SLF2

Chr 10AR

SMC5/6 complex localization factor 2

Also known as: ATELS1, C10orf6, FAM178A, hNSE6

NCBI Gene: 55719 ENSG00000119906 UniProt: Q8IX21 OMIM: 610348

SLF2 encodes a protein that regulates DNA double-strand break repair by promoting recruitment of the SMC5-SMC6 DNA repair complex to sites of DNA damage and replication stress. Biallelic mutations cause Atelis syndrome 1, an autosomal recessive disorder characterized by genomic instability. The gene is highly constrained against loss-of-function variants (LOEUF 0.544), indicating that complete loss of protein function is poorly tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Enables ubiquitin protein ligase binding activity. Involved in several processes, including positive regulation of cellular component organization; positive regulation of double-strand break repair; and protein localization to site of double-strand break. Located in PML body; chromatin; and site of double-strand break. Implicated in mosaic variegated aneuploidy syndrome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Atelis syndrome 1MIM #620184

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Atelis syndrome 1; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.54

LOEUF

—

Mechanism

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.54LOEUF

pLI 0.000

Z-score 4.17

OE 0.37 (0.26–0.54)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

0.97Z-score

OE missense 0.89 (0.83–0.95)

528 obs / 594.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.26–0.54)

0≤0.351.4

Missense OE?0.89 (0.83–0.95)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 19 / 51.2Missense obs/exp: 528 / 594.6Syn Z: 0.07

Background carrier burden — how many people carry a rare variant somewhere in SLF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 51

1,473 rare PASS variants

Rare truncating (LoF)

1 in 870

213 rare PASS variants

Rare synonymous (reference)

1 in 86

570 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SLF2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 73	1 in 1,000
South Asian	~43k	1 in 36	1 in 640
Remaining (unassigned)	~30k	1 in 49	1 in 410
European (Finnish)	~27k	1 in 170	1 in 2,100
Admixed American	~22k	1 in 37	1 in 2,200
African / African American	~21k	1 in 42	1 in 970
East Asian	~20k	1 in 53	1 in 1,000
Ashkenazi Jewish	~13k	1 in 250	1 in 1,900
Middle Eastern	~2,884	1 in 47	1 in 570

Each group is summed over the variants that are rare in that group. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 16 of 20 coding exons well covered in gnomAD exomes; exons 4, 8, 10, 12 marginal. Genomes: all 20.? see exons ↓