SMC5

Chr 9AR

structural maintenance of chromosomes 5

Also known as: ATELS2, SMC5L1

NCBI Gene: 23137ENSG00000198887UniProt: Q8IY18

Enables DNA secondary structure binding activity. Involved in several processes, including DNA recombination; negative regulation by host of viral genome replication; and positive regulation of cell cycle process. Located in cell junction; chromosome; and nuclear body. Part of Smc5-Smc6 complex. Is active in nucleus. Implicated in mosaic variegated aneuploidy syndrome. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Atelis syndrome 2MIM #620185
AR
0
ClinVar variants
0
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SMC5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
Some data sources returned errors (1)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.49LOEUF
pLI 0.000
Z-score 4.92
OE 0.34 (0.24–0.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.08Z-score
OE missense 0.87 (0.81–0.94)
487 obs / 558.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.24–0.49)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.81–0.94)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 22 / 64.7Missense obs/exp: 487 / 558.9Syn Z: 0.25

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SMC5 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SMC5-related developmental disorder

moderate
ARUndeterminedAltered Gene Product Structure, Uncertain
Dev. Disorders
G2P ↗
missense variantinframe deletionstop gained NMD triggering

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Atelis syndrome 2

MIM #620185

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy.
Grange LJ et al.·Nat Commun
2022
In-frame deletion of SMC5 related with the phenotype of primordial dwarfism, chromosomal instability and insulin resistance.
Zhu W et al.·Clin Transl Med
2023
NFATC2IP is a mediator of SUMO-dependent genome integrity.
Cho T et al.·Genes Dev
2024
Investigation of DNA Damage Response Genes Validates the Role of DNA Repair in Pediatric Cancer Risk and Identifies SMARCAL1 as a Novel Osteosarcoma Predisposition Gene.
Oak N et al.·J Clin Oncol
2025
The structural maintenance of chromosomes 5 is a possible biomarker for individualized treatment of colorectal cancer.
Gong X et al.·Cancer Med
2023
Role of Nse1 Subunit of SMC5/6 Complex as a Ubiquitin Ligase.
Kolesar P et al.·Cells
2022
Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.
Pei L et al.·Clin Transl Oncol
2024
Biological Roles of Hepatitis B Viral X Protein in the Viral Replication and Hepatocarcinogenesis.
Otsuka M·Acta Med Okayama
2023Review
Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.
Saunus JM et al.·J Pathol
2015
Toll-like receptor 7 agonist GS-9620 induces prolonged inhibition of HBV via a type I interferon-dependent mechanism.
Niu C et al.·J Hepatol
2018Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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External Resources

Links to major genomics databases and tools