TRPS1

Chr 8AD

transcriptional repressor GATA binding 1

Also known as: GC79, LGCR

NCBI Gene: 7227ENSG00000104447UniProt: Q9UHF7

This gene encodes a transcription factor that represses GATA-regulated genes and binds to a dynein light chain protein. Binding of the encoded protein to the dynein light chain protein affects binding to GATA consensus sequences and suppresses its transcriptional activity. Defects in this gene are a cause of tricho-rhino-phalangeal syndrome (TRPS) types I-III. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Trichorhinophalangeal syndrome, type IMIM #190350
AD
Trichorhinophalangeal syndrome, type IIIMIM #190351
AD
Trichorhinophalangeal syndrome, type IMIM #190350
AD
UniProtTricho-rhino-phalangeal syndrome 1
UniProtTricho-rhino-phalangeal syndrome 2
UniProtTricho-rhino-phalangeal syndrome 3
584
ClinVar variants
148
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
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
148 Pathogenic / Likely Pathogenic· 254 VUS of 584 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.54Z-score
OE missense 0.83 (0.78–0.89)
562 obs / 674.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.02 (0.01–0.11)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.83 (0.78–0.89)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 1 / 42.9Missense obs/exp: 562 / 674.8Syn Z: -0.60

ClinVar Variant Classifications

584 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic117
Likely Pathogenic31
VUS254
Likely Benign129
Benign32
Conflicting21
117
Pathogenic
31
Likely Pathogenic
254
VUS
129
Likely Benign
32
Benign
21
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
53
1
63
0
117
Likely Pathogenic
18
7
6
0
31
VUS
2
244
6
2
254
Likely Benign
0
30
12
87
129
Benign
0
4
17
11
32
Conflicting
—21
Total73286104100584

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.

Gene2Phenotype Curations

TRPS1-related trichorhinopharangeal syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. DisordersSkinSkeletal
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

2 OMIM entries

OMIM

Trichorhinophalangeal syndrome, type I

MIM #190350

Molecular basis of disorder known

Autosomal dominant

Trichorhinophalangeal syndrome, type III

MIM #190351

Molecular basis of disorder known

Autosomal dominant

Trichorhinophalangeal syndrome, type I

MIM #190350

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — TRPS1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TRPS1 is a Highly Sensitive Marker for Breast Cancer: A Tissue Microarray Study Evaluating More Than 19,000 Tumors From 152 Different Tumor Entities.
Lennartz M et al.·Am J Surg Pathol
2024
Functional mechanisms of TRPS1 in disease progression and its potential role in personalized medicine.
Yang L et al.·Pathol Res Pract
2022Functional
Analysis of the function, mechanism and clinical application prospect of TRPS1, a new marker for breast cancer.
He X et al.·Gene
2025Review
Exploring the molecular landscape of cutaneous mixed tumors characterized by TRPS1::PLAG1 gene fusion.
Alsugair Z et al.·J Pathol
2024
Case-Case Genome-Wide Analyses Identify Subtype-Informative Variants That Confer Risk for Breast Cancer.
Sun X et al.·Cancer Res
2024
[TRPS1 expression in salivary gland-type breast carcinoma and its clinical application].
Xu C et al.·Zhonghua Bing Li Xue Za Zhi
2023
Expanding the clinical and molecular features of trichorhino- phalangeal syndrome with a novel variant.
Öztürk N et al.·Turk J Pediatr
2023
Digenic impairments of haploinsufficient genes in patients with craniosynostosis.
Yu JW et al.·JCI Insight
2025Cohort
TRPS1 expression in breast angiosarcoma.
Pancsa T et al.·Virchows Arch
2025
Upregulation of TRPS1 promotes proliferation, migration, and invasion in ovarian clear cell carcinoma and correlates with poor patient prognosis.
Liu J et al.·J Ovarian Res
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools