SLF1

protein-coding

SMC5-SMC6 complex localization factor 1, the group of Ankyrin repeat domain containing

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 site of double-strand break. [provided by Alliance of Genome Resources, Jun 2026]

Previous symbols:

BRCTD1
ANKRD32

MANE transcript

NM_032290.4

Inheritance

—

ClinVar variants

U:148B:16

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.5

Max pathogenic AF

—

Genomic locus

chr5:94,618,669-94,739,436

External References & Databases

Ensembl (ENSG00000133302)

Transcript & Mutation Effects

hg38 • Region Span ~120.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SLF1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 151

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032290.4. 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	1 clinvar	2 clinvar	5
missense			143 clinvar	12 clinvar	1 clinvar	156
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	148	13	3	164

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 34 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032290.4	RefSeq	NP_115666.2	20	MANE Select
ENST00000265140.10	Ensembl	ENSP00000265140.5	20	MANE Select
ENST00000466957.1	Ensembl	ENSP00000430335.1	4	Standard
ENST00000504099.5	Ensembl	ENSP00000425022.1	3	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

nucleosome
nucleus
cytoplasm
centrosome
site of double-strand break

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265140
Coding exons: 20
Length: 121090
Individuals with no LoFs: 125701
Homozygous LoFs: 0
Heterozygous LoFs: 47
Defined: 125748
p: 0.000187

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.453	446	474	0.941	0.0000226	6978
Missense (PolyPhen)		95	147.35	0.64471		2092
Synonymous	0.101	163	165	0.990	0.00000804	1893
Loss of Function	3.15	23	46.1	0.499	0.00000217	728

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00031	rare
Latino/Admixed American	0.000095	0.000087	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000093	0.000092	rare
European (Non-Finnish)	0.00027	0.00026	rare
South Asian	0.000099	0.000098	rare
Other	0.00033	0.00033	rare

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 SLF2 and the SMC5-SMC6 complex to DNA lesions (PubMed:25931565). {ECO:0000269|PubMed:25931565}.;

Intolerance Scores

RVIS EVS: -0.27
RVIS percentile EVS: 34.6

Essentials

Essential (gene trap): N