TUFT1

Chr 1AR

tuftelin 1

Also known as: WHSF

NCBI Gene: 7286ENSG00000143367UniProt: Q9NNX1

Tuftelin is an acidic protein that is thought to play a role in dental enamel mineralization and is implicated in caries susceptibility. It is also thought to be involved with adaptation to hypoxia, mesenchymal stem cell function, and neurotrophin nerve growth factor mediated neuronal differentiation. [provided by RefSeq, Aug 2014]

Primary Disease Associations & Inheritance

Woolly hair-skin fragility syndromeMIM #620415
AR
88
ClinVar variants
13
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TUFT1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
13 Pathogenic / Likely Pathogenic· 55 VUS of 88 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.71LOEUF
pLI 0.000
Z-score 2.67
OE 0.43 (0.27–0.71)
Tolerant

Typical tolerance to LoF variation

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.
0.90Z-score
OE missense 0.83 (0.74–0.94)
186 obs / 223.8 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.0.43 (0.27–0.71)
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 (0.74–0.94)
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.0.85
0≤1.21.6
LoF obs/exp: 11 / 25.6Missense obs/exp: 186 / 223.8Syn Z: 1.04

ClinVar Variant Classifications

88 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic12
Likely Pathogenic1
VUS55
Likely Benign5
Benign2
12
Pathogenic
1
Likely Pathogenic
55
VUS
5
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
10
0
12
Likely Pathogenic
0
0
1
0
1
VUS
0
52
3
0
55
Likely Benign
0
5
0
0
5
Benign
0
2
0
0
2
Total25914075

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

View in ClinVar →

Protein Context — Lollipop Plot

TUFT1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

TUFT1-related woolly hair and superficial skin fragility

limited
ARUndeterminedAltered Gene Product Structure
Skin
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
TUFTELIN; TUFT1
MIM #600087 · *

Woolly hair-skin fragility syndrome

MIM #620415

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deficiency of Transcription Factor Sp1 Contributes to Hypertrophic Cardiomyopathy.
Zhang F et al.·Circ Res
2024
TUFT1 regulates cancer progression by suppressing centrosome amplification and mitotic spindle multipolarity.
Feng S et al.·Cell Death Dis
2025
Assessment of TUFT1 and Rac1-GTP levels in triple-negative breast cancer patients: clinical and pathological correlations.
Shi SF et al.·Clin Transl Oncol
2024Cohort
Biallelic TUFT1 variants cause woolly hair, superficial skin fragility and desmosomal defects.
Jackson A et al.·Br J Dermatol
2023
Dental caries: Genetic and protein interactions.
Cavallari T et al.·Arch Oral Biol
2019
Oncogenic tuftelin 1 as a potential molecular-targeted for inhibiting hepatocellular carcinoma growth.
Wu MN et al.·World J Gastroenterol
2021
Disruption of TUFT1, a Desmosome-Associated Protein, Causes Skin Fragility, Woolly Hair, and Palmoplantar Keratoderma.
Verkerk AJMH et al.·J Invest Dermatol
2024
The Role of Tuftelin-1 in Mesomesenchymal Transition of Pleural Mesothelial Cells and the Progression of Pleural Fibrosis.
Jeffers A et al.·Am J Respir Cell Mol Biol
2025
SUMOylation of TUFT1 is essential for gastric cancer progression through AKT/mTOR signaling pathway activation.
Wang T et al.·Cancer Sci
2023
Impact of tooth mineral tissues genes on dental caries: A birth-cohort study.
Chisini LA et al.·J Dent
2023Cohort
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