TCFL5

Chr 20

transcription factor like 5

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

NCBI Gene: 10732 ENSG00000101190 UniProt: Q9UL49 OMIM: 604745

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.

OMIM ResearchSummary from RefSeq, UniProt

Enables DNA-binding transcription repressor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of transcription by RNA polymerase II; regulation of cell population proliferation; and spermatogenesis. Located in nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.26

Clinical Summary— TCFL5

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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.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.26LOEUF

pLI 0.991

Z-score 3.78

OE 0.05 (0.02–0.26)

Highly constrained

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

Missense Constraint?

1.10Z-score

OE missense 0.78 (0.69–0.89)

157 obs / 200.8 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.05 (0.02–0.26)

0≤0.351.4

Missense OE?0.78 (0.69–0.89)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 1 / 18.6Missense obs/exp: 157 / 200.8Syn Z: -0.38

This gene — mechanism propensity

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.