FANCL

Chr 2AR

FA complementation group L

Also known as: FAAP43, PHF9, POG

NCBI Gene: 55120ENSG00000115392UniProt: Q9NW38

This gene encodes a ubiquitin ligase that is a member of the Fanconi anemia complementation group (FANC). Members of this group are related by their assembly into a common nuclear protein complex rather than by sequence similarity. This gene encodes the protein for complementation group L that mediates monoubiquitination of FANCD2 as well as FANCI. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2018]

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group LMIM #614083
AR
Fanconi anemia, complementation group LMIM #614083
AR
UniProtFanconi anemia complementation group L
5
Active trials
8
Pathogenic / LP
91
ClinVar variants
15
Pubs (1 yr)
-1.3
Missense Z
1.61
LOEUF
Clinical Summary— FANCL
🧬
Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group L · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 43 VUS of 91 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — FANCL
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.61LOEUF
pLI 0.000
Z-score -0.93
OE 1.20 (0.90–1.61)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.31Z-score
OE missense 1.26 (1.14–1.40)
251 obs / 199.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE1.20 (0.90–1.61)
0≤0.351.4
Missense OE1.26 (1.14–1.40)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 31 / 25.9Missense obs/exp: 251 / 199.0Syn Z: -0.60

ClinVar Variant Classifications

91 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
Likely Pathogenic6
VUS43
Likely Benign36
Benign4
2
Pathogenic
6
Likely Pathogenic
43
VUS
36
Likely Benign
4
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
0
0
0
2
Likely Pathogenic
5
0
1
0
6
VUS
0
40
3
0
43
Likely Benign
0
2
18
16
36
Benign
0
0
4
0
4
Total742261691

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

FANCL · protein map & ClinVar variants

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

Gene2Phenotype Curations

FANCL-related Fanconi anemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗
frameshift variantstop gainedmissense variantinframe deletionsynonymous variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
ATM Gene MutationBRCA1 Gene MutationBRCA2 Gene Mutation

Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects

ACTIVE NOT RECRUITING
NCT04030559Phase PHASE2Marc Dall'Era, MDStarted 2020-02-25
NiraparibNiraparib Tosylate MonohydrateRadical Prostatectomy
Triple Negative Breast CancerBreast Cancer

Serial Circulating Tumor DNA (ctDNA) Monitoring During Adjuvant Capecitabine in Early Triple-negative Breast Cancer

RECRUITING
NCT04768426Phase PHASE2Stanford UniversityStarted 2021-02-03
Capecitabine
Renal Cell CarcinomaMetastatic Renal Cell CarcinomaKidney Cancer

Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations

RECRUITING
NCT03786796Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2019-06-03
Olaparib
Polycythemia VeraEssential ThrombocythaemiaMyelofibrosis

Prevalence Of Germline Gene Mutations In Patients With Myeloproliferative Neoplasms With Family History

NOT YET RECRUITING
NCT06923670Phase NAFondazione Policlinico Universitario Agostino Gemelli IRCCSStarted 2025-05-21
NGS testingNGS analysis for mutations in genes involved in familial predisposition to hematological malignancies
Advanced or Metastatic Solid TumorsBreast CancerOvarian Cancer

A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors

RECRUITING
NCT05787587Phase PHASE1IDEAYA BiosciencesStarted 2023-04-18
IDE-161Pembrolizumab
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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