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NM_000183.3(HADHB):c.1331G>A (p.Arg444Lys) AND Mitochondrial trifunctional protein deficiency 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 1, 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:
RCV003156217.8

Allele description [Variation Report for NM_000183.3(HADHB):c.1331G>A (p.Arg444Lys)]

NM_000183.3(HADHB):c.1331G>A (p.Arg444Lys)

Gene:
HADHB:hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p23.3
Genomic location:
Preferred name:
NM_000183.3(HADHB):c.1331G>A (p.Arg444Lys)
Other names:
R411K
HGVS:
  • NC_000002.12:g.26285513G>A
  • NG_007294.1:g.45561G>A
  • NM_000183.3:c.1331G>AMANE SELECT
  • NM_001281512.2:c.1286G>A
  • NM_001281513.2:c.1265G>A
  • NP_000174.1:p.Arg444Lys
  • NP_001268441.1:p.Arg429Lys
  • NP_001268442.1:p.Arg422Lys
  • NC_000002.11:g.26508381G>A
  • P55084:p.Arg444Lys
Protein change:
R422K; ARG411LYS
Links:
UniProtKB: P55084#VAR_017409; OMIM: 143450.0004; dbSNP: rs121913134
NCBI 1000 Genomes Browser:
rs121913134
Molecular consequence:
  • NM_000183.3:c.1331G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281512.2:c.1286G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001281513.2:c.1265G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Mitochondrial trifunctional protein deficiency 2 (MTPD2)
Identifiers:
MONDO: MONDO:0958185; MedGen: C5830374; OMIM: 620300

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000036239OMIM
no assertion criteria provided
Pathogenic
(Dec 1, 2009) 		germlineliterature only

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

Help

Summary from all submissions

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

Citations

PubMed

Genomic and mutational analysis of the mitochondrial trifunctional protein beta-subunit (HADHB) gene in patients with trifunctional protein deficiency.

Orii KE, Aoyama T, Wakui K, Fukushima Y, Miyajima H, Yamaguchi S, Orii T, Kondo N, Hashimoto T.

Hum Mol Genet. 1997 Aug;6(8):1215-24.

PubMed [citation]
PMID:
9259266

Clinical and molecular aspects of Japanese patients with mitochondrial trifunctional protein deficiency.

Purevsuren J, Fukao T, Hasegawa Y, Kobayashi H, Li H, Mushimoto Y, Fukuda S, Yamaguchi S.

Mol Genet Metab. 2009 Dec;98(4):372-7. doi: 10.1016/j.ymgme.2009.07.011. Epub 2009 Jul 23.

PubMed [citation]
PMID:
19699128

Details of each submission

From OMIM, SCV000036239.4

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

Description

In a Japanese patient with mitochondrial trifunctional protein deficiency (MTPD2; 620300), Orii et al. (1997) found homozygosity for a 1331G-A transition, resulting in an arg411-to-lys (R411K) amino acid substitution. The patient had onset at age 15 years of muscle pain and weakness associated with rhabdomyolysis. Development was normal. In another Japanese patient, the R411K mutation was present in compound heterozygous state with an exonic single T insertion, creating a new cryptic 5-prime splice site (143450.0005). This patient had a more severe phenotype, with onset at 13 months of age of lethargy, hypotonia, and recurrent respiratory infections. He had cardiac arrest, liver dysfunction, and delayed psychomotor development.

By in vitro functional expression studies, Purevsuren et al. (2009) demonstrated that the R411K mutant had 14% residual enzyme activity at 37 degrees C and faint expression of alpha- and beta-subunit proteins. However, residual activity at 30 degrees C increased significantly to more than 50% of wildtype.

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

Last Updated: Nov 3, 2024