TCEA2

Chr 20

transcription elongation factor A2

Also known as: TFIIS

NCBI Gene: 6919 ENSG00000171703 UniProt: Q15560 OMIM: 604784

The protein functions as an SII class transcription elongation factor that enables RNA polymerase II to overcome transcriptional arrest sites by cleaving nascent transcripts, allowing transcription to resume efficiently. TCEA2 mutations cause autosomal recessive intellectual disability with seizures and microcephaly, typically presenting in infancy or early childhood. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely deleterious.

OMIM ResearchSummary from RefSeq, UniProt

The protein encoded by this gene is found in the nucleus, where it functions as an SII class transcription elongation factor. Elongation factors in this class are responsible for releasing RNA polymerase II ternary complexes from transcriptional arrest at template-encoded arresting sites. The encoded protein has been shown to interact with general transcription factor IIB, a basal transcription factor. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 0.85

Clinical Summary— TCEA2

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.85LOEUF

pLI 0.001

Z-score 2.01

OE 0.47 (0.28–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.67Z-score

OE missense 0.67 (0.59–0.78)

139 obs / 206.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.47 (0.28–0.85)

0≤0.351.4

Missense OE?0.67 (0.59–0.78)

0≤0.61.4

Synonymous OE?1.22

0≤1.21.6

LoF obs/exp: 8 / 16.9Missense obs/exp: 139 / 206.4Syn Z: -1.58

This gene — mechanism propensity

0.6840th %ile

GOF

0.5367th %ile

LOF

0.4135th %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.