Human Gene Module / Chromosome X / TCEAL1

TCEAL1transcription elongation factor A like 1

SFARI Gene Score
3S
Suggestive Evidence, Syndromic Criteria 3.1, Syndromic
Autism Reports / Total Reports
1 / 4
Rare Variants / Common Variants
12 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
Xq22.2
Associated Disorders
-
Relevance to Autism

TCEAL1 has previously been proposed to be a candidate gene for a neurological disease trait associated with Xq22.2 deletions in females consisting of hypotonia, intellectual disability, neurobehavioral abnormalities, and mildly dysmorphic facial features (Hijazi et al., 2020). Applying a gene-first approach and worldwide gene-matching, Hijazi et al., 2022 identified eight individuals with variants in the TCEAL1 gene presenting with a neurodevelopmental syndrome that overlapped with that described in females with Xq22.2 deletions, implicating TCEAL1 as the driver gene; individuals with TCEAL1 variants presented with a more-defined syndrome characterized by hypotonia, abnormal gait, developmental delay/intellectual disability, autistic behavior, and mildly dysmorphic facial features. A de novo frameshift variant in the TCEAL1 gene was also identified in a female ASD proband from the SPARK cohort in Zhou et al., 2022.

Molecular Function

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.

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Reports related to TCEAL1 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Hadia Hijazi et al. (2020) No Behavioral abnormalities
2 Support - Zhou X et al. (2022) Yes -
3 Primary - Hijazi H et al. (2022) No ASD or autistic behavior, stereotypy, epilepsy/sei
4 Support - Fatimah Albuainain et al. (2024) No Autistic features, stereotypy
Rare Variants   (12)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
- - copy_number_loss De novo - Simplex 36368327 Hijazi H et al. (2022)
c.259C>T p.Gln87Ter stop_gained De novo - Simplex 36368327 Hijazi H et al. (2022)
c.447G>A p.Trp149Ter stop_gained De novo - Simplex 36368327 Hijazi H et al. (2022)
c.269G>A p.Cys90Tyr missense_variant De novo - Simplex 36368327 Hijazi H et al. (2022)
c.285_286del p.His95GlnfsTer3 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.61G>T p.Glu21Ter stop_gained De novo - Simplex 38200082 Fatimah Albuainain et al. (2024)
c.151G>T p.Glu51Ter stop_gained De novo - Simplex 38200082 Fatimah Albuainain et al. (2024)
c.169del p.Leu57SerfsTer36 frameshift_variant De novo - Simplex 36368327 Hijazi H et al. (2022)
c.346G>A p.Asp116Asn missense_variant Familial Maternal Simplex 36368327 Hijazi H et al. (2022)
c.299_302del p.Gly100AlafsTer22 frameshift_variant De novo - Simplex 36368327 Hijazi H et al. (2022)
c.311_314del p.Glu104GlyfsTer18 frameshift_variant De novo - Simplex 38200082 Fatimah Albuainain et al. (2024)
c.324_333del p.Ser109AsnfsTer11 frameshift_variant De novo - Simplex 38200082 Fatimah Albuainain et al. (2024)
Common Variants  

No common variants reported.

SFARI Gene score
3S

Suggestive Evidence, Syndromic

Score Delta: Score remained at 3S

criteria met
See SFARI Gene'scoring criteria
3

Suggestive Evidence

See all Category 3 Genes

The literature is replete with relatively small studies of candidate genes, using either common or rare variant approaches, which do not reach the criteria set out for categories 1 and 2. Genes that had two such lines of supporting evidence were placed in category 3, and those with one line of evidence were placed in category 4. Some additional lines of "accessory evidence" (indicated as "acc" in the score cards) could also boost a gene from category 4 to 3.

S

Syndromic

See all Category S Genes

The syndromic category includes mutations that are associated with a substantial degree of increased risk and consistently linked to additional characteristics not required for an ASD diagnosis. If there is independent evidence implicating a gene in idiopathic ASD, it will be listed as "#S" (e.g., 2S, 3S, etc.). If there is no such independent evidence, the gene will be listed simply as "S."

1/1/2023
icon
3S

Increased from to 3S

Krishnan Probability Score

Score 0.46025957647048

Ranking 9482/25841 scored genes


[Show Scoring Methodology]
Krishnan and colleagues generated probability scores genome-wide by using a machine learning approach on a human brain-specific gene network. The method was first presented in Nat Neurosci 19, 1454-1462 (2016), and scores for more than 25,000 RefSeq genes can be accessed in column G of supplementary table 3 (see: http://www.nature.com/neuro/journal/v19/n11/extref/nn.4353-S5.xlsx). A searchable browser, with the ability to view networks of associated ASD risk genes, can be found at asd.princeton.edu.
Original Source
ExAC Score

Score 0.48864100396142

Ranking 5511/18225 scored genes


[Show Scoring Methodology]
The Exome Aggregation Consortium (ExAC) is a summary database of 60,706 exomes that has been widely used to estimate 'constraint' on mutation for individual genes. It was introduced by Lek et al. Nature 536, 285-291 (2016), and the ExAC browser can be found at exac.broadinstitute.org. The pLI score was developed as measure of intolerance to loss-of- function mutation. A pLI > 0.9 is generally viewed as highly constrained, and thus any loss-of- function mutations in autism in such a gene would be more likely to confer risk. For a full list of pLI scores see: ftp://ftp.broadinstitute.org/pub/ExAC_release/release0.3.1/functional_gene_constraint/fordist_cle aned_exac_nonTCGA_z_pli_rec_null_data.txt
Original Source
Sanders TADA Score

Score 0.89983189707659

Ranking 6364/18665 scored genes


[Show Scoring Methodology]
The TADA score ('Transmission and De novo Association') was introduced by He et al. PLoS Genet 9(8):e1003671 (2013), and is a statistic that integrates evidence from both de novo and transmitted mutations. It forms the basis for the claim of 65 individual genes being strongly associated with autism risk at a false discovery rate of 0.1 (Sanders et al. Neuron 87, 1215-1233 (2015)). The calculated TADA score for 18,665 RefSeq genes can be found in column P of Supplementary Table 6 in the Sanders et al. paper (the column headed 'tadaFdrAscSscExomeSscAgpSmallDel'), which represents a combined analysis of exome data and small de novo deletions (see www.cell.com/cms/attachment/2038545319/2052606711/mmc7.xlsx).
Original Source
Zhang D Score

Score -0.30423448422372

Ranking 17267/20870 scored genes


[Show Scoring Methodology]
The DAMAGES score (disease-associated mutation analysis using gene expression signatures), or D score, was developed to combine evidence from de novo loss-of- function mutation with evidence from cell-type- specific gene expression in the mouse brain (specifically translational profiles of 24 specific mouse CNS cell types isolated from 6 different brain regions). Genes with positive D scores are more likely to be associated with autism risk, with higher-confidence genes having higher D scores. This statistic was first presented by Zhang & Shen (Hum Mutat 38, 204- 215 (2017), and D scores for more than 20,000 RefSeq genes can be found in column M in supplementary table 2 from that paper.
Original Source
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