BAMBI

Summary

BAMBI (BMP and activin membrane bound inhibitor, HGNC:30251) is a protein-coding gene on chromosome 10p12.1, encoding BMP and activin membrane-bound inhibitor homolog (Q13145). Negatively regulates TGF-beta signaling.

This gene encodes a transmembrane glycoprotein related to the type I receptors of the transforming growth factor-beta (TGF-beta) family, whose members play important roles in signal transduction in many developmental and pathological processes. The encoded protein however is a pseudoreceptor, lacking an intracellular serine/threonine kinase domain required for signaling. Similar proteins in frog, mouse and zebrafish function as negative regulators of TGF-beta, which has led to the suggestion that the encoded protein may function to limit the signaling range of the TGF-beta family during early embryogenesis.

Source: NCBI Gene 25805 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 48 total — 2 pathogenic
• GTEx eGene: eQTL in 20 tissues, sQTL in 0 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.30 (unconstrained)
• MANE Select transcript: NM_012342

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30251
Approved symbol	BAMBI
Name	BMP and activin membrane bound inhibitor
Location	10p12.1
Locus type	gene with protein product
Status	Approved
Aliases	NMA
Ensembl gene	ENSG00000095739
Ensembl biotype	protein_coding
OMIM	604444
Entrez	25805

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000375533

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 1

ENST00000375533, ENST00000497699, ENST00000913233, ENST00000963594, ENST00001058283, ENST00001142349

RefSeq mRNA: 1 — MANE Select: NM_012342 NM_012342

CCDS: CCDS7162

Canonical transcript exons

ENST00000375533 — 3 exons

Exon	Start	End
ENSE00000696847	28681258	28681545
ENSE00000816317	28681983	28682932
ENSE00001911553	28677521	28677973

Expression profiles

Bgee: expression breadth ubiquitous, 273 present calls, max score 98.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.0465 / max 342.3412, expressed in 1431 samples.

Highest expression (Bgee): tibia, periodontal ligament, endometrium epithelium, ovary, cardiac muscle of right atrium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BAMBI is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 20 tissues and its splicing (sQTL) in 0 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

20 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	5.9e-51	-0.69	10:28808361:G:C
Cells Cultured fibroblasts	eqtl	5.6e-29	+0.52	10:28678252:C:A
Stomach	eqtl	2.4e-10	-0.38	10:28679377:A:G
Testis	eqtl	2.5e-09	-0.27	10:29009454:C:G
Muscle Skeletal	eqtl	2.0e-08	-0.23	10:28661288:G:A
Esophagus Muscularis	eqtl	7.1e-05	+0.30	10:28659912:G:A
Thyroid	eqtl	4.5e-04	-0.28	10:28954088:G:A
Artery Tibial	eqtl	1.3e-03	+0.22	10:28672503:G:A
Skin Sun Exposed Lower leg	eqtl	1.4e-03	+0.18	10:28676844:C:G
Spleen	eqtl	4.5e-03	-0.26	10:29187149:C:T
Colon Sigmoid	eqtl	4.5e-03	+0.29	10:28486557:C:T
Adipose Subcutaneous	eqtl	1.1e-02	-0.18	10:29233464:A:G
Cells EBV-transformed lymphocytes	eqtl	1.4e-02	+0.56	10:28116807:T:A
Adipose Visceral Omentum	eqtl	1.6e-02	+0.24	10:28678252:C:A
Colon Transverse	eqtl	1.7e-02	-0.24	10:28664172:G:T
Brain Anterior cingulate cortex BA24	eqtl	2.3e-02	-0.89	10:29080329:C:T
Nerve Tibial	eqtl	3.0e-02	-0.17	10:29014582:C:T
Skin Not Sun Exposed Suprapubic	eqtl	3.4e-02	+0.16	10:28655663:A:T
Heart Atrial Appendage	eqtl	3.9e-02	-0.18	10:28936357:C:T
Kidney Cortex	eqtl	4.8e-02	+1.89	10:28510097:C:T

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
104504	12.7293	1235
104503	4.3172	1157

Top tissues by expression

showing 100 of 291 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
tibia	UBERON:0000979	98.13	gold quality
periodontal ligament	UBERON:0008266	97.46	gold quality
endometrium epithelium	UBERON:0004811	95.62	gold quality
left ovary	UBERON:0002119	94.76	gold quality
cardiac muscle of right atrium	UBERON:0003379	94.56	gold quality
right atrium auricular region	UBERON:0006631	93.99	gold quality
cardiac atrium	UBERON:0002081	93.95	gold quality
cartilage tissue	UBERON:0002418	93.66	gold quality
ovary	UBERON:0000992	93.38	gold quality
adrenal tissue	UBERON:0018303	92.28	gold quality
right ovary	UBERON:0002118	92.11	gold quality
renal glomerulus	UBERON:0000074	90.53	gold quality
adrenal cortex	UBERON:0001235	90.11	gold quality
adrenal gland	UBERON:0002369	90.10	gold quality
left adrenal gland	UBERON:0001234	90.08	gold quality
right adrenal gland cortex	UBERON:0035827	89.87	gold quality
metanephric glomerulus	UBERON:0004736	89.83	gold quality
right adrenal gland	UBERON:0001233	89.68	gold quality
left adrenal gland cortex	UBERON:0035825	89.65	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.35	gold quality
metanephros	UBERON:0000081	89.00	gold quality
ascending aorta	UBERON:0001496	88.99	gold quality
placenta	UBERON:0001987	88.94	gold quality
thoracic aorta	UBERON:0001515	88.83	gold quality
spinal cord	UBERON:0002240	88.78	gold quality
myocardium	UBERON:0002349	88.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.30	gold quality
heart	UBERON:0000948	88.17	gold quality
seminal vesicle	UBERON:0000998	87.96	gold quality
urinary bladder	UBERON:0001255	87.83	gold quality
endothelial cell	CL:0000115	87.38	gold quality
germinal epithelium of ovary	UBERON:0001304	86.85	gold quality
left coronary artery	UBERON:0001626	86.63	gold quality
pigmented layer of retina	UBERON:0001782	86.53	gold quality
heart left ventricle	UBERON:0002084	86.04	gold quality
cardiac ventricle	UBERON:0002082	85.77	gold quality
mucosa of urinary bladder	UBERON:0001259	85.66	gold quality
descending thoracic aorta	UBERON:0002345	85.66	gold quality
body of uterus	UBERON:0009853	85.63	gold quality
kidney epithelium	UBERON:0004819	85.60	gold quality
coronary artery	UBERON:0001621	85.53	gold quality
epithelium of mammary gland	UBERON:0003244	85.51	gold quality
adult mammalian kidney	UBERON:0000082	85.42	gold quality
spleen	UBERON:0002106	85.31	gold quality
right lung	UBERON:0002167	85.16	gold quality
mammary duct	UBERON:0001765	84.94	gold quality
inferior vagus X ganglion	UBERON:0005363	84.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.76	gold quality
cortex of kidney	UBERON:0001225	84.71	gold quality
islet of Langerhans	UBERON:0000006	84.54	gold quality
myometrium	UBERON:0001296	84.47	gold quality
metanephros cortex	UBERON:0010533	84.45	gold quality
apex of heart	UBERON:0002098	84.08	gold quality
kidney	UBERON:0002113	84.03	gold quality
decidua	UBERON:0002450	83.95	gold quality
right coronary artery	UBERON:0001625	83.92	gold quality
parotid gland	UBERON:0001831	83.86	gold quality
mucosa of paranasal sinus	UBERON:0005030	83.72	gold quality
amygdala	UBERON:0001876	83.58	gold quality
corpus callosum	UBERON:0002336	83.46	gold quality
left ventricle myocardium	UBERON:0006566	83.36	silver quality
substantia nigra	UBERON:0002038	83.34	gold quality
hypothalamus	UBERON:0001898	83.27	gold quality
right lobe of liver	UBERON:0001114	83.00	gold quality
trachea	UBERON:0003126	82.85	gold quality
palpebral conjunctiva	UBERON:0001812	82.70	gold quality
midbrain	UBERON:0001891	82.60	gold quality
gingival epithelium	UBERON:0001949	82.49	gold quality
tongue squamous epithelium	UBERON:0006919	82.40	silver quality
aorta	UBERON:0000947	82.36	gold quality
mammary gland	UBERON:0001911	82.28	gold quality
thoracic mammary gland	UBERON:0005200	82.28	gold quality
nasal cavity epithelium	UBERON:0005384	82.12	gold quality
smooth muscle tissue	UBERON:0001135	81.82	gold quality
liver	UBERON:0002107	81.50	gold quality
calcaneal tendon	UBERON:0003701	81.31	gold quality
caudate nucleus	UBERON:0001873	81.21	gold quality
stromal cell of endometrium	CL:0002255	80.96	gold quality
subthalamic nucleus	UBERON:0001906	80.94	gold quality
upper lobe of left lung	UBERON:0008952	80.94	gold quality
pancreatic ductal cell	CL:0002079	80.84	silver quality
nasal cavity mucosa	UBERON:0001826	80.82	gold quality
upper lobe of lung	UBERON:0008948	80.70	gold quality
vena cava	UBERON:0004087	80.54	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	80.49	gold quality
visceral pleura	UBERON:0002401	80.46	gold quality
nephron tubule	UBERON:0001231	80.43	gold quality
female reproductive system	UBERON:0000474	80.38	gold quality
superior vestibular nucleus	UBERON:0007227	80.33	gold quality
heart right ventricle	UBERON:0002080	80.31	gold quality
saphenous vein	UBERON:0007318	80.15	gold quality
tibial nerve	UBERON:0001323	80.00	gold quality
Ammon’s horn	UBERON:0001954	79.90	gold quality
putamen	UBERON:0001874	79.86	gold quality
blood vessel layer	UBERON:0004797	79.79	gold quality
choroid plexus epithelium	UBERON:0003911	79.67	gold quality
lung	UBERON:0002048	79.39	gold quality
amniotic fluid	UBERON:0000173	79.14	gold quality
prefrontal cortex	UBERON:0000451	79.13	gold quality
nucleus accumbens	UBERON:0001882	79.09	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-MTAB-8205	yes	548.35
E-MTAB-3929	yes	254.61
E-HCAD-4	yes	177.46
E-MTAB-6701	yes	58.14
E-CURD-112	yes	16.39
E-MTAB-8271	yes	9.63
E-ANND-3	yes	8.61
E-MTAB-9388	yes	7.74

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Ovary	tissue	54.4	not detected
Adrenal gland	tissue	41.7	low
Placenta	tissue	36.9	low
Choroid plexus	tissue	26.5
Heart muscle	tissue	24.5	medium
Liver	tissue	22.4	low
Breast	tissue	22.3	low
Urinary bladder	tissue	18.6	low
Kidney	tissue	18.5	low
Thalamus	tissue	18.3
Endometrium 1	tissue	16.8	low
Spinal cord	tissue	16.2
Seminal vesicle	tissue	15.7	low
Spleen	tissue	15.6	low
Superior colliculi	tissue	13.2
Pons	tissue	12.8
Retina	tissue	12.4
Midbrain	tissue	11.9
Substantia nigra	tissue	11.7
Smooth muscle	tissue	11.4	medium
Hippocampus	tissue	11.2	low
Locus coeruleus	tissue	11.1
Hypothalamus	tissue	10.3
Periaqueductal gray	tissue	10.0
Nucleus accumbens	tissue	9.6
Pituitary gland	tissue	9.3
Lung	tissue	9.3	medium
Medulla oblongata	tissue	8.6
Putamen	tissue	8.2
Hippocampal formation	tissue	8.2
Amygdala	tissue	8.0
Prefrontal cortex	tissue	7.8
Cerebral cortex	tissue	7.8	medium
Parathyroid gland	tissue	7.7	medium
Entorhinal cortex	tissue	7.4
Motor cortex	tissue	7.3
Cerebellum	tissue	7.3	low
Insular cortex	tissue	7.3
Testis	tissue	7.1	medium
Prostate	tissue	7.0	low
Septum	tissue	7.0
Retrosplenial and cingulate cortex	tissue	6.7
Retrosplenial cortex	tissue	6.7
Temporal cortex	tissue	6.6
Occipital cortex	tissue	6.6
Pancreas	tissue	6.5	low
Ventral forebrain	tissue	6.4
Somatosensory cortex	tissue	6.4
Basal ganglia	tissue	5.9	low
Vagina	tissue	5.8	not detected
Postcentral gyrus	tissue	5.8
Bone marrow	tissue	5.6	medium
Salivary gland	tissue	5.5	not detected
Olfactory bulb	tissue	5.4
Gallbladder	tissue	5.0	low
Cervix	tissue	4.6	not detected
Rectum	tissue	4.4	low
Corpus callosum	tissue	4.2
Stomach 1	tissue	3.5	low
Colon	tissue	3.5	low

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Cerebellar white matter (29.9), Kolliker-Fuse nucleus (28.0), Corpus callosum, genu (white matter) (26.6), Nucleus raphe pallidus (25.5), Blood vessel (25.4).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, FOXF2, HDAC1, IRF6, SMAD3, SMAD4, TCF4, TCF7L2

miRNA regulators (miRDB)

Targeting BAMBI by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 85 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607

Functional genomics

gnomAD constraint: pLI 2.45e-07, LOEUF 1.3, missense Z -1.08 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000375533 — one region, missense o/e 1.18.

Literature-anchored findings (GeneRIF, showing 40)

• beta-catenin interferes with transforming growth factor-beta-mediated growth arrest by inducing the expression of BAMBI (PMID:14660579)
• Our findings suggest that BAMBI transcription is regulated by TGF-beta signaling through direct binding of SMAD3 and SMAD4 to the BAMBI promoter. (PMID:15240101)
• BAMBI was linked to a potentially aggressive tumor phenotype and predicted tumor recurrence and cancer-related death in CRC. (PMID:18756595)
• BAMBI interacts with Wnt receptor Frizzled5, coreceptor LRP6, and Dishevelled2 and increases the interaction between Frizzled5 and Dishevelled2 (PMID:18838381)
• hypermethylation of the BAMBI gene promoter that leads to BAMBI gene suppression may be one of the epigenetic events affecting the invasiveness or aggressiveness of bladder cancers (PMID:19326429)
• A colorectal cancer expression profile that includes transforming growth factor beta inhibitor BAMBI predicts metastatic potential. (PMID:19328798)
• Mechanistically, in addition to interfering with the complex formation between the type I and type II receptors, hBAMBI cooperates with Smad7 to inhibit TGF-beta signaling (PMID:19758997)
• Authors demonstrate for the first time a nuclear co-translocation of BAMBI with Smad2/3 upon TGF-geta treatment. Moreover, overexpression of BAMBI in an in vitro model led to significantly increased proliferation. (PMID:20189233)
• Expression of the TGF pseudoreceptor BAMBI in the human lung, which is upregulated in response to nontypeable Haemophilus influenzae infection in COPD lung tissue in vivo and in vitro. (PMID:20513241)
• BAMBI protein is expressed in endothelial cells and is regulated by autophagy and lysosomal degradation. (PMID:20886049)
• Data show that hepatoprotective effects of adiponectin include induction of BAMBI which is reduced in human fatty liver. (PMID:21496456)
• Alterations in BAMBI may play a role in the (patho)physiology of obesity, and manipulation of BAMBI may present a novel therapeutic approach to improve adipose tissue function. (PMID:22187378)
• Metformin-mediated Bambi expression in hepatic stellate cells induces prosurvival Wnt/beta-catenin signaling (PMID:22406377)
• Overexpression of BAMBI is associated with the growth and invasion of human osteosarcoma. (PMID:23807684)
• study demonstrates that LPS- and TNF-alpha-induced NF-kappaBp50-HDAC1 interaction represses BAMBI transcriptional activity, which contributes to TLR4-mediated enhancement of TGF-beta signaling in hepatic stellate cells during liver fibrosis. (PMID:24448807)
• BAMBI alone or in combination with Smad7 was significantly associated with the OS and DFS. These findings suggest that BAMBI and Smad7 may cooperatively inhibit the TGF-beta signaling, and thus promote the progression of gastric cancer. (PMID:24752577)
• The observations illuminated that BAMBI inhibits adipogenesis by a feedback loop (BAMBI–>beta-catenin nuclear translocation–>BAMBI), which forms with Wnt/beta-catenin signaling. (PMID:24798646)
• betacatenin expression was downregulated as a result of knocking down of BAMBI, and TGF-beta was downregulated in a similar manner. (PMID:24912656)
• TGFbeta target genes including TGFBI, BAMBI, COL3A1 and SERPINE1 are significantly increased in Diamond Blackfan Anemia induced pluripotent stem cells (PMID:26258650)
• Low BAMB1 expression is associated with Non-Small Cell Lung Cancer. (PMID:27197161)
• Lipopolysaccharides-mediated TLR4 signaling enhances TGF-beta response through downregulating BAMBI during prostatic hyperplasia. (PMID:27243216)
• Data show that BAMBI is expressed in both circulating CD4+ T cells and plasma and may be characterized as a novel immune regulator for COPD. Strikingly, BAMBI expression was significantly stronger in COPD patients and displayed strong correlations with enhanced plasma TGF-beta 1 levels and the Th17/Treg ratio. (PMID:27549738)
• These results showed that BMP2 activated SMAD1/5/8 phosphorylation and up-regulated BAMBI mRNA in human granulosa-lutein cells. (PMID:28578012)
• BAMBI promotes macrophage proliferation and differentiation in gliomas. (PMID:29286116)
• BAMBI expression is reduced in ALS4 patients due to methylation of promoter caused by decreased formation of R-loops due to mutation in senataxin (SETX) gene. (PMID:29395064)
• BAMBI is a direct target of miR-942 in the hepatic stellate cells in liver fibrosis. BAMBI expression is decreased in human hepatic fibrosis. (PMID:30097701)
• human BAMBI may function as a molecular switch to control TGFbeta signalling strength and the Th17/Treg cell balance (PMID:30320351)
• overexpression of BAMBI could decrease the ability of M2 macrophages to induce Treg differentiation (PMID:30728014)
• It was noted that BAMBI is a target of miR519d3p and miR519d3p promotes transforming growth factor beta/mothers against decapentaplegic homolog 9mediated postoperative epidural scar formation via suppression of BAMBI. (PMID:31485673)
• Downregulation of circDNMT3B contributes to vascular dysfunction in diabetic retinas through regulating miR-20b-5p and BAMBI, providing a potential treatment strategy for diabetic retinopathy (PMID:31636010)
• Bone morphogenetic protein 2 induces the activation of WNT/beta-catenin signaling and human trophoblast invasion through up-regulating BAMBI. (PMID:31786181)
• Adipose-specific BMP and activin membrane-bound inhibitor (BAMBI) deletion promotes adipogenesis by accelerating ROS production. (PMID:33158991)
• Overexpression of BAMBI and SMAD7 impacts prognosis of acute myeloid leukemia patients: A potential TERT non-canonical role. (PMID:33780363)
• miR-125a-3p aggravates ox-LDL-induced HUVEC injury through BAMBI. (PMID:35993694)
• BMP and activin membrane-bound inhibitor regulate connective tissue growth factor controlling mesothelioma cell proliferation. (PMID:36109807)
• Expression and Function of BMP and Activin Membrane-Bound Inhibitor (BAMBI) in Chronic Liver Diseases and Hepatocellular Carcinoma. (PMID:36834884)
• Hypoxia-responsive PPARGC1A/BAMBI/ACSL5 axis promotes progression and resistance to lenvatinib in hepatocellular carcinoma. (PMID:36932115)
• The regulatory effect of the YY1/miR-HCC2/BAMBI axis on the stemness of liver cancer cells. (PMID:36999621)
• Circular RNA circSP5 promotes liver metastasis of colorectal cancer via SP5-mediated BAMBI transcription. (PMID:37596430)
• Increased Levels of BAMBI Inhibit Canonical TGF-beta Signaling in Chronic Wound Tissues. (PMID:37626905)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bambia	ENSDARG00000055381
danio_rerio	bambib	ENSDARG00000099677
mus_musculus	Bambi	ENSMUSG00000024232
rattus_norvegicus	Bambi	ENSRNOG00000016066

Paralogs (1): CATIP (ENSG00000158428)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1915260) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 8 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal testis morphology	1
small testis	1
decreased body weight	1
abnormal pain threshold	1
increased thermal nociceptive threshold	1
hyporesponsive to tactile stimuli	1
increased chemical nociceptive threshold	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Ovis aries	Q8HYZ0	94.6%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
WAC	protein-coding	51322
LINC01517	ncRNA	101929218
LINC00837	ncRNA	100507605

Protein

Protein identifiers

BMP and activin membrane-bound inhibitor homolog — Q13145 (reviewed: Q13145)

Alternative names: Non-metastatic gene A protein, Putative transmembrane protein NMA

All UniProt accessions (1): Q13145

UniProt curated annotations — full annotation on UniProt →

Function. Negatively regulates TGF-beta signaling.

Subcellular location. Membrane.

Tissue specificity. High expression in kidney medulla, placenta and spleen; low in kidney cortex, liver, prostate and gut. Not expressed in normal skin, expression is high in melanocytes and in 3 out of 11 melanoma metastases tested.

Similarity. Belongs to the BAMBI family.

RefSeq proteins (1): NP_036474* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009345	BAMBI	Family
IPR045806	BAMBI_C	Domain
IPR045807	BAMBI_N	Domain
IPR045860	Snake_toxin-like_sf	Homologous_superfamily

Pfam: PF06211, PF19337

UniProt features (6 total): topological domain 2, signal peptide 1, chain 1, transmembrane region 1, glycosylation site 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13145-F1	64.81	0.04

Human Protein Atlas

Protein class: Predicted membrane proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): vesicles; lipid droplets; nucleoli fibrillar center

Antibody reliability (HPA): IH approved · IF approved

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	87

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-2173788	Downregulation of TGF-beta receptor signaling	curated
R-HSA-162582	Signal Transduction	—
R-HSA-170834	Signaling by TGF-beta Receptor Complex	—
R-HSA-9006936	Signaling by TGFB family members	—
R-HSA-2173789	TGF-beta receptor signaling activates SMADs	—

MSigDB gene sets: 305 (showing top): LI_CISPLATIN_RESISTANCE_DN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, HNF3ALPHA_Q6, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, PEREZ_TP63_TARGETS, ENK_UV_RESPONSE_KERATINOCYTE_UP, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOZGIT_ESR1_TARGETS_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, CHX10_01, AAAYRNCTG_UNKNOWN, YY1_Q6

GO Biological Process (10): transforming growth factor beta receptor signaling pathway (GO:0007179), positive regulation of cell population proliferation (GO:0008284), regulation of cell shape (GO:0008360), positive regulation of epithelial to mesenchymal transition (GO:0010718), cell migration (GO:0016477), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of osteoblast differentiation (GO:0045668), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of canonical Wnt signaling pathway (GO:0090263)

GO Molecular Function (3): frizzled binding (GO:0005109), type II transforming growth factor beta receptor binding (GO:0005114), protein binding (GO:0005515)

GO Cellular Component (3): cytoplasm (GO:0005737), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
TGF-beta receptor signaling activates SMADs	1
Signaling by TGFB family members	1
Signaling by TGF-beta Receptor Complex	1
Signal Transduction	1

GO top-level categories

34 GO namespaces:

Category	Terms
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	2
cellular anatomical structure	2
cellular response to transforming growth factor beta stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
positive regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
G protein-coupled receptor binding	1
transforming growth factor beta receptor binding	1
binding	1
intracellular anatomical structure	1
membrane	1
cell periphery	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 12 of 16 annotations. The rest are phylogenetic / computational / electronic (IEA).

12 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	direct assay
negative regulation of BMP signaling pathway	BP	mutant phenotype
negative regulation of osteoblast differentiation	BP	mutant phenotype
negative regulation of transforming growth factor beta receptor signaling pathway	BP	direct assay
positive regulation of DNA-templated transcription	BP	direct assay
positive regulation of canonical Wnt signaling pathway	BP	direct assay
positive regulation of cell population proliferation	BP	mutant phenotype
positive regulation of epithelial to mesenchymal transition	BP	mutant phenotype
regulation of cell shape	BP	mutant phenotype
cytoplasm	CC	direct assay
plasma membrane	CC	direct assay
frizzled binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 840 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BAMBI	TMSB10	P13472	827
BAMBI	TGFB1	P01137	612
BAMBI	SMAD6	O43541	559
BAMBI	CHRD	Q9H2X0	558
BAMBI	S100A6	P06703	554
BAMBI	SMAD7	O15105	541
BAMBI	TLR4	O00206	498
BAMBI	BMP4	P12644	492
BAMBI	GREM1	O60565	479
BAMBI	SMAD4	Q13485	476
BAMBI	TGFBR1	P36897	456
BAMBI	DLX3	O60479	455
BAMBI	FST	P19883	453
BAMBI	ACVR2A	P27037	452
BAMBI	NOG	Q13253	445

IntAct

Human interaction partners of BAMBI in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

6 partners by confidence:

Partner	Interaction type	MIscore	Records
NKG7	physical association	0.560	3
DVL2	physical association	0.400	1
FZD5	physical association	0.400	1
LRP6	physical association	0.400	1
SELENOF	physical association	0.370	1
SOX30	physical association	0.370	1

BioGRID (24 interactions; top human partners by supporting records): SMAD7 (Affinity Capture-Western; 2 records), TGFBR1 (Reconstituted Complex; 2 records), ACVR1 (Reconstituted Complex), ACVR1B (Reconstituted Complex), ACVRL1 (Reconstituted Complex), BMPR1A (Reconstituted Complex), BMPR1B (Reconstituted Complex), NKG7 (Two-hybrid), PARP10 (Proximity Label-MS), SEP15 (Two-hybrid), SETD3 (Affinity Capture-MS), SLC30A8 (Affinity Capture-MS), SLC43A1 (Affinity Capture-MS), SLC4A1 (Affinity Capture-MS), SMAD6 (Affinity Capture-Western)

SIGNOR signaling

2 signaling interactions:

A	Effect	B	Mechanism
BAMBI	up-regulates	DVL2	binding
BAMBI	up-regulates	FZD5	binding

Disease & clinical

Genetic variants

Variant evidence for BAMBI: 48 ClinVar records (2 pathogenic / likely pathogenic); 9 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	39
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (2)

Showing all 2 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59700	GRCh38/hg38 10p12.1-11.23(chr10:27767970-30046085)x3	Pathogenic	criteria provided, single submitter	1
4682768	GRCh37/hg19 10p12.1(chr10:27659942-29401622)x1	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore BAMBI’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 177):

Position(s)	Effect	Δscore	Sites
10:28677974–28677975	donor_loss	1.0000	3
10:28677974–28677975	donor_loss	0.9900	2
10:28680364	donor_gain	0.9800
10:28681404	acceptor_gain	0.9800
10:28681981–28681982	acceptor_loss	0.9800	6
10:28681546–28681547	donor_loss	0.9600	5
10:28681970	acceptor_loss	0.9600
10:28681256–28681257	acceptor_loss	0.9400	6
10:28681547	donor_loss	0.9400
10:28681974	acceptor_loss	0.9200

AlphaMissense

643 missense substitutions predicted likely pathogenic (of 1,721 scored), across 153 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M43	9	0.944	0.996
M103	9	0.911	0.997
M175	9	0.901	0.997
D102	8	0.991	0.998
N105	8	0.988	1.000
F150	8	0.982	0.999
H67	8	0.966	0.996
D33	8	0.961	0.996
C37	7	0.999	1.000
C30	7	0.998	1.000
C32	7	0.998	1.000
C44	7	0.998	0.999
C51	7	0.998	1.000
C69	7	0.998	0.999
C104	7	0.996	0.999
C99	7	0.995	0.998
C98	7	0.989	0.997
F52	7	0.982	0.997
C80	7	0.974	0.984
W149	7	0.969	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	1.01e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.00015
Colon Adenocarcinoma (validation)	unfavorable	0.000795

Disease associations

OMIM: gene MIM:604444 | disease phenotypes:

GWAS associations

9 associations:

Study	Trait	p-value
GCST90000025_625	Appendicular lean mass	1e-23
GCST90014268_40	Cataracts	2e-21
GCST005580_199	Intraocular pressure	6e-9
GCST009963_11	Cataracts (operation)	4e-8
GCST002942_3	Percentage gas trapping	1e-6
GCST009391_458	Metabolite levels	3e-6
GCST008504_8	Fasting glucose change (long-term)	4e-6
GCST001949_6	Preeclampsia	6e-6
GCST009391_461	Metabolite levels	6e-6

EFO canonical traits (from GWAS)

4 canonical traits:

EFO ID	Trait name
EFO:0007628	gas trapping measurement
EFO:0004695	intraocular pressure measurement
EFO:0010522	phosphoenolpyruvic acid measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, affects expression, affects methylation (+1 more)	9
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
Benzo(a)pyrene	decreases expression, increases expression	4
Tetrachlorodibenzodioxin	affects cotreatment, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Formaldehyde	increases expression	3
Tretinoin	decreases expression, increases expression	3
Cyclosporine	decreases expression	3
bisphenol A	decreases expression, increases expression	2
arsenite	increases methylation, affects binding, increases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Nickel	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, increases methylation	2
Cadmium Chloride	decreases expression, increases expression	2
tert-Butylhydroperoxide	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
Glupearl 19S	increases expression	1
5-(3-(4-(4-benzylpiperazin-1-yl)-N-(4-phenylthiazol-2-yl))propanamide	decreases expression, decreases reaction, increases expression	1
sotorasib	increases expression, affects cotreatment	1
methylmercuric chloride	increases expression	1
lead acetate	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2SM	Abcam HEK293T BAMBI KO	Transformed cell line	Female
CVCL_D9A0	Ubigene HEK293 BAMBI KO	Transformed cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.