TTF1

Chr 9

transcription termination factor 1

Also known as: TTF-1, TTF-I

The protein is a multifunctional nucleolar transcription termination factor that terminates ribosomal gene transcription by binding to Sal box terminator elements and regulates RNA polymerase I transcription on chromatin. The gene has extremely low loss-of-function intolerance (pLI ~0) and normal LOEUF score (0.94), indicating mutations are likely tolerated without causing disease. No specific disease associations are established for this gene based on the provided information.

Summary from RefSeq, UniProt
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1
Active trials
75
Pubs (1 yr)
35
P/LP submissions
0%
P/LP missense
0.94
LOEUF
DN
Mechanism· predicted
Clinical SummaryTTF1
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
35 unique Pathogenic / Likely Pathogenic· 137 VUS of 206 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.85
OE 0.67 (0.490.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.11Z-score
OE missense 0.99 (0.911.06)
476 obs / 482.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.490.94)
00.351.4
Missense OE0.99 (0.911.06)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 25 / 37.2Missense obs/exp: 476 / 482.6Syn Z: -0.55
DN
0.6745th %ile
GOF
0.5464th %ile
LOF
0.3841th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

206 submitted variants in ClinVar

Classification Summary

Pathogenic34
Likely Pathogenic1
VUS137
Likely Benign19
Benign5
Conflicting1
34
Pathogenic
1
Likely Pathogenic
137
VUS
19
Likely Benign
5
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
34
0
34
Likely Pathogenic
0
0
1
0
1
VUS
2
125
10
0
137
Likely Benign
0
17
0
2
19
Benign
0
3
0
2
5
Conflicting
1
Total2145454197

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

View in ClinVar →

Protein Context — Lollipop Plot

TTF1 · protein map & ClinVar variants

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

Clinical Literature
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