ADM

Summary

ADM (adrenomedullin, HGNC:259) is a protein-coding gene on chromosome 11p15.4, encoding Pro-adrenomedullin (P35318). Adrenomedullin/ADM and proadrenomedullin N-20 terminal peptide/PAMP are peptide hormones that act as potent hypotensive and vasodilatator agents.

The protein encoded by this gene is a preprohormone which is cleaved to form two biologically active peptides, adrenomedullin and proadrenomedullin N-terminal 20 peptide. Adrenomedullin is a 52 aa peptide with several functions, including vasodilation, regulation of hormone secretion, promotion of angiogenesis, and antimicrobial activity. The antimicrobial activity is antibacterial, as the peptide has been shown to kill E. coli and S. aureus at low concentration.

Source: NCBI Gene 133 — RefSeq curated summary.

At a glance

• GWAS associations: 17
• Clinical variants (ClinVar): 34 total — 1 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_001124

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:259
Approved symbol	ADM
Name	adrenomedullin
Location	11p15.4
Locus type	gene with protein product
Status	Approved
Aliases	AM
Ensembl gene	ENSG00000148926
Ensembl biotype	protein_coding
OMIM	103275
Entrez	133

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 14 protein_coding

ENST00000278175, ENST00000524948, ENST00000525063, ENST00000526492, ENST00000528544, ENST00000528655, ENST00000530439, ENST00000534464, ENST00000879128, ENST00000879129, ENST00000912086, ENST00000912087, ENST00000963835, ENST00000963836

RefSeq mRNA: 1 — MANE Select: NM_001124 NM_001124

CCDS: CCDS7801

Canonical transcript exons

ENST00000278175 — 4 exons

Exon	Start	End
ENSE00000988124	10305680	10305798
ENSE00000988125	10305949	10306098
ENSE00002156887	10306332	10307397
ENSE00002194755	10305073	10305229

Expression profiles

Bgee: expression breadth ubiquitous, 288 present calls, max score 99.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 107.3058 / max 1932.6086, expressed in 1665 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
113020	106.0339	1665
113025	0.7437	401
113023	0.2076	103
113026	0.0995	26
113022	0.0960	33
113021	0.0907	37
113024	0.0344	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
vena cava	UBERON:0004087	99.76	gold quality
type B pancreatic cell	CL:0000169	99.62	gold quality
pericardium	UBERON:0002407	99.60	gold quality
cartilage tissue	UBERON:0002418	99.39	gold quality
saphenous vein	UBERON:0007318	99.05	gold quality
penis	UBERON:0000989	98.78	gold quality
stromal cell of endometrium	CL:0002255	98.76	gold quality
placenta	UBERON:0001987	98.49	gold quality
decidua	UBERON:0002450	98.49	gold quality
synovial joint	UBERON:0002217	98.48	gold quality
renal glomerulus	UBERON:0000074	98.45	gold quality
esophagus squamous epithelium	UBERON:0006920	98.44	gold quality
metanephric glomerulus	UBERON:0004736	98.31	gold quality
squamous epithelium	UBERON:0006914	98.18	gold quality
omental fat pad	UBERON:0010414	98.11	gold quality
subcutaneous adipose tissue	UBERON:0002190	98.10	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.06	gold quality
peritoneum	UBERON:0002358	98.05	gold quality
adipose tissue	UBERON:0001013	97.92	gold quality
amniotic fluid	UBERON:0000173	97.66	gold quality
gingival epithelium	UBERON:0001949	97.66	gold quality
connective tissue	UBERON:0002384	97.48	gold quality
cervix squamous epithelium	UBERON:0006922	97.42	gold quality
nephron tubule	UBERON:0001231	97.38	gold quality
epithelium of esophagus	UBERON:0001976	97.36	gold quality
pharyngeal mucosa	UBERON:0000355	97.16	gold quality
olfactory bulb	UBERON:0002264	97.13	gold quality
trachea	UBERON:0003126	97.05	gold quality
skin of leg	UBERON:0001511	96.68	gold quality
gingiva	UBERON:0001828	96.68	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	2135.85
E-MTAB-6701	yes	1959.91
E-MTAB-6108	yes	1835.24
E-GEOD-114530	yes	1438.83
E-MTAB-10283	yes	1021.03
E-MTAB-9388	yes	972.89
E-MTAB-10018	yes	358.83
E-ENAD-21	yes	287.48
E-GEOD-135922	yes	50.41
E-MTAB-10553	yes	42.85
E-MTAB-10137	no	1620.15
E-ENAD-17	no	270.43
E-MTAB-6911	no	87.51
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, CREB1, DMTF1, EPAS1, FOXO1, GTF3A, HIF1A, IRF6, KLF15, KLF2, LHX2, MYC, NR3C1, SP1, SPIC, STAT3, TBXT, TFAP2A

miRNA regulators (miRDB)

71 targeting ADM, 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-3924	100.00	72.09	2394
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 40)

• Adrenomedullin has broad bacteriocidal activity against gram-positive and gram-negative bacteria. (PMID:10225288)
• Endogenous ADM system plays a potentially important role in the paracrine or autocrine functional control of Conn’s adenomas. (PMID:11712085)
• Adrenomedullin increases cycl AMP through amylin and CGRP1 receptors. (PMID:11744163)
• There were evident postburn changes in plasma adrenomedullin(ADM) contents, and the results implied that ADM played some roles in the development of postburn physiological disturbance. (PMID:11774814)
• role in microvasculature - review (PMID:11879669)
• data show a reduction of adrenomedullin and CGRP mRNAs in placenta specimens of women with preeclampsia or HELLP syndrome (PMID:11905404)
• role in carcinogenesis - review (PMID:11921362)
• role in the inflammatory response - review (PMID:11921363)
• The cardiovascular response in sepsis: proposed mechanisms of the beneficial effect of adrenomedullin and its binding protein (review). (PMID:11956648)
• the heart and the lungs release adrenomedullin peptides in moderate congestive heart failure and this secretion breaks down in severe CHF (PMID:11972292)
• Follicular fluid adrenomedullin concentrations in spontaneous and stimulated cycles are relationed to ovarian function and endothelin-1 and nitric oxide. (PMID:12137974)
• Cells that overexpressed adrenomedullin displayed a more pleiotropic morphology, an increased angiogenic potential both in vitro and in vivo, and less apoptosis after serum deprivation. (PMID:12189226)
• results indicate that adrenomedullin (AM) inhibits doxorubicin-induced cardiac myocyte apoptosis through a cAMP-dependent mechanism and suggest that augmented production of AM by doxorubicin has an endogenous antiapoptotic effect (PMID:12193565)
• Release of this peptide into the blood is affected by exercise and altitude (PMID:12220731)
• The mature form of adrenomedullin is pathophysiologically significant as a useful marker of circulating blood volume in hemodialysis patients. (PMID:12324915)
• concentrations of mature adrenomedullin were elevated in pregnant women compared with non-pregnant women and its concentration in the third trimester was significantly higher than that in the first trimester (PMID:12375542)
• The changes of plasma ADM and PAMP concentrations at different stages of CHF indicate intramolecular regulation disturbances of vasodilator peptides of proadrenomedullin, and ADM may play a more important role in the development of CHF. (PMID:12376296)
• Immunoreactive-AM levels in the aqueous humor were significantly elevated in patients with uveitis and vitroretinal disorders and may be involved in the physiopathology of the uveitis and some vitreoretinal disorders. (PMID:12383875)
• plasma levels of AM, atrial natriuretic peptide(ANP)and brain natriuretic peptide (BNP)increased with aging; ANP and BNP increased in association with pulse pressure; possible relation between levels and age-related changes in cardiovascular system (PMID:12484513)
• Responses to CGRP and ADM are mediated by CGRP(8-37)-sensitive receptors and that the endothelial ADM receptor induces vasodilation by a nitric oxide-guanylyl cyclase mechanism, whereas a smooth muscle CGRP receptor signals by a cAMP-dependent mechanism (PMID:12529288)
• ratio of mature AM/total AM was significantly decreased in the fetal membranes of the patients with chorioamnionitis compared with normal pregnancies, but not in the placenta; results suggested that mature AM may have some role in chorioamnionitis (PMID:12565880)
• Novel correlation of adrenomedullin and aquaporin 2(AQP2) which overlays an AVP-AQP2 system may play a key role in fluid homeostasis during general anesthesia. (PMID:12566732)
• Data show that mean values of plasma total nitrite and adrenomedullin levels in the autistic children are significantly higher than control values. (PMID:12579522)
• In patients with primary hyperparathyroidism, plasma adrenomedullin concentrations are increased and correlate with serum intact parathyroid hormone and blood pressure values. (PMID:12601625)
• adrenomedullin promotes proliferation and migration of vascular endothelial cells via a cAMP/PKA dependent pathway (PMID:12630817)
• existence of the 19-repeat allele is associated with genetic predispositions to develop essential hypertension and diabetic nephropathy. (PMID:12630823)
• decreased levels of AMBP-1 play a critical role in producing vascular AM (adrenomedullin) hyporesponsiveness during the late stage of sepsis (AMBP-1) (PMID:12643861)
• adrenomedullin has an autocrine/paracrine type of anti-proliferative effect via a cAMP-dependent pathway and may play a role in the local modulation of a process of de-differentiation by culturing chondrocyte phenotype cells (PMID:12646214)
• Increase in AM expression in endometrium may be responsible for frequent occurrence of irregular bleeding during initial 3 months of levonorgestrel-releasing intra-uterine system use. (PMID:12660258)
• Data show that an endogenous adrenomedullin system promotes the growth of keratinocytes and fibroblasts cultured in vitro, by enhancing their proliferative activity and lowering their apoptotic deletion. (PMID:12684703)
• AM levels were increased in bladder in children with detrusor instability (PMID:12687457)
• Increased oxidative stress is associated with elevated blood adrenomedullin levels in hypertensive NIDDM patients. (PMID:12716843)
• The expression of adrenomedullin in invasive squamous cell carcinoma of the cervix may crucial role in promoting carcinoma progression. (PMID:12720100)
• The microsatellite DNA polymorphism of AM gene may be associated with the genetic predisposition to develop nephropathy in Japanese patients with type 2 diabetes mellitus. (PMID:12753312)
• Adrenomedullin is increased after liver transplant with increased creatinine and atrial natriuretic peptide, suggesting a potential role for ADM in volume regulation after liver transplantation. (PMID:12763641)
• AM plays significant roles in vascular regeneration, associated with PKA- and PI3K-dependent activation of Akt in endothelial cells, and possesses therapeutic potential for vascular injury and tissue ischemia (PMID:12782295)
• Adrenomedullin protects against myocardial infarction, arrhythmia, and apoptosis in ischemia and reperfusion injury via suppression of oxidative stress-induced Bax and p38 MAPK phosphorylation and activation of the Akt-Bad-Bcl-2 signaling pathway. (PMID:12805025)
• Transplantation of adrenomedullin gene-transduced endothelial progenitor cells [EPCs] caused greater improvement in pulmonary hypertension in MCT rats than transplantation of EPCs alone (PMID:12835224)
• Gastric epithelial cells exposed to inflammatory cytokines, Helicobacter pylori, E. coli, S. enterica, or Streptococcus bovis increased adrenomedullin expression & secretion. Epithelial infection, inflammation, & adrenomedullin expression are associated. (PMID:12853384)
• Human adrenomedullin produced a significant decrease in rat heart contractile force and perfusion pressure, but only amylin fragment 8-37 caused a decline in heart rate at the highest dose. (PMID:12903912)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	adma	ENSDARG00000015263
danio_rerio	admb	ENSDARG00000069027
mus_musculus	Adm	ENSMUSG00000030790
rattus_norvegicus	Adm	ENSRNOG00000027030

Paralogs (1): ADM2 (ENSG00000128165)

Protein

Protein identifiers

Pro-adrenomedullin — P35318 (reviewed: P35318)

All UniProt accessions (5): P35318, E9PL83, E9PML4, E9PQE6, E9PQT2

UniProt curated annotations — full annotation on UniProt →

Function. Adrenomedullin/ADM and proadrenomedullin N-20 terminal peptide/PAMP are peptide hormones that act as potent hypotensive and vasodilatator agents. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, ADM is diuretic and natriuretic, and both ADM and PAMP inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels. Peptide hormone that act as potent hypotensive and vasodilatator agents. ADM function is mediated by the CALCRL-RAMP2 and CALCRL-RAMP3 receptor complexes with ADM showing the highest potency for the CALCRL-RAMP2 complex. Peptide hormone that act as potent hypotensive and vasodilatator agents by inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells. Acts as a ligand for MRGPRX2 receptor in mast cells. Peptide hormone that act as potent hypotensive and vasodilatator agents by inhibiting catecholamine secretion from sympathetic nerve endings and adrenal chromaffin cells. Acts as a ligand for MRGPRX2 receptor in mast cells.

Subcellular location. Secreted.

Tissue specificity. Highest levels found in pheochromocytoma and adrenal medulla. Also found in lung, ventricle and kidney tissues.

Similarity. Belongs to the adrenomedullin family.

RefSeq proteins (1): NP_001115* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001710	Pro-ADM	Family
IPR021116	Calcitonin/adrenomedullin	Family
IPR051665	Adrenomedullin-reg_peptide	Family

Pfam: PF00214

UniProt features (21 total): peptide 3, helix 3, strand 3, modified residue 2, sequence variant 2, propeptide 2, region of interest 2, site 2, signal peptide 1, disulfide bond 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
4RWF	X-RAY DIFFRACTION	1.76
6V2E	X-RAY DIFFRACTION	1.83
6UUS	ELECTRON MICROSCOPY	2.4
5V6Y	X-RAY DIFFRACTION	2.8
6UUN	ELECTRON MICROSCOPY	3
7VV0	ELECTRON MICROSCOPY	3.5
2FLY	SOLUTION NMR
2L7S	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P35318-F1	62.35	0.00

Antibody-complex structures (SAbDab): 2 — 6UUN, 6UUS

Functional residue map

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

Catalytic / active sites (2): 116 (required for calcrl receptor interaction); 125 (required for calcrl receptor interaction)

Post-translational modifications (2): 41, 146

Disulfide bonds (1): 110–115

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-418555	G alpha (s) signalling events
R-HSA-419812	Calcitonin-like ligand receptors
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 604 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_G_PROTEIN_COUPLED_RECEPTOR_INTERNALIZATION, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, LI_CISPLATIN_RESISTANCE_DN, MODULE_416, MODULE_92, GOBP_REGULATION_OF_VASCULOGENESIS, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, MCLACHLAN_DENTAL_CARIES_UP, GOBP_REGULATION_OF_BLOOD_PRESSURE, HARRIS_HYPOXIA, GOBP_CIRCULATORY_SYSTEM_PROCESS

GO Biological Process (23): vasculogenesis (GO:0001570), neural tube closure (GO:0001843), G protein-coupled receptor internalization (GO:0002031), regulation of systemic arterial blood pressure (GO:0003073), inflammatory response (GO:0006954), signal transduction (GO:0007165), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), heart development (GO:0007507), cell population proliferation (GO:0008283), positive regulation of cell population proliferation (GO:0008284), positive regulation of heart rate (GO:0010460), receptor internalization (GO:0031623), regulation of urine volume (GO:0035809), negative regulation of vascular permeability (GO:0043116), positive regulation of angiogenesis (GO:0045766), negative regulation of vasoconstriction (GO:0045906), developmental growth (GO:0048589), branching involved in labyrinthine layer morphogenesis (GO:0060670), vascular associated smooth muscle cell development (GO:0097084), adrenomedullin receptor signaling pathway (GO:1990410), positive regulation of progesterone biosynthetic process (GO:2000184), positive regulation of vasculogenesis (GO:2001214), calcitonin family receptor signaling pathway (GO:0097646)

GO Molecular Function (4): signaling receptor binding (GO:0005102), hormone activity (GO:0005179), adrenomedullin receptor binding (GO:0031700), receptor ligand activity (GO:0048018)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), secretory granule lumen (GO:0034774)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Signaling by GPCR	2
GPCR downstream signalling	1
Class B/2 (Secretin family receptors)	1
Response of endothelial cells to shear stress	1
Signal Transduction	1
GPCR ligand binding	1
Cellular responses to stimuli	1
Cellular responses to mechanical stimuli	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	2
cellular anatomical structure	2
cell differentiation	1
blood vessel morphogenesis	1
primary neural tube formation	1
tube closure	1
desensitization of G protein-coupled receptor signaling pathway	1
receptor internalization	1
regulation of blood pressure	1
defense response	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
animal organ development	1
circulatory system development	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of heart rate	1
positive regulation of heart contraction	1
receptor-mediated endocytosis	1
renal system process	1
regulation of body fluid levels	1
regulation of vascular permeability	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
regulation of vasoconstriction	1
vasoconstriction	1
negative regulation of multicellular organismal process	1
developmental process	1
growth	1
embryonic morphogenesis	1
labyrinthine layer morphogenesis	1
morphogenesis of a branching epithelium	1
vascular associated smooth muscle cell differentiation	1
muscle cell development	1

Protein interactions and networks

STRING

1422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ADM	RAMP3	O60896	999
ADM	RAMP2	O60895	999
ADM	CALCRL	Q16602	999
ADM	RAMP1	O60894	976
ADM	ACKR5	O15218	961
ADM	IAPP	P10997	946
ADM	CALCB	P10092	918
ADM	CALCR	P30988	917
ADM	ADM2	Q7Z4H4	881
ADM	ACKR3	P25106	871
ADM	REN	P00797	861
ADM	NPPA	P01160	858
ADM	CALCA	P01258	831
ADM	EDN1	P05305	830
ADM	CRCP	O75575	819

IntAct

2 interactions, top by confidence:

A	B	Type	Score
ADM	NAP1L5	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (8): DPYS (Affinity Capture-MS), ADM (Affinity Capture-RNA), NAP1L5 (Affinity Capture-MS), ADM (Reconstituted Complex), ADM (Two-hybrid), ADM (Affinity Capture-MS), ADM (Affinity Capture-RNA), ADM (Affinity Capture-MS)

ESM2 similar proteins: O00230, O00253, O14836, O46541, O62827, O77559, P01160, P01169, P07499, P0C8A3, P0C8S2, P0CG36, P0CG37, P13204, P16859, P18104, P23582, P24393, P35318, P47851, P49192, P51461, P53366, P55206, P55207, P56283, P56388, P56413, P56473, P81172, P81277, P84715, P97297, Q5CZK2, Q5NVR8, Q61839, Q62715, Q62716, Q6PAL1, Q7TNK8

Diamond homologs: O62827, O77559, P35318, P43145, P53366, P97297

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
ADM	“up-regulates activity”	“Adrenomedullin receptor AM2 complex”	binding
ADM	“up-regulates activity”	“Adrenomedullin receptor AM1 complex”	binding
DMTF1	“up-regulates quantity by expression”	ADM	“transcriptional regulation”
CEBPB	“up-regulates quantity by expression”	ADM	“transcriptional regulation”
TFAP2A	“up-regulates quantity by expression”	ADM	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	23
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
147607	GRCh38/hg38 11p15.4-15.2(chr11:9989516-16825806)x1	Pathogenic

SpliceAI

223 predictions. Top by Δscore:

Variant	Effect	Δscore
11:10305676:CCAG:C	acceptor_gain	1.0000
11:10305676:CCAGG:C	acceptor_loss	1.0000
11:10305677:CAGG:C	acceptor_gain	1.0000
11:10305678:A:AC	acceptor_loss	1.0000
11:10305678:A:AG	acceptor_gain	1.0000
11:10305678:AG:A	acceptor_gain	1.0000
11:10305678:AGG:A	acceptor_gain	1.0000
11:10305678:AGGGT:A	acceptor_gain	1.0000
11:10305679:G:A	acceptor_gain	1.0000
11:10305679:G:GC	acceptor_gain	1.0000
11:10305679:G:T	acceptor_gain	1.0000
11:10305679:GGG:G	acceptor_gain	1.0000
11:10305679:GGGT:G	acceptor_gain	1.0000
11:10305679:GGGTC:G	acceptor_gain	1.0000
11:10305794:AAGAA:A	donor_gain	1.0000
11:10305795:AGAA:A	donor_gain	1.0000
11:10305796:G:GT	donor_gain	1.0000
11:10305796:GAA:G	donor_gain	1.0000
11:10305797:AA:A	donor_gain	1.0000
11:10305798:AG:A	donor_loss	1.0000
11:10305799:G:GG	donor_gain	1.0000
11:10305939:T:TA	acceptor_gain	1.0000
11:10305944:TCCA:T	acceptor_loss	1.0000
11:10305945:CCAG:C	acceptor_loss	1.0000
11:10305947:A:AG	acceptor_gain	1.0000
11:10305947:AG:A	acceptor_gain	1.0000
11:10305947:AGGT:A	acceptor_gain	1.0000
11:10305947:AGGTG:A	acceptor_gain	1.0000
11:10305948:G:GA	acceptor_gain	1.0000
11:10305948:GG:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000068140 (11:10304362 C>T), RS1000453457 (11:10305646 G>A,C,T), RS1000505179 (11:10305431 T>A,G), RS1002195794 (11:10303858 A>C), RS1003676074 (11:10307667 G>A), RS1004026634 (11:10305169 T>C), RS1004066005 (11:10306376 G>A,C), RS1004417819 (11:10306707 G>A,C), RS1005293734 (11:10307720 G>T), RS1005649769 (11:10303827 A>C,T), RS1007474908 (11:10307215 C>A,T), RS1007529303 (11:10306779 G>A,C), RS1007902341 (11:10307802 C>A,G), RS1008284084 (11:10305583 A>C), RS1008754046 (11:10303755 A>G)

Disease associations

OMIM: gene MIM:103275 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000755_10	HDL cholesterol	5.000000e-08
GCST000774_1	Schizophrenia, bipolar disorder and depression (combined)	4.000000e-08
GCST001227_2	Systolic blood pressure	3.000000e-12
GCST001228_2	Diastolic blood pressure	6.000000e-08
GCST001235_10	Blood pressure	4.000000e-07
GCST001853_7	Circulating vasoactive peptide levels	1.000000e-12
GCST003770_37	Neuroticism	3.000000e-09
GCST006258_19	Diastolic blood pressure	4.000000e-08
GCST006259_3	Systolic blood pressure	3.000000e-12
GCST007094_206	Diastolic blood pressure	2.000000e-13
GCST007095_36	Systolic blood pressure	5.000000e-07
GCST007095_37	Systolic blood pressure	6.000000e-06
GCST007096_138	Pulse pressure	6.000000e-13
GCST007099_144	Systolic blood pressure	1.000000e-20
GCST008362_2	Birth weight	3.000000e-15
GCST009731_26	Blood protein levels in cardiovascular risk	7.000000e-14
GCST011346_65	Total cholesterol levels	4.000000e-08

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0005196	vasoactive peptide measurement
EFO:0007660	neuroticism measurement
EFO:0004344	birth weight
EFO:0010627	pro‐adrenomedullin measurement
EFO:0004574	total cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2062356 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11042725	Efficacy	3	paroxetine	Major Depressive Disorder

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11042725	ADM, SBF2	3	3.25	1	paroxetine

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Oxygen	increases expression, increases reaction, decreases reaction	10
Valproic Acid	decreases reaction, increases expression, affects expression, decreases expression, increases methylation	8
Benzo(a)pyrene	increases expression, increases methylation	7
cobaltous chloride	decreases reaction, increases expression, increases secretion	6
Estradiol	decreases reaction, increases secretion, affects expression, affects binding, decreases expression (+2 more)	5
Tetrachlorodibenzodioxin	decreases reaction, increases expression	4
Tretinoin	decreases expression, increases expression	4
Particulate Matter	affects expression, increases reaction, increases expression, decreases expression, increases abundance	4
methylmercuric chloride	decreases expression, increases expression	3
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
nickel chloride	increases expression	3
Cisplatin	affects expression, increases expression	3
Tobacco Smoke Pollution	increases expression	3
tert-Butylhydroperoxide	affects cotreatment, increases expression, decreases reaction	3
arsenite	increases expression, affects binding, increases reaction, increases abundance	2
manganese chloride	affects cotreatment, increases abundance, increases expression	2
nickel sulfate	decreases expression, increases expression	2
Arsenic Trioxide	decreases reaction, decreases expression, increases expression	2
Acetaminophen	increases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance	2
Arsenic	increases methylation, affects cotreatment, increases abundance, increases expression	2
Vehicle Emissions	increases expression, affects expression, increases reaction, increases abundance	2
Copper	increases expression, affects binding, decreases expression	2
Dexamethasone	increases expression	2
Hydrogen Peroxide	affects expression, increases expression	2
Manganese	increases abundance, increases expression, affects cotreatment	2
Ozone	affects cotreatment, decreases expression, increases abundance, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silver	increases expression	2
Cyclosporine	decreases expression, increases expression	2

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2067245	Binding	Binding affinity to human synthetic proadrenomedullin N-terminal 20 peptide assessed as reduction in absorbance at 1 uM after 1 hr by monoclonal antibody method	Identification of first proadrenomedullin N-terminal 20 peptide (PAMP) modulator by means of virtual screening and NMR interaction experiments. — Eur J Med Chem

Clinical trials (associated diseases)

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