TUFT1

Chr 1

tuftelin 1

Also known as: WHSF

NCBI Gene: 7286 ENSG00000143367 UniProt: Q9NNX1

Tuftelin is an acidic protein involved in dental enamel mineralization and structural organization of the epidermis. Mutations cause woolly hair-skin fragility syndrome, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants (LOEUF 0.711), reflecting its importance in epidermal and dental development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtWoolly hair-skin fragility syndrome

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.71

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.71LOEUF

pLI 0.000

Z-score 2.67

OE 0.43 (0.27–0.71)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.90Z-score

OE missense 0.83 (0.74–0.94)

186 obs / 223.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.43 (0.27–0.71)

0≤0.351.4

Missense OE?0.83 (0.74–0.94)

0≤0.61.4

Synonymous OE?0.85

0≤1.21.6

LoF obs/exp: 11 / 25.6Missense obs/exp: 186 / 223.8Syn Z: 1.04

Background carrier burden — how many people carry a rare variant somewhere in TUFT1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 140

488 rare PASS variants

Rare truncating (LoF)

1 in 1,100

79 rare PASS variants

Rare synonymous (reference)

1 in 320

183 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for TUFT1. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 210	1 in 1,400
South Asian	~43k	1 in 75	1 in 1,900
Remaining (unassigned)	~30k	1 in 130	1 in 1,000
European (Finnish)	~27k	1 in 510	1 in 2,400
Admixed American	~22k	1 in 130	1 in 2,800
African / African American	~21k	1 in 88	1 in 3,200
East Asian	~20k	1 in 170	1 in 1,500
Ashkenazi Jewish	~13k	1 in 230	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 95	1 in 480

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓