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NM_014365.3(HSPB8):c.423G>C (p.Lys141Asn) AND Neuronopathy, distal hereditary motor, type 2A

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 1, 2004
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:
RCV000002735.11

Allele description [Variation Report for NM_014365.3(HSPB8):c.423G>C (p.Lys141Asn)]

NM_014365.3(HSPB8):c.423G>C (p.Lys141Asn)

Gene:
HSPB8:heat shock protein family B (small) member 8 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q24.23
Genomic location:
Preferred name:
NM_014365.3(HSPB8):c.423G>C (p.Lys141Asn)
Other names:
HSPB8, 423G-C, LYS141ASN; K141N
HGVS:
  • NC_000012.12:g.119187080G>C
  • NG_007953.2:g.13291G>C
  • NM_014365.3:c.423G>CMANE SELECT
  • NP_055180.1:p.Lys141Asn
  • LRG_249t1:c.423G>C
  • LRG_249:g.13291G>C
  • LRG_249p1:p.Lys141Asn
  • NC_000012.11:g.119624885G>C
  • NM_014365.2:c.423G>C
  • Q9UJY1:p.Lys141Asn
Protein change:
LYS141ASN
Links:
UniProtKB: Q9UJY1#VAR_018505; OMIM: 608014.0001; dbSNP: rs104894345
NCBI 1000 Genomes Browser:
rs104894345
Molecular consequence:
  • NM_014365.3:c.423G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuronopathy, distal hereditary motor, type 2A
Synonyms:
CHARCOT-MARIE-TOOTH DISEASE, SPINAL, IIA; HMN IIA; NEURONOPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL DOMINANT 2; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008025; MedGen: C1834692; Orphanet: 139525; OMIM: 158590

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000022893OMIM
no assertion criteria provided
Pathogenic
(Jun 1, 2004) 		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

Linkage analysis of distal hereditary motor neuropathy type II (distal HMN II) in a single pedigree.

Timmerman V, Raeymaekers P, Nelis E, De Jonghe P, Muylle L, Ceuterick C, Martin JJ, Van Broeckhoven C.

J Neurol Sci. 1992 May;109(1):41-8.

PubMed [citation]
PMID:
1517763

Hot-spot residue in small heat-shock protein 22 causes distal motor neuropathy.

Irobi J, Van Impe K, Seeman P, Jordanova A, Dierick I, Verpoorten N, Michalik A, De Vriendt E, Jacobs A, Van Gerwen V, Vennekens K, Mazanec R, Tournev I, Hilton-Jones D, Talbot K, Kremensky I, Van Den Bosch L, Robberecht W, Van Vandekerckhove J, Van Broeckhoven C, Gettemans J, De Jonghe P, et al.

Nat Genet. 2004 Jun;36(6):597-601. Epub 2004 May 2.

PubMed [citation]
PMID:
15122253

Details of each submission

From OMIM, SCV000022893.2

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

Description

In affected members of a Belgian family with autosomal dominant distal hereditary motor neuronopathy type II (158590) previously reported by Timmerman et al. (1992), and in affected members of a large Czech family with dHMN2, Irobi et al. (2004) identified a heterozygous 423G-C transversion in exon 2 of the HSPB8 gene, resulting in a lys141-to-asn (K141N) substitution. The mutation cosegregated with the disease in both families. The K141N mutation affects a highly conserved residue in the central alpha-crystallin domain of the protein. Normally, HSPB8 interacts with HSPB1 (602195). Expression studies of the K141N mutant protein in COS cells showed an increased interaction between HSPB8 and HSPB1, leading to the formation of intracellular aggregates. A different mutation in the same codon was identified in 2 other families with dHMN2 (608014.0002).

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

Last Updated: Nov 3, 2024