NMS

Summary

NMS (neuromedin S, HGNC:32203) is a protein-coding gene on chromosome 2q11.2, encoding Neuromedin-S (Q5H8A3). Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.

This gene encodes a member of the neuromedin family of neuropeptides. The encoded preproprotein is proteolytically processed to generate a biologically active neuropeptide that plays a role in the regulation of circadian rhythm, anorexigenic action, antidiuretic action, cardiovascular function and stimulation of oxytocin and vasopressin release.

Source: NCBI Gene 129521 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001011717

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32203
Approved symbol	NMS
Name	neuromedin S
Location	2q11.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204640
Ensembl biotype	protein_coding
OMIM	619337
Entrez	129521

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000376865

RefSeq mRNA: 1 — MANE Select: NM_001011717 NM_001011717

CCDS: CCDS33259

Canonical transcript exons

ENST00000376865 — 10 exons

Exon	Start	End
ENSE00001471963	100483252	100483280
ENSE00001471964	100482277	100482311
ENSE00001471966	100481126	100481167
ENSE00001471967	100480496	100480531
ENSE00001471970	100479353	100479427
ENSE00001471971	100477361	100477414
ENSE00001471972	100477244	100477267
ENSE00001471975	100473489	100473539
ENSE00001471976	100472795	100472850
ENSE00001471978	100470482	100470564

Expression profiles

Bgee: expression breadth broad, 23 present calls, max score 41.96.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	41.96	silver quality
hypothalamus	UBERON:0001898	41.20	gold quality
right testis	UBERON:0004534	37.61	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	36.94	gold quality
left testis	UBERON:0004533	36.68	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
testis	UBERON:0000473	35.87	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
muscle of leg	UBERON:0001383	33.88	gold quality
gastrocnemius	UBERON:0001388	33.69	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
fundus of stomach	UBERON:0001160	30.61	silver quality
prefrontal cortex	UBERON:0000451	30.49	silver quality
leukocyte	CL:0000738	29.87	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
urinary bladder	UBERON:0001255	29.38	silver quality
monocyte	CL:0000576	29.28	silver quality
superior frontal gyrus	UBERON:0002661	28.66	silver quality
frontal cortex	UBERON:0001870	28.26	silver quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
blood	UBERON:0000178	26.57	silver quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 4)

• NMS is implicated in the regulation of circadian rhythm and feeding behavior (PMID:17870195)
• both NMU receptor and peptide are expressed in human cardiovascular tissues and have shown that NMU-25 and NMS act as potent vasoconstrictors in human vascular beds (PMID:18987052)
• In man, NMS elicits vasoconstriction in isolated saphenous vein with comparable potency with NMU, but significantly reduces maximum contractile response. (PMID:19519756)
• Neuromedin s neurons define a subpopulation of pacemakers that control suprachiasmatic nucleus network synchrony. (PMID:25741729)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nms	ENSMUSG00000067604
rattus_norvegicus	NMS	ENSRNOG00000038979

Protein

Protein identifiers

Neuromedin-S — Q5H8A3 (reviewed: Q5H8A3)

All UniProt accessions (2): Q5H8A3, A0A250SI41

UniProt curated annotations — full annotation on UniProt →

Function. Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.

Subcellular location. Secreted.

Similarity. Belongs to the NmU family.

RefSeq proteins (1): NP_001011717* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR018070	Neuromedin-U_amidation-site	PTM
IPR043253	NmS	Family

UniProt features (8 total): propeptide 4, signal peptide 1, peptide 1, modified residue 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
7W56	ELECTRON MICROSCOPY	2.9
7W57	ELECTRON MICROSCOPY	3.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5H8A3-F1	62.61	0.00

Antibody-complex structures (SAbDab): 2 — 7W56, 7W57

Functional residue map

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

Post-translational modifications (1): 141

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-416476	G alpha (q) signalling events
R-HSA-418594	G alpha (i) signalling events

MSigDB gene sets: 17 (showing top): REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, REACTOME_CLASS_A_1_RHODOPSIN_LIKE_RECEPTORS, REACTOME_G_ALPHA_Q_SIGNALLING_EVENTS, chr2q11, GOBP_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, KINNEY_DNMT1_METHYLATION_TARGETS, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, WP_CIRCADIAN_RHYTHM_GENES, REACTOME_GPCR_LIGAND_BINDING, REACTOME_G_ALPHA_I_SIGNALLING_EVENTS, GSE7218_UNSTIM_VS_ANTIGEN_STIM_THROUGH_IGM_BCELL_UP, GOBP_NEUROPEPTIDE_SIGNALING_PATHWAY, REACTOME_SIGNALING_BY_GPCR, GSE37605_TREG_VS_TCONV_C57BL6_FOXP3_IRES_GFP_UP, GSE37605_C57BL6_VS_NOD_FOXP3_FUSION_GFP_TREG_UP

GO Biological Process (1): neuropeptide signaling pathway (GO:0007218)

GO Molecular Function (0):

GO Cellular Component (1): extracellular region (GO:0005576)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
GPCR downstream signalling	2
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
cellular anatomical structure	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NMS	NMUR2	Q9GZQ4	978
NMS	NMUR1	Q9HB89	972
NMS	NMB	P08949	620
NMS	GRP	P07491	605
NMS	NPS	P0C0P6	583
NMS	NPB	Q8NG41	545
NMS	PRLH	P81277	512
NMS	VIP	P01282	512
NMS	PROK2	Q9HC23	499
NMS	NMU	P48645	493
NMS	VIPR2	P41587	476
NMS	NTS	P30990	469
NMS	NPW	Q8N729	464
NMS	TOR2A	Q5JU69	432
NMS	NPY	P01303	423

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NMS	MANBA	psi-mi:“MI:0914”(association)	0.350

BioGRID (26): COL14A1 (Affinity Capture-MS), CERCAM (Affinity Capture-MS), TCTN1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), FUT11 (Affinity Capture-MS), NLGN2 (Affinity Capture-MS), GPR98 (Affinity Capture-MS), LRP1B (Affinity Capture-MS), BCHE (Affinity Capture-MS), MANBA (Affinity Capture-MS), FRAS1 (Affinity Capture-MS), WDR47 (Affinity Capture-MS), UBAC1 (Affinity Capture-MS), PCYOX1L (Affinity Capture-MS), CD109 (Affinity Capture-MS)

ESM2 similar proteins: A0A077DF94, D2Z1D6, D6WT67, E2A3M7, E2E4E4, E2E4L2, E7EZ53, F1QQI2, I7C2V3, O42471, O96690, P07808, P08947, P08948, P0DQF0, P0DQY8, P15743, P16043, P16240, P28672, P28673, P33439, P33689, P43443, P51919, P57774, P70074, P81401, P84213, P85527, Q0VBW8, Q0VC44, Q1HA14, Q1HA20, Q29B55, Q4QXT8, Q4V645, Q5H8A1, Q5H8A3, Q91330

Diamond homologs: P12760, P48645, P81872, Q0VBW8, Q5H8A1, Q5H8A2, Q5H8A3, Q9QXK8, P34962, P34964, P34965, P20056, Q1HA14, Q1HA20, Q4QXT8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
NMS	up-regulates	NMUR1	binding
NMS	up-regulates	NMUR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1303 predictions. Top by Δscore:

Variant	Effect	Δscore
2:100472866:GTAAT:G	donor_gain	1.0000
2:100477359:A:AG	acceptor_gain	1.0000
2:100477360:G:GA	acceptor_gain	1.0000
2:100477360:GTT:G	acceptor_gain	1.0000
2:100477360:GTTTT:G	acceptor_gain	1.0000
2:100479350:CA:C	acceptor_loss	1.0000
2:100479351:A:AC	acceptor_loss	1.0000
2:100479351:A:AG	acceptor_gain	1.0000
2:100479352:G:GG	acceptor_gain	1.0000
2:100479352:GT:G	acceptor_gain	1.0000
2:100479424:GCGA:G	donor_gain	1.0000
2:100479425:CGA:C	donor_gain	1.0000
2:100479425:CGAGT:C	donor_loss	1.0000
2:100479426:GA:G	donor_gain	1.0000
2:100479426:GAG:G	donor_gain	1.0000
2:100479427:AGT:A	donor_loss	1.0000
2:100479428:G:GG	donor_gain	1.0000
2:100479428:GTAC:G	donor_loss	1.0000
2:100480490:TTGCA:T	acceptor_loss	1.0000
2:100480491:TGCA:T	acceptor_loss	1.0000
2:100480492:GCA:G	acceptor_loss	1.0000
2:100480493:CAG:C	acceptor_loss	1.0000
2:100480494:A:AG	acceptor_gain	1.0000
2:100480494:A:AT	acceptor_loss	1.0000
2:100480494:AG:A	acceptor_gain	1.0000
2:100480495:G:A	acceptor_loss	1.0000
2:100480495:G:GG	acceptor_gain	1.0000
2:100480495:GG:G	acceptor_gain	1.0000
2:100480591:G:GT	donor_gain	1.0000
2:100480658:GACCC:G	donor_gain	1.0000

AlphaMissense

1001 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:100477367:T:C	F72L	0.971
2:100477369:T:A	F72L	0.971
2:100477369:T:G	F72L	0.971
2:100477361:T:C	F70L	0.967
2:100477363:T:A	F70L	0.967
2:100477363:T:G	F70L	0.967
2:100481162:T:C	F137L	0.943
2:100481164:C:A	F137L	0.943
2:100481164:C:G	F137L	0.943
2:100477263:A:T	K68I	0.925
2:100477264:A:C	K68N	0.924
2:100477264:A:T	K68N	0.924
2:100477362:T:C	F70S	0.916
2:100477368:T:C	F72S	0.890
2:100481156:T:C	F135L	0.890
2:100481158:C:A	F135L	0.890
2:100481158:C:G	F135L	0.890
2:100482282:G:C	R140S	0.888
2:100482282:G:T	R140S	0.888
2:100481153:T:C	F134L	0.876
2:100481155:T:A	F134L	0.876
2:100481155:T:G	F134L	0.876
2:100481167:G:C	R138S	0.867
2:100481167:G:T	R138S	0.867
2:100477362:T:G	F70C	0.858
2:100477365:T:C	L71S	0.852
2:100477367:T:G	F72V	0.839
2:100477368:T:G	F72C	0.835
2:100477372:C:A	H73Q	0.830
2:100477372:C:G	H73Q	0.830

dbSNP variants (sampled 300 via entrez): RS1000055394 (2:100475166 G>A,C), RS1000174363 (2:100471942 C>A,T), RS1000345900 (2:100477437 C>A), RS1000395533 (2:100480118 G>A), RS1000411578 (2:100483453 A>G,T), RS1000938062 (2:100474073 G>A), RS1000938728 (2:100473815 A>G), RS1001598177 (2:100469411 GA>G,GAA), RS1001662229 (2:100478335 T>C), RS1001681620 (2:100472269 A>G), RS1001778265 (2:100478062 A>G), RS1002048651 (2:100469635 C>G), RS1002222944 (2:100482649 C>G), RS1002435226 (2:100473447 C>A,T), RS1002487824 (2:100473711 CTT>C)

Disease associations

OMIM: gene MIM:619337 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST002598_48	Educational attainment	8.000000e-06
GCST006922_7	Regular attendance at a religious group	3.000000e-11
GCST007155_1	Household income	2.000000e-08
GCST009524_101	Household income (MTAG)	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004784	self reported educational attainment
EFO:0009592	social interaction measurement
EFO:0009695	household income

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
2-palmitoylglycerol	increases expression	1
Benzo(a)pyrene	increases methylation	1

Clinical trials (associated diseases)

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