SLX4

Chr 16AR

SLX4 structure-specific endonuclease subunit

Also known as: BTBD12, FANCP, MUS312

NCBI Gene: 84464 ENSG00000188827 UniProt: Q8IY92 OMIM: 613278

This protein functions as a regulatory subunit that assembles and activates multiple structure-specific endonucleases essential for DNA repair, resolving complex DNA structures that arise during replication and recombination. Mutations cause Fanconi anemia complementation group P, inherited in an autosomal recessive pattern. The gene shows no constraint against loss-of-function variants (very low pLI), consistent with recessive inheritance where heterozygous carriers are typically unaffected.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a protein that functions as an assembly component of multiple structure-specific endonucleases. These endonuclease complexes are required for repair of specific types of DNA lesions and critical for cellular responses to replication fork failure. Mutations in this gene were found in patients with Fanconi anemia. [provided by RefSeq, Sep 2016]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group PMIM #613951

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.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.87

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — SLX4

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

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

📖

GeneReview available — SLX4

Authoritative clinical overview · NCBI Bookshelf · Recommended first read

Open GeneReview ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Malignant Neoplasm of BreastBreast Cancer

Comprehensive Analysis of Predictors of the Treatment With Pembrolizumab and Olaparib in Patients With Unresectable or Metastatic HER2 Negative Breast Cancer and a Deleterious Germline Mutation or a Homologous Recombination Deficiency (COMPRENDO

ACTIVE NOT RECRUITING

NCT05033756Phase PHASE2Institut fuer FrauengesundheitStarted 2022-07-30

Pembrolizumab Injection [Keytruda]Olaparib Oral Tablet [Lynparza]

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Detection and analysis of common pathogenic germline mutations in Peutz-Jeghers syndrome

Gu GL et al.·World J Gastroenterol

2021