TCEAL1

Chr X

transcription elongation factor A like 1

Also known as: HIJRS, NEDGFAX, SIIR, WEX9, p21, pp21

NCBI Gene: 9338 ENSG00000172465 UniProt: Q15170

TCEAL1 encodes a transcriptional regulator that modulates viral and cellular promoter activity in a context-dependent manner without directly binding DNA. Mutations cause Hijazi-Reis syndrome, an X-linked dominant disorder affecting neurological development. The gene shows moderate constraint against loss-of-function variants.

ResearchSummary from OMIM, UniProt

This gene encodes a member of the transcription elongation factor A (SII)-like (TCEAL) gene family. Members of this family may function as nuclear phosphoproteins that modulate transcription in a promoter context-dependent manner. The encoded protein is similar to transcription elongation factor A/transcription factor SII and contains a zinc finger-like motif as well as a sequence related to the transcription factor SII Pol II-binding region. It may exert its effects via protein-protein interactions with other transcriptional regulators rather than via direct binding of DNA. Multiple family members are located on the X chromosome. Alternative splicing results in multiple transcript variants encoding a single isoform. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

DNmechanismLOEUF 1.07

Clinical Summary— TCEAL1

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.59) — some intolerance to loss-of-function variants.

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ClinVar Variants

14 unique Pathogenic / Likely Pathogenic· 18 VUS of 43 total submissions

Explore recent and relevant literature in Research Assistant →

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

1.07LOEUF

pLI 0.586

Z-score 1.53

OE 0.00 (0.00–1.07)

Moderately constrained

Highly tolerant — LoF variants common in population

Missense Constraint?

1.05Z-score

OE missense 0.61 (0.47–0.81)

35 obs / 57.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.00 (0.00–1.07)

0≤0.351.4

Missense OE?0.61 (0.47–0.81)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 2.7Missense obs/exp: 35 / 57.3Syn Z: -0.03

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateTCEAL1-related neurodevelopmental disorderOTHERXLR

This gene — mechanism propensity

0.6260th %ile

GOF

0.5953th %ile

LOF

0.4038th %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.

ClinVar Variant Classifications

43 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic1

Likely Pathogenic13

VUS18

Likely Benign4

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	1	0	0	0	1
Likely Pathogenic	10	1	2	0	13
VUS	3	15	0	0	18
Likely Benign	0	2	0	2	4
Benign	0	0	0	0	0
Conflicting	—				1
Total	14	18	2	2	37

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

View in ClinVar →

83 pathogenic / likely-pathogenic (of 90) ClinVar copy-number / structural variants overlap TCEAL1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →