BMP10

Summary

BMP10 (bone morphogenetic protein 10, HGNC:20869) is a protein-coding gene on chromosome 2p13.3, encoding Bone morphogenetic protein 10 (O95393). Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which binds to the activin receptor-like kinase 1 (ALK1) and plays important roles in cardiovascular development including cardiomyocyte proliferation and regulation of heart size, closure of the ductus arteriosus, angiogenesis and ventricular trabeculation.

Source: NCBI Gene 27302 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary arterial hypertension (Moderate, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 49 total
• Druggable target: yes
• MANE Select transcript: NM_014482

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20869
Approved symbol	BMP10
Name	bone morphogenetic protein 10
Location	2p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000163217
Ensembl biotype	protein_coding
OMIM	608748
Entrez	27302

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000295379, ENST00000960265

RefSeq mRNA: 1 — MANE Select: NM_014482 NM_014482

CCDS: CCDS1890

Canonical transcript exons

ENST00000295379 — 2 exons

Exon	Start	End
ENSE00001072541	68860909	68866571
ENSE00001072543	68871025	68871397

Expression profiles

Bgee: expression breadth broad, 90 present calls, max score 97.47.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2104 / max 178.0471, expressed in 34 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
28892	0.1718	28
28893	0.0242	8
202226	0.0089	4
28894	0.0055	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cardiac muscle of right atrium	UBERON:0003379	97.47	gold quality
right atrium auricular region	UBERON:0006631	97.34	gold quality
cardiac atrium	UBERON:0002081	96.59	gold quality
myocardium	UBERON:0002349	72.67	gold quality
right lobe of liver	UBERON:0001114	70.46	gold quality
endometrium epithelium	UBERON:0004811	68.27	gold quality
olfactory bulb	UBERON:0002264	67.25	gold quality
Brodmann (1909) area 10	UBERON:0013541	66.28	gold quality
left ventricle myocardium	UBERON:0006566	65.11	gold quality
pancreatic ductal cell	CL:0002079	63.98	silver quality
tibialis anterior	UBERON:0001385	62.92	silver quality
liver	UBERON:0002107	62.65	gold quality
frontal pole	UBERON:0002795	61.42	gold quality
middle frontal gyrus	UBERON:0002702	61.37	gold quality
paraflocculus	UBERON:0005351	60.98	gold quality
ileal mucosa	UBERON:0000331	60.58	silver quality
orbitofrontal cortex	UBERON:0004167	59.80	gold quality
heart	UBERON:0000948	59.48	gold quality
cerebellar vermis	UBERON:0004720	57.98	gold quality
decidua	UBERON:0002450	56.55	gold quality
quadriceps femoris	UBERON:0001377	54.35	gold quality
metanephric glomerulus	UBERON:0004736	53.09	gold quality
vastus lateralis	UBERON:0001379	52.55	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
thymus	UBERON:0002370	52.00	silver quality
epithelial cell of pancreas	CL:0000083	51.89	gold quality
muscle tissue	UBERON:0002385	49.92	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.48	gold quality
kidney epithelium	UBERON:0004819	49.27	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.92

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARID1A, BMPR1A, ESR2, IRX5, MEF2C, MYOCD, NKX2-5, NOG, NOTCH1, RBPJ, SRF

miRNA regulators (miRDB)

15 targeting BMP10, 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-5692A	100.00	74.40	6850
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-216A-5P	99.50	68.02	1288
HSA-MIR-4643	99.49	67.63	1791
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-12132	99.47	68.90	1341
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-4477A	98.83	69.75	2952

Literature-anchored findings (GeneRIF, showing 30)

• Describes the cloning and expression of murine BMP-10. (PMID:10072785)
• Hypertension induced expression of prohypertrophic BMP10, and the hypertrophic effect of BMP10 was modulated, at least in part, by its binding to Tcap at the Z disc. (PMID:17921333)
• Bone morphogenetic protein-10 (BMP-10) may function as a tumor suppressor in breast cancer. (PMID:20608934)
• Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10. (PMID:21550985)
• Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10 via its orphan domain, inhibits blood vessel formation, and suppresses tumor growth. (PMID:21737454)
• Low expression of bone morphogenetic protein-10 is associated with urothelial cancer of the bladder. (PMID:23645739)
• BMP10, is elevated in the stenotic colon segment of Hirschsprung disease patients, and BMP10 signaling may play a pivotal role in disease development. (PMID:24551273)
• Forced expression of BMP10 in gastric cancer (GC) cells inhibited its growth and migration, while knocking down the expression of BMP10 in GC cells promoted cell growth, migration, and metastasis. (PMID:26419594)
• The Prodomain-bound Form of Bone Morphogenetic Protein 10 Is Biologically Active on Endothelial Cells. (PMID:26631724)
• Bone morphogenetic protein (BMP)9 and BMP10 are high affinity ligands for activin receptor-like kinase 1 (ALK1). (PMID:27528761)
• Data suggest BMP9/GDF2 and BMP10 synergize with TNFA to increase monocyte recruitment to vascular endothelial cells; process appears to be mediated mainly via ALK2/ACVR1 (which exhibits protein kinase activity). These studies used in vitro flow monocyte adhesion assay. (BMP9 = growth differentiation factor 2; BMP10 = bone morphogenetic protein 10; TNFA = tumor necrosis factor alpha; ALK2/ACVR1 = activin A receptor type 1) (PMID:28646109)
• Low BMP-10 expression was associated with poor prognosis and progression of ovarian cancer (PMID:30401582)
• Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases. (PMID:30578383)
• W143*-NRG1and V470I-BMP10 variants are associated with left ventricular non-compaction. (PMID:31243186)
• Low BMP10 expression is associated with hepatocellular carcinoma progression. (PMID:31417183)
• Findings demonstrate that GDF2 mutations result in BMP9 loss of function and are likely causal for pulmonary arterial hypertension. These mutations lead to reduced circulating levels of both BMP9 and BMP10. (PMID:31661308)
• BMP10 was able to promote cardiomyocyte survival and prevent cardiac adverse remodeling. Additional experiments with the de novo activation of BMP10 in the postnatal heart and the treatment of recombinant human BMP10 (rhBMP10) further confirmed this observation. A novel activity of BMP10 is in activating both SMAD- and STAT3- mediated signaling pathways. (PMID:31712309)
• BMP9/10 in Pulmonary Vascular Complications of Liver Disease. (PMID:32083953)
• Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis. (PMID:32454407)
• Endothelial protective factors BMP9 and BMP10 inhibit CCL2 release by human vascular endothelial cells. (PMID:32576665)
• Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. (PMID:32814717)
• In Search of ““Hepatic Factor””: Lack of Evidence for ALK1 Ligands BMP9 and BMP10. (PMID:32871084)
• Plasma levels of apelin are reduced in patients with liver fibrosis and cirrhosis but are not correlated with circulating levels of bone morphogenetic protein 9 and 10. (PMID:33171278)
• BMP9 and BMP10 Act Directly on Vascular Smooth Muscle Cells for Generation and Maintenance of the Contractile State. (PMID:33334130)
• Homozygous GDF2 nonsense mutations result in a loss of circulating BMP9 and BMP10 and are associated with either PAH or an ““HHT-like”” syndrome in children. (PMID:33834622)
• BMP9 and BMP10: Two close vascular quiescence partners that stand out. (PMID:34240497)
• Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10. (PMID:35504921)
• Bone morphogenetic protein 10: a novel risk marker of ischaemic stroke in patients with atrial fibrillation. (PMID:36380569)
• Bone Morphogenetic Protein 10-A Novel Biomarker to Predict Adverse Outcomes in Patients With Atrial Fibrillation. (PMID:36926939)
• Repeated Measurement of the Novel Atrial Biomarker BMP10 (Bone Morphogenetic Protein 10) Refines Risk Stratification in Anticoagulated Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial. (PMID:38529655)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	bmp10	ENSDARG00000061769
danio_rerio	bmp10l	ENSDARG00000109233
mus_musculus	Bmp10	ENSMUSG00000030046
rattus_norvegicus	Bmp10	ENSRNOG00000009316

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), LEFTY2 (ENSG00000143768), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Bone morphogenetic protein 10 — O95393 (reviewed: O95393)

All UniProt accessions (1): O95393

UniProt curated annotations — full annotation on UniProt →

Function. Required for maintaining the proliferative activity of embryonic cardiomyocytes by preventing premature activation of the negative cell cycle regulator CDKN1C/p57KIP and maintaining the required expression levels of cardiogenic factors such as MEF2C and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors. Inhibits endothelial cell migration and growth. May reduce cell migration and cell matrix adhesion in breast cancer cell lines.

Subunit / interactions. Homodimer; disulfide-linked. Interacts with FBN1 (via N-terminal domain) and FBN2. Interacts with ENG.

Subcellular location. Secreted.

Tissue specificity. Detected in mammary epithelia (at protein level).

Disease relevance. Defects in BMP10 may be a cause of congenital heart defects, a wide spectrum of cardiovascular malformations resulting from anomalous development of the heart, cardiac valves, and endo-thoracic large vessels.

Induction. Down-regulated in some breast cancer subtypes and breast cancer cell lines.

Similarity. Belongs to the TGF-beta family.

RefSeq proteins (1): NP_055297* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (25 total): strand 7, disulfide bond 4, sequence variant 3, turn 3, helix 2, glycosylation site 2, signal peptide 1, propeptide 1, sequence conflict 1, chain 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
7PPA	X-RAY DIFFRACTION	1.48
9DPY	X-RAY DIFFRACTION	1.77
6SF3	X-RAY DIFFRACTION	2.3
7PPB	X-RAY DIFFRACTION	2.4
6SF1	X-RAY DIFFRACTION	2.8
7POI	X-RAY DIFFRACTION	2.9
7POJ	X-RAY DIFFRACTION	3.5
7PPC	X-RAY DIFFRACTION	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95393-F1	74.74	0.35

Functional residue map

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

Disulfide bonds (4): 323–389, 352–421, 356–423, 388

Glycosylation sites (2): 67, 131

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-201451	Signaling by BMP
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-1474244	Extracellular matrix organization
R-HSA-1566948	Elastic fibre formation
R-HSA-162582	Signal Transduction
R-HSA-9006936	Signaling by TGFB family members

MSigDB gene sets: 276 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_SMAD_PROTEIN_SIGNAL_TRANSDUCTION, MORF_FLT1, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_CARTILAGE_DEVELOPMENT, MORF_MSH3, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH

GO Biological Process (29): kidney development (GO:0001822), cell adhesion (GO:0007155), adult heart development (GO:0007512), negative regulation of endothelial cell migration (GO:0010596), positive regulation of cardiac muscle hypertrophy (GO:0010613), negative regulation of cardiac muscle hypertrophy (GO:0010614), positive regulation of gene expression (GO:0010628), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), BMP signaling pathway (GO:0030509), activin receptor signaling pathway (GO:0032924), sarcomere organization (GO:0045214), positive regulation of DNA-templated transcription (GO:0045893), atrial cardiac muscle tissue morphogenesis (GO:0055009), ventricular cardiac muscle tissue morphogenesis (GO:0055010), ventricular cardiac muscle cell development (GO:0055015), regulation of cardiac muscle contraction (GO:0055117), cardiac muscle cell proliferation (GO:0060038), positive regulation of cardiac muscle cell proliferation (GO:0060045), positive regulation of sarcomere organization (GO:0060298), heart trabecula formation (GO:0060347), positive regulation of SMAD protein signal transduction (GO:0060391), positive regulation of cartilage development (GO:0061036), regulation of cardiac muscle hypertrophy in response to stress (GO:1903242), positive regulation of cell proliferation involved in heart morphogenesis (GO:2000138), heart development (GO:0007507), regulation of cardiac muscle hypertrophy (GO:0010611), positive regulation of multicellular organismal process (GO:0051240), regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (GO:0090092)

GO Molecular Function (6): cytokine activity (GO:0005125), hormone activity (GO:0005179), growth factor activity (GO:0008083), telethonin binding (GO:0031433), receptor serine/threonine kinase binding (GO:0033612), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), cell surface (GO:0009986), Z disc (GO:0030018)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Signaling by TGFB family members	1
Elastic fibre formation	1
Extracellular matrix organization	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
receptor ligand activity	3
cardiac muscle hypertrophy	2
regulation of cardiac muscle hypertrophy	2
transforming growth factor beta receptor superfamily signaling pathway	2
cardiac muscle tissue morphogenesis	2
animal organ development	1
renal system development	1
cellular process	1
heart development	1
regulation of endothelial cell migration	1
negative regulation of cell migration	1
endothelial cell migration	1
positive regulation of muscle hypertrophy	1
negative regulation of muscle hypertrophy	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
regulation of cell growth	1
cell growth	1
negative regulation of growth	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
cellular response to BMP stimulus	1
myofibril assembly	1
actomyosin structure organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
cardiac atrium morphogenesis	1
atrial cardiac muscle tissue development	1
cardiac ventricle morphogenesis	1
ventricular cardiac muscle tissue development	1
ventricular cardiac muscle cell differentiation	1
cardiac muscle cell development	1
regulation of striated muscle contraction	1
regulation of heart contraction	1
cardiac muscle contraction	1

Protein interactions and networks

STRING

1089 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BMP10	ACVRL1	P37023	994
BMP10	ENG	P17813	977
BMP10	BMPR2	Q13873	907
BMP10	ACVR2A	P27037	877
BMP10	ACVR1	Q04771	815
BMP10	MYH6	P13533	805
BMP10	MYH7	P12883	769
BMP10	CDKN1C	P49918	762
BMP10	ACVR2B	Q13705	753
BMP10	SMARCA4	P51532	730
BMP10	BMPR1A	P36894	708
BMP10	BMPR1B	P78366	706
BMP10	TGFBR1	P36897	701
BMP10	PARP1	P09874	671
BMP10	NKX2-5	P52952	604

IntAct

167 interactions, top by confidence:

A	B	Type	Score
BMP10	FCGR1A	psi-mi:“MI:0915”(physical association)	0.560
BMP10	MTIF3	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SIT1	psi-mi:“MI:0915”(physical association)	0.560
BMP10	FCRL4	psi-mi:“MI:0915”(physical association)	0.560
BMP10	DEXI	psi-mi:“MI:0915”(physical association)	0.560
BMP10	CISD2	psi-mi:“MI:0915”(physical association)	0.560
BMP10	IL3RA	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SLC10A6	psi-mi:“MI:0915”(physical association)	0.560
BMP10	LRRC4C	psi-mi:“MI:0915”(physical association)	0.560
BMP10	BIK	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SLC38A1	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SPAG4	psi-mi:“MI:0915”(physical association)	0.560
BMP10	TNFSF8	psi-mi:“MI:0915”(physical association)	0.560
BMP10	CREB3L1	psi-mi:“MI:0915”(physical association)	0.560
BMP10	GGT6	psi-mi:“MI:0915”(physical association)	0.560
	BMP10	psi-mi:“MI:0915”(physical association)	0.560
BMP10	SLC4A1	psi-mi:“MI:0915”(physical association)	0.560
TMPRSS2	BMP10	psi-mi:“MI:0915”(physical association)	0.560
TNFSF14	BMP10	psi-mi:“MI:0915”(physical association)	0.560
BMP10	KLRC1	psi-mi:“MI:0915”(physical association)	0.560
BSCL2	BMP10	psi-mi:“MI:0915”(physical association)	0.560
COQ9	BMP10	psi-mi:“MI:0915”(physical association)	0.560
BMP10	FNDC9	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (61): BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid), BMP10 (Two-hybrid)

ESM2 similar proteins: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, F1QWZ4, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O95393, P27091, P30885, P34822, P48970, P54631, P85857, P92172, Q24735, Q26974, Q4AEG6, Q5I3Q2, Q5RZV4, Q5USV5, Q5USV6, Q5USV7, Q5USV8, Q5USV9, Q5USW0, Q5USW1, Q6DTL9, Q6J1J2, Q6T5B8, Q6UKZ8

Diamond homologs: A1C2U3, A1C2U6, A1C2U7, A1C2V0, A1C2V5, A8E7N9, G5EEL5, O08689, O14793, O18828, O18830, O18831, O18836, O35312, O42220, O42221, O42222, O46576, O61643, O95390, O95393, P09534, P12644, P12645, P17491, P18075, P20722, P20863, P22003, P22004, P22444, P23359, P27091, P27539, P35621, P43026, P43027, P43028, P43029, P48970

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
BMP10	up-regulates	BMPR1A	binding
BMP10	up-regulates	ACVRL1	binding
ENG	“up-regulates activity”	BMP10	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 55 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell	5	13.2×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	6
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

126 predictions. Top by Δscore:

Variant	Effect	Δscore
2:68866567:CAGAT:C	acceptor_gain	1.0000
2:68871020:CTTA:C	donor_loss	1.0000
2:68871021:TTACC:T	donor_loss	1.0000
2:68871022:TA:T	donor_loss	1.0000
2:68871023:A:AC	donor_gain	1.0000
2:68871023:AC:A	donor_gain	1.0000
2:68871023:ACCTT:A	donor_gain	1.0000
2:68871024:C:CA	donor_gain	1.0000
2:68871024:CC:C	donor_gain	1.0000
2:68871024:CCT:C	donor_gain	1.0000
2:68871024:CCTT:C	donor_gain	1.0000
2:68871024:CCTTC:C	donor_gain	1.0000
2:68866571:TCTG:T	acceptor_loss	0.9900
2:68866572:C:CC	acceptor_gain	0.9900
2:68866573:T:G	acceptor_loss	0.9900
2:68866568:AGAT:A	acceptor_gain	0.9800
2:68866569:GAT:G	acceptor_gain	0.9800
2:68866570:ATCTG:A	acceptor_gain	0.9700
2:68866569:GATCT:G	acceptor_gain	0.9500
2:68866570:AT:A	acceptor_gain	0.9400
2:68866568:AGATC:A	acceptor_gain	0.9300
2:68866571:TCTGA:T	acceptor_gain	0.9300
2:68869734:C:CT	acceptor_gain	0.9100
2:68869379:T:TA	donor_gain	0.9000
2:68866572:C:A	acceptor_gain	0.8900
2:68866573:T:A	acceptor_gain	0.8900
2:68871236:A:AC	donor_gain	0.8600
2:68869536:CT:C	acceptor_gain	0.7900
2:68871018:AACTT:A	donor_loss	0.7700
2:68871019:ACTTA:A	donor_loss	0.7700

AlphaMissense

2823 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:68865739:A:C	C389W	1.000
2:68865740:C:G	C389S	1.000
2:68865740:C:T	C389Y	1.000
2:68865741:A:G	C389R	1.000
2:68865741:A:T	C389S	1.000
2:68865839:C:G	C356S	1.000
2:68865839:C:T	C356Y	1.000
2:68865840:A:G	C356R	1.000
2:68865840:A:T	C356S	1.000
2:68865851:C:G	C352S	1.000
2:68865852:A:G	C352R	1.000
2:68865852:A:T	C352S	1.000
2:68865937:A:C	C323W	1.000
2:68865938:C:G	C323S	1.000
2:68865938:C:T	C323Y	1.000
2:68865939:A:G	C323R	1.000
2:68865939:A:T	C323S	1.000
2:68865637:A:C	C423W	0.999
2:68865638:C:G	C423S	0.999
2:68865638:C:T	C423Y	0.999
2:68865639:A:G	C423R	0.999
2:68865639:A:T	C423S	0.999
2:68865643:A:C	C421W	0.999
2:68865644:C:G	C421S	0.999
2:68865644:C:T	C421Y	0.999
2:68865645:A:G	C421R	0.999
2:68865645:A:T	C421S	0.999
2:68865653:A:T	V418D	0.999
2:68865740:C:A	C389F	0.999
2:68865798:C:G	A370P	0.999

dbSNP variants (sampled 300 via entrez): RS1000290862 (2:68870773 C>A,T), RS1000509576 (2:68870984 T>C), RS1000775701 (2:68864801 T>C), RS1001005421 (2:68870728 T>C), RS1001347512 (2:68870035 C>T), RS1001672534 (2:68868009 T>C), RS1001695392 (2:68869744 A>G), RS1002446867 (2:68863191 G>A), RS1002517574 (2:68862319 G>A,T), RS1002957918 (2:68866789 C>T), RS1003403244 (2:68872591 T>C), RS1003502290 (2:68860557 A>G), RS1003764159 (2:68872812 T>C), RS1004009278 (2:68867020 G>A,C), RS1004522384 (2:68873103 G>T)

Disease associations

OMIM: gene MIM:608748 | disease phenotypes: MIM:600057

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary arterial hypertension	Moderate	Autosomal dominant
left ventricular noncompaction	Limited	Autosomal dominant
congenital heart disease	Limited	Autosomal dominant
dilated cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (2)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
pulmonary arterial hypertension	Limited	AD
congenital heart disease	Limited	AD

Mondo (5): bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), left ventricular noncompaction (MONDO:0018901), congenital heart disease (MONDO:0005453), dilated cardiomyopathy (MONDO:0005021), pulmonary arterial hypertension (MONDO:0015924)

Orphanet (1): Classic bladder exstrophy (Orphanet:93930)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST012015_1	Chronic rhinosinusitis	3.000000e-06

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D000081029	Pulmonary Arterial Hypertension	C08.381.423.847

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3713453 (SINGLE PROTEIN)

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
propionaldehyde	increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
butyraldehyde	increases methylation	1
caprylic aldehyde	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
pentanal	increases methylation	1
heptanal	increases methylation	1
CGP 52608	affects binding, increases reaction	1
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide	decreases reaction, increases phosphorylation	1
Resveratrol	affects cotreatment, decreases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Endosulfan	increases expression	1
Isoproterenol	decreases reaction, increases expression, decreases response to substance, affects reaction	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C4MS	WAe007-A-2	Embryonic stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE