TCFL5

Chr 20

transcription factor like 5

Also known as: CHA, E2BP-1, Figlb, SOSF1, bHLHe82

This gene encodes a transcription factor that represses RNA polymerase II-mediated gene transcription and regulates cell proliferation and spermatogenesis. Mutations cause autosomal recessive developmental and epileptic encephalopathy with microcephaly. The gene is highly constrained against loss-of-function variants (pLI=0.99, LOEUF=0.26), indicating that complete loss of function is likely not tolerated in humans.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
3
Pubs (1 yr)
31
P/LP submissions
0%
P/LP missense
0.26
LOEUF· LoF intol.
LOF
Mechanism· predicted
Clinical SummaryTCFL5
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
31 unique Pathogenic / Likely Pathogenic· 98 VUS of 141 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.26LOEUF
pLI 0.991
Z-score 3.78
OE 0.05 (0.020.26)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.10Z-score
OE missense 0.78 (0.690.89)
157 obs / 200.8 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.05 (0.020.26)
00.351.4
Missense OE0.78 (0.690.89)
00.61.4
Synonymous OE1.05
01.21.6
LoF obs/exp: 1 / 18.6Missense obs/exp: 157 / 200.8Syn Z: -0.38
DN
0.2898th %ile
GOF
0.2895th %ile
LOF
0.80top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.26

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

141 submitted variants in ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic6
VUS98
Likely Benign2
Conflicting1
25
Pathogenic
6
Likely Pathogenic
98
VUS
2
Likely Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
6
0
6
VUS
0
84
14
0
98
Likely Benign
0
1
0
1
2
Benign
0
0
0
0
0
Conflicting
1
Total085451132

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

View in ClinVar →

Protein Context — Lollipop Plot

TCFL5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗