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POMC

proopiomelanocortin
3 disorders 2 causative 1 no genetic record 2p23.3 gene with protein product
HGNC:9201MonarchNCBI Gene 5443ENSG00000115138UniProt P01189OMIM 176830

Aliases: MSH, POC, CLIP, ACTH, NPP, LPH.

Curated summary · agent-written · kb/genes/curated/hgnc_9201.md
All 16 claims checked against the KB draft

POMC across dismech

POMC (proopiomelanocortin) is named by 3 disorder entries. It encodes proopiomelanocortin, the prohormone cleaved into ACTH, the melanocyte-stimulating hormones and beta-endorphin.

Normal function

The ai-gene-review core functions for POMC include the molecular functions corticotropin hormone receptor binding; hormone activity; opioid peptide activity; type 1 melanocortin receptor binding; type 4 melanocortin receptor binding.

Causative records

The entries that type POMC as causative are Obesity; Obesity Due to MC4R Pathway Disruption. Obesity records the variants as germline and places the gene on the node Hypothalamic Dysregulation. Obesity Due to MC4R Pathway Disruption records them as germline and places the gene on MC4R pathway signaling failure.

Pituitary adenoma

USP8-related pituitary adenoma 4 names POMC on the nodes Increased POMC transcriptional activation and Increased corticotropin secretion, which reach the mechanism module corticotroph_egfr_pomc_acth_activation, but has no genetic record for the gene (USP8-related pituitary adenoma 4).

Where the layers disagree

The KB's mechanism annotations for POMC name the processes adenylate cyclase-activating G protein-coupled receptor signaling pathway; corticotropin secretion; feeding behavior; positive regulation of transcription by RNA polymerase II. None of these is among the gene's ai-gene-review core functions, so the two layers share 0 GO process terms. ClinGen classifies the gene for 0 diseases.

Underlined values are claims re-computed from the knowledge base each time this page is built. The tables below are the source of truth.

Normal function · from ai-gene-review (P01189, commit 79fe13b38970) · AI-generated, not KB evidence

Pro-opiomelanocortin is a paradigm for post-translational polyprotein processing. A single 267 AA precursor is proteolytically cleaved by prohormone convertases (PC1/3, PC2) into multiple bioactive peptides with distinct and sometimes ANTAGONISTIC functions. Key products include ACTH (stimulates cortisol release from adrenal cortex), alpha-MSH (anorexigenic, increases pigmentation via MC1R), beta-endorphin (orexigenic opiate), and met-enkephalin. Critically, tissue-specific processing produces different peptide combinations: anterior pituitary corticotrophs produce mainly ACTH; hypothalamic neurons produce both alpha-MSH (appetite suppression) and beta-endorphin (appetite stimulation). GO annotations at the gene level conflate functions that are peptide-specific - ideally annotations should use PRO ontology IDs for peptide-specific functions. POMC mutations cause obesity with adrenal insufficiency and red hair (PMID:9620771).

Serves as a polyprotein precursor that is proteolytically processed by prohormone convertases (PC1/PC3, PC2) in a tissue-specific manner to generate multiple bioactive neuropeptide hormones including ACTH, melanocyte-stimulating hormones (alpha-, beta-, gamma-MSH), beta-endorphin, and beta-lipotropin. Processing occurs in secretory granules within neuroendocrine cells of the pituitary and hypothalamus.
molecular function: hormone activity · directly involved in: neuropeptide signaling pathway; peptide hormone processing · locations: secretory granule lumen; secretory granule; extracellular region · anatomical locations: adenohypophysis; hypothalamus
Regulates the hypothalamic-pituitary-adrenal (HPA) axis via the cleavage product ACTH (corticotropin, residues 138-176). ACTH binds MC2R (corticotropin receptor) on adrenal cortex cells to stimulate glucocorticoid (cortisol in humans) secretion. Loss of POMC causes isolated ACTH deficiency with secondary adrenal insufficiency.
molecular function: corticotropin hormone receptor binding · directly involved in: positive regulation of glucocorticoid secretion; positive regulation of cortisol secretion; cell-cell signaling · locations: extracellular region · anatomical locations: adenohypophysis; adrenal cortex
Suppresses appetite and promotes negative energy balance via the cleavage product alpha-MSH (melanotropin alpha, residues 138-150). In hypothalamic arcuate nucleus POMC neurons, alpha-MSH is released and binds MC4R to reduce food intake and increase energy expenditure. Loss of POMC causes severe early-onset obesity due to absence of this anorexigenic signal. Note: This is ANTAGONISTIC to beta-endorphin's orexigenic function.
molecular function: type 4 melanocortin receptor binding · directly involved in: negative regulation of appetite; energy homeostasis · locations: extracellular region · anatomical locations: hypothalamus
Stimulates melanin production and skin/hair pigmentation via the cleavage products alpha-MSH (138-150) and beta-MSH (217-234). These melanocortins bind MC1R on melanocytes to activate cAMP signaling and induce eumelanin synthesis. Loss of POMC causes red hair pigmentation and fair skin phenotype due to absence of MC1R agonism.
molecular function: type 1 melanocortin receptor binding · directly involved in: cellular pigmentation; melanin biosynthetic process · locations: extracellular region · anatomical locations: skin of body
Functions as an endogenous opioid via the cleavage product beta-endorphin (residues 237-267). Beta-endorphin binds mu-opioid receptor (OPRM1) to modulate pain perception, stress response, and reward. Critically, beta-endorphin is OREXIGENIC (appetite-stimulating), which is ANTAGONISTIC to alpha-MSH's anorexigenic function. Both peptides are released from the same hypothalamic POMC neurons but stored in separate granules with distinct release mechanisms.
molecular function: opioid peptide activity · directly involved in: positive regulation of appetite; regulation of sensory perception of pain · locations: extracellular region · anatomical locations: hypothalamus; adenohypophysis
In the knowledge base · computed from kb/ at build time

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

DisorderRelationshipWhere the gene appears
Obesity causative germline
mechanism: Hypothalamic Dysregulation
Obesity Due to MC4R Pathway Disruption causative germline
mechanism: MC4R pathway signaling failure
subtype: POMC
scoped to subtype: POMC
USP8-related pituitary adenoma 4 no genetic record
mechanism: Increased POMC transcriptional activation; Increased corticotropin secretion
Mechanism modules · computed from kb/

Identity from HGNC (snapshot 2026-10-01). Page layers are described in the gene pages documentation.