BTBD10

Summary

BTBD10 (BTB domain containing 10, HGNC:21445) is a protein-coding gene on chromosome 11p15.3, encoding BTB/POZ domain-containing protein 10 (Q9BSF8). Plays a major role as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated.

Predicted to be involved in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction and type B pancreatic cell proliferation. Located in fibrillar center and nucleoplasm.

Source: NCBI Gene 84280 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 48 total
• MANE Select transcript: NM_032320

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21445
Approved symbol	BTBD10
Name	BTB domain containing 10
Location	11p15.3
Locus type	gene with protein product
Status	Approved
Aliases	GMRP1, GMRP-1, MGC13007
Ensembl gene	ENSG00000148925
Ensembl biotype	protein_coding
OMIM	615933
Entrez	84280

Gene structure

Transcript identifiers

Ensembl transcripts: 30 — 24 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000278174, ENST00000525108, ENST00000525661, ENST00000525864, ENST00000526841, ENST00000527102, ENST00000527858, ENST00000528120, ENST00000529708, ENST00000530907, ENST00000532261, ENST00000874027, ENST00000874028, ENST00000874029, ENST00000874030, ENST00000874031, ENST00000874032, ENST00000874033, ENST00000874034, ENST00000874035, ENST00000874036, ENST00000874037, ENST00000874038, ENST00000939227, ENST00000939228, ENST00000944226, ENST00000944227, ENST00000944228, ENST00000944229, ENST00000944230

RefSeq mRNA: 3 — MANE Select: NM_032320 NM_001297741, NM_001297742, NM_032320

CCDS: CCDS73261, CCDS76388, CCDS7811

Canonical transcript exons

ENST00000278174 — 9 exons

Exon	Start	End
ENSE00001101244	13445024	13445181
ENSE00002162805	13463092	13463222
ENSE00002200612	13388008	13389141
ENSE00003495010	13417158	13417260
ENSE00003529188	13421642	13421838
ENSE00003586756	13413530	13413650
ENSE00003591188	13405659	13405856
ENSE00003612602	13419460	13419745
ENSE00003684872	13403168	13403278

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 97.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.5320 / max 559.7910, expressed in 1798 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
118725	20.9055	1798
118724	0.2616	72
118722	0.2414	54
118723	0.0727	34
118721	0.0508	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	97.63	gold quality
oocyte	CL:0000023	97.56	gold quality
middle temporal gyrus	UBERON:0002771	96.94	gold quality
cortical plate	UBERON:0005343	95.62	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.23	gold quality
pons	UBERON:0000988	94.94	gold quality
upper arm skin	UBERON:0004263	94.93	gold quality
esophagus squamous epithelium	UBERON:0006920	94.58	gold quality
prefrontal cortex	UBERON:0000451	94.54	gold quality
left ventricle myocardium	UBERON:0006566	94.44	silver quality
Brodmann (1909) area 46	UBERON:0006483	94.20	gold quality
amniotic fluid	UBERON:0000173	93.78	gold quality
embryo	UBERON:0000922	93.73	gold quality
ganglionic eminence	UBERON:0004023	93.73	gold quality
calcaneal tendon	UBERON:0003701	93.49	gold quality
lateral nuclear group of thalamus	UBERON:0002736	93.38	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.36	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.29	gold quality
frontal cortex	UBERON:0001870	93.19	gold quality
frontal lobe	UBERON:0016525	93.19	gold quality
corpus callosum	UBERON:0002336	93.15	gold quality
kidney epithelium	UBERON:0004819	92.86	silver quality
neocortex	UBERON:0001950	92.70	gold quality
superior vestibular nucleus	UBERON:0007227	92.70	gold quality
nasal cavity epithelium	UBERON:0005384	92.63	gold quality
superior frontal gyrus	UBERON:0002661	92.56	gold quality
occipital lobe	UBERON:0002021	92.24	gold quality
islet of Langerhans	UBERON:0000006	92.22	gold quality
nucleus accumbens	UBERON:0001882	92.17	gold quality
primary visual cortex	UBERON:0002436	92.05	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting BTBD10, 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-3646	100.00	73.56	5283
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769

Literature-anchored findings (GeneRIF, showing 4)

• BTBD10 appears to behave as a suppressor of cell death including neuronal cell death related to amyotrophic lateral sclerosis and an enhancer of cell growth via its positive regulation of Akt phosphorylation. (PMID:18160256)
• GMRP1 regulates pancreatic beta cell proliferation and apoptosis via activation of Akt signalling pathway. (PMID:21267538)
• Collectively, these results suggest that the reduced expression of BTBD10 leads to motor neuron death both in vitro and in vivo. (PMID:22388351)
• findings suggest that reduced BTBD10 expression is closely linked to the pathogenesis of sporadic amyotrophic lateral sclerosis (PMID:23320755)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	btbd10b	ENSDARG00000020252
danio_rerio	btbd10a	ENSDARG00000062674
mus_musculus	Btbd10	ENSMUSG00000038187
rattus_norvegicus	Btbd10	ENSRNOG00000014341
rattus_norvegicus		ENSRNOG00000064782
drosophila_melanogaster	mri	FBGN0035107
caenorhabditis_elegans		WBGENE00019888

Paralogs (1): KCTD20 (ENSG00000112078)

Protein

Protein identifiers

BTB/POZ domain-containing protein 10 — Q9BSF8 (reviewed: Q9BSF8)

Alternative names: Glucose metabolism-related protein 1

All UniProt accessions (7): Q9BSF8, B7Z503, D3DQW7, E9PKM7, E9PKU9, E9PN21, E9PPD8

UniProt curated annotations — full annotation on UniProt →

Function. Plays a major role as an activator of AKT family members by inhibiting PPP2CA-mediated dephosphorylation, thereby keeping AKTs activated. Plays a role in preventing motor neuronal death and accelerating the growth of pancreatic beta cells.

Subunit / interactions. Interacts (via C-terminal 330-amino-acid region) with AKT1; AKT2 and AKT3. Interacts with PPP2CA and PPP1CA.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Ubiquitously expressed. Highly expressed in adult brain, testis, aorta and small intestine and weakly expressed in the heart, lung, liver, kidney, pancreas, spleen, thymus, prostate, ovary and colon. Down-regulated in glioma.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9BSF8-1	1	yes
Q9BSF8-2	2

RefSeq proteins (3): NP_001284670, NP_001284671, NP_115696* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR039885	BTBD10/KCTD20_BTB/POZ	Domain
IPR039886	BTBD10/KCTD20	Family

Pfam: PF16017

UniProt features (12 total): compositionally biased region 5, region of interest 3, chain 1, domain 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BSF8-F1	69.79	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 143 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, TGCACTT_MIR519C_MIR519B_MIR519A, AAGCCAT_MIR135A_MIR135B, BRN2_01, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P, ACTTTAT_MIR1425P, GOBP_EPITHELIAL_CELL_PROLIFERATION, CTTTGTA_MIR524, E2F_Q6_01, DURCHDEWALD_SKIN_CARCINOGENESIS_DN, TGGAAA_NFAT_Q4_01, NUYTTEN_EZH2_TARGETS_DN

GO Biological Process (2): type B pancreatic cell proliferation (GO:0044342), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): fibrillar center (GO:0001650), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
epithelial cell proliferation	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
binding	1
nucleolus	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

528 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTBD10	KCTD19	Q17RG1	641
BTBD10	KCTD1	Q719H9	635
BTBD10	TNFAIP1	Q13829	600
BTBD10	SHKBP1	Q8TBC3	587
BTBD10	KCNRG	Q8N5I3	579
BTBD10	KCTD10	Q9H3F6	563
BTBD10	KCTD5	Q9NXV2	557
BTBD10	GSTT4	A0A1W2PR19	527
BTBD10	KCTD21	Q4G0X4	508
BTBD10	KCTD6	Q8NC69	502
BTBD10	KCTD11	Q693B1	501
BTBD10	KCTD8	Q6ZWB6	482
BTBD10	KCTD12	Q96CX2	482
BTBD10	KCTD13	Q8WZ19	468
BTBD10	KCTD2	Q14681	466

IntAct

30 interactions, top by confidence:

A	B	Type	Score
CUL3	BTBD10	psi-mi:“MI:0915”(physical association)	0.740
BUB3	ZNF207	psi-mi:“MI:0914”(association)	0.690
CUL3	ENC1	psi-mi:“MI:0914”(association)	0.640
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
CUL3	ZSWIM8	psi-mi:“MI:0914”(association)	0.530
SDC1	ILVBL	psi-mi:“MI:0915”(physical association)	0.400
BTBD10	PPP1CA	psi-mi:“MI:0915”(physical association)	0.370
BTBD10	CDC37	psi-mi:“MI:0915”(physical association)	0.370
BTBD10	MAPK3	psi-mi:“MI:0915”(physical association)	0.370
C9orf72	CHD2	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
CUL3	KLHL2	psi-mi:“MI:0914”(association)	0.350
BUB3	ZNF207	psi-mi:“MI:0914”(association)	0.350
RYBP	PIPSL	psi-mi:“MI:0914”(association)	0.350
RYBP	FAM186A	psi-mi:“MI:0914”(association)	0.350
TLK2	IGKV1D-13	psi-mi:“MI:0914”(association)	0.350
HCN1	USP27X	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
ARRDC5	PLPP1	psi-mi:“MI:0914”(association)	0.350
DUSP16	MEIOC	psi-mi:“MI:0914”(association)	0.350
PPP1CC	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TSSK1B	HERC4	psi-mi:“MI:0914”(association)	0.350
FXR2	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
FMR1	BTBD10	psi-mi:“MI:0915”(physical association)	0.000
BTBD10	FOS	psi-mi:“MI:0915”(physical association)	0.000
BTBD10	DLG5	psi-mi:“MI:0915”(physical association)	0.000
BTBD10	ACIN1	psi-mi:“MI:0915”(physical association)	0.000
BTBD10	LAMA5	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (PCA), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-RNA), DLG5 (Two-hybrid), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS), BTBD10 (Affinity Capture-MS)

ESM2 similar proteins: A2AHJ4, A4IID4, A9JRL3, A9X1A0, B0KWC1, B1MTG7, B2KI64, B2RQE8, B3EX61, B4UT09, G5EBH0, O00418, O00763, O02697, O02810, O08561, O08796, O08874, P25455, P48736, P70531, Q07139, Q28C33, Q49GP3, Q4U2V3, Q5R585, Q641K1, Q6DD21, Q6F6B3, Q6GN16, Q6NRE7, Q6PCL9, Q80X66, Q86X55, Q8BKC8, Q8BPM2, Q8CI95, Q8IVH8, Q924I2, Q99JP0

Diamond homologs: Q5R585, Q7Z5Y7, Q80X66, Q8CDD8, Q9BSF8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2178 predictions. Top by Δscore:

Variant	Effect	Δscore
11:13389138:TAAC:T	acceptor_gain	1.0000
11:13389139:AAC:A	acceptor_gain	1.0000
11:13389140:AC:A	acceptor_gain	1.0000
11:13389141:CC:C	acceptor_gain	1.0000
11:13389141:CCTGA:C	acceptor_loss	1.0000
11:13389142:C:CC	acceptor_gain	1.0000
11:13389142:CTGAA:C	acceptor_loss	1.0000
11:13403279:C:CC	acceptor_gain	1.0000
11:13405654:CGTA:C	donor_gain	1.0000
11:13405655:GTACT:G	donor_loss	1.0000
11:13405656:TAC:T	donor_loss	1.0000
11:13405657:A:AC	donor_gain	1.0000
11:13405658:C:CT	donor_gain	1.0000
11:13405658:CT:C	donor_gain	1.0000
11:13405658:CTTT:C	donor_gain	1.0000
11:13413528:A:AC	donor_gain	1.0000
11:13413529:C:CT	donor_gain	1.0000
11:13413648:ATCC:A	acceptor_loss	1.0000
11:13413649:TCC:T	acceptor_loss	1.0000
11:13413651:C:A	acceptor_loss	1.0000
11:13413652:T:A	acceptor_loss	1.0000
11:13417152:ACTC:A	donor_loss	1.0000
11:13417153:CTCAC:C	donor_loss	1.0000
11:13417154:TCAC:T	donor_loss	1.0000
11:13417155:CAC:C	donor_loss	1.0000
11:13417156:A:AC	donor_gain	1.0000
11:13417157:C:A	donor_loss	1.0000
11:13417157:C:CC	donor_gain	1.0000
11:13417209:T:A	donor_gain	1.0000
11:13417256:ACATC:A	acceptor_gain	1.0000

AlphaMissense

3131 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:13388976:A:G	L428P	1.000
11:13388976:A:T	L428H	1.000
11:13388988:G:A	S424F	1.000
11:13388990:T:A	K423N	1.000
11:13388990:T:G	K423N	1.000
11:13388991:T:A	K423I	1.000
11:13388992:T:C	K423E	1.000
11:13388993:A:C	S422R	1.000
11:13388993:A:T	S422R	1.000
11:13388995:T:G	S422R	1.000
11:13388996:C:A	K421N	1.000
11:13388996:C:G	K421N	1.000
11:13388998:T:C	K421E	1.000
11:13389000:A:T	V420E	1.000
11:13389002:A:C	C419W	1.000
11:13389003:C:G	C419S	1.000
11:13389003:C:T	C419Y	1.000
11:13389004:A:G	C419R	1.000
11:13389004:A:T	C419S	1.000
11:13389005:C:A	Q418H	1.000
11:13389005:C:G	Q418H	1.000
11:13389008:A:C	F417L	1.000
11:13389008:A:T	F417L	1.000
11:13389009:A:C	F417C	1.000
11:13389009:A:G	F417S	1.000
11:13389010:A:C	F417V	1.000
11:13389010:A:G	F417L	1.000
11:13389010:A:T	F417I	1.000
11:13389011:G:C	D416E	1.000
11:13389011:G:T	D416E	1.000

dbSNP variants (sampled 300 via entrez): RS1000001638 (11:13464337 G>C), RS1000010380 (11:13418796 T>C,G), RS1000022253 (11:13458512 A>C), RS1000063888 (11:13413871 T>C), RS1000090330 (11:13407229 G>C), RS1000121698 (11:13406819 A>C), RS1000139056 (11:13447154 T>C), RS1000249491 (11:13440224 A>G), RS1000297969 (11:13432412 C>T), RS1000328282 (11:13390659 C>T), RS1000335535 (11:13390839 G>A), RS1000445463 (11:13433146 G>A), RS1000541088 (11:13464728 T>A), RS1000632079 (11:13433743 A>G), RS1000668604 (11:13392470 G>A)

Disease associations

OMIM: gene MIM:615933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST004897_4	Progression free survival in serous epithelial ovarian cancer treated with carboplatin and paclitaxel	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004920	progression free survival

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression, decreases expression	3
Benzo(a)pyrene	decreases methylation, increases expression	3
Aflatoxin B1	affects expression, increases expression	3
Valproic Acid	affects expression, decreases methylation	2
Cyclosporine	increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
beta-methylcholine	affects expression	1
abrine	increases expression	1
Sunitinib	increases expression	1
Arsenic	increases abundance, increases expression	1
Cisplatin	increases expression	1
Demecolcine	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Lead	affects splicing	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Theophylline	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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