NM_015074.3(KIF1B):c.4442G>A (p.Ser1481Asn) AND Neuroblastoma 1

Clinical significance:risk factor (Last evaluated: Oct 1, 2008)

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:
RCV000004926.2

Allele description [Variation Report for NM_015074.3(KIF1B):c.4442G>A (p.Ser1481Asn)]

NM_015074.3(KIF1B):c.4442G>A (p.Ser1481Asn)

Gene:
KIF1B:kinesin family member 1B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p36.22
Genomic location:
Preferred name:
NM_015074.3(KIF1B):c.4442G>A (p.Ser1481Asn)
HGVS:
  • NC_000001.11:g.10365476G>A
  • NG_008069.1:g.159771G>A
  • NM_001365951.2:c.4580G>A
  • NM_001365952.1:c.4580G>A
  • NM_015074.3:c.4442G>A
  • NP_001352880.1:p.Ser1527Asn
  • NP_001352881.1:p.Ser1527Asn
  • NP_055889.2:p.Ser1481Asn
  • LRG_252t1:c.4442G>A
  • LRG_252:g.159771G>A
  • LRG_252p1:p.Ser1481Asn
  • NC_000001.10:g.10425534G>A
Protein change:
S1481N; SER1481ASN
Links:
OMIM: 605995.0005; dbSNP: rs121908164
NCBI 1000 Genomes Browser:
rs121908164
Molecular consequence:
  • NM_001365951.2:c.4580G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365952.1:c.4580G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015074.3:c.4442G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuroblastoma 1 (NBLST1)
Synonyms:
NEUROBLASTOMA, SUSCEPTIBILITY TO, 1
Identifiers:
MONDO: MONDO:0009741; MedGen: C2749485; OMIM: 256700

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000025102OMIMno assertion criteria providedrisk factor
(Oct 1, 2008)
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

A germline mutation of the KIF1B beta gene on 1p36 in a family with neural and nonneural tumors.

Yeh IT, Lenci RE, Qin Y, Buddavarapu K, Ligon AH, Leteurtre E, Do Cao C, Cardot-Bauters C, Pigny P, Dahia PL.

Hum Genet. 2008 Oct;124(3):279-85. doi: 10.1007/s00439-008-0553-1. Epub 2008 Aug 26.

PubMed [citation]
PMID:
18726616

The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor.

Schlisio S, Kenchappa RS, Vredeveld LC, George RE, Stewart R, Greulich H, Shahriari K, Nguyen NV, Pigny P, Dahia PL, Pomeroy SL, Maris JM, Look AT, Meyerson M, Peeper DS, Carter BD, Kaelin WG Jr.

Genes Dev. 2008 Apr 1;22(7):884-93. doi: 10.1101/gad.1648608. Epub 2008 Mar 11.

PubMed [citation]
PMID:
18334619
PMCID:
PMC2279200

Details of each submission

From OMIM, SCV000025102.1

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

Description

In a pheochromocytoma (171300) tumor sample and in germline DNA from the corresponding patient, Schlisio et al. (2008) identified a 4442G-A transition in exon 41 of the KIF1B gene, resulting in a ser1481-to-asn (S1481N) substitution. The wildtype allele was retained in the tumor sample. The proband was a 28-year-old female who presented at 17 months of age with a neuroblastoma (256700) and in adulthood developed a mature ganglioneuroma and bilateral pheochromocytoma. Her paternal grandfather harbored the mutant S1481N allele and also developed bilateral pheochromocytoma. In vitro functional expression studies showed that the mutant protein was deficient in the ability to induce apoptosis of sympathetic precursor cells in response to growth factor withdrawal compared to wildtype KIF1B.

Yeh et al. (2008) reported further analysis of the family reported by Schlisio et al. (2008). The proband developed a leiomyosarcoma, and her father, who also carried the S1481N mutation, developed adenocarcinoma of the lung (211980). Analysis of tumor tissue revealed that all 4 neural crest tumors and the leiomyosarcoma retained both KIF1B alleles and showed no loss of heterozygosity (LOH), consistent with a haploinsufficiency mechanism. Yeh et al. (2008) postulated that the leiomyosarcoma may have evolved secondary to the proband's childhood treatment for neuroblastoma. In contrast, about 45% of cells from the lung tumor showed LOH at this locus, suggesting a possible role for gene dosage in development of this nonneural tumor.

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

Last Updated: Jan 16, 2021

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