UV-sensitive syndrome 3

Summary

UV-sensitive syndrome 3 (MONDO:0013834) is a disease caused by UVSSA (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: UVSSA (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	UV-sensitive syndrome 3
Mondo ID	MONDO:0013834
OMIM	614640
NCIT	C173107
UMLS	C3553328
MedGen	766242
GARD	0015828
Is cancer (heuristic)	no

Also known as: UV-sensitive syndrome 3 · UV-sensitive syndrome caused by mutation in UVSSA · UV-sensitive syndrome type 3 · UVSS3 · UVSSA UV-sensitive syndrome

Data availability: 8 ClinVar variants · 3 GenCC gene-disease records · 5 cell lines.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › autosomal genetic disease › autosomal recessive disease › UV-sensitive syndrome › UV-sensitive syndrome 3

Related subtypes (2): UV-sensitive syndrome 1, UV-sensitive syndrome 2

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 3 likely pathogenic, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
31569	NM_020894.4(UVSSA):c.367A>T (p.Lys123Ter)	UVSSA	Pathogenic	no assertion criteria provided
31570	NM_020894.4(UVSSA):c.87del (p.Ile31fs)	UVSSA	Pathogenic	no assertion criteria provided
31571	NM_020894.4(UVSSA):c.94T>C (p.Cys32Arg)	UVSSA	Pathogenic	no assertion criteria provided
4530689	NM_020894.4(UVSSA):c.250C>T (p.Gln84Ter)	UVSSA	Pathogenic	criteria provided, single submitter
3383367	NM_020894.4(UVSSA):c.-2_12dup (p.Leu5fs)	UVSSA	Likely pathogenic	criteria provided, single submitter
4845707	NM_020894.4(UVSSA):c.707_713del (p.Gly236fs)	UVSSA	Likely pathogenic	criteria provided, single submitter
4849428	NM_020894.4(UVSSA):c.909C>G (p.Tyr303Ter)	UVSSA	Likely pathogenic	criteria provided, single submitter
802047	NM_020894.4(UVSSA):c.1859C>T (p.Pro620Leu)	UVSSA	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
UVSSA	Definitive	Autosomal recessive	UV-sensitive syndrome 3	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UVSSA	Orphanet:178338	UV-sensitive syndrome

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UVSSA	HGNC:29304	ENSG00000163945	Q2YD98	UV-stimulated scaffold protein A	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
UVSSA	UV-stimulated scaffold protein A	Factor involved in transcription-coupled nucleotide excision repair (TC-NER), a mechanism that rapidly removes RNA polymerase II-blocking lesions from the transcribed strand of active genes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UVSSA	Other/Unknown	no		ENTH_VHS, UVSSA, UVSSA_N_a-solenoid_rpt

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
oviduct epithelium	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
UVSSA	255	ubiquitous	marker	oviduct epithelium, pancreatic ductal cell, corpus epididymis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
UVSSA	949

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
UVSSA	Q2YD98	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1	265.6×	0.006	UVSSA
Formation of TC-NER Pre-Incision Complex	1	211.5×	0.006	UVSSA
Gap-filling DNA repair synthesis and ligation in TC-NER	1	178.4×	0.006	UVSSA
Dual incision in TC-NER	1	173.0×	0.006	UVSSA

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
transcription-coupled nucleotide-excision repair	1	1203.7×	0.002	UVSSA
response to UV	1	366.4×	0.004	UVSSA
protein ubiquitination	1	41.4×	0.024	UVSSA

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
UVSSA	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	UVSSA

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
UVSSA	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.