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NM_001374504.1(TMPRSS6):c.1537G>A (p.Glu513Lys) AND Iron-refractory iron deficiency anemia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 28, 2009
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:
RCV000023787.5

Allele description [Variation Report for NM_001374504.1(TMPRSS6):c.1537G>A (p.Glu513Lys)]

NM_001374504.1(TMPRSS6):c.1537G>A (p.Glu513Lys)

Gene:
TMPRSS6:transmembrane serine protease 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q12.3
Genomic location:
Preferred name:
NM_001374504.1(TMPRSS6):c.1537G>A (p.Glu513Lys)
Other names:
E522K
HGVS:
  • NC_000022.11:g.37073550C>T
  • NG_012856.2:g.41014G>A
  • NM_001289000.2:c.1537G>A
  • NM_001289001.2:c.1537G>A
  • NM_001374504.1:c.1537G>AMANE SELECT
  • NM_153609.4:c.1537G>A
  • NP_001275929.1:p.Glu513Lys
  • NP_001275930.1:p.Glu513Lys
  • NP_001361433.1:p.Glu513Lys
  • NP_705837.2:p.Glu513Lys
  • LRG_1128t1:c.1537G>A
  • LRG_1128t2:c.1537G>A
  • LRG_1128:g.41014G>A
  • LRG_1128p1:p.Glu513Lys
  • LRG_1128p2:p.Glu513Lys
  • NC_000022.10:g.37469590C>T
  • Q8IU80:p.Glu522Lys
Protein change:
E513K; GLU522LYS
Links:
UniProtKB: Q8IU80#VAR_068671; OMIM: 609862.0013; dbSNP: rs387907018
NCBI 1000 Genomes Browser:
rs387907018
Molecular consequence:
  • NM_001289000.2:c.1537G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001289001.2:c.1537G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001374504.1:c.1537G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_153609.4:c.1537G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Iron-refractory iron deficiency anemia (IRIDA)
Synonyms:
ANEMIA, HYPOCHROMIC MICROCYTIC, WITH DEFECT IN IRON METABOLISM; IRON-HANDLING DISORDER, HEREDITARY; PSEUDO-IRON-DEFICIENCY ANEMIA; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008788; MedGen: C0085576; Orphanet: 209981; OMIM: 206200

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000045078OMIM
no assertion criteria provided
Pathogenic
(May 28, 2009) 		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

Molecular mechanisms of the defective hepcidin inhibition in TMPRSS6 mutations associated with iron-refractory iron deficiency anemia.

Silvestri L, Guillem F, Pagani A, Nai A, Oudin C, Silva M, Toutain F, Kannengiesser C, Beaumont C, Camaschella C, Grandchamp B.

Blood. 2009 May 28;113(22):5605-8. doi: 10.1182/blood-2008-12-195594. Epub 2009 Apr 8.

PubMed [citation]
PMID:
19357398

Details of each submission

From OMIM, SCV000045078.4

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

Description

In a French boy with iron-refractory iron deficiency anemia (IRIDA; 206200), Silvestri et al. (2009) identified compound heterozygosity for 2 mutations in the TMPRSS6 gene: D521N (609862.0006) and a 1564G-A transition in exon 13, resulting in a glu522-to-lys (E522K) substitution. Both mutations were predicted to affect the LDLRA domain. By in vitro functional expression studies in HeLa cells, Silvestri et al. (2009) demonstrated that the E522K-mutant protein was partially retained in the Golgi apparatus and had low expression at the plasma membrane. The mutant protein was ineffective in cleaving membrane-bound hemojuvelin (HJV; 608374), despite a detectable physical interaction with HJV. Hepcidin (606464) expression was only partially repressed by the E522K-mutant protein compared to wildtype protein.

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

Last Updated: Apr 23, 2022