BTBD7

Summary

BTBD7 (BTB domain containing 7, HGNC:18269) is a protein-coding gene on chromosome 14q32.12, encoding BTB/POZ domain-containing protein 7 (Q9P203). Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression.

Predicted to be involved in regulation of branching involved in salivary gland morphogenesis. Predicted to be located in nucleus.

Source: NCBI Gene 55727 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 168 total
• MANE Select transcript: NM_001002860

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18269
Approved symbol	BTBD7
Name	BTB domain containing 7
Location	14q32.12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ10648, FUP1
Ensembl gene	ENSG00000011114
Ensembl biotype	protein_coding
OMIM	610386
Entrez	55727

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000298896, ENST00000334746, ENST00000355125, ENST00000553975, ENST00000554565, ENST00000554644, ENST00000554968, ENST00000555525, ENST00000893707, ENST00000893708, ENST00000893709, ENST00000893710

RefSeq mRNA: 3 — MANE Select: NM_001002860 NM_001002860, NM_001289133, NM_018167

CCDS: CCDS32146, CCDS32147, CCDS73684

Canonical transcript exons

ENST00000334746 — 11 exons

Exon	Start	End
ENSE00001596176	93293858	93294937
ENSE00002311238	93295970	93296157
ENSE00002518880	93332820	93333036
ENSE00003496629	93263785	93263993
ENSE00003553696	93253647	93253790
ENSE00003609910	93261602	93261677
ENSE00003636601	93257195	93257355
ENSE00003657687	93245825	93246286
ENSE00003662289	93251463	93251652
ENSE00003663209	93237550	93243088
ENSE00003666574	93248476	93248654

Expression profiles

Bgee: expression breadth ubiquitous, 141 present calls, max score 88.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5043 / max 416.4947, expressed in 1791 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144637	13.3932	1791
144638	0.1111	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.22	gold quality
corpus callosum	UBERON:0002336	87.42	gold quality
endometrium	UBERON:0001295	87.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.58	gold quality
bone marrow cell	CL:0002092	85.44	gold quality
stromal cell of endometrium	CL:0002255	85.23	gold quality
ventricular zone	UBERON:0003053	84.95	gold quality
islet of Langerhans	UBERON:0000006	84.50	gold quality
lower esophagus mucosa	UBERON:0035834	84.47	gold quality
ganglionic eminence	UBERON:0004023	84.38	gold quality
embryo	UBERON:0000922	84.37	gold quality
skeletal muscle tissue	UBERON:0001134	84.03	gold quality
bone marrow	UBERON:0002371	84.01	gold quality
calcaneal tendon	UBERON:0003701	83.73	gold quality
kidney	UBERON:0002113	83.71	gold quality
metanephros cortex	UBERON:0010533	83.68	gold quality
uterus	UBERON:0000995	83.66	gold quality
tonsil	UBERON:0002372	83.56	gold quality
muscle tissue	UBERON:0002385	83.54	gold quality
adult mammalian kidney	UBERON:0000082	83.46	gold quality
urinary bladder	UBERON:0001255	83.41	gold quality
rectum	UBERON:0001052	83.39	gold quality
smooth muscle tissue	UBERON:0001135	83.34	gold quality
monocyte	CL:0000576	82.99	gold quality
cortex of kidney	UBERON:0001225	82.86	gold quality
leukocyte	CL:0000738	82.80	gold quality
colonic epithelium	UBERON:0000397	82.73	gold quality
popliteal artery	UBERON:0002250	82.61	gold quality
tibial artery	UBERON:0007610	82.61	gold quality
cortical plate	UBERON:0005343	82.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.96

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

278 targeting BTBD7, 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-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754

Literature-anchored findings (GeneRIF, showing 10)

• Cox regression analysis revealed that high BTBD7 expression integrated with high microvessel density was a powerful independent predictive factor of hepatocellular carcinoma clinical outcome. (PMID:23325674)
• Btbd7 contributes to reduced expression of E-cadherin and may be a promising cancer marker in non-small cell lung cancer. (PMID:25253020)
• BTBD7 expression was significantly correlated with Slug expression in SACC (P< 0.05). Increased BTBD7 expression was significantly associated with the TNM stage, tissue typing, distant metastasis and patients’ poor clinical outcome. (PMID:27540976)
• Silencing of Btbd7 significantly inhibited the self-renewal and EMT process in CD133+ cells. we found that downregulation of Btbd7 promoted cell apoptosis and increased the sensitivity to paclitaxel in CD133+ and parental cells. (PMID:27983936)
• BTBD7 was crucial for the migration and invasion of SACC-LM cells. We further demonstrated that downregulation of BTBD7 inhibited the EMT through downregulation of Slug in SACC. (PMID:28946551)
• our data indicate that detection of high miR-23b and Btbd7 levels in the primary tumor of CRC patients can be correlated with the development of cancer metastasis and thus patients with these biological features should be treated more aggressively and have closer follow-ups. (PMID:31303496)
• Studied the role of BTB domain containing 7 (BTBD7) in regulation of E-Cadherin in the development of lung cancer. (PMID:31886230)
• BTB domain-containing 7 predicts low recurrence and suppresses tumor progression by deactivating Notch1 signaling in breast cancer. (PMID:32772271)
• Extracellular Vesicles Carrying miR-887-3p Promote Breast Cancer Cell Drug Resistance by Targeting BTBD7 and Activating the Notch1/Hes1 Signaling Pathway. (PMID:35655918)
• The Role of BTBD7 in Normal Development and Tumor Progression. (PMID:37050886)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	btbd7	ENSDARG00000003069
mus_musculus	Btbd7	ENSMUSG00000041702
rattus_norvegicus	Btbd7	ENSRNOG00000008598
drosophila_melanogaster	CG16952	FBGN0030701
caenorhabditis_elegans		WBGENE00016540

Protein

Protein identifiers

BTB/POZ domain-containing protein 7 — Q9P203 (reviewed: Q9P203)

All UniProt accessions (5): Q9P203, G3V2J4, G3V3T2, H0YJ41, H3BLV3

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression. Induced following accumulation of fibronectin in forming clefts, leading to local expression of the cell-scattering SNAIL2 and suppression of E-cadherin levels, thereby altering cell morphology and reducing cell-cell adhesion. This stimulates cell separation at the base of forming clefts by local, dynamic intercellular gap formation and promotes cleft progression.

Subcellular location. Nucleus.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9P203-1	1	yes
Q9P203-3	3
Q9P203-5	5

RefSeq proteins (3): NP_001002860, NP_001276062, NP_060637 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000210	BTB/POZ_dom	Domain
IPR011333	SKP1/BTB/POZ_sf	Homologous_superfamily
IPR011705	BACK	Domain
IPR042345	Btbd7	Family
IPR047934	BTBD7_BTB_POZ_first	Domain
IPR047935	BTBD7_BTB_POZ_second	Domain
IPR047936	BTBD7_BACK	Domain

Pfam: PF00651, PF07707

UniProt features (23 total): compositionally biased region 6, splice variant 4, domain 3, region of interest 3, modified residue 2, sequence conflict 2, initiator methionine 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P203-F1	61.50	0.32

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): 722, 1012, 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 209 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_GLAND_MORPHOGENESIS, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, GOBP_SALIVARY_GLAND_DEVELOPMENT, TGCACTT_MIR519C_MIR519B_MIR519A, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, CTATGCA_MIR153, GTGCCTT_MIR506, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, CATTTCA_MIR203, TGTGTGA_MIR377, GOBP_EXOCRINE_SYSTEM_DEVELOPMENT, TGTTTAC_MIR30A5P_MIR30C_MIR30D_MIR30B_MIR30E5P

GO Biological Process (2): regulation of branching involved in salivary gland morphogenesis (GO:0060693), morphogenesis of a branching epithelium (GO:0061138)

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

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
branching involved in salivary gland morphogenesis	1
regulation of morphogenesis of a branching structure	1
regulation of morphogenesis of an epithelium	1
regulation of animal organ morphogenesis	1
morphogenesis of a branching structure	1
morphogenesis of an epithelium	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

450 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BTBD7	SNAI2	O43623	773
BTBD7	CDH1	P12830	644
BTBD7	DIDO1	Q9BTC0	581
BTBD7	SEC31A	O94979	545
BTBD7	SULF2	Q8IWU5	507
BTBD7	KLHL18	O94889	493
BTBD7	RYR3	Q15413	480
BTBD7	DNAJC16	Q9Y2G8	460
BTBD7	KLHL25	Q9H0H3	458
BTBD7	DYM	Q7RTS9	455
BTBD7	KCTD2	Q14681	454
BTBD7	UNC79	Q9P2D8	449
BTBD7	KBTBD8	Q8NFY9	446
BTBD7	ANKFY1	Q9P2R3	432
BTBD7	ACVR2A	P27037	407

IntAct

6 interactions, top by confidence:

A	B	Type	Score
CUL3	RHOBTB1	psi-mi:“MI:0914”(association)	0.530
BTBD7	NCL	psi-mi:“MI:0915”(physical association)	0.400
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
CUL3	PXDNL	psi-mi:“MI:0914”(association)	0.350
KLHL14	ARHGAP32	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-RNA), BTBD7 (Proximity Label-MS), BTBD7 (Negative Genetic), BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-RNA), BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-RNA), BTBD7 (Affinity Capture-MS), BTBD7 (Affinity Capture-MS), CCDC18 (Cross-Linking-MS (XL-MS)), EEA1 (Cross-Linking-MS (XL-MS)), SCAMP3 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A0A072VIM5, A0A0K0PU92, A0JM23, A2CIR7, F4IG73, F4JD14, G3LSH3, G8GTN7, O00750, O42132, O75460, O80560, P03372, P0CI65, P50241, P50242, P57717, P57753, Q0JJ01, Q29040, Q2HW56, Q2QXZ2, Q2RAQ5, Q53AD2, Q5D0W8, Q5M9H0, Q5YLM1, Q5ZLG9, Q6AZT7, Q6KAE5, Q6NLQ8, Q6PJI9, Q6WQJ1, Q7EZ44, Q7T0L6, Q7TNH6, Q7XAP4, Q7Z494, Q8C0M0, Q8CFE5

Diamond homologs: A4IFG2, A9JRD8, B1WBS3, B2RXF5, D3YUB6, D4A0X3, O88939, O93567, O95365, P0DMR5, P97302, P97303, Q08BL9, Q0P4X6, Q24174, Q2LE78, Q2M2N2, Q52KB5, Q56A24, Q5PQR3, Q5TZE1, Q5XKL5, Q6GR09, Q6IQ16, Q6NYM1, Q6TFL4, Q717B2, Q717B4, Q7T330, Q811H0, Q8BRG6, Q8C726, Q8CFE5, Q8CII0, Q8K2J9, Q8NAP8, Q8NCP5, Q8R0A2, Q96Q07, Q9BYV9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	152
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2414 predictions. Top by Δscore:

Variant	Effect	Δscore
14:93245821:TTA:T	donor_loss	1.0000
14:93245822:TA:T	donor_loss	1.0000
14:93245823:ACCAC:A	donor_loss	1.0000
14:93245824:CCA:C	donor_gain	1.0000
14:93248470:TCCTA:T	donor_loss	1.0000
14:93248471:CCTAC:C	donor_loss	1.0000
14:93248472:CTA:C	donor_loss	1.0000
14:93248473:TA:T	donor_loss	1.0000
14:93248474:ACC:A	donor_loss	1.0000
14:93248651:GGAA:G	acceptor_gain	1.0000
14:93248652:GAA:G	acceptor_gain	1.0000
14:93248653:AA:A	acceptor_gain	1.0000
14:93248654:AC:A	acceptor_loss	1.0000
14:93248655:C:CC	acceptor_gain	1.0000
14:93251459:TTAC:T	donor_loss	1.0000
14:93251460:TACCT:T	donor_loss	1.0000
14:93251461:ACC:A	donor_loss	1.0000
14:93251462:C:A	donor_loss	1.0000
14:93251649:CTGA:C	acceptor_gain	1.0000
14:93251650:TGA:T	acceptor_gain	1.0000
14:93251651:GA:G	acceptor_gain	1.0000
14:93251653:C:CC	acceptor_gain	1.0000
14:93251653:C:T	acceptor_loss	1.0000
14:93253641:CATTA:C	donor_loss	1.0000
14:93253642:ATTAC:A	donor_loss	1.0000
14:93253643:TTAC:T	donor_loss	1.0000
14:93253644:TACC:T	donor_loss	1.0000
14:93253791:C:CC	acceptor_gain	1.0000
14:93257193:A:AC	donor_gain	1.0000
14:93257194:C:CC	donor_gain	1.0000

AlphaMissense

7394 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:93248546:A:T	V684D	1.000
14:93253718:A:G	W561R	1.000
14:93253718:A:T	W561R	1.000
14:93294061:A:T	I320K	1.000
14:93294277:T:A	D248V	1.000
14:93294352:A:G	L223P	1.000
14:93294415:A:G	L202P	1.000
14:93294530:A:G	C164R	1.000
14:93294532:C:A	R163M	1.000
14:93294532:C:G	R163T	1.000
14:93294583:A:G	L146S	1.000
14:93294616:A:G	L135P	1.000
14:93248480:A:G	L706S	0.999
14:93248515:T:A	R694S	0.999
14:93248515:T:G	R694S	0.999
14:93248516:C:A	R694I	0.999
14:93248516:C:G	R694T	0.999
14:93248519:A:G	L693P	0.999
14:93248525:C:G	R691P	0.999
14:93248579:G:T	A673D	0.999
14:93248606:A:G	L664P	0.999
14:93248615:A:G	L661P	0.999
14:93251570:A:G	L612P	0.999
14:93251570:A:T	L612H	0.999
14:93251645:A:G	L587P	0.999
14:93253652:C:G	A583P	0.999
14:93261641:A:G	W470R	0.999
14:93261641:A:T	W470R	0.999
14:93263892:C:G	A422P	0.999
14:93263897:C:G	R420P	0.999

dbSNP variants (sampled 300 via entrez): RS1000004197 (14:93312778 A>G,T), RS1000010005 (14:93292581 A>C), RS1000018635 (14:93248700 A>C,G), RS1000075090 (14:93314337 A>G), RS1000081590 (14:93309428 T>A,C), RS1000141765 (14:93320150 G>A,C), RS1000217649 (14:93285917 G>A), RS1000226035 (14:93302559 A>C), RS1000307619 (14:93250783 G>GT), RS1000310744 (14:93255206 C>T), RS1000351139 (14:93244241 A>G), RS1000358398 (14:93238330 CAT>C), RS1000429541 (14:93330335 T>C), RS1000432143 (14:93329944 A>T), RS1000456470 (14:93269569 T>C)

Disease associations

OMIM: gene MIM:610386 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST002783_196	Body mass index	8.000000e-07
GCST002783_351	Body mass index	1.000000e-07
GCST002783_591	Body mass index	7.000000e-06
GCST004904_175	Body mass index	5.000000e-11
GCST006032_10	Sodium levels	8.000000e-14
GCST010989_66	Body size at age 10	2.000000e-08
GCST011176_9	Stroke	5.000000e-07
GCST90002401_83	Platelet distribution width	7.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0009282	sodium measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Silicon Dioxide	increases expression	2
Tobacco Smoke Pollution	increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
tris(1,3-dichloro-2-propyl)phosphate	affects expression	1
butyraldehyde	decreases expression	1
methacrylaldehyde	decreases expression, increases oxidation, increases abundance, affects cotreatment	1
beta-methylcholine	affects expression	1
pentanal	decreases expression	1
avobenzone	decreases reaction, increases expression, decreases expression	1
CGP 52608	increases reaction, affects binding	1
abrine	decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	increases oxidation, increases abundance, affects cotreatment, decreases expression	1
Air Pollutants	increases oxidation, affects cotreatment, decreases expression, increases abundance	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dietary Carbohydrates	decreases expression	1
Estradiol	decreases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Niclosamide	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1SB	HAP1 BTBD7 (-) 1	Cancer cell line	Male
CVCL_E1SC	HAP1 BTBD7 (-) 2	Cancer cell line	Male
CVCL_E1SD	HAP1 BTBD7 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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