Atelis syndrome 2

Summary

Atelis syndrome 2 (MONDO:0859576) is a disease caused by SMC5 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: SMC5 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Atelis syndrome 2
Mondo ID	MONDO:0859576
OMIM	620185
UMLS	C5774282
MedGen	1824055
GARD	0026749
Is cancer (heuristic)	no

Data availability: 4 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › hereditary neoplastic syndrome › mosaic variegated aneuploidy syndrome › Atelis syndrome 2

Related subtypes (6): mosaic variegated aneuploidy syndrome 1, mosaic variegated aneuploidy syndrome 2, mosaic variegated aneuploidy syndrome 3, mosaic variegated aneuploidy syndrome 4, mosaic variegated aneuploidy syndrome 7 with inflammation and tumor predisposition, Atelis syndrome 1

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

4 retrieved; paginated sample, class counts are floors:

3 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2443706	NM_015110.4(SMC5):c.1110GAG[1] (p.Arg372del)	SMC5	Pathogenic	no assertion criteria provided
2443707	NM_015110.4(SMC5):c.1273C>T (p.Arg425Ter)	SMC5	Pathogenic	no assertion criteria provided
2443708	NM_015110.4(SMC5):c.2968C>G (p.His990Asp)	SMC5	Pathogenic	no assertion criteria provided
4845894	NM_015110.4(SMC5):c.1694_1697del (p.Ser564_Tyr565insTer)	SMC5	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 0 · 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
SMC5	Strong	Autosomal recessive	Atelis syndrome 2	4

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
SMC5	HGNC:20465	ENSG00000198887	Q8IY18	Structural maintenance of chromosomes protein 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SMC5	Structural maintenance of chromosomes protein 5	Core component of the SMC5-SMC6 complex, a complex involved in repair of DNA double-strand breaks by homologous recombination.

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)
SMC5	Other/Unknown	no		P-loop_NTPase, Rad50/SbcC_AAA

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
calcaneal tendon	1
left ovary	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SMC5	286	ubiquitous	marker	sural nerve, calcaneal tendon, left ovary

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SMC5	4,063

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SMC5	Q8IY18	4

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 5. 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
SUMO E3 ligases SUMOylate target proteins	1	178.4×	0.011	SMC5
SUMOylation	1	163.1×	0.011	SMC5
SUMOylation of DNA damage response and repair proteins	1	146.4×	0.011	SMC5
Post-translational protein modification	1	19.2×	0.065	SMC5
Metabolism of proteins	1	12.4×	0.081	SMC5

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
mitotic cell cycle phase transition	1	5617.3×	0.002	SMC5
positive regulation of maintenance of mitotic sister chromatid cohesion	1	3370.4×	0.002	SMC5
protein localization to chromosome, centromeric region	1	2106.5×	0.002	SMC5
telomere maintenance via recombination	1	1532.0×	0.002	SMC5
host-mediated suppression of viral genome replication	1	1532.0×	0.002	SMC5
positive regulation of chromosome segregation	1	1296.3×	0.002	SMC5
chromatin looping	1	1203.7×	0.002	SMC5
chromosome condensation	1	842.6×	0.002	SMC5
regulation of telomere maintenance	1	842.6×	0.002	SMC5
stem cell population maintenance	1	421.3×	0.004	SMC5
protein sumoylation	1	324.1×	0.004	SMC5
cellular senescence	1	295.6×	0.005	SMC5
chromosome segregation	1	173.7×	0.007	SMC5
double-strand break repair via homologous recombination	1	156.0×	0.007	SMC5
DNA damage response	1	53.5×	0.020	SMC5
cell division	1	46.2×	0.022	SMC5

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
SMC5	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	SMC5

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)
SMC5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.