• 3
    Haplo
    Score
  • 0
    Triplo
    Score

Gene Facts External Data Attribution

HGNC Symbol
TRPS1 (HGNC:12340) HGNC Entrez Ensembl OMIM UCSC Uniprot GeneReviews LOVD LSDB ClinVar
HGNC Name
transcriptional repressor GATA binding 1
Gene type
protein-coding gene
Locus type
gene with protein product
Previous symbols
No previous names found
Alias symbols
LGCR, GC79
%HI
1.26(Read more about the DECIPHER Haploinsufficiency Index)
pLI
1(Read more about gnomAD pLI score)
LOEUF
0.11(Read more about gnomAD LOEUF score)
Cytoband
8q23.3
Genomic Coordinates
GRCh37/hg19: chr8:116420724-116681202 NCBI Ensembl UCSC
GRCh38/hg38: chr8:115408496-115668975 NCBI Ensembl UCSC
MANE Select Transcript
NM_014112.5 ENST00000395715.8 (Read more about MANE Select)
Function
Transcriptional repressor. Binds specifically to GATA sequences and represses expression of GATA-regulated genes at selected sites and stages in vertebrate development. Regulates chondrocyte proliferation and differentiation. Executes multiple functions in proliferating chondrocytes, expanding the region of distal chondrocytes, activating proliferation in columnar cells and supporting the differentiation of columnar into hypertrophic chondrocytes. {ECO:0000269|PubMed:12885770, ECO:0000269|PubMed... (Source: Uniprot)

Dosage Sensitivity Summary (Gene)

Dosage ID:
ISCA-26078
Curation Status:
Complete
Issue Type:
Dosage Curation - Gene
Haploinsufficiency:
Sufficient Evidence for Haploinsufficiency (3)
Triplosensitivity:
No Evidence for Triplosensitivity (0)
Last Evaluated:
07/08/2020

Haploinsufficiency (HI) Score Details

HI Score:
3
HI Evidence Strength:
Sufficient Evidence for Haploinsufficiency (Disclaimer)
HI Disease:
  • trichorhinophalangeal syndrome type I Monarch
HI Evidence:
  • PUBMED: 31662300
    In 2019, Zepeda-Mendoza et al. used chromosomal microarray (CMA), mate-pair sequencing (MPseq), RNA sequencing (RNA-seq), and next generation sequencing (NGS) on an 11-year-old with trichorhinophalangeal syndrome type I. Analysis identified a de novo, intragenic duplication variant in TRPS1 in the proband predicted to cause protein truncation.
  • PUBMED: 21740822
    In 2011, Shao et al. described a 17-year-old with trichorhinophalangeal syndrome type 1. Using PCR, the authors identified a de novo, single base insertion in exon 4 of TRPS1. Per the authors, "Occuring prior to the nuclear localization signals (NLS), this mutation (1096insA) is predicted to result in a truncated, nonfunctional TRPS1 protein absent of NLS." Of note, the proband also had severe osteoporosis. Another case of trichorhinophalangeal syndrome type I and severe osteoporosis is described in PMID: 24357341.
  • PUBMED: 11112658
    In 2000, Lüdecke et al. studied 51 unrelated individuals with trichorhinophalangeal syndrome type I and III. The authors employed PCR and direct sequencing to identify potential variants in TRPS1. Analysis identified 35 different variants in TRPS1 in 44 patients with normal chromosomes. There were 24 confirmed sporadic cases and 19 familial cases. Of these variants, 29 were nonsense variants, 1 was a splice site variant, and 5 were missense variants. Only 4 of the sporadic cases involved missense variants.
HI Evidence Comments:
Additional evidence includes: PMID: 23510776 In 2013, Nan et al. used PCR and direct sequencing on an individual with trichorhinophalangeal syndrome type I to identify potential variants in TRPS1. Analysis identified a frameshift variant in TRPS1. Per the authors, “this deletion is an unquestionable loss-of-function mutation, deleting all functionally important parts of the protein.” This variant was not found in the proband’s unaffected sister. PMID: 28256045 In 2016, Gilman et al. used SNP microarray followed by sequencing of TRPS1 on an individual with autism spectrum disorder (ASD) and Legg-Perthes disease. Analysis identified a frameshift variant (p.Ser1067ArgfsStop3) in TRPS1 resulting in protein truncation. The parents of the proband were unaffected but did not undergo testing. PMID: 23621477 In 2013, Farooq et al. used PCR and sequence analysis on a 9-year-old with trichorhinophalangeal syndrome type I to search for causative variants in TRPS1. The authors identified a nonsense variant (p.R257X) in TRPS1 which they predict results in nonsense-mediated mRNA decay. This variant was absent in the proband's unaffected parents, and is thus de novo. PMID: 30914275 In 2019, Karaca et al. used PCR and Sanger sequencing on an individual with brachydactyly to identify potential variants in TRPS1. The authors noted that pathogenic variants in the genes PTHLH and PDE4D were excluded. Analysis identified a nonsense variant in exon 4 (p. Arg624*). This variant was also present in the proband’s affected mother and sister.

Triplosensitivity (TS) Score Details

TS Score:
0
TS Evidence Strength:
No Evidence for Triplosensitivity (Disclaimer)

Genomic View

Select assembly: (NC_000008.10) (NC_000008.11)