PMCH

Summary

PMCH (pro-melanin concentrating hormone, HGNC:9109) is a protein-coding gene on chromosome 12q23.2, encoding Pro-MCH (P20382). MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal.

This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include melanin-concentrating hormone (MCH), neuropeptide-glutamic acid-isoleucine (NEI), and neuropeptide-glycine-glutamic acid (NGE). Melanin-concentrating hormone is a 19-amino acid neuropeptide that stimulates hunger and may additionally regulate energy homeostasis, reproductive function, and sleep. Pseudogenes of this gene have been identified on chromosome 5.

Source: NCBI Gene 5367 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_002674

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9109
Approved symbol	PMCH
Name	pro-melanin concentrating hormone
Location	12q23.2
Locus type	gene with protein product
Status	Approved
Aliases	MCH
Ensembl gene	ENSG00000183395
Ensembl biotype	protein_coding
OMIM	176795
Entrez	5367

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000329406

RefSeq mRNA: 1 — MANE Select: NM_002674 NM_002674

CCDS: CCDS31885

Canonical transcript exons

ENST00000329406 — 3 exons

Exon	Start	End
ENSE00001300598	102197522	102197833
ENSE00001305011	102196459	102196701
ENSE00001326024	102196973	102197171

Expression profiles

Bgee: expression breadth ubiquitous, 131 present calls, max score 88.10.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1421 / max 50.3056, expressed in 37 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
132931	0.0832	13
132932	0.0589	28

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hypothalamus	UBERON:0001898	88.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.48	silver quality
cartilage tissue	UBERON:0002418	70.98	gold quality
endometrium epithelium	UBERON:0004811	63.81	gold quality
mucosa of stomach	UBERON:0001199	62.88	gold quality
sperm	CL:0000019	60.37	gold quality
male germ cell	CL:0000015	59.72	gold quality
mucosa of urinary bladder	UBERON:0001259	58.55	silver quality
lymph node	UBERON:0000029	57.14	gold quality
substantia nigra	UBERON:0002038	54.81	gold quality
thymus	UBERON:0002370	54.12	gold quality
midbrain	UBERON:0001891	53.98	gold quality
amygdala	UBERON:0001876	51.91	gold quality
oviduct epithelium	UBERON:0004804	51.08	gold quality
bone marrow	UBERON:0002371	50.58	silver quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
superficial temporal artery	UBERON:0001614	50.24	silver quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
vermiform appendix	UBERON:0001154	49.98	gold quality
ventral tegmental area	UBERON:0002691	49.79	silver quality
quadriceps femoris	UBERON:0001377	49.78	gold quality
vastus lateralis	UBERON:0001379	49.40	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
ganglionic eminence	UBERON:0004023	49.26	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
nasal cavity epithelium	UBERON:0005384	49.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.59

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting PMCH, 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-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-5700	99.64	69.88	2280
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-155-5P	99.35	70.16	1509
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-125B-2-3P	96.69	68.38	1210

Literature-anchored findings (GeneRIF, showing 16)

• Melanin-concentrating hormone is expressed and functional in human skin (PMID:12176038)
• RT-PCR analysis revealed a low expression of prepro-MCH and MCH receptor 1 (MCHR1) but not of MCHR2 transcript in tissular and peripheral blood immune cells (PMID:12220661)
• Review. Melanin-concentrating hormone (MCH) is a cyclic neuropeptide, which centrally regulates food intake and stress. MCH-R1 antagonists can probe additional functions of the peptide, both in the brain and in the peripheral nervous system. (PMID:12885269)
• Serum levels could serve as useful peripheral markers of changes in energy homeostasis. (PMID:15546902)
• hMCH increased water intake independent of food intake. It significantly increased both sucrose solution and food intake. (PMID:15870910)
• Single nucleotide polymorphisms in pro-melanin-concentrating hormone may be associated with obesity and a greater body mass index in olanzapine-treated schizophrenic patients (PMID:17541984)
• expression of PMCH by activated Th2 cells in vivo may directly link allergic inflammation to energy homeostasis and may contribute to the association between asthma and obesity (PMID:17640905)
• The total number of hypocretin-1 neurons was significantly reduced by 30% in HD brains (P = 0.015), while the total number of MCH neurons was not significantly altered (P = 0.100). (PMID:18498421)
• MCH has a role in inflammatory processes in the intestine (PMID:18650383)
• PMCH mRNA expression level was increased 1.85 times (P < 0.01) in vitiligo uninvolved skin and 5.36 times (P < 0.01) in involved skin compared to healthy control skin. (PMID:20888736)
• Melanin-concentrating hormone (MCH) neurons of human hypothalamus, as well as the MCH neurons of mouse hypothalamus, contain IL-6Ralpha. (PMID:22295972)
• the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala, are reported. (PMID:23462990)
• Cerebrospinal fluid (CSF) levels were measured in 33 patients with Alzheimer’s disease (AD) and 33 healthy subjects, to investigate the role of MCH and HCRT-1 in AD. (PMID:23667582)
• MCH is an anabolic neuropeptide with multiple and diverse physiological functions including a key role in energy homoeostasis; evidence suggests that, in the reproductive context, MCH is a modulator rather than a primary regulator. (PMID:23884861)
• Melanin-concentrating hormone and food intake control: Sites of action, peptide interactions, and appetition. (PMID:33370567)
• Melanin-Concentrating Hormone Is Associated With Delayed Neurocognitive Recovery in Older Adult Patients With Preoperative Sleep Disorders Undergoing Spinal Anesthesia. (PMID:38051670)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pmch	ENSDARG00000073959
danio_rerio	pmchl	ENSDARG00000076978
mus_musculus	Pmch	ENSMUSG00000035383
rattus_norvegicus	Pmch	ENSRNOG00000066777

Protein

Protein identifiers

Pro-MCH — P20382 (reviewed: P20382)

All UniProt accessions (1): P20382

UniProt curated annotations — full annotation on UniProt →

Function. MCH may act as a neurotransmitter or neuromodulator in a broad array of neuronal functions directed toward the regulation of goal-directed behavior, such as food intake, and general arousal. May also have a role in spermatocyte differentiation.

Subcellular location. Secreted.

Tissue specificity. Predominantly expressed in lateral hypothalamus, also detected in pallidum, neocortex and cerebellum. Also found in thymus, brown adipose tissue, duodenum and testis (spermatogonia, early spermatocytes and Sertoli cells). No expression in peripheral blood. In brain exclusively mature MCH and NEI peptides are present. In peripheral tissues a large product, encompassing the NEI and MCH domains of the precursor, is found predominantly.

Post-translational modifications. Differentially processed in the brain and in peripheral organs producing two neuropeptides; NEI and MCH. A third peptide, NGE, may also be produced. Preferential processing in neurons by prohormone convertase 2 (PC2) generates NEI. MCH is generated in neurons of the lateral hypothalmic area by several prohormone convertases including PC1/3, PC2 and PC5/6.

Similarity. Belongs to the melanin-concentrating hormone family.

RefSeq proteins (1): NP_002665* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005456	Prepro-melanin_conc_hormone	Family

Pfam: PF05824

UniProt features (12 total): peptide 3, sequence conflict 3, strand 2, signal peptide 1, chain 1, modified residue 1, disulfide bond 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
8WST	ELECTRON MICROSCOPY	2.4
8WWK	ELECTRON MICROSCOPY	2.61
8WWN	ELECTRON MICROSCOPY	2.65
8WWL	ELECTRON MICROSCOPY	2.78
8WWM	ELECTRON MICROSCOPY	2.81
8WSS	ELECTRON MICROSCOPY	3.01

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P20382-F1	57.25	0.00

Antibody-complex structures (SAbDab): 6 — 8WSS, 8WST, 8WWK, 8WWL, 8WWM, 8WWN

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): 143

Disulfide bonds (1): 153–162

Function

Pathways and Gene Ontology

Reactome pathways

8 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
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 109 (showing top): GOBP_BEHAVIOR, GOBP_MALE_GAMETE_GENERATION, FOXO1_01, AAAYRNCTG_UNKNOWN, GRAHAM_CML_QUIESCENT_VS_NORMAL_QUIESCENT_DN, GOBP_CELL_CELL_SIGNALING, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, GOBP_NEGATIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION, HFH8_01, GOBP_SYNAPTIC_TRANSMISSION_DOPAMINERGIC, TGANTCA_AP1_C, GOBP_SYNAPTIC_SIGNALING, HFH1_01, NKX22_01, GOMF_G_PROTEIN_COUPLED_RECEPTOR_BINDING

GO Biological Process (6): neuropeptide signaling pathway (GO:0007218), chemical synaptic transmission (GO:0007268), spermatogenesis (GO:0007283), feeding behavior (GO:0007631), cell differentiation (GO:0030154), negative regulation of synaptic transmission, dopaminergic (GO:0032227)

GO Molecular Function (3): melanin-concentrating hormone activity (GO:0030354), type 1 melanin-concentrating hormone receptor binding (GO:0031777), hormone activity (GO:0005179)

GO Cellular Component (3): extracellular region (GO:0005576), nucleus (GO:0005634), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
GPCR downstream signalling	2
Signaling by GPCR	2
Class A/1 (Rhodopsin-like receptors)	1
Signal Transduction	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	1
anterograde trans-synaptic signaling	1
developmental process involved in reproduction	1
male gamete generation	1
behavior	1
cellular developmental process	1
synaptic transmission, dopaminergic	1
regulation of synaptic transmission, dopaminergic	1
negative regulation of synaptic transmission	1
hormone activity	1
melanin-concentrating hormone receptor binding	1
receptor ligand activity	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
cell junction	1

Protein interactions and networks

STRING

1338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PMCH	MCHR1	Q99705	996
PMCH	MCHR2	Q969V1	996
PMCH	HCRT	O43612	983
PMCH	NPY	P01303	879
PMCH	PARPBP	Q9NWS1	871
PMCH	POMC	P01189	868
PMCH	AGRP	O00253	850
PMCH	CARTPT	Q16568	773
PMCH	LEP	P41159	769
PMCH	PDYN	P01213	760
PMCH	HCRTR1	O43613	755
PMCH	MECP2	P51608	750
PMCH	SCG3	Q8WXD2	749
PMCH	GHRL	Q9UBU3	678
PMCH	GAL	P22466	675
PMCH	CRH	P06850	675

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PMCH	B4GALT5	psi-mi:“MI:0914”(association)	0.350
PMCH	VGF	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): NPY (Phenotypic Enhancement), SULF1 (Affinity Capture-MS), TPST1 (Affinity Capture-MS), VWDE (Affinity Capture-MS), MIB2 (Affinity Capture-MS), BIRC6 (Affinity Capture-MS), HERC2 (Affinity Capture-MS), CDKN2D (Affinity Capture-MS), SERPINC1 (Affinity Capture-MS), MAEA (Affinity Capture-MS), B4GALT5 (Affinity Capture-MS), ITIH2 (Affinity Capture-MS), NPW (Affinity Capture-MS), TMEM59 (Affinity Capture-MS), VGF (Affinity Capture-MS)

ESM2 similar proteins: A8CL69, B2KKR4, B2ZB95, B2ZB96, B2ZB98, B2ZB99, B2ZBA0, B2ZBA1, C0HKS6, C0HKY1, C0HL17, C3Z6E6, D6WT67, E1ZXU8, E1ZZF9, E2AFK9, E2AYH6, G7NYP9, O02036, O18641, O45027, O76818, P01360, P01361, P01362, P07712, P08950, P09040, P09971, P11159, P16240, P17685, P17686, P19713, P20382, P32648, P35905, P49794, P56942, P61364

Diamond homologs: O62688, O62689, O62690, O62691, P14200, P20382, P56942, Q5XXR2, O62692, O62693, O62694, Q16048, Q9BQD1, P17640, P19713, P33745, P49794, P56943, P69155, P69156, P69157

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PMCH	up-regulates	MCHR1	binding
PMCH	up-regulates	MCHR2	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

183 predictions. Top by Δscore:

Variant	Effect	Δscore
12:102196700:CA:C	acceptor_gain	1.0000
12:102196702:C:CC	acceptor_gain	1.0000
12:102197517:CTTA:C	donor_loss	1.0000
12:102197518:TTA:T	donor_loss	1.0000
12:102197519:TACC:T	donor_loss	1.0000
12:102197520:A:AC	donor_gain	1.0000
12:102197520:AC:A	donor_gain	1.0000
12:102197521:C:CT	donor_gain	1.0000
12:102197521:CC:C	donor_gain	1.0000
12:102197521:CCT:C	donor_gain	1.0000
12:102196697:GAGCA:G	acceptor_gain	0.9900
12:102196699:GCA:G	acceptor_gain	0.9900
12:102196700:CAC:C	acceptor_gain	0.9900
12:102196702:CT:C	acceptor_loss	0.9900
12:102196971:A:AC	donor_gain	0.9900
12:102196972:C:CC	donor_gain	0.9900
12:102196972:CTGT:C	donor_gain	0.9900
12:102197521:CCTT:C	donor_gain	0.9900
12:102196698:AGCA:A	acceptor_gain	0.9800
12:102196972:CT:C	donor_gain	0.9800
12:102197521:CCTTT:C	donor_gain	0.9800
12:102196964:ACTAC:A	donor_loss	0.9700
12:102196965:CTACT:C	donor_loss	0.9700
12:102196966:TACTC:T	donor_loss	0.9700
12:102196967:AC:A	donor_loss	0.9700
12:102196968:C:CG	donor_loss	0.9700
12:102196969:TCACT:T	donor_loss	0.9700
12:102196970:C:CC	donor_loss	0.9700
12:102196971:A:T	donor_loss	0.9700
12:102196971:ACTGT:A	donor_gain	0.9700

AlphaMissense

1087 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:102196661:C:A	W163C	0.999
12:102196661:C:G	W163C	0.999
12:102196663:A:G	W163R	0.999
12:102196663:A:T	W163R	0.999
12:102196664:A:C	C162W	0.998
12:102196683:C:A	G156V	0.998
12:102196684:C:G	G156R	0.998
12:102196684:C:T	G156R	0.998
12:102196691:A:C	C153W	0.998
12:102196693:A:G	C153R	0.998
12:102196665:C:T	C162Y	0.997
12:102196666:A:G	C162R	0.997
12:102196683:C:T	G156E	0.997
12:102196692:C:G	C153S	0.997
12:102196693:A:T	C153S	0.997
12:102196981:T:A	D147V	0.997
12:102196692:C:T	C153Y	0.996
12:102196694:T:A	R152S	0.996
12:102196694:T:G	R152S	0.996
12:102196698:A:T	L151H	0.996
12:102196981:T:G	D147A	0.996
12:102196679:T:A	R157S	0.995
12:102196679:T:G	R157S	0.995
12:102196692:C:A	C153F	0.995
12:102196695:C:A	R152I	0.995
12:102196695:C:G	R152T	0.995
12:102196975:T:A	D149V	0.995
12:102196977:A:C	F148L	0.995
12:102196977:A:T	F148L	0.995
12:102196979:A:G	F148L	0.995

dbSNP variants (sampled 300 via entrez): RS1000860445 (12:102197511 T>C), RS1001268466 (12:102198714 C>T), RS1001918834 (12:102199507 C>G,T), RS1002266258 (12:102199144 A>T), RS1003915128 (12:102198736 T>G), RS1007140725 (12:102199514 A>G), RS1007172647 (12:102199778 G>A), RS1008099953 (12:102198652 A>G), RS1008583061 (12:102198187 C>T), RS1009496834 (12:102198200 A>T), RS1009647863 (12:102197265 T>G), RS1009777132 (12:102196820 T>A), RS1010158546 (12:102197850 T>C), RS1010395076 (12:102199042 C>G), RS1013624320 (12:102197179 G>T)

Disease associations

OMIM: gene MIM:176795 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000522_7	Height	8.000000e-06
GCST007324_71	Adventurousness	8.000000e-14
GCST007326_10	Number of sexual partners	2.000000e-08
GCST008476_15	Emphysema annual change measurement in smokers (percent low attenuation area)	9.000000e-06
GCST010703_2	Brain morphology (MOSTest)	3.000000e-37

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0007626	emphysema imaging measurement
EFO:0004346	neuroimaging measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs7973796	Toxicity	3	olanzapine	Schizophrenia

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7973796	PMCH	3	1.50	1	olanzapine
rs11111201	PARPBP, PMCH		0.00	0

CTD chemical–gene interactions

13 total (human), top 13 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
perfluorooctanoic acid	affects cotreatment, increases expression	1
perfluorooctane sulfonic acid	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Allergens	increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Mercury	decreases expression	1
Nickel	increases expression	1
Silicon Dioxide	decreases expression	1
Testosterone	decreases expression, affects cotreatment	1
Thimerosal	increases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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