UVSSA

protein-coding

UV stimulated scaffold protein A

Gene summary

The protein encoded by this gene appears to be involved in ubiquitination and dephosphorylation of RNA polymerase II subunits that stall after UV irradiation. The encoded protein interacts with several members of the nucleotide excision repair complex, and is thought to be involved in the transcription-coupled nucleotide excision repair (TC-NER) pathway to help remove lesions in the DNA that block transcription. Defects in this gene can cause UV-sensitive syndrome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

Previous symbols:

KIAA1530

MANE transcript

NM_020894.4

Inheritance

ClinVar variants

P:13U:168B:29

Top phenotype

UV-sensitive syndrome 3

gnomAD constraint

pLI —, LoF o/e 1.12

Max pathogenic AF

—

Genomic locus

chr4:1,345,691-1,395,989

External References & Databases

Ensembl (ENSG00000163945)

Transcript & Mutation Effects

hg38 • Region Span ~50.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

UV-sensitive syndrome 3DEFINITIVE

Inheritance Pattern: AR

Disease ID:MONDO:0013834

Submitter: G2P

UV-sensitive syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0015797

Submitter: Orphanet

UV-sensitive syndrome 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013834

Submitter: Labcorp Genetics (formerly Invitae)

UV-sensitive syndrome 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0013834

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

UV-sensitive syndrome 3AR

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Comments: Increased risk of skin tumors has not been reported

Refs: 7513056; 3974603; 3774595; 22466610; 22466612

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to UVSSA variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 169

not providedTotal: 20

UVSSA-related disorderTotal: 12

UV-sensitive syndrome 3Total: 10

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020894.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	9 clinvar	1 clinvar	13
missense	1 clinvar		162 clinvar	19 clinvar		182
nonsense	2 clinvar	3 clinvar				5
start loss						0
frameshift	2 clinvar	3 clinvar				5
splice donor/acceptor (+/-2bp)	1 clinvar	1 clinvar	3 clinvar			5
Total	6	7	168	28	1	210

Highest pathogenic variant AF is 0.000006927031

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 57 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020894.4	RefSeq	NP_065945.2	13	MANE Select
ENST00000389851.10	Ensembl	ENSP00000374501.4	13	MANE Select
NM_001317934.2	RefSeq	NP_001304863.1	13	Standard
NM_001317935.2	RefSeq	NP_001304864.1	13	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

transcription-coupled nucleotide-excision repair
response to UV
protein ubiquitination

Molecular Function

RNA polymerase II complex binding
protein binding

Cellular Component

nucleoplasm
chromosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389851
Coding exons: 13
Length: 40784
Individuals with no LoFs: 125647
Homozygous LoFs: 0
Heterozygous LoFs: 101
Defined: 125748
p: 0.000402

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-2.03	593	469	1.26	0.0000325	4581
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00045	0.00043	rare
Latino/Admixed American	0.00012	0.00012	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00077	0.00076	rare
Finnish	0.0011	0.0010	notable
European (Non-Finnish)	0.00020	0.00019	rare
South Asian	0.0012	0.00098	notable
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

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.;

Intolerance Scores

RVIS EVS: -1.03
RVIS percentile EVS: 7.87

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N

Gene Damage Prediction

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