BTBD16

Summary

BTBD16 (BTB domain containing 16, HGNC:26340) is a protein-coding gene on chromosome 10q26.13, encoding BTB/POZ domain-containing protein 16 (Q32M84).

This gene encodes a protein that contains a BTB/POZ domain. This domain mediates protein-protein interactions. A mutation in this gene may be associated with bipolar disorder.

Source: NCBI Gene 118663 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_144587

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26340
Approved symbol	BTBD16
Name	BTB domain containing 16
Location	10q26.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25359, Em:AC061711.1
Ensembl gene	ENSG00000138152
Ensembl biotype	protein_coding
Entrez	118663

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding_CDS_not_defined, 1 protein_coding

ENST00000260723, ENST00000495370, ENST00000507495

RefSeq mRNA: 2 — MANE Select: NM_144587 NM_001318189, NM_144587

CCDS: CCDS31301

Canonical transcript exons

ENST00000260723 — 16 exons

Exon	Start	End
ENSE00000933498	122329480	122329571
ENSE00000933499	122331176	122331258
ENSE00000988009	122286105	122286248
ENSE00000988011	122289909	122289998
ENSE00000988012	122291080	122291194
ENSE00001099114	122275040	122275099
ENSE00001099118	122283851	122283924
ENSE00001099120	122307189	122307308
ENSE00001099124	122276791	122276939
ENSE00001099125	122297768	122297837
ENSE00001099127	122299004	122299134
ENSE00001099128	122271296	122271514
ENSE00002020693	122336494	122336682
ENSE00002046547	122338017	122338159
ENSE00003461341	122332436	122332513
ENSE00003596832	122334881	122334979

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 85.85.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4610 / max 142.9186, expressed in 96 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
107440	0.1671	71
107433	0.1136	19
107435	0.0831	16
107436	0.0252	9
107434	0.0188	8
107431	0.0177	3
107439	0.0144	9
206016	0.0081	4
107432	0.0073	3
107437	0.0056	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.85	silver quality
C1 segment of cervical spinal cord	UBERON:0006469	81.45	gold quality
skin of leg	UBERON:0001511	80.44	gold quality
urinary bladder	UBERON:0001255	79.69	gold quality
spinal cord	UBERON:0002240	77.82	gold quality
skin of abdomen	UBERON:0001416	76.98	gold quality
zone of skin	UBERON:0000014	75.65	gold quality
right lobe of liver	UBERON:0001114	73.36	gold quality
left testis	UBERON:0004533	72.78	gold quality
right testis	UBERON:0004534	71.30	gold quality
testis	UBERON:0000473	70.80	gold quality
putamen	UBERON:0001874	67.96	gold quality
amygdala	UBERON:0001876	67.78	gold quality
substantia nigra	UBERON:0002038	67.14	gold quality
Brodmann (1909) area 9	UBERON:0013540	66.04	gold quality
hypothalamus	UBERON:0001898	64.23	gold quality
midbrain	UBERON:0001891	63.91	gold quality
liver	UBERON:0002107	63.90	gold quality
prefrontal cortex	UBERON:0000451	63.59	gold quality
mucosa of stomach	UBERON:0001199	63.43	gold quality
caudate nucleus	UBERON:0001873	63.29	gold quality
upper leg skin	UBERON:0004262	62.81	silver quality
corpus callosum	UBERON:0002336	62.51	gold quality
Ammon’s horn	UBERON:0001954	61.01	gold quality
nucleus accumbens	UBERON:0001882	60.66	gold quality
gastrocnemius	UBERON:0001388	58.87	gold quality
left uterine tube	UBERON:0001303	58.80	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	58.65	gold quality
right frontal lobe	UBERON:0002810	58.30	gold quality
cerebellar vermis	UBERON:0004720	57.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	18.20

Regulation

Is transcription factor: no

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	btbd16	ENSDARG00000027710
mus_musculus	Btbd16	ENSMUSG00000040298
rattus_norvegicus	Btbd16	ENSRNOG00000036675
drosophila_melanogaster	gcl	FBGN0005695
caenorhabditis_elegans		WBGENE00013382

Paralogs (3): GMCL1 (ENSG00000087338), C10orf120 (ENSG00000183559), GMCL2 (ENSG00000244234)

Protein

Protein identifiers

BTB/POZ domain-containing protein 16 — Q32M84 (reviewed: Q32M84)

All UniProt accessions (1): Q32M84

Isoforms (2)

UniProt ID	Names	Canonical?
Q32M84-1	1	yes
Q32M84-2	2

RefSeq proteins (2): NP_001305118, NP_653188* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR042833	BTBD16	Family
IPR048859	BTBD16_C	Domain
IPR056426	BTB_BTBDG	Domain

Pfam: PF21059, PF23998

UniProt features (8 total): sequence variant 4, chain 1, domain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q32M84-F1	78.92	0.43

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 16 (showing top): ELK1_01, RFX1_02, GLI1_UP.V1_DN, GSE8685_IL2_ACT_IL2_STARVED_VS_IL21_ACT_IL2_STARVED_CD4_TCELL_UP, FAN_EMBRYONIC_CTX_OLIG, ETS2_B, ZNF140_TARGET_GENES, GSE17974_IL4_AND_ANTI_IL12_VS_UNTREATED_24H_ACT_CD4_TCELL_UP, CARRILLOREIXACH_HEPATOBLASTOMA_VS_NORMAL_DN, ETS1_B, GSE6259_FLT3L_INDUCED_33D1_POS_DC_VS_CD8_TCELL_DN, chr10q26, GSE19941_UNSTIM_VS_LPS_AND_IL10_STIM_IL10_KO_NFKBP50_KO_MACROPHAGE_UP, PEA3_Q6, ELF1_Q6

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

336 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTBD16	PLEKHA1	Q9HB21	575
BTBD16	CCDC191	Q8NCU4	480
BTBD16	DPY19L3	Q6ZPD9	453
BTBD16	ZBTB16	Q05516	430
BTBD16	ARMS2	P0C7Q2	407
BTBD16	NDUFAF6	Q330K2	400
BTBD16	CDX4	O14627	399
BTBD16	TACC2	O95359	398
BTBD16	CATSPERG	Q6ZRH7	396
BTBD16	PRKCQ	Q04759	393
BTBD16	MBLAC1	A4D2B0	392
BTBD16	B9ZVM9	B9ZVM9	380
BTBD16	TTC34	A8MYJ7	375
BTBD16	EGR2	P11161	369
BTBD16	CD1D	P15813	369

IntAct

1 interactions, top by confidence:

BioGRID (2): BTBD16 (Two-hybrid), BTBD16 (Two-hybrid)

ESM2 similar proteins: A0JM23, A2VDM0, A5WW08, A6NFN9, B5DE70, E9Q173, F6U5F9, H0UZ81, O13034, P0C6R2, P25022, P34089, P50851, P97573, Q0VCL9, Q0VGW0, Q14B46, Q2I0E5, Q2MHQ9, Q32L18, Q32M84, Q3TTL0, Q4QR86, Q5F479, Q5FWP4, Q5JPI3, Q5XGX5, Q5XIB9, Q5ZLG9, Q60760, Q66H33, Q6AXU1, Q6AZT6, Q6AZT7, Q6P256, Q6PJI9, Q793I8, Q7Z494, Q8C0M0, Q8C0W1

Diamond homologs: E9Q173, Q32L18, Q32M84, Q6AXU1, Q95J53

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	12
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3073 predictions. Top by Δscore:

Variant	Effect	Δscore
10:122283839:T:G	acceptor_gain	1.0000
10:122284786:A:AG	acceptor_gain	1.0000
10:122284787:A:G	acceptor_gain	1.0000
10:122284898:TCCA:T	donor_gain	1.0000
10:122284902:G:GG	donor_gain	1.0000
10:122285480:A:G	donor_gain	1.0000
10:122289907:A:AG	acceptor_gain	1.0000
10:122289908:G:GG	acceptor_gain	1.0000
10:122289908:GCTC:G	acceptor_gain	1.0000
10:122289908:GCTCA:G	acceptor_gain	1.0000
10:122291192:AAGGT:A	donor_loss	1.0000
10:122291195:G:A	donor_loss	1.0000
10:122291196:T:A	donor_loss	1.0000
10:122299002:A:AG	acceptor_gain	1.0000
10:122299003:G:GC	acceptor_gain	1.0000
10:122299003:GTAC:G	acceptor_gain	1.0000
10:122331256:GCA:G	donor_gain	1.0000
10:122331259:G:GG	donor_gain	1.0000
10:122331290:TCG:T	donor_gain	1.0000
10:122331292:G:GT	donor_gain	1.0000
10:122336488:TTGCA:T	acceptor_loss	1.0000
10:122336492:A:AG	acceptor_gain	1.0000
10:122336493:G:A	acceptor_loss	1.0000
10:122336493:G:GA	acceptor_gain	1.0000
10:122336493:GA:G	acceptor_gain	1.0000
10:122336493:GAGA:G	acceptor_gain	1.0000
10:122336493:GAGAA:G	acceptor_gain	1.0000
10:122271511:AACGG:A	donor_loss	0.9900
10:122271512:ACGGT:A	donor_loss	0.9900
10:122271513:CGGTA:C	donor_loss	0.9900

AlphaMissense

3349 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:122286134:T:A	W91R	0.984
10:122286134:T:C	W91R	0.984
10:122336677:A:C	S483R	0.974
10:122336679:C:A	S483R	0.974
10:122336679:C:G	S483R	0.974
10:122286136:G:C	W91C	0.969
10:122286136:G:T	W91C	0.969
10:122307193:T:C	F266L	0.966
10:122307195:T:A	F266L	0.966
10:122307195:T:G	F266L	0.966
10:122336650:T:C	F474L	0.964
10:122336652:T:A	F474L	0.964
10:122336652:T:G	F474L	0.964
10:122334920:T:C	F402L	0.962
10:122334922:C:A	F402L	0.962
10:122334922:C:G	F402L	0.962
10:122286114:T:C	L84P	0.957
10:122307235:T:A	W280R	0.957
10:122307235:T:C	W280R	0.957
10:122286141:T:C	L93P	0.953
10:122286174:T:C	L104S	0.952
10:122286119:T:C	C86R	0.948
10:122336623:T:C	F465L	0.947
10:122336625:C:A	F465L	0.947
10:122336625:C:G	F465L	0.947
10:122286114:T:A	L84H	0.944
10:122334927:T:C	F404S	0.942
10:122291095:T:C	L164P	0.940
10:122291160:G:C	A186P	0.939
10:122307241:T:C	F282L	0.939

dbSNP variants (sampled 300 via entrez): RS1000038018 (10:122309739 C>T), RS1000087639 (10:122270044 C>G), RS1000119579 (10:122287167 T>G), RS1000184541 (10:122276851 C>G), RS1000209791 (10:122332832 G>A), RS1000241115 (10:122333133 A>C,G), RS1000296944 (10:122300862 T>C,G), RS1000313498 (10:122294022 T>G), RS1000314143 (10:122294214 G>C), RS1000320554 (10:122313005 T>G), RS1000361413 (10:122281993 C>T), RS1000404533 (10:122321162 T>A,C), RS1000408487 (10:122281752 A>G), RS1000409230 (10:122294631 G>A), RS1000423986 (10:122287528 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): prostate cancer (MONDO:0008315)

Orphanet (1): Familial prostate cancer (Orphanet:1331)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST001986_3	Age-related macular degeneration	8.000000e-27
GCST001987_1	Age-related macular degeneration (extreme sampling)	3.000000e-29
GCST006288_26	Heel bone mineral density	2.000000e-08
GCST006288_723	Heel bone mineral density	6.000000e-06
GCST006979_612	Heel bone mineral density	2.000000e-20
GCST009265_6	Superior parietal cortex volume	5.000000e-06
GCST009391_193	Metabolite levels	9.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0010482	gamma-aminoisobutyric acid measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	2
Aflatoxin B1	decreases expression, increases methylation	2
aristolochic acid I	increases expression	1
methyleugenol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
bisphenol S	increases methylation	1
(+)-JQ1 compound	decreases expression	1
Rosiglitazone	decreases expression	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	affects expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00035997	PHASE4	COMPLETED	Open-label Trial on the Effect of I.V. Zoledronic Acid 4 mg on Bone Density in Hormone Sensitive Prostate Cancer Patients With Bone Metastasis
NCT00063609	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Loss in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy
NCT00103623	PHASE4	SUSPENDED	The Plenaxis® Experience Study
NCT00106392	PHASE4	COMPLETED	A Safety and Efficacy Study of Prograf in the Prevention of Erectile Dysfunction After Radical Prostatectomy
NCT00185029	PHASE4	UNKNOWN	MR-Lymphography and Lymph Node Staging in Prostate Cancer
NCT00199485	PHASE4	COMPLETED	Angelica Sinensis for the Treatment of Hot Flashes in Men Undergoing LHRH Therapy for Prostate Cancer
NCT00219219	PHASE4	COMPLETED	Zoledronic Acid in the Prevention of Skeletal-related Events in Hormone Refractory and Hormone-sensitive Prostate Cancer Patients With Bone Metastases
NCT00219271	PHASE4	COMPLETED	Effect Of Zoledronic Acid On Circulating And Bone Marrow-Residing Prostate Cancer Cells In Patients With Clinically Localized Prostate Cancer
NCT00237146	PHASE4	COMPLETED	Study to Evaluate Zoledronic Acid on Quality of Life and Skeletal-related Events as Adjuvant Treatment in Patients With Hormone-naïve Prostate Cancer and Bone Metastasis Who Have Undergone Orchiectomy
NCT00242554	PHASE4	COMPLETED	Open-label Phase IV Clinical Trial to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Prostate Cancer and Bone Metastases
NCT00280098	PHASE4	COMPLETED	Docetaxel in the Treatment of Hormone Refractory Prostate Cancer
NCT00293696	PHASE4	COMPLETED	Casodex/Zoladex Biomarkers in Localised Prostate Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00375765	PHASE4	COMPLETED	Effects On Dihydrotestosterone Regulated Gene Expression In Benign Prostatic Hyperplasia Or Prostate Cancer
NCT00391690	PHASE4	COMPLETED	Evaluation of Bone Markers as Diagnostic Tools for Early Detection of Bone Metastases in Patients With High Risk Prostate Cancer
NCT00422708	PHASE4	COMPLETED	Local Anesthesia for Prostate Biopsy
NCT00526331	PHASE4	COMPLETED	Evaluation of Arterial Pressure Based Cardiac Output for Goal-Directed Perioperative Therapy
NCT00590213	PHASE4	COMPLETED	Compare the Value of Prophylactic Versus Therapeutic Breast Radiotherapy in CASODEX
NCT00629330	PHASE4	TERMINATED	Dissemination of Prostate Cancer Screening to PCP’s in African American Communities
NCT00771966	PHASE4	COMPLETED	Radical Prostatectomy and Perioperative Fluid Therapy
NCT00805701	PHASE4	COMPLETED	Study Assessing The Efficacy And Safety Of Avodart (Dutasteride) At Improving Urinary Symptoms In Men With Prostate Cancer Who Are Undergoing Seed Implantation
NCT00859027	PHASE4	COMPLETED	Effect Of Risedronate On Bone Mass In Older Men Receiving Neoadjuvant Therapy For Prostate Cancer
NCT00906269	PHASE4	UNKNOWN	Can Hyperbaric Oxygen Improve Erectile Function Following Surgery for Prostate Cancer
NCT00953277	PHASE4	COMPLETED	Study of Nerve Reconstruction Using AVANCE in Subjects Who Undergo Robotic Assisted Prostatectomy for Treatment of Prostate Cancer
NCT00982800	PHASE4	COMPLETED	Does Postoperative Gabapentin Reduce Pain, Opioid Consumption and Anxiety and Have a Positive Effect on Health Related Quality of Life After Radical Prostatectomy?
NCT01083199	PHASE4	COMPLETED	Global Performance Evaluation of the AMS CONTINUUM™ Device
NCT01136226	PHASE4	COMPLETED	Evaluate Recovery of Testosterone for Patients Using Eligard
NCT01161563	PHASE4	COMPLETED	Randomized Crossover Trial to Assess the Tolerability of Gonadotropin Releasing Hormone (GnRH) Analogue Administration
NCT01230905	PHASE4	COMPLETED	Study to Monitor the Effects of Androgen Suppression Treatment on the Heart
NCT01296672	PHASE4	COMPLETED	3 Month Finasteride Challenge Test Can Significantly Improve the Performance of Screening for Prostate Cancer
NCT01365143	PHASE4	TERMINATED	Prospective Randomized Trial Comparing Robotic Versus Open Radical Prostatectomy
NCT01379742	PHASE4	UNKNOWN	Comparison of Between ThinSeed™ and OncoSeed™ for Permanent Prostate Brachytherapy
NCT01486563	PHASE4	COMPLETED	Hydroxyethyl Starch and Renal Function After Radical Prostatectomy
NCT01511874	PHASE4	COMPLETED	Efficacy and Safety Study of ELIGARD 22.5mg With Prostate Cancer
NCT01512472	PHASE4	TERMINATED	Firmagon (Degarelix) Intermittent Therapy
NCT01547416	PHASE4	COMPLETED	The Effect of Combined General/Epidural Anesthesia Versus General Anesthesia on Diaphragmatic Function
NCT01571544	PHASE4	COMPLETED	The Use of Thermal Suits as Preventing Hypothermia During Surgery
NCT01581749	PHASE4	UNKNOWN	Evaluation of Truebeam for Low-Intermediate Risk Prostate Cancer
NCT01649635	PHASE4	COMPLETED	Study of Cabazitaxel Combined With Prednisone and Prophylaxis of Neutropenia Complications in the Treatment of Patients With Metastatic Castration-resistant Prostate Cancer