SMC5

Chr 9

structural maintenance of chromosomes 5

Also known as: ATELS2, SMC5L1

SMC5 encodes a core component of the SMC5-SMC6 complex that repairs DNA double-strand breaks through homologous recombination, maintains telomeres, and ensures proper sister chromatid cohesion during cell division. Mutations cause Atelis syndrome 2, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variants, indicating its critical cellular function.

ResearchSummary from RefSeq, OMIM, UniProt
DNmechanismLOEUF 0.49
Clinical SummarySMC5
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
44 unique Pathogenic / Likely Pathogenic· 124 VUS of 202 total submissions
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.49LOEUF
pLI 0.000
Z-score 4.92
OE 0.34 (0.240.49)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
1.08Z-score
OE missense 0.87 (0.810.94)
487 obs / 558.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.34 (0.240.49)
00.351.4
Missense OE0.87 (0.810.94)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 22 / 64.7Missense obs/exp: 487 / 558.9Syn Z: 0.25
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
moderateSMC5-related developmental disorderOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6549th %ile
GOF
0.5366th %ile
LOF
0.2777th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

202 submitted variants in ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic9
VUS124
Likely Benign6
Benign5
35
Pathogenic
9
Likely Pathogenic
124
VUS
6
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
2
32
0
35
Likely Pathogenic
1
0
8
0
9
VUS
0
119
5
0
124
Likely Benign
0
5
0
1
6
Benign
0
1
1
3
5
Total2127464179

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC