TCF25

Chr 16

TCF25 ribosome quality control complex subunit

Also known as: FKSG26, Hulp1, NULP1, PRO2620, hKIAA1049

NCBI Gene: 22980ENSG00000141002UniProt: Q9BQ70

TCF25 is a member of the basic helix-loop-helix (bHLH) family of transcription factors that are important in embryonic development (Steen and Lindholm, 2008 [PubMed 18068114]).[supplied by OMIM, Sep 2008]

0
Active trials
39
Pathogenic / LP
202
ClinVar variants
6
Pubs (1 yr)
-0.0
Missense Z
0.40
LOEUF
Clinical Summary— TCF25
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 146 VUS of 202 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.40LOEUF
pLI 0.416
Z-score 4.32
OE 0.22 (0.13–0.40)
Moderately constrained

More LoF-intolerant than ~75% 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.
-0.04Z-score
OE missense 1.01 (0.93–1.09)
424 obs / 421.8 exp
Tolerant

Tolerant to missense variation

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.0.22 (0.13–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.93–1.09)
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.1.21
0≤1.21.6
LoF obs/exp: 8 / 35.9Missense obs/exp: 424 / 421.8Syn Z: -2.16

ClinVar Variant Classifications

202 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic6
VUS146
Likely Benign16
Benign1
33
Pathogenic
6
Likely Pathogenic
146
VUS
16
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
33
0
33
Likely Pathogenic
0
0
6
0
6
VUS
0
121
25
0
146
Likely Benign
0
13
1
2
16
Benign
0
0
1
0
1
Total0134662202

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

View in ClinVar →

Protein Context — Lollipop Plot

TCF25 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Transcriptional profile of ribosome-associated quality control components and their associated phenotypes in mammalian cells
Dos Santos OAL et al.·Sci Rep
2024
Transcription factor 25 modulates gametocytogenesis and ribosome biogenesis in the malaria parasite Plasmodium falciparum.
Wu J et al.·Front Cell Infect Microbiol
2025
The ribosome-associated quality control factor TCF25 imposes K48 specificity on Listerin-mediated ubiquitination of nascent chains by binding and specifically orienting the acceptor ubiquitin
Abaeva IS et al.·bioRxiv
2024
Unraveling the population genetic structure and identifying candidate genes for dorsal plumage color in Liangshan Yanying chickens
Yu J et al.·Poult Sci
2025
Whole genome resequencing uncovers candidate genes related to plumage color in Yuexi frizzled feather chicken
Peng S et al.·Poult Sci
2025
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 3 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients