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NM_000939.4(POMC):c.706C>G (p.Arg236Gly) AND Obesity, early-onset, susceptibility to

Germline classification:
risk factor (1 submission)
Last evaluated:
Aug 15, 2002
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000014284.11

Allele description [Variation Report for NM_000939.4(POMC):c.706C>G (p.Arg236Gly)]

NM_000939.4(POMC):c.706C>G (p.Arg236Gly)

Gene:
POMC:proopiomelanocortin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_000939.4(POMC):c.706C>G (p.Arg236Gly)
HGVS:
  • NC_000002.12:g.25161179G>C
  • NG_008997.1:g.12512C>G
  • NM_000939.4:c.706C>GMANE SELECT
  • NM_001035256.3:c.706C>G
  • NM_001319204.2:c.706C>G
  • NM_001319205.2:c.706C>G
  • NP_000930.1:p.Arg236Gly
  • NP_001030333.1:p.Arg236Gly
  • NP_001030333.1:p.Arg236Gly
  • NP_001306133.1:p.Arg236Gly
  • NP_001306134.1:p.Arg236Gly
  • NC_000002.11:g.25384048G>C
  • NM_000939.3:c.706C>G
  • NM_001035256.1:c.706C>G
  • NM_001035256.2:c.706C>G
  • P01189:p.Arg236Gly
Protein change:
R236G; ARG236GLY
Links:
UniProtKB: P01189#VAR_010701; OMIM: 176830.0004; dbSNP: rs28932472
NCBI 1000 Genomes Browser:
rs28932472
Molecular consequence:
  • NM_000939.4:c.706C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001035256.3:c.706C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319204.2:c.706C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001319205.2:c.706C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Obesity, early-onset, susceptibility to
Identifiers:
MedGen: C4016341

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000034533OMIM
no assertion criteria provided
risk factor
(Aug 15, 2002) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A missense mutation disrupting a dibasic prohormone processing site in pro-opiomelanocortin (POMC) increases susceptibility to early-onset obesity through a novel molecular mechanism.

Challis BG, Pritchard LE, Creemers JW, Delplanque J, Keogh JM, Luan J, Wareham NJ, Yeo GS, Bhattacharyya S, Froguel P, White A, Farooqi IS, O'Rahilly S.

Hum Mol Genet. 2002 Aug 15;11(17):1997-2004.

PubMed [citation]
PMID:
12165561

Details of each submission

From OMIM, SCV000034533.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

Challis et al. (2002) sequenced the POMC coding region in 262 Caucasian subjects with a history of severe obesity from childhood (see 601665). Two children were found to be heterozygous for an arg236-to-gly (R236G) missense mutation, which is predicted to disrupt the dibasic cleavage site between beta-melanocyte-stimulating hormone (beta-MSH) and beta-endorphin. Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein. This fusion protein bound to the human melanocortin-4 receptor (MC4R) with an affinity similar to its natural ligands, but had a markedly reduced ability to activate the receptor. This variant cosegregated with early-onset obesity in the 3-generation family of 1 of the children and was absent in 412 normal weight Caucasian controls. Combining results from 5 studies, mutations disrupting this processing site were present in 0.88% of subjects with early-onset obesity and 0.22% of normal weight controls. The authors suggested that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signaling.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024