FANCC

Chr 9AR

FA complementation group C

Also known as: FA3, FAC, FACC

NCBI Gene: 2176ENSG00000158169UniProt: Q00597

The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group C. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Fanconi anemia, complementation group CMIM #227645
AR
Fanconi anemia, complementation group CMIM #227645
AR
UniProtFanconi anemia complementation group C
5
Active trials
58
Pathogenic / LP
500
ClinVar variants
7
Pubs (1 yr)
-0.2
Missense Z
1.04
LOEUF
Clinical Summary— FANCC
🧬
Gene-Disease Validity (ClinGen)
Fanconi anemia complementation group C · 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
58 Pathogenic / Likely Pathogenic· 259 VUS of 500 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
📖
GeneReview available — FANCC
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?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.04LOEUF
pLI 0.000
Z-score 1.36
OE 0.74 (0.54–1.04)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.19Z-score
OE missense 1.03 (0.94–1.13)
306 obs / 296.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.74 (0.54–1.04)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.03 (0.94–1.13)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.09
0≤1.21.6
LoF obs/exp: 24 / 32.3Missense obs/exp: 306 / 296.6Syn Z: -0.72

ClinVar Variant Classifications

500 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic31
VUS259
Likely Benign169
Benign2
Conflicting12
27
Pathogenic
31
Likely Pathogenic
259
VUS
169
Likely Benign
2
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
12
0
15
0
27
Likely Pathogenic
22
2
7
0
31
VUS
1
232
20
6
259
Likely Benign
0
12
52
105
169
Benign
0
0
2
0
2
Conflicting
—12
Total3524696111500

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

View in ClinVar →

Protein Context — Lollipop Plot

FANCC · protein map & ClinVar variants

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

Gene2Phenotype Curations

FANCC-related Fanconi anemia

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
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
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]
Advanced Solid TumorsEwing SarcomaHepatocellular Carcinoma (HCC)

A Phase 1/1B Study of ST-01156, a Small Molecule RBM39 Degrader, in Patients With Advanced Solid Malignancies

RECRUITING
NCT07197554Phase PHASE1SEED Therapeutics, Inc.Started 2025-12-01
ST-01156
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
Metastatic Pancreatic Ductal AdenocarcinomaHomologous Recombination Deficiency (HRD)

A Study of Pembrolizumab and Olaparib for People With Metastatic Pancreatic Ductal Adenocarcinoma and Homologous Recombination Deficiency or Exceptional Treatment Response to Platinum-Based Therapy

ACTIVE NOT RECRUITING
NCT04666740Phase PHASE2Memorial Sloan Kettering Cancer CenterStarted 2020-12-18
PembrolizumabOlaparib
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
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
Fanconi anemia complementation group C gene (FANCC) association with hereditary and sporadic renal tumors.
Desai D et al.·Oncologist
2026Open Access
Activation of GLP-1R ameliorates microglial pyroptosis after spinal cord injury by restoring FANCC expression.
Li G et al.·Brain Behav Immun
2026
Pathogenic FANCC Variants Are Associated with Accessory Breasts in a Sub-Saharan African Multiplex Family.
Danbaki AS et al.·Curr Issues Mol Biol
2025Open Access
Integrated single-cell and spatial transcriptomics uncover the prognostic, epigenetic, and immunological roles of FANCC in low-grade glioma.
Zhang Z et al.·Neurol Res
2025
Activation of FANCC attenuates mitochondrial ROS-driven necroptosis by targeting TBK1-dependent mitophagy in astrocytes after spinal cord injury.
Xia M et al.·Theranostics
2025Open Access
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