SLF2

protein-coding

SMC5-SMC6 complex localization factor 2

Gene summary

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]

Previous symbols:

C10orf6
FAM178A

MANE transcript

NM_018121.4

Inheritance

ClinVar variants

P:8U:158B:20

Top phenotype

Atelis syndrome 1

gnomAD constraint

pLI —, LoF o/e 0.37

Max pathogenic AF

—

Genomic locus

chr10:100,912,963-100,965,134

External References & Databases

Ensembl (ENSG00000119906)

Transcript & Mutation Effects

hg38 • Region Span ~52.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Atelis syndrome 1STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859575

Submitter: PanelApp Australia

Atelis syndrome 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859575

Submitter: Ambry Genetics

Atelis syndrome 1MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0859575

Submitter: G2P

Clinical Genomic Database (CGD)

Atelis syndrome 1AR

Manifestation: Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Neurologic

Intervention: Allergy/Immunology/Infectious; Cardiovascular

Rationale: The condition can include susceptibility to infections, and awareness may allow early and agressive treatment of infections; Individuals have been described with congenital heart anomalies, and awareness may enable prompt recognition and management

Refs: 36333305

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLF2 variants in ClinVar

4 Conditions Cataloged

Inborn genetic diseasesTotal: 158

not providedTotal: 18

Atelis syndrome 1Total: 9

SLF2-related disorderTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018121.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	6 clinvar		8
missense	1 clinvar		153 clinvar	13 clinvar	1 clinvar	168
nonsense	1 clinvar		1 clinvar			2
start loss						0
frameshift	3 clinvar	3 clinvar				6
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	5	3	158	19	1	186

Highest pathogenic variant AF is 0.0000065748814

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 30 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018121.4	RefSeq	NP_060591.3	20	MANE Select
ENST00000238961.9	Ensembl	ENSP00000238961.3	20	MANE Select
NM_001136123.2	RefSeq	NP_001129595.1	19	Standard
NM_001243770.2	RefSeq	NP_001230699.1	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

DNA repair
cellular response to DNA damage stimulus
positive regulation of protein complex assembly
positive regulation of maintenance of mitotic sister chromatid cohesion
protein localization to site of double-strand break

Molecular Function

protein binding
ubiquitin protein ligase binding
protein-containing complex binding

Cellular Component

chromatin
extracellular space
nucleus
site of double-strand break
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000370269
Coding exons: 19
Length: 52568
Individuals with no LoFs: 125717
Homozygous LoFs: 0
Heterozygous LoFs: 31
Defined: 125748
p: 0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.970	528	595	0.888	0.0000291	7750
Missense (PolyPhen)		123	178.29	0.68989		2465
Synonymous	0.0708	211	212	0.994	0.0000102	2243
Loss of Function	4.17	19	51.2	0.371	0.00000248	726

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000047	0.000046	rare
European (Non-Finnish)	0.00015	0.00015	rare
South Asian	0.00043	0.00039	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Plays a role in the DNA damage response (DDR) pathway by regulating postreplication repair of UV-damaged DNA and genomic stability maintenance (PubMed:25931565). The SLF1-SLF2 complex acts to link RAD18 with the SMC5-SMC6 complex at replication- coupled interstrand cross-links (ICL) and DNA double-strand breaks (DSBs) sites on chromatin during DNA repair in response to stalled replication forks (PubMed:25931565). Promotes the recruitment of the SMC5-SMC6 complex to DNA lesions (PubMed:25931565). {ECO:0000269|PubMed:25931565}.;

Recessive Scores

pRec: 0.0954

Intolerance Scores

RVIS EVS: 0.36
RVIS percentile EVS: 74.66

Essentials

Essential (gene trap): E