POMC

proopiomelanocortin, the group of Neuropeptides

Basic information

Region (hg38): 2:25160852-25168903

Links

ENSG00000115138 ∙ NCBI:5443 ∙ OMIM:176830 ∙ HGNC:9201 ∙ Uniprot:P01189 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• obesity due to pro-opiomelanocortin deficiency (Strong), mode of inheritance: AR
• inherited obesity (Strong), mode of inheritance: Semidominant
• obesity due to pro-opiomelanocortin deficiency (Moderate), mode of inheritance: AR
• obesity due to pro-opiomelanocortin deficiency (Strong), mode of inheritance: AR
• obesity due to pro-opiomelanocortin deficiency (Supportive), mode of inheritance: AR
• inherited obesity (Limited), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Obesity, early onset, with adrenal insufficiency and red hair	AR	Endocrine	The condition can present with adrenal insufficiency, and medical treatment (eg, with glucocorticoid replacement therapy) can be beneficial, though may not affect certain manifestations such as obesity; Medical management of obesity with melanocortin-4 receptor (MC4R) agonist (setmelanotide) may be beneficial	Dermatologic; Endocrine	9620771; 14557433; 18765507; 22570972; 23293326; 35528826

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the POMC gene.

• not provided (62 variants)
• Obesity due to pro-opiomelanocortin deficiency (31 variants)
• Obesity (26 variants)
• POMC-related condition (17 variants)
• not specified (9 variants)
• Inborn genetic diseases (9 variants)
• Obesity due to pro-opiomelanocortin deficiency;Obesity (4 variants)
• Inherited obesity (2 variants)
• Obesity due to pro-opiomelanocortin deficiency;Inherited obesity (2 variants)
• Inherited obesity;Obesity due to pro-opiomelanocortin deficiency (2 variants)
• Obesity;Obesity due to pro-opiomelanocortin deficiency (2 variants)
• Monogenic Non-Syndromic Obesity (2 variants)
• POMC-Related Disorders (1 variants)
• Abnormality of skin pigmentation;Obesity (1 variants)
• Obesity;Abnormality of skin pigmentation (1 variants)
• Obesity, early-onset, susceptibility to (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the POMC gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	9	2	15
missense			47	1		48
nonsense	3	1	2			6
start loss						0
frameshift	2	2	2			6
inframe indel			6	1		7
splice donor/acceptor (+/-2bp)	1					1
splice region			1			1
non coding	1		6		5	12
Total	7	3	67	11	7

Highest pathogenic variant AF is 0.0000197

Variants in POMC

This is a list of pathogenic ClinVar variants found in the POMC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-25160961-T-C		Obesity • Obesity due to pro-opiomelanocortin deficiency	Uncertain significance (Jan 13, 2018)
2-25161018-G-A		Obesity • Obesity due to pro-opiomelanocortin deficiency	Benign (Jun 19, 2021)
2-25161052-GA-G		Monogenic Non-Syndromic Obesity • Obesity due to pro-opiomelanocortin deficiency	Uncertain significance (Jun 14, 2016)
2-25161084-C-T		Obesity due to pro-opiomelanocortin deficiency • Obesity • POMC-related disorder	Conflicting classifications of pathogenicity (Jul 20, 2022)
2-25161087-G-A			Likely benign (Aug 02, 2023)
2-25161090-C-T		POMC-related disorder	Likely benign (Feb 17, 2021)
2-25161140-G-A			Uncertain significance (Dec 24, 2022)
2-25161155-C-G			Uncertain significance (Mar 20, 2018)
2-25161156-G-A		POMC-related disorder	Likely benign (Mar 14, 2023)
2-25161169-C-T			Uncertain significance (Jan 11, 2022)
2-25161175-T-C			Uncertain significance (Nov 10, 2022)
2-25161179-G-C		Obesity, early-onset, susceptibility to • Obesity due to pro-opiomelanocortin deficiency • Obesity due to pro-opiomelanocortin deficiency;Inherited obesity • POMC-related disorder	Conflicting classifications of pathogenicity (Jan 31, 2024)
2-25161192-C-T			Likely benign (Apr 01, 2022)
2-25161217-A-G		POMC-related disorder	Uncertain significance (Jan 15, 2024)
2-25161223-T-C		Obesity • Obesity due to pro-opiomelanocortin deficiency • POMC-related disorder	Conflicting classifications of pathogenicity (Feb 22, 2024)
2-25161236-CCTT-C		POMC-related disorder	Uncertain significance (Feb 09, 2024)
2-25161243-C-T		Obesity • Obesity due to pro-opiomelanocortin deficiency	Uncertain significance (Jan 13, 2018)
2-25161244-T-C		not specified • Obesity • POMC-related disorder	Likely benign (Jan 25, 2024)
2-25161247-G-A		Obesity • Obesity due to pro-opiomelanocortin deficiency	Uncertain significance (Dec 21, 2023)
2-25161259-A-G		POMC-related disorder	Uncertain significance (Oct 20, 2023)
2-25161267-C-T			Likely benign (Jan 31, 2018)
2-25161269-C-A			Uncertain significance (Jan 22, 2024)
2-25161280-T-TGGGCCC		Abnormality of skin pigmentation;Obesity	Uncertain significance (Jan 22, 2024)
2-25161283-G-A		POMC-related disorder	Uncertain significance (Dec 20, 2023)
2-25161286-C-A		Inborn genetic diseases	Uncertain significance (May 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
POMC	protein_coding	protein_coding	ENST00000405623	2	8051

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000117	0.625	125607	0	138	125745	0.000549

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.103	188	192	0.979	0.0000136	1701
Missense in Polyphen		59	62.589	0.94266		611
Synonymous	0.785	83	92.6	0.896	0.00000747	529
Loss of Function	0.740	7	9.46	0.740	4.97e-7	94

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000231	0.000231
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00168	0.00162
European (Non-Finnish)	0.000732	0.000712
Middle Eastern	0.0000544	0.0000544
South Asian	0.000337	0.000327
Other	0.000501	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Corticotropin: Stimulates the adrenal glands to release cortisol.; FUNCTION: Melanocyte-stimulating hormone beta: Increases the pigmentation of skin by increasing melanin production in melanocytes.; FUNCTION: Met-enkephalin: Endogenous opiate.
• Disease: DISEASE: Obesity (OBESITY) [MIM:601665]: A condition characterized by an increase of body weight beyond the limitation of skeletal and physical requirements, as the result of excessive accumulation of body fat. {ECO:0000269|PubMed:12165561}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.; DISEASE: Obesity, early-onset, with adrenal insufficiency and red hair (OBAIRH) [MIM:609734]: An autosomal recessive disorder characterized by early-onset obesity due to severe hyperphagia, pigmentary abnormalities, mainly pale skin and red hair, and secondary hypocortisolism. {ECO:0000269|PubMed:9620771}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Cortisol synthesis and secretion - Homo sapiens (human);Aldosterone synthesis and secretion - Homo sapiens (human);Adipocytokine signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Glucocorticoid Pathway (HPA Axis), Pharmacodynamics;Levomethadyl Acetate Action Action Pathway;Fluoxetine Action Pathway;Citalopram Action Pathway;Escitalopram Action Pathway;Imipramine Action Pathway;Desipramine Action Pathway;Levallorphan Action Pathway;Dimethylthiambutene Action Pathway;Ethylmorphine Action Pathway;Pentazocine Action Pathway;Naltrexone Action Pathway;Buprenorphine Action Pathway;Alvimopan Action Pathway;Naloxone Action Pathway;Dihydromorphine Action Pathway;Corticotropin Activation of Cortisol Production;Nicotine Action Pathway;Nalbuphine Action Pathway;Ketobemidone Action Pathway;Lidocaine (Local Anaesthetic) Action Pathway;Mepivacaine Action Pathway;Chloroprocaine Action Pathway;Cocaine Action Pathway;Dibucaine Action Pathway;Levobupivacaine Action Pathway;Benzocaine Action Pathway;Bupivacaine Action Pathway;Levorphanol Action Pathway;Propoxyphene Action Pathway;Tramadol Action Action Pathway;Diphenoxylate Action Pathway;Anileridine Action Pathway;Methadone Action Pathway;Oxycodone Action Pathway;Oxybuprocaine Action Pathway;Prilocaine Action Pathway;Procaine Action Pathway;Proparacaine Action Pathway;Ropivacaine Action Pathway;Codeine Action Pathway;Morphine Action Pathway;Heroin Action Pathway;Alfentanil Action Pathway;Oxymorphone Action Pathway;Hydrocodone Action Pathway;Hydromorphone Action Pathway;Sufentanil Action Pathway;Remifentanil Action Pathway;Fentanyl Action Pathway;Carfentanil Action Pathway;3-Methylthiofentanyl Action Pathway;Methadyl Acetate Action Pathway;Dezocine Action Pathway;Corticotropin-releasing hormone signaling pathway;Serotonin and anxiety;Interleukin-4 and 13 signaling;Signaling by GPCR;Signal Transduction;Peptide hormone metabolism;Phase I - Functionalization of compounds;Metabolism of lipids;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Endogenous sterols;Cytochrome P450 - arranged by substrate type;Biological oxidations;Metabolism;G alpha (s) signalling events;Peptide ligand-binding receptors;Androgen biosynthesis;Metabolism of steroid hormones;Metabolism of steroids;Class A/1 (Rhodopsin-like receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;Glucocorticoid receptor regulatory network;Glucocorticoid biosynthesis;G-protein activation;Opioid Signalling;G alpha (i) signalling events;GPCR signaling-G alpha i;GPCR downstream signalling;Syndecan-3-mediated signaling events;Steroid hormones;Peptide hormone biosynthesis (Consensus)

Recessive Scores

• pRec: 0.981

Haploinsufficiency Scores

• pHI: 0.422
• hipred: N
• hipred_score: 0.170
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.708

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pomc
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); neoplasm; pigmentation phenotype; liver/biliary system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; endocrine/exocrine gland phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: pomca
• Affected structure: melanocyte
• Phenotype tag: abnormal
• Phenotype quality: aggregated

Gene ontology

• Biological process: generation of precursor metabolites and energy;signal transduction;G protein-coupled receptor signaling pathway;neuropeptide signaling pathway;cell-cell signaling;regulation of blood pressure;regulation of signaling receptor activity;cytokine-mediated signaling pathway;regulation of appetite;negative regulation of tumor necrosis factor production;cellular pigmentation;glucose homeostasis;positive regulation of transcription by RNA polymerase II;regulation of glycogen metabolic process;regulation of corticosterone secretion
• Cellular component: extracellular region;extracellular space;cytoplasm;secretory granule;secretory granule lumen
• Molecular function: G protein-coupled receptor binding;signaling receptor binding;hormone activity;type 3 melanocortin receptor binding;type 4 melanocortin receptor binding;type 1 melanocortin receptor binding