UV-sensitive syndrome

Summary

UV-sensitive syndrome (MONDO:0015797) is a disease with 3 cohort genes. The dominant Reactome pathway is Transcription-Coupled Nucleotide Excision Repair (TC-NER) (3 cohort genes).

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 3

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		7	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	UV-sensitive syndrome
Mondo ID	MONDO:0015797
MeSH	C563466
OMIM	600630
Orphanet	178338
DOID	DOID:0060240
SNOMED CT	698253007
UMLS	C1833561
MedGen	322222
GARD	0010947
Is cancer (heuristic)	no

Also known as: UV sensitive syndrome · UVSS

Data availability: 3 GenCC gene-disease records · 9 cell lines.

Disease family

An umbrella term covering 3 Mondo subtypes.

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

Related subtypes (218): immunodeficiency-centromeric instability-facial anomalies syndrome, hypercalcemia, infantile, Ochoa syndrome, autosomal recessive Ehlers-Danlos syndrome, vascular type, hydrolethalus syndrome, 3-M syndrome, isolated hyperchlorhidrosis, dacryocystitis-osteopoikilosis syndrome, Hutchinson-Gilford progeria syndrome, achalasia microcephaly syndrome, acrorenal syndrome, autosomal recessive, beta-ketothiolase deficiency, autosomal recessive Alport syndrome, Alstrom syndrome, microphthalmia with limb anomalies, camptodactyly-arthropathy-coxa vara-pericarditis syndrome, Behr syndrome, bifid nose, autosomal recessive, Bloom syndrome, Bowen-Conradi syndrome, camptodactyly with fibrous tissue hyperplasia and skeletal dysplasia, heart defects-limb shortening syndrome, autosomal recessive palmoplantar keratoderma and congenital alopecia, COFS syndrome, craniometaphyseal dysplasia, autosomal recessive, Fraser syndrome, cystic fibrosis, polycystic lipomembranous osteodysplasia with sclerosing leukoencephaly, persistent hyperplastic primary vitreous, autosomal recessive, Donnai-Barrow syndrome, Schöpf-Schulz-Passarge syndrome, cleft lip/palate-ectodermal dysplasia syndrome, Ellis-van Creveld syndrome, Wolcott-Rallison syndrome, autosomal recessive faciodigitogenital syndrome, acromesomelic dysplasia 2B, brittle cornea syndrome, triple-A syndrome, autosomal recessive humeroradial synostosis, multinucleated neurons-anhydramnios-renal dysplasia-cerebellar hypoplasia-hydranencephaly syndrome, hydrocephalus, nonsyndromic, autosomal recessive 1, autosomal recessive hydrocephalus due to congenital stenosis of aqueduct of Sylvius, hypertelorism, microtia, facial clefting syndrome, hypoparathyroidism-retardation-dysmorphism syndrome, Vici syndrome, Johanson-Blizzard syndrome, autosomal recessive Kenny-Caffey syndrome, Papillon-Lefevre disease, Haim-Munk syndrome, Laurence-Moon syndrome, Donohue syndrome, lipase deficiency, combined, autosomal recessive familial Mediterranean fever, thiamine-responsive megaloblastic anemia syndrome, cartilage-hair hypoplasia, Nijmegen breakage syndrome, pseudo-TORCH syndrome, Galloway-Mowat syndrome, mulibrey nanism, myotonia congenita, autosomal recessive, Schwartz-Jampel syndrome, proteosome-associated autoinflammatory syndrome, Netherton syndrome, Niemann-Pick disease type A, oculodentodigital dysplasia, autosomal recessive, odonto-onycho-dermal dysplasia, autosomal recessive omodysplasia, osteoporosis-pseudoglioma syndrome, Shwachman-Diamond syndrome, phenylketonuria, Bjornstad syndrome, Laron syndrome, autosomal recessive polycystic kidney disease, autosomal recessive inherited pseudoxanthoma elasticum, autosomal recessive multiple pterygium syndrome, rapadilino syndrome, short-rib thoracic dysplasia 9 with or without polydactyly, autosomal recessive Robinow syndrome, Sjogren-Larsson syndrome, scapuloperoneal spinal muscular atrophy, autosomal recessive, spondyloepiphyseal dysplasia tarda, autosomal recessive, inherited threoninemia, Pendred syndrome, autosomal recessive spondylocostal dysostosis, Werner syndrome, ABCD syndrome, Naxos disease, autosomal recessive amelia, human HOXA1 syndromes, sickle cell disease, autosomal recessive proximal renal tubular acidosis, hyper-IgM syndrome type 2, temtamy preaxial brachydactyly syndrome, TH-deficient dopa-responsive dystonia, craniosynostosis syndrome, autosomal recessive, Niemann-Pick disease type B, skin fragility-woolly hair-palmoplantar keratoderma syndrome, CoQ-responsive OXPHOS deficiency, familial adenomatous polyposis 2, Pierson syndrome, palmoplantar keratoderma-XX sex reversal-predisposition to squamous cell carcinoma syndrome, cardiomyopathy-hypotonia-lactic acidosis syndrome, PHARC syndrome, Kahrizi syndrome, cutis laxa with severe pulmonary, gastrointestinal and urinary anomalies, congenital prothrombin deficiency, immunodeficiency 31B, dyskeratosis congenita, autosomal recessive 2, dyskeratosis congenita, autosomal recessive 3, Nestor-Guillermo progeria syndrome, leukoencephalopathy with calcifications and cysts, mitochondrial pyruvate carrier deficiency, branched-chain keto acid dehydrogenase kinase deficiency, dyskeratosis congenita, autosomal recessive 5, hypohidrosis-enamel hypoplasia-palmoplantar keratoderma-intellectual disability syndrome, alacrima, achalasia, and intellectual disability syndrome, hyperlipoproteinemia, type 1D, microcephaly and chorioretinopathy 2, congenital stationary night blindness 1G, combined oxidative phosphorylation deficiency 29, hypermanganesemia with dystonia 2, growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy, gnb5-related intellectual disability-cardiac arrhythmia syndrome, autosomal recessive spastic paraplegia type 78, autosomal recessive limb-girdle muscular dystrophy, Bardet-Biedl syndrome, autosomal recessive cerebellar ataxia, neuronopathy, distal hereditary motor, autosomal recessive, Ehlers-Danlos syndrome, kyphoscoliotic type 1, Cockayne syndrome, hyperphenylalaninemia due to tetrahydrobiopterin deficiency, leukoencephalopathy-palmoplantar keratoderma syndrome, autosomal recessive hypohidrotic ectodermal dysplasia, Warburg micro syndrome, autosomal recessive primary microcephaly, autosomal recessive progressive external ophthalmoplegia, Meier-Gorlin syndrome, autosomal recessive sideroblastic anemia, autosomal recessive intermediate Charcot-Marie-Tooth disease, Perrault syndrome, autosomal recessive hypophosphatemic rickets, de Barsy syndrome, leukocyte adhesion deficiency, Senior-Loken syndrome, autosomal recessive spastic ataxia, childhood-onset autosomal recessive myopathy with external ophthalmoplegia, autosomal recessive cerebral atrophy, GM3 synthase deficiency, autosomal recessive distal renal tubular acidosis, pigmentation defects-palmoplantar keratoderma-skin carcinoma syndrome, autosomal recessive brachyolmia, Aicardi-Goutieres syndrome, homocystinuria without methylmalonic aciduria, Niemann-Pick disease type C, nephronophthisis, autosomal recessive osteopetrosis, peroxisome biogenesis disorder, congenital non-bullous ichthyosiform erythroderma, Seckel syndrome, Usher syndrome, autosomal recessive cutis laxa type 1, autosomal recessive cutis laxa type 2, hearing loss, autosomal recessive, microcephaly, growth restriction, and increased sister chromatid exchange 2, encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 1, congenital vertebral-cardiac-renal anomalies syndrome, hair defect with photosensitivity and intellectual disability syndrome, autosomal recessive severe congenital neutropenia, severe combined immunodeficiency due to CARMIL2 deficiency, extraoral halitosis due to methanethiol oxidase deficiency, neurodevelopmental disorder with microcephaly, impaired language, epilepsy, and gait abnormalities, mitochondrial complex 2 deficiency, nuclear type 3, mitochondrial complex 2 deficiency, nuclear type 4, mismatch repair cancer syndrome, spondyloepimetaphyseal dysplasia with joint laxity, type 3, Kilquist syndrome, Duane anomaly-myopathy-scoliosis syndrome, autosomal recessive axonal charcot-marie-tooth disease due to copper metabolism defect, immune dysregulation-inflammatory bowel disease-arthritis-recurrent infections-lymphopenia syndrome, optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome, congenital myopathy with reduced type 2 muscle fibers, NAD(P)HX dehydratase deficiency, autosomal recessive ocular albinism, ichthyosis linearis circumflexa, eosinophil peroxidase deficiency, hyperphenylalaninemia due to DNAJC12 deficiency, autosomal recessive epidermolytic ichthyosis, Ehlers-Danlos syndrome, classic-like, 2, joint laxity, short stature, and myopia, HELIX syndrome, auditory neuropathy-optic atrophy syndrome, glycosylphosphatidylinositol biosynthesis defect 15, neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures, SCN4A-related myopathy, autosomal recessive, Uner Tan Syndrome, nephropathic cystinosis, Imerslund-Grasbeck syndrome type 1, Imerslund-Grasbeck syndrome type 2, permanent neonatal diabetes mellitus 1, growth hormone insensitivity with immune dysregulation 1, autosomal recessive, Rajab interstitial lung disease with brain calcifications 1, Roberts-SC phocomelia syndrome, neurodevelopmental disorder with microcephaly, impaired language, and gait abnormalities, RPE65-related recessive retinopathy, GUCY2D-related recessive retinopathy, autosomal recessive titinopathy, intellectual disability, autosomal recessive, ALPL-related autosomal recessive hypophosphatasia, spastic paraplegia 18b, autosomal recessive, CEP164-related ciliopathy, RP1-related recessive retinopathy, pseudohypoaldosteronism, type IB2, autosomal recessive, pseudohypoaldosteronism, type IB3, autosomal recessive, spastic paraplegia 30B, autosomal recessive, cerebral arteriopathy, autosomal recessive, with subcortical infarcts and leukoencephalopathy 1, brain small vessel disease 2B, autosomal recessive, IMPG1-related recessive retinopathy, PROM1-related recessive retinopathy

Subtypes (3): UV-sensitive syndrome 1, UV-sensitive syndrome 2, UV-sensitive syndrome 3

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

No tiered GWAS variants or ClinVar records for this disease.

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 25 · Orphanet: 10 · 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
ERCC6	Strong	Autosomal recessive	UV-sensitive syndrome 1	11
ERCC8	Strong	Autosomal recessive	UV-sensitive syndrome 2	10

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
UVSSA	Orphanet:178338	UV-sensitive syndrome
ERCC6	Orphanet:1466	COFS syndrome
ERCC6	Orphanet:178338	UV-sensitive syndrome
ERCC6	Orphanet:90321	Cockayne syndrome type 1
ERCC6	Orphanet:90322	Cockayne syndrome type 2
ERCC6	Orphanet:90324	Cockayne syndrome type 3
ERCC8	Orphanet:178338	UV-sensitive syndrome
ERCC8	Orphanet:90321	Cockayne syndrome type 1
ERCC8	Orphanet:90322	Cockayne syndrome type 2
ERCC8	Orphanet:90324	Cockayne syndrome type 3

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
UVSSA	HGNC:29304	ENSG00000163945	Q2YD98	UV-stimulated scaffold protein A	gencc
ERCC6	HGNC:3438	ENSG00000225830	P0DP91	Chimeric ERCC6-PGBD3 protein	gencc
ERCC8	HGNC:3439	ENSG00000049167	Q13216	DNA excision repair protein ERCC-8	gencc

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.
ERCC6	Chimeric ERCC6-PGBD3 protein	Involved in repair of DNA damage following UV irradiation, acting either in the absence of ERCC6 or synergistically with ERCC6.
ERCC8	DNA excision repair protein ERCC-8	Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesio…

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 2 · 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
Scaffold/PPI	1	5.8×	0.327
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
UVSSA	Other/Unknown	no		ENTH_VHS, UVSSA, UVSSA_N_a-solenoid_rpt
ERCC6	Other/Unknown	no		PGBD, PiggyBac_TE-derived, CC_ERCC-6_N
ERCC8	Scaffold/PPI	no		WD40_rpt, WD40/YVTN_repeat-like_dom_sf, WD40_repeat_CS

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
corpus epididymis	1
oviduct epithelium	1
pancreatic ductal cell	1
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1
adrenal tissue	1
primordial germ cell in gonad	1
ventricular zone	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
ERCC6	257	ubiquitous	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
ERCC8	218	ubiquitous	yes	adrenal tissue, ventricular zone, primordial germ cell in gonad

Protein interactions among cohort

Intra-cohort edges: 3.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ERCC8	1,550
UVSSA	949
ERCC6	13

Intra-cohort edges

A	B	Sources
ERCC6	ERCC8	biogrid_interaction
ERCC6	UVSSA	biogrid_interaction
ERCC8	UVSSA	biogrid_interaction, string_interaction

Structural data

PDB: 3 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ERCC8	Q13216	16
UVSSA	Q2YD98	12
ERCC6	P0DP91	12

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 3 evidence-associated genes (3 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 3 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)	3	265.6×	4e-07	UVSSA, ERCC6, ERCC8
Formation of TC-NER Pre-Incision Complex	3	211.5×	4e-07	UVSSA, ERCC6, ERCC8
Gap-filling DNA repair synthesis and ligation in TC-NER	3	178.4×	4e-07	UVSSA, ERCC6, ERCC8
Dual incision in TC-NER	3	173.0×	4e-07	UVSSA, ERCC6, ERCC8
RNA Polymerase I Transcription Initiation	1	74.6×	0.021	ERCC6
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	1	50.8×	0.026	ERCC6
B-WICH complex positively regulates rRNA expression	1	40.5×	0.028	ERCC6
Neddylation	1	15.8×	0.062	ERCC8

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 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	3	1203.7×	2e-08	UVSSA, ERCC6, ERCC8
double-strand break repair via classical nonhomologous end joining	2	1123.5×	2e-05	ERCC6, ERCC8
single strand break repair	2	936.2×	2e-05	ERCC6, ERCC8
response to X-ray	2	591.3×	4e-05	ERCC6, ERCC8
response to UV	2	244.2×	2e-04	UVSSA, ERCC8
positive regulation of DNA repair	2	239.0×	2e-04	ERCC6, ERCC8
regulation of transcription-coupled nucleotide-excision repair	1	5617.3×	0.001	ERCC8
response to oxidative stress	2	87.1×	0.001	ERCC6, ERCC8
positive regulation of peptidyl-serine phosphorylation of STAT protein	1	2808.7×	0.002	ERCC6
pyrimidine dimer repair	1	1404.3×	0.003	ERCC6
response to superoxide	1	1123.5×	0.004	ERCC6
regulation of DNA-templated transcription elongation	1	936.2×	0.004	ERCC6
DNA protection	1	936.2×	0.004	ERCC6
transcription elongation by RNA polymerase I	1	702.2×	0.004	ERCC6
negative regulation of double-strand break repair via nonhomologous end joining	1	702.2×	0.004	ERCC6
response to UV-B	1	624.1×	0.005	ERCC6
protein ubiquitination	2	27.6×	0.005	UVSSA, ERCC8
positive regulation of DNA-templated transcription, elongation	1	432.1×	0.006	ERCC6
positive regulation of transcription by RNA polymerase III	1	312.1×	0.008	ERCC6
regulation of transcription elongation by RNA polymerase II	1	267.5×	0.009	ERCC6
response to auditory stimulus	1	244.2×	0.009	ERCC8
positive regulation of transcription by RNA polymerase I	1	216.1×	0.010	ERCC6
response to gamma radiation	1	193.7×	0.010	ERCC6
protein localization to chromatin	1	193.7×	0.010	ERCC6
positive regulation of defense response to virus by host	1	175.5×	0.010	ERCC6
base-excision repair	1	156.0×	0.011	ERCC6
DNA damage checkpoint signaling	1	130.6×	0.013	ERCC6
positive regulation of double-strand break repair via homologous recombination	1	127.7×	0.013	ERCC6
photoreceptor cell maintenance	1	119.5×	0.013	ERCC6
intrinsic apoptotic signaling pathway in response to DNA damage	1	108.0×	0.014	ERCC6

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 3 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
ERCC6	0	0
ERCC8	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	3	UVSSA, ERCC6, ERCC8

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
UVSSA	0	—
ERCC6	0	—
ERCC8	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.