Human Gene Module / Chromosome 3 / XPC

XPCxeroderma pigmentosum, complementation group C

SFARI Gene Score
S
Syndromic Syndromic
Autism Reports / Total Reports
3 / 12
Rare Variants / Common Variants
8 / 0
Aliases
XPC, XP3,  XPCC
Associated Syndromes
-
Chromosome Band
3p25.1
Associated Disorders
ASD
Relevance to Autism

Rare mutations in the XPC gene have been identified with autism (Khan et al., 1998). In addition, XPC mutations have been found to be identified with xeroderma pigmentosum (syndromic with autism), where a subpopulation of individuals with XP develop autism.

Molecular Function

This gene encodes a component of the nucleotide excision repair (NER) pathway. It acts as a damage-sensing and DNA-binding factor component of the XPC complex.

External Links
Gene CardOpen Targets PlatformgnomAD browserPubMed
Human
Entrez GeneOMIMUniProtHumanBaseVariCarta
SFARI Genomic Platforms
GPF browser SFARI genome browser
Reports related to XPC (12 Reports)
# Type Title Author, Year Autism Report Associated Disorders
1 Highly Cited Hypoglycinaemia and psychomotor delay in a child with xeroderma pigmentosum Quackenbush EJ , et al. (1999) No -
2 Highly Cited UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin ligase complex Sugasawa K , et al. (2005) No -
3 Highly Cited Structure of a peptide:N-glycanase-Rad23 complex: insight into the deglycosylation for denatured glycoproteins Lee JH , et al. (2005) No -
4 Highly Cited The DNA repair-ubiquitin-associated HR23 proteins are constituents of neuronal inclusions in specific neurodegenerative disorders without hampering DNA repair Bergink S , et al. (2006) No -
5 Support Extending the phenotypic spectrum of RBFOX1 deletions: Sporadic focal epilepsy Lal D , et al. (2015) No -
6 Support Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks Ruzzo EK , et al. (2019) Yes -
7 Support Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes Feliciano P et al. (2019) Yes -
8 Support - Zhou X et al. (2022) Yes -
9 Recent Recommendation High susceptibility to ultraviolet-induced carcinogenesis in mice lacking XPC Sands AT , et al. (1995) No -
10 Recent Recommendation HHR23B, a human Rad23 homolog, stimulates XPC protein in nucleotide excision repair in vitro Sugasawa K , et al. (1996) No -
11 Recent Recommendation Two human homologs of Rad23 are functionally interchangeable in complex formation and stimulation of XPC repair activity Sugasawa K , et al. (1997) No -
12 Primary Xeroderma pigmentosum group C splice mutation associated with autism and hypoglycinemia Khan SG , et al. (1998) No ASD
Rare Variants   (8)
Status Allele Change Residue Change Variant Type Inheritance Pattern Parental Transmission Family Type PubMed ID Author, Year
c.-44+8A>G - intron_variant De novo - - 35982159 Zhou X et al. (2022)
c.1615G>T p.Glu539Ter stop_gained De novo - - 35982159 Zhou X et al. (2022)
T>G IVS9DS splice_site_variant Unknown - Unknown 9804340 Khan SG , et al. (1998)
c.1569A>G p.Arg523%3D synonymous_variant De novo - - 35982159 Zhou X et al. (2022)
c.406-54C>T - stop_gained Familial Maternal Multiplex 31398340 Ruzzo EK , et al. (2019)
c.408G>A p.Ala136= splice_region_variant De novo - - 31452935 Feliciano P et al. (2019)
c.2047A>C p.Thr683Pro missense_variant De novo - Multiplex 35982159 Zhou X et al. (2022)
c.1761+1G>A - splice_site_variant Familial Paternal Multiplex 31398340 Ruzzo EK , et al. (2019)
Common Variants  

No common variants reported.

SFARI Gene score
S

Syndromic

Mutations in the XPC gene are responsible for xeroderma pigmentosum group C (OMIM 278720), a condition characterized by increased sensitivity to UV irradiation and increased risk of skin cancer. Splice-site variants in the XPC gene have been identified in patients with xeroderma pigmentosum group C and unusual neurologic features, including absent speech, hyperactivity, and autistic features (Khan et al., 1998; Quackenbush et al., 1999).

Score Delta: Score remained at S

criteria met
See SFARI Gene'scoring criteria
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."

10/1/2019
S
icon
S

Score remained at S

New Scoring Scheme
Description

Mutations in the XPC gene are responsible for xeroderma pigmentosum group C (OMIM 278720), a condition characterized by increased sensitivity to UV irradiation and increased risk of skin cancer. Splice-site variants in the XPC gene have been identified in patients with xeroderma pigmentosum group C and unusual neurologic features, including absent speech, hyperactivity, and autistic features (Khan et al., 1998; Quackenbush et al., 1999).

Reports Added
[Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes2019] [New Scoring Scheme]
7/1/2019
S
icon
S

Score remained at S

Description

Mutations in the XPC gene are responsible for xeroderma pigmentosum group C (OMIM 278720), a condition characterized by increased sensitivity to UV irradiation and increased risk of skin cancer. Splice-site variants in the XPC gene have been identified in patients with xeroderma pigmentosum group C and unusual neurologic features, including absent speech, hyperactivity, and autistic features (Khan et al., 1998; Quackenbush et al., 1999).

Reports Added
[Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.2019]
Krishnan Probability Score

Score 0.40783634723575

Ranking 23003/25841 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 1.3171334179309E-10

Ranking 16896/18225 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 0.9495032514751

Ranking 18117/18665 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 0.30666231655106

Ranking 2635/20870 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
External PIN Data
BioGRIDHuman Protein Reference Database
Interactome
Interaction Table
Interactor Symbol Interactor Name Interactor Organism Interactor Type Entrez ID Uniprot ID
ALX3 Homeobox protein aristaless-like 3 Human Protein Binding 257 O95076
APLF Aprataxin and PNK-like factor Human Protein Binding 200558 Q8IW19
APOBEC3C DNA dC->dU-editing enzyme APOBEC-3C Human Protein Binding 27350 Q9NRW3
NAA40 N-alpha-acetyltransferase 40 Human Protein Binding 79829 Q86UY6
POLB DNA polymerase beta Human Protein Binding 5423 P06746
RPA4 Replication protein A 30 kDa subunit Human Protein Binding 29935 Q13156
SPIN2B Spindlin-2B Human Protein Binding 474343 Q9BPZ2
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