TTYH3

Chr 7

tweety family member 3

ENSG00000136295UniProt: Q9C0H2

Calcium-independent, swelling-dependent volume-regulated anion channel (VRAC-swell) which plays a pivotal role in the process of regulatory volume decrease (RVD) in the brain through the efflux of anions like chloride and organic osmolytes like glutamate (By similarity). Probable large-conductance Ca(2+)-activated chloride channel (PubMed:15010458)

0
ClinVar variants
0
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— TTYH3
⚡
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.
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

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.
0.21LOEUF
pLI 0.999
Z-score 4.68
OE 0.07 (0.03–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
0.81Z-score
OE missense 0.88 (0.80–0.96)
291 obs / 332.4 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.0.07 (0.03–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.88 (0.80–0.96)
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.0.96
0≤1.21.6
LoF obs/exp: 2 / 29.3Missense obs/exp: 291 / 332.4Syn Z: 0.42

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

TTYH3 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The TTYH3/MK5 Positive Feedback Loop regulates Tumor Progression via GSK3-β/β-catenin signaling in HCC.
Wang Y et al.·Int J Biol Sci
2022
TTYH3, a potential prognosis biomarker associated with immune infiltration and immunotherapy response in lung cancer.
Wei Z et al.·Int Immunopharmacol
2022
Machine learning modeling and prognostic value analysis of invasion-related genes in cutaneous melanoma.
Yang E et al.·Comput Biol Med
2023Functional
Variable developmental delays and characteristic facial features-A novel 7p22.3p22.2 microdeletion syndrome?
Yu AC et al.·Am J Med Genet A
2017
The potential role of RNA sequencing in diagnosing unexplained insensitivity to conventional chemotherapy in pediatric patients with B-cell acute lymphoblastic leukemia.
Li X et al.·BMC Med Genomics
2024Cohort
Significance of Aneuploidy in Predicting Prognosis and Treatment Response of Uveal Melanoma.
Zhang X et al.·Curr Med Chem
2025
Clinicopathologic features of kinase fusion-related thyroid carcinomas: an integrative analysis with molecular characterization.
Chu YH et al.·Mod Pathol
2020
Rare copy number variants in the genome of Chinese female children and adolescents with Turner syndrome.
Li L et al.·Biosci Rep
2019
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Upregulation of TTYH3 by lncRNA LUCAT1 through interacting with ALYREF facilitates the metastasis in non-small cell lung cancer.
Fang F et al.·Cancer Biol Ther
2025🔓 Open Access
TTYH3 Promotes Cervical Cancer Progression by Activating the Wnt/β-Catenin Signaling Pathway.
Huang X et al.·Cancer Invest
2024
TTYH3 promotes the malignant progression of oral squamous cell carcinoma SCC-9 cells by regulating tumor-associated macrophage polarization.
Cao Y et al.·Arch Oral Biol
2024
TTYH3 Modulates Bladder Cancer Proliferation and Metastasis via FGFR1/H-Ras/A-Raf/MEK/ERK Pathway.
Biswas PK et al.·Int J Mol Sci
2022🔓 Open Access
A Novel Identified Long Intergenic Noncoding RNA, LINC01574, Contributes to Breast Cancer Deterioration via the Regulation of miR-6745/TTYH3 Axis.
Zhang L et al.·J Immunol Res
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools