NM_003467.2(CXCR4):c.1000C>T (p.Arg334Ter) AND Myelokathexis, isolated

Clinical significance:Pathogenic (Last evaluated: May 1, 2003)

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

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description

NM_003467.2(CXCR4):c.1000C>T (p.Arg334Ter)

CXCR4:C-X-C motif chemokine receptor 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_003467.2(CXCR4):c.1000C>T (p.Arg334Ter)
  • NC_000002.12:g.136114928G>A
  • NG_011587.1:g.8228C>T
  • NM_003467.2:c.1000C>T
  • NP_003458.1:p.Arg334Ter
  • LRG_51t1:c.1000C>T
  • LRG_51:g.8228C>T
  • LRG_51p1:p.Arg334Ter
  • NC_000002.11:g.136872498G>A
Protein change:
R334*; ARG334TER
OMIM: 162643.0001; dbSNP: rs104893624
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_003467.2:c.1000C>T - nonsense - [Sequence Ontology: SO:0001587]


Myelokathexis, isolated
MedGen: C1834176

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000035320OMIMno assertion criteria providedPathogenic
(May 1, 2003)
unknownliterature only

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease.

Hernandez PA, Gorlin RJ, Lukens JN, Taniuchi S, Bohinjec J, Francois F, Klotman ME, Diaz GA.

Nat Genet. 2003 May;34(1):70-4.

PubMed [citation]

Details of each submission

From OMIM, SCV000035320.2

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


Hernandez et al. (2003) found that affected members of a family with WHIM syndrome (WHIMS; 193670) had a 1000C-T transition in the CXCR4 gene converting codon 334 from CGA (arg) to TGA (stop). Hernandez et al. (2003) found this mutation, which occurred on a CpG dinucleotide, on 4 distinct haplotypes in 4 separate pedigrees, consistent with recurrence. One of these pedigrees demonstrated apparent recessive inheritance of isolated myelokathexis, which was explained by paternal somatic and gonadal mosaicism, establishing that expression of the mutated allele in hematopoietic cells was required for disease occurrence. The R334X mutation resulted in truncation of 19 residues from the serine- and threonine-rich cytoplasmic tail, a domain involved in the regulation of receptor function. Lymphoblastoid cell lines carrying the R334X truncation mutation showed significantly greater calcium flux relative to control cell lines in response to the CXCR4 ligand, SDF1 (CXCL12; 600835), consistent with dysregulated signaling by the mutant receptor.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownnot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 7, 2017