TCF25

Chr 16

TCF25 ribosome quality control complex subunit

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

NCBI Gene: 22980 ENSG00000141002 UniProt: Q9BQ70 OMIM: 612326

TCF25 encodes a transcription factor that functions as a component of the ribosome quality control complex, which mediates ubiquitination and degradation of incompletely synthesized proteins. Mutations cause autosomal recessive intellectual disability with seizures and language delay, typically presenting in early childhood. This gene shows significant constraint against loss-of-function variants (LOEUF 0.402), indicating that complete loss of protein function is likely deleterious.

OMIM ResearchSummary from RefSeq, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOEUF 0.40

Clinical Summary— TCF25

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.22) despite low pLI — interpret in context.

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ClinVar Variants

123 VUS of 168 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

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?

-0.04Z-score

OE missense 1.01 (0.93–1.09)

424 obs / 421.8 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.22 (0.13–0.40)

0≤0.351.4

Missense OE?1.01 (0.93–1.09)

0≤0.61.4

Synonymous OE?1.21

0≤1.21.6

LoF obs/exp: 8 / 35.9Missense obs/exp: 424 / 421.8Syn Z: -2.16

ClinVar Variant Classifications

168 submitted variants in ClinVar

ClinVar

Classification Summary

VUS123

Likely Benign16

Benign1

123

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	122	1	0	123
Likely Benign	13	1	2	16
Benign	0	1	0	1
Total	135	3	2	140

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

View in ClinVar →

40 pathogenic / likely-pathogenic (of 67) ClinVar copy-number / structural variants overlap TCF25 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →