	ENSMUSG00000062098
rattus_norvegicus	Btbd3	ENSRNOG00000008088
drosophila_melanogaster	BTBD9	FBGN0030228
drosophila_melanogaster	CG17068	FBGN0031098
drosophila_melanogaster	lute	FBGN0262871
caenorhabditis_elegans		WBGENE00015463

Paralogs (11): BTBD1 (ENSG00000064726), ABTB1 (ENSG00000114626), SPOP (ENSG00000121067), KBTBD4 (ENSG00000123444), BTBD2 (ENSG00000133243), SPOPL (ENSG00000144228), ABTB3 (ENSG00000151136), ABTB2 (ENSG00000166016), KLHL11 (ENSG00000178502), BTBD9 (ENSG00000183826), BTBD6 (ENSG00000184887)

Protein

Protein identifiers

BTB/POZ domain-containing protein 3 — Q9Y2F9 (reviewed: Q9Y2F9)

All UniProt accessions (5): Q9Y2F9, B0QYQ9, B0QYR0, B0QYR1, F8WAQ4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a key regulator of dendritic field orientation during development of sensory cortex. Also directs dendrites toward active axon terminals when ectopically expressed.

Subcellular location. Cytoplasm. Cytosol. Nucleus.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y2F9-1	1	yes
Q9Y2F9-2	2

RefSeq proteins (13): NP_001269479, NP_001269480, NP_001269481, NP_001269483, NP_001381932, NP_001381933, NP_001381934, NP_001381935, NP_001381936, NP_001381937, NP_001381938, NP_055777, NP_852108 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR012983	PHR	Domain
IPR038648	PHR_sf	Homologous_superfamily

Pfam: PF00651, PF07707, PF08005

UniProt features (6 total): domain 2, chain 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y2F9-F1	83.60	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 276 (showing top): GOBP_DENDRITE_DEVELOPMENT, RNGTGGGC_UNKNOWN, MODULE_52, RRAGTTGT_UNKNOWN, TGCGCANK_UNKNOWN, RORA1_01, TTTGTAG_MIR520D, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_NEUROGENESIS, TGACCTY_ERR1_Q2, CHX10_01, AAAYRNCTG_UNKNOWN, CAGCTG_AP4_Q5, EFC_Q6

GO Biological Process (4): cerebral cortex development (GO:0021987), neurogenesis (GO:0022008), dendrite morphogenesis (GO:0048813), nervous system development (GO:0007399)

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
pallium development	1
anatomical structure development	1
nervous system development	1
cell differentiation	1
dendrite development	1
cell morphogenesis involved in neuron differentiation	1
neuron projection morphogenesis	1
system development	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTBD3	TRIM2	Q9C040	524
BTBD3	DLGAP1	P78335	491
BTBD3	GMEB2	Q9UKD1	462
BTBD3	KIF16B	Q96L93	431
BTBD3	TASP1	Q9H6P5	427
BTBD3	NAA25	Q14CX7	421
BTBD3	DOC2A	Q14183	419
BTBD3	CFH	P08603	417
BTBD3	SYT1	P21579	414
BTBD3	SLC35B3	Q9H1N7	401
BTBD3	SLX4IP	Q5VYV7	400
BTBD3	STX1A	Q16623	393
BTBD3	LDAF1	Q96B96	384
BTBD3	ISM1	B1AKI9	379
BTBD3	CIMIP2C	A6NJV1	371

IntAct

35 interactions, top by confidence:

A	B	Type	Score
UBE2I	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
CDC37	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
BTBD3	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
CUL3	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
TEPSIN	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
BTBD6	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
GORASP2	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
RNF4	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
SUMO1	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	BTBD3	psi-mi:“MI:0915”(physical association)	0.560
PLXNB3	BTBD3	psi-mi:“MI:0915”(physical association)	0.370
CLTA	CLTB	psi-mi:“MI:0914”(association)	0.350
CDC37	BTBD3	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	BTBD3	psi-mi:“MI:0915”(physical association)	0.000
CUL3	BTBD3	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	SUMO1	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	BTBD6	psi-mi:“MI:0915”(physical association)	0.000
GORASP2	BTBD3	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	UBE2I	psi-mi:“MI:0915”(physical association)	0.000
TEPSIN	BTBD3	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
BTBD3	RNF4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-MS), BTBD3 (Affinity Capture-RNA), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid), BTBD3 (Two-hybrid)

ESM2 similar proteins: A0A0G2K344, A0A1B8YAB1, A2ALK8, A4IFG2, A9JRD8, B1H285, B3M1E1, B4GZ20, B4HJC0, B4KA23, B4QVW6, F7ASZ0, M3XQV7, P26045, P32871, P42336, P42337, P58544, P58545, Q08CL3, Q0V9W6, Q0VD31, Q16832, Q29B63, Q2LE78, Q3UQV5, Q5PQR3, Q5RAG3, Q5RGQ2, Q5TZE1, Q5ZIJ9, Q62371, Q62915, Q7K0L4, Q7Z7L7, Q8BH70, Q8BTI9, Q8C726, Q8K2J9, Q8LEV3

Diamond homologs: A1L4W5, B7U179, B9DHT4, E9Q4F2, F7ASZ0, G5E8B9, M3XQV7, O22286, O43791, O94889, O95199, O95625, P17789, P28575, P42282, P57790, P58545, Q0IHH9, Q0V9W6, Q0VCW1, Q14145, Q1EBV6, Q2LE78, Q2M2N2, Q54D84, Q5BL35, Q5NVK7, Q5R774, Q5RCZ7, Q5TC79, Q5TZE1, Q684M4, Q6DEL7, Q6IQ16, Q6NRH0, Q6P8B3, Q6YCH2, Q6ZWS8, Q7T330, Q7ZX06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

956 predictions. Top by Δscore:

Variant	Effect	Δscore
20:11890951:GGCG:G	donor_gain	1.0000
20:11890952:GCGG:G	donor_gain	1.0000
20:11890952:GCGGT:G	donor_loss	1.0000
20:11890953:CGGTG:C	donor_loss	1.0000
20:11890955:GTGA:G	donor_loss	1.0000
20:11890956:T:A	donor_loss	1.0000
20:11890957:GAGT:G	donor_loss	1.0000
20:11919716:A:AG	acceptor_gain	1.0000
20:11919716:AGTAT:A	acceptor_gain	1.0000
20:11919717:G:GG	acceptor_gain	1.0000
20:11919717:GT:G	acceptor_gain	1.0000
20:11919717:GTAT:G	acceptor_gain	1.0000
20:11919717:GTATG:G	acceptor_gain	1.0000
20:11919834:G:GT	donor_gain	1.0000
20:11919834:GAA:G	donor_gain	1.0000
20:11919834:GAAG:G	donor_loss	1.0000
20:11919835:AA:A	donor_gain	1.0000
20:11919835:AAG:A	donor_loss	1.0000
20:11919836:AGTA:A	donor_loss	1.0000
20:11919837:G:GG	donor_gain	1.0000
20:11919838:T:G	donor_loss	1.0000
20:11922632:A:AG	acceptor_gain	1.0000
20:11922633:G:GG	acceptor_gain	1.0000
20:11890941:G:GT	donor_gain	0.9900
20:11890952:GCG:G	donor_gain	0.9900
20:11890955:G:GG	donor_gain	0.9900
20:11918333:GAGAC:G	acceptor_gain	0.9900
20:11918597:GAGAG:G	donor_gain	0.9900
20:11918599:GAG:G	donor_gain	0.9900
20:11918602:G:GG	donor_gain	0.9900

AlphaMissense

3488 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:11919130:T:C	F124S	1.000
20:11919136:T:A	V126D	1.000
20:11919169:G:A	G137E	1.000
20:11919722:T:A	V141D	1.000
20:11919725:T:C	L142S	1.000
20:11919727:G:C	A143P	1.000
20:11919728:C:A	A143D	1.000
20:11919736:A:C	S146R	1.000
20:11919738:C:A	S146R	1.000
20:11919738:C:G	S146R	1.000
20:11919743:T:A	V148E	1.000
20:11919746:T:C	F149S	1.000
20:11919833:T:C	L178P	1.000
20:11922687:T:C	L197P	1.000
20:11922695:G:C	A200P	1.000
20:11922696:C:A	A200D	1.000
20:11922701:A:G	K202E	1.000
20:11922703:G:C	K202N	1.000
20:11922703:G:T	K202N	1.000
20:11922704:T:C	Y203H	1.000
20:11922704:T:G	Y203D	1.000
20:11922705:A:C	Y203S	1.000
20:11922705:A:G	Y203C	1.000
20:11922711:T:A	V205D	1.000
20:11922720:T:C	L208P	1.000
20:11922731:T:C	C212R	1.000
20:11922732:G:A	C212Y	1.000
20:11922733:T:G	C212W	1.000
20:11922744:T:A	L216Q	1.000
20:11922744:T:C	L216P	1.000

dbSNP variants (sampled 300 via entrez): RS1000034732 (20:11894546 C>T), RS1000040497 (20:11891420 G>A,T), RS1000092227 (20:11897974 A>G), RS1000116236 (20:11916140 CAG>C), RS1000273896 (20:11916428 C>T), RS1000567510 (20:11915128 A>C,G), RS1000644760 (20:11892778 G>C), RS1000683887 (20:11909991 G>A), RS1000707396 (20:11921345 C>T), RS1000782248 (20:11904077 G>C), RS1000904451 (20:11904648 T>C), RS1001045974 (20:11893156 A>G), RS1001092607 (20:11899010 C>G,T), RS1001126757 (20:11898737 G>A), RS1001140891 (20:11898361 A>C,G)

Disease associations

OMIM: gene MIM:615566 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST000960_19	Cardiac hypertrophy	9.000000e-06
GCST001762_224	Obesity-related traits	4.000000e-06
GCST002543_5	Hearing function	5.000000e-07
GCST003075_64	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST003075_77	Cognitive decline rate in late mild cognitive impairment	1.000000e-06
GCST005650_10	Serum metabolite ratios in chronic kidney disease	5.000000e-16
GCST005650_4	Serum metabolite ratios in chronic kidney disease	4.000000e-16
GCST005650_5	Serum metabolite ratios in chronic kidney disease	2.000000e-12
GCST005650_6	Serum metabolite ratios in chronic kidney disease	2.000000e-15
GCST005650_7	Serum metabolite ratios in chronic kidney disease	6.000000e-14
GCST005650_8	Serum metabolite ratios in chronic kidney disease	6.000000e-15
GCST005650_9	Serum metabolite ratios in chronic kidney disease	5.000000e-14
GCST006412_127	Intraocular pressure	4.000000e-16
GCST006630_19	Diastolic blood pressure	5.000000e-14
GCST007005_9	Logical memory (immediate recall) in normal cognition	1.000000e-07
GCST007006_17	Logical memory (delayed recall) in normal cognition	5.000000e-06
GCST008169_11	Benign prostatic hyperplasia	2.000000e-06
GCST008169_5	Benign prostatic hyperplasia	1.000000e-06
GCST009391_87	Metabolite levels	8.000000e-06
GCST012020_503	Serum metabolite levels	6.000000e-12
GCST012020_504	Serum metabolite levels	1.000000e-56
GCST012020_505	Serum metabolite levels	3.000000e-11
GCST012020_506	Serum metabolite levels	3.000000e-22
GCST012020_550	Serum metabolite levels	5.000000e-25
GCST012020_551	Serum metabolite levels	4.000000e-23
GCST012020_552	Serum metabolite levels	2.000000e-15
GCST90011898_99	Alanine aminotransferase levels	2.000000e-14

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0002503	cardiac hypertrophy
EFO:0007710	cognitive decline measurement
EFO:0004695	intraocular pressure measurement
EFO:0006336	diastolic blood pressure
EFO:0004874	memory performance

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	2
Acrolein	affects cotreatment, decreases expression, increases abundance	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases abundance, increases methylation, affects cotreatment, decreases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Estradiol	affects expression, affects cotreatment, increases expression	2
Ozone	affects cotreatment, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
testosterone undecanoate	affects cotreatment, decreases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
nickel sulfate	decreases expression	1
bicalutamide	increases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
Irinotecan	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	decreases expression	1
Vehicle Emissions	increases expression, increases abundance	1
Gallic Acid	decreases expression	1
Manganese	affects cotreatment, decreases expression, increases abundance	1
Methapyrilene	increases methylation	1

Clinical trials (associated diseases)

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