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NM_002585.4(PBX1):c.701G>C (p.Arg234Pro) AND Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 26, 2018
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:
RCV000626308.1

Allele description [Variation Report for NM_002585.4(PBX1):c.701G>C (p.Arg234Pro)]

NM_002585.4(PBX1):c.701G>C (p.Arg234Pro)

Gene:
PBX1:PBX homeobox 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q23.3
Genomic location:
Preferred name:
NM_002585.4(PBX1):c.701G>C (p.Arg234Pro)
HGVS:
  • NC_000001.11:g.164799889G>C
  • NG_028246.2:g.245530G>C
  • NM_001204961.2:c.701G>C
  • NM_001204963.2:c.701G>C
  • NM_001353130.1:c.452G>C
  • NM_001353131.2:c.701G>C
  • NM_002585.4:c.701G>CMANE SELECT
  • NP_001191890.1:p.Arg234Pro
  • NP_001191892.1:p.Arg234Pro
  • NP_001340059.1:p.Arg151Pro
  • NP_001340060.1:p.Arg234Pro
  • NP_002576.1:p.Arg234Pro
  • NP_002576.1:p.Arg234Pro
  • NC_000001.10:g.164769126G>C
  • NM_002585.3:c.701G>C
Protein change:
R151P; ARG234PRO
Links:
OMIM: 176310.0005; dbSNP: rs1553248112
NCBI 1000 Genomes Browser:
rs1553248112
Molecular consequence:
  • NM_001204961.2:c.701G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001204963.2:c.701G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353130.1:c.452G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001353131.2:c.701G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002585.4:c.701G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Congenital anomalies of kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay
Identifiers:
MONDO: MONDO:0060549; MedGen: C4539968; OMIM: 617641

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000746970OMIM
no assertion criteria provided
Pathogenic
(Apr 26, 2018) 		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

De novo, deleterious sequence variants that alter the transcriptional activity of the homeoprotein PBX1 are associated with intellectual disability and pleiotropic developmental defects.

Slavotinek A, Risolino M, Losa M, Cho MT, Monaghan KG, Schneidman-Duhovny D, Parisotto S, Herkert JC, Stegmann APA, Miller K, Shur N, Chui J, Muller E, DeBrosse S, Szot JO, Chapman G, Pachter NS, Winlaw DS, Mendelsohn BA, Dalton J, Sarafoglou K, Karachunski PI, et al.

Hum Mol Genet. 2017 Dec 15;26(24):4849-4860. doi: 10.1093/hmg/ddx363.

PubMed [citation]
PMID:
29036646
PMCID:
PMC6455034

Details of each submission

From OMIM, SCV000746970.1

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

Description

In a 2-year-old girl (patient 4) with congenital anomalies of the kidney and urinary tract syndrome with or without hearing loss, abnormal ears, or developmental delay (CAKUTHED; 617641), Slavotinek et al. (2017) identified a de novo heterozygous c.701G-C transversion (c.701G-C, NM_002585.3) in exon 4-5 of the PBX1 gene, resulting in an arg234-to-pro (R234P) substitution at a highly conserved residue in the homeodomain. The affected codon crosses a splice site. The mutation was not found in the ExAC, 1000 Genomes Project, or dbSNP databases. In vitro functional expression studies in HEK293 cells that had endogenous PBX1 showed that the mutation resulted in decreased transactivation activity of PBX1 compared to wildtype. The mutation also decreased transactivation capability when expressed in a cellular system with markedly decreased levels of PBX1, suggesting that the mutation intrinsically alters this function. This patient did not have dysplastic ears or hearing loss but had developmental delay.

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

Last Updated: Jul 15, 2024