NM_005912.3(MC4R):c.523G>A (p.Ala175Thr) AND BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20

Clinical significance:Pathogenic (Last evaluated: Mar 20, 2003)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000768579.1

Allele description [Variation Report for NM_005912.3(MC4R):c.523G>A (p.Ala175Thr)]

NM_005912.3(MC4R):c.523G>A (p.Ala175Thr)

Gene:
MC4R:melanocortin 4 receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
18q21.32
Genomic location:
Preferred name:
NM_005912.3(MC4R):c.523G>A (p.Ala175Thr)
HGVS:
  • NC_000018.10:g.60371827C>T
  • NG_016441.1:g.5942G>A
  • NM_005912.3:c.523G>AMANE SELECT
  • NP_005903.2:p.Ala175Thr
  • LRG_1346t1:c.523G>A
  • LRG_1346:g.5942G>A
  • LRG_1346p1:p.Ala175Thr
  • NC_000018.9:g.58039060C>T
  • NM_005912.2:c.523G>A
  • P32245:p.Ala175Thr
Protein change:
A175T; ALA175THR
Links:
UniProtKB: P32245#VAR_038646; OMIM: 155541.0015; dbSNP: rs121913563
NCBI 1000 Genomes Browser:
rs121913563
Molecular consequence:
  • NM_005912.3:c.523G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
BODY MASS INDEX QUANTITATIVE TRAIT LOCUS 20 (BMIQ20)
Synonyms:
MELANOCORTIN 4 RECEPTOR DEFICIENCY; MC4R DEFICIENCY
Identifiers:
MedGen: C4759928; OMIM: 618406

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000035667OMIMno assertion criteria providedPathogenic
(Mar 20, 2003)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene.

Farooqi IS, Keogh JM, Yeo GS, Lank EJ, Cheetham T, O'Rahilly S.

N Engl J Med. 2003 Mar 20;348(12):1085-95.

PubMed [citation]
PMID:
12646665

Human Gain-of-Function MC4R Variants Show Signaling Bias and Protect against Obesity.

Lotta LA, MokrosiƄski J, Mendes de Oliveira E, Li C, Sharp SJ, Luan J, Brouwers B, Ayinampudi V, Bowker N, Kerrison N, Kaimakis V, Hoult D, Stewart ID, Wheeler E, Day FR, Perry JRB, Langenberg C, Wareham NJ, Farooqi IS.

Cell. 2019 Apr 18;177(3):597-607.e9. doi: 10.1016/j.cell.2019.03.044.

PubMed [citation]
PMID:
31002796
PMCID:
PMC6476272

Details of each submission

From OMIM, SCV000035667.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a mother and son with early-onset obesity (BMIQ20; 618406), Farooqi et al. (2003) found heterozygosity for an ala175-to-thr (A175T) mutation in the MC4R gene. The protein showed partial activity on in vitro assay.

In time-resolved assays quantifying cAMP production and beta-arrestin-2 (ARBB2; 107941) recruitment, Lotta et al. (2019) observed loss-of-function effects with the A175T mutant compared to wildtype MC4R.

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

Last Updated: Sep 6, 2021

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