TRPS1

Chr 8AD

transcriptional repressor GATA binding 1

Also known as: GC79, LGCR

NCBI Gene: 7227ENSG00000104447UniProt: Q9UHF7OMIM: 604386

The protein encoded by this gene is a transcription factor that represses GATA-regulated genes, with its activity modulated through binding to dynelin light chain proteins. Mutations cause trichorhinophalangeal syndrome types I and III through an autosomal dominant inheritance pattern. The pathogenic mechanism involves loss of function of this transcriptional repressor.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.113 OMIM phenotypes
Clinical Summary— TRPS1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
50 unique Pathogenic / Likely Pathogenic· 180 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.11LOEUF
pLI 1.000
Z-score 5.92
OE 0.02 (0.01–0.11)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
1.54Z-score
OE missense 0.83 (0.78–0.89)
562 obs / 674.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.02 (0.01–0.11)
0≤0.351.4
Missense OE0.83 (0.78–0.89)
0≤0.61.4
Synonymous OE1.05
0≤1.21.6
LoF obs/exp: 1 / 42.9Missense obs/exp: 562 / 674.8Syn Z: -0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveTRPS1-related trichorhinopharangeal syndromeLOFAD
DN
0.2299th %ile
GOF
0.2098th %ile
LOF
0.87top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · 78% of P/LP variants are LoF · LOEUF 0.11
DN1 literature citation

Literature Evidence

DNThe patient with type I TRPS had haploinsufficiency of TRPS1, whereas the patient with type III TRPS had an allele causing functional modification of the GATA-type motif, possibly inducing a dominant-negative effect on DNA transcription regulation and leading to a more severe phenotype.PMID:19610100
LOFLanger-Giedion's syndrome (LGS) or trichorhinophalangeal syndrome type II (TRPS II; MIM:150230) is a contiguous gene deletion syndrome caused by the haploinsufficiency of the TRPS1 and EXT1 genes.PMID:31976145

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic20
VUS180
Likely Benign44
Benign8
Conflicting4
30
Pathogenic
20
Likely Pathogenic
180
VUS
44
Likely Benign
8
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
24
0
6
0
30
Likely Pathogenic
15
4
1
0
20
VUS
2
176
2
0
180
Likely Benign
0
7
5
32
44
Benign
0
1
1
6
8
Conflicting
—4
Total411881538286

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

TRPS1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients