SLF2

SMC5-SMC6 complex localization factor 2

Basic information

Region (hg38): 10:100912963-100965134

Previous symbols: [ "C10orf6", "FAM178A" ]

Links

ENSG00000119906 ∙ ∙ OMIM:610348 ∙ HGNC:17814 ∙ Uniprot:Q8IX21 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Atelis syndrome 1 (Moderate), mode of inheritance: AR
• Atelis syndrome 1 (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Atelis syndrome 1	AR	Allergy/Immunology/Infectious; Cardiovascular	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	Allergy/Immunology/Infectious; Cardiovascular; Craniofacial; Dental; Dermatologic; Hematologic; Neurologic	36333305

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SLF2 gene.

• Inborn_genetic_diseases (144 variants)
• not_provided (7 variants)
• Atelis_syndrome_1 (5 variants)
• SLF2-related_disorder (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SLF2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000018121.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				1		1
missense	1		139	8	1	149
nonsense	1					1
start loss						0
frameshift	3					3
splice donor/acceptor (+/-2bp)						0
Total	5	0	139	9	1

Highest pathogenic variant AF is 0.00000657488

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SLF2	protein_coding	protein_coding	ENST00000370269	19	52568

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000289	1.00	125717	0	31	125748	0.000123

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.970	528	595	0.888	0.0000291	7750
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000474	0.0000462
European (Non-Finnish)	0.000155	0.000149
Middle Eastern	0.00	0.00
South Asian	0.000428	0.000392
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.120
• hipred: N
• hipred_score: 0.328
• ghis: 0.536

Essentials

• essential_gene_gene_trap: E

Mouse Genome Informatics

• Gene name: Slf2

Gene ontology

• 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;positive regulation of double-strand break repair
• Cellular component: chromatin;extracellular space;nucleus;site of double-strand break;intracellular membrane-bounded organelle
• Molecular function: protein binding;ubiquitin protein ligase binding;protein-containing complex binding