SLX4

Chr 16AR

SLX4 structure-specific endonuclease subunit

ENSG00000188827UniProt: Q8IY92OMIM: 613278

Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks

OMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group PMIM #613951
AR
UniProtFanconi anemia complementation group P

Clinical highlights

Gene-disease validity (ClinGen)
hereditary breast carcinoma · ADRefutedevidence has disproved this relationship3 gene-disease associations curated in total
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
47
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.87
LOEUF
LOF
Mechanism· G2P
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?
0.87LOEUF
pLI 0.000
Z-score 2.41
OE 0.68 (0.54–0.87)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?
-1.88Z-score
OE missense 1.16 (1.11–1.22)
1224 obs / 1052.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?
LoF OE?0.68 (0.54–0.87)
0≤0.351.4
Missense OE?1.16 (1.11–1.22)
0≤0.61.4
Synonymous OE?1.24
0≤1.21.6
LoF obs/exp: 45 / 66.2Missense obs/exp: 1224 / 1052.2Syn Z: -4.09

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

SLX4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients