Human Gene Module / Chromosome 3 / UBA7

UBA7ubiquitin like modifier activating enzyme 7

SFARI Gene Score
2
Strong Candidate Criteria 2.1
Autism Reports / Total Reports
4 / 4
Rare Variants / Common Variants
6 / 0
Aliases
-
Associated Syndromes
-
Chromosome Band
3p21.31
Associated Disorders
-
Relevance to Autism

Bandi et al., 2026 reported three unrelated individuals with homozygous truncating variants in the UBA7 gene presenting with a neurodevelopmental disorder characterized by developmental delay, intellectual disability, autism, and nonspecific dysmorphic features; truncating variants resulted in loss of catalytic activity, protein stability, and localization, and patient fibroblasts with the p.Lys709SerfsTer45 variant demonstrated reduced UBA7 transcript, production of a truncated and unstable UBA7 protein, and an inability to induce ISGylation upon interferon beta treatment, indicating a dysfunctional ISGylation system. De novo and inherited heterozygous loss-of-function and missense variants have been identified in ASD probands from the Autism Sequencing Consortium, the SPARK cohort, and the mAGRE cohort (Satterstrom et al., 2020; Trost et al., 2022; Cirnigliaro et al., 2023).

Molecular Function

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme is a retinoid target that triggers promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) degradation and apoptosis in acute promyelocytic leukemia, where it is involved in the conjugation of the ubiquitin-like interferon-stimulated gene 15 protein.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to UBA7 (4 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Support - Zhou X et al. (2022) Yes -
2 Support - Trost B et al. (2022) Yes -
3 Support - Cirnigliaro M et al. (2023) Yes -
4 Primary - Bandi, Venkateshwarlu et al. (2026) Yes Epilepsy/seizures
Rare Variants   (6)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.542T>C p.Ile181Thr missense_variant De novo - Multiplex 36368308 Trost B et al. (2022)
c.508_523dup p.Glu175GlyfsTer36 frameshift_variant De novo - - 35982159 Zhou X et al. (2022)
c.694+1G>A p.? splice_site_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.933G>A p.Trp311Ter stop_gained Familial Both parents Simplex 42023152 Bandi, Venkateshwarlu et al. (2026)
c.2126_2129del p.Lys709SerfsTer45 frameshift_variant Familial Maternal Multiplex 37506195 Cirnigliaro M et al. (2023)
c.2126_2129del p.Lys709SerfsTer45 frameshift_variant Familial Both parents Simplex 42023152 Bandi, Venkateshwarlu et al. (2026)
Common Variants  

No common variants reported.

SFARI Gene score
2

Strong Candidate

criteria met
See SFARI Gene'scoring criteria
2

Strong Candidate

See all Category 2 Genes

We considered a rigorous statistical comparison between cases and controls, yielding genome-wide statistical significance, with independent replication, to be the strongest possible evidence for a gene. These criteria were relaxed slightly for category 2.

4/1/2026
2

Initial score established: 2

Krishnan Probability Score

Score 0.32995417666229

Ranking 24901/25841 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 2.6822779774153E-14

Ranking 17572/18225 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 0.94871613462763

Ranking 17797/18665 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 -0.035679955692141

Ranking 9890/20870 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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