UVSSA

UV stimulated scaffold protein A

Basic information

Region (hg38): 4:1345691-1395989

Previous symbols: [ "KIAA1530" ]

Links

ENSG00000163945 ∙ NCBI:57654 ∙ OMIM:614632 ∙ HGNC:29304 ∙ Uniprot:Q2YD98 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• UV-sensitive syndrome 3 (Definitive), mode of inheritance: AR
• UV-sensitive syndrome (Supportive), mode of inheritance: AR
• UV-sensitive syndrome 3 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
UV-sensitive syndrome 3	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dermatologic	7513056; 3974603; 3774595; 22466610; 22466612
Increased risk of skin tumors has not been reported

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the UVSSA gene.

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the UVSSA gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				8	3	11
missense			59	13	2	74
nonsense						0
start loss			1			1
frameshift	1					1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				2		2
non coding			62	24	5	91
Total	1	0	122	45	10

Variants in UVSSA

This is a list of pathogenic ClinVar variants found in the UVSSA region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
4-1348089-G-GATATGGATCAGAAA		UV-sensitive syndrome 3	Likely pathogenic (Nov 08, 2024)
4-1348150-T-C		not specified	Uncertain significance (Oct 21, 2024)
4-1348177-AG-A		UV-sensitive syndrome 3	Pathogenic (May 01, 2012)
4-1348185-T-C		UV-sensitive syndrome 3	Pathogenic (May 01, 2012)
4-1349546-C-T		not specified	Uncertain significance (Mar 06, 2023)
4-1349548-C-T		UVSSA-related disorder	Benign (Feb 25, 2020)
4-1349553-A-G		not specified	Uncertain significance (Aug 10, 2024)
4-1349591-G-A		not specified	Uncertain significance (Oct 08, 2024)
4-1349646-A-G		not specified	Uncertain significance (Sep 27, 2021)
4-1349671-C-A		not specified	Uncertain significance (May 15, 2024)
4-1349678-G-A		not specified	Uncertain significance (Sep 27, 2024)
4-1349703-C-G		not specified	Uncertain significance (Oct 04, 2024)
4-1349728-C-T		UVSSA-related disorder	Likely benign (Oct 28, 2019)
4-1349739-C-T		not specified	Likely benign (Aug 16, 2021)
4-1349740-G-A			Likely benign (Dec 31, 2019)
4-1349768-C-G		not specified	Uncertain significance (Jul 09, 2024)
4-1349768-C-T		not specified	Uncertain significance (Dec 15, 2023)
4-1349774-G-A		not specified	Uncertain significance (Mar 05, 2024)
4-1349792-A-T		UV-sensitive syndrome 3	Pathogenic (May 01, 2012)
4-1349811-A-G		not specified	Uncertain significance (Nov 25, 2024)
4-1349843-C-G			Uncertain significance (Jan 07, 2020)
4-1351731-C-T		not specified	Uncertain significance (Sep 06, 2022)
4-1351740-G-A		not specified	Uncertain significance (Dec 19, 2023)
4-1351744-T-G		not specified	Uncertain significance (Dec 19, 2022)
4-1351766-G-A		not specified	Uncertain significance (Aug 22, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
UVSSA	protein_coding	protein_coding	ENST00000389851	13	40784

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.41e-25	0.0000916	125647	0	101	125748	0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.03	593	469	1.26	0.0000325	4581
Missense in Polyphen		193	151.42	1.2746		1566
Synonymous	-1.51	228	201	1.14	0.0000147	1405
Loss of Function	-0.606	35	31.3	1.12	0.00000142	387

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000569	0.000547
Ashkenazi Jewish	0.00	0.00
East Asian	0.000772	0.000761
Finnish	0.00106	0.00102
European (Non-Finnish)	0.000201	0.000193
Middle Eastern	0.000772	0.000761
South Asian	0.00125	0.000980
Other	0.000329	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Factor involved in transcription-coupled nucleotide excision repair (TC-NER) in response to UV damage. TC-NER allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes. Acts by promoting stabilization of ERCC6 by recruiting deubiquitinating enzyme USP7 to TC-NER complexes, preventing UV-induced degradation of ERCC6 by the proteasome. Interacts with the elongating form of RNA polymerase II (RNA pol IIo) and facilitates its ubiquitination at UV damage sites, leading to promote RNA pol IIo backtracking to allow access to the nucleotide excision repair machinery. Not involved in processing oxidative damage. {ECO:0000269|PubMed:22466610, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612}.
• Disease: DISEASE: UV-sensitive syndrome 3 (UVSS3) [MIM:614640]: An autosomal recessive disorder characterized by cutaneous photosensitivity and slight dyspigmentation, without an increased risk of skin tumors. {ECO:0000269|PubMed:22466610, ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: DNA Repair;Formation of TC-NER Pre-Incision Complex;Dual incision in TC-NER;Gap-filling DNA repair synthesis and ligation in TC-NER;Transcription-Coupled Nucleotide Excision Repair (TC-NER);Nucleotide Excision Repair (Consensus)

Intolerance Scores

• rvis_EVS: -1.03
• rvis_percentile_EVS: 7.87

Haploinsufficiency Scores

• pHI: 0.0819
• hipred: N
• hipred_score: 0.170
• ghis: 0.558

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Uvssa

Gene ontology

• Biological process: transcription-coupled nucleotide-excision repair;response to UV;protein ubiquitination
• Cellular component: nucleoplasm;chromosome
• Molecular function: RNA polymerase II complex binding;protein binding