Fanconi anemia complementation group C

Summary

Fanconi anemia complementation group C (MONDO:0009213) is a disease caused by FANCC (GenCC Definitive), with 3 cohort genes.

At a glance

• Causal gene: FANCC (GenCC Definitive)
• Cohort genes: 3
• ClinVar variants: 559

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group C
Mondo ID	MONDO:0009213
OMIM	227645
DOID	DOID:0111087
NCIT	C125704
UMLS	C3468041
MedGen	483324
GARD	0015168
Is cancer (heuristic)	no

Also known as: FA3 · FACC · FANCC · Fanconi anaemia complementation group type C · Fanconi anemia complementation group C · Fanconi anemia complementation group type C · Fanconi anemia, complementation group C · Fanconi Anemia, complementation group type C

Data availability: 559 ClinVar variants · 5 GenCC gene-disease records · 15 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › hematologic disorder › anemia › congenital anemia › Fanconi anemia › Fanconi anemia complementation group C

Related subtypes (21): Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group B, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group D1, Fanconi anemia complementation group I, Fanconi anemia complementation group J, Fanconi anemia complementation group N, Fanconi anemia complementation group O, Fanconi anemia complementation group P, Fanconi anemia complementation group G, Fanconi anemia complementation group L, Fanconi anemia complementation group Q, Fanconi anemia complementation group T, Fanconi anemia complementation group V, Fanconi anemia complementation group R, Fanconi anemia complementation group U, Fanconi anemia, complementation group W, Fanconi anemia, complementation group S, fanconi anemia, complementation group 10

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

559 retrieved; paginated sample, class counts are floors:

195 uncertain significance, 91 conflicting classifications of pathogenicity, 78 likely pathogenic, 73 pathogenic/likely pathogenic, 47 likely benign, 37 pathogenic, 23 benign/likely benign, 15 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
1072437	NM_000136.3(FANCC):c.1377_1378del (p.Ser459fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12043	NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12047	NM_000136.3(FANCC):c.1642C>T (p.Arg548Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12048	NM_000136.3(FANCC):c.1555dup (p.Thr519fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
12050	NM_000136.3(FANCC):c.1487T>G (p.Leu496Arg)	AOPEP	Pathogenic	no assertion criteria provided
127547	NM_000136.3(FANCC):c.843+1G>A	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322874	NM_000136.3(FANCC):c.1002del (p.Phe335fs)	AOPEP	Pathogenic	criteria provided, single submitter
1685808	NM_000136.3(FANCC):c.1653dup (p.Lys552Ter)	AOPEP	Pathogenic	criteria provided, single submitter
182467	NM_000136.3(FANCC):c.1302dup (p.Gly435fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
189053	NM_000136.3(FANCC):c.844-1G>C	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1921563	NM_000136.3(FANCC):c.1200dup (p.Gly401fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2181587	NM_000136.3(FANCC):c.935_936del (p.Ile312fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
219717	NM_000136.3(FANCC):c.1290C>A (p.Tyr430Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
265137	NM_000136.3(FANCC):c.996+1G>T	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675468	NM_000136.3(FANCC):c.1453del (p.Gln485fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2910228	NM_000136.3(FANCC):c.844-1G>A	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370186	NM_000136.3(FANCC):c.1333C>T (p.Gln445Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370412	NM_000136.3(FANCC):c.1628C>A (p.Ser543Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
370437	NM_000136.3(FANCC):c.1517G>A (p.Trp506Ter)	AOPEP	Pathogenic	criteria provided, single submitter
371351	NM_000136.3(FANCC):c.640dup (p.Ile214fs)	AOPEP	Pathogenic	criteria provided, single submitter
419252	NM_000136.3(FANCC):c.1069C>T (p.Gln357Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
420449	NM_000136.3(FANCC):c.808A>T (p.Arg270Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
422160	NM_000136.3(FANCC):c.1043_1044del (p.Leu348fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4701735	NM_000136.3(FANCC):c.1593C>A (p.Tyr531Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
4847097	NM_000136.3(FANCC):c.571del (p.Ile191fs)	AOPEP	Pathogenic	criteria provided, single submitter
485554	NM_000136.3(FANCC):c.946C>T (p.Gln316Ter)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
545768	NM_000136.3(FANCC):c.1257dup (p.Thr420fs)	AOPEP	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
551836	NM_000136.3(FANCC):c.1417C>T (p.Gln473Ter)	AOPEP	Pathogenic	criteria provided, multiple submitters, no conflicts
552933	NM_000136.3(FANCC):c.1549_1553del (p.Glu517fs)	AOPEP	Pathogenic	criteria provided, single submitter
557322	NM_000136.3(FANCC):c.1177_1178dup (p.Ser393fs)	AOPEP	Pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 11 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
FANCC	Definitive	Autosomal recessive	Fanconi anemia complementation group C	11

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FANCC	Orphanet:84	Fanconi anemia

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	3

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	gencc,clinvar
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	clinvar
DCLRE1B	HGNC:17641	ENSG00000118655	Q9H816	5’ exonuclease Apollo	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
DCLRE1B	5’ exonuclease Apollo	5’-3’ exonuclease that plays a central role in telomere maintenance and protection during S-phase.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Protease	1	12.2×	0.159
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FANCC	Other/Unknown	no		FANCC
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
DCLRE1B	Other/Unknown	no		DRMBL, RibonucZ/Hydroxyglut_hydro

Expression context

Cohort genes with no expression data: 0.

2 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
pancreatic ductal cell	1
right lobe of liver	1
apex of heart	1
ascending aorta	1
right coronary artery	1
oocyte	1
primordial germ cell in gonad	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta
DCLRE1B	224	ubiquitous	yes	secondary oocyte, primordial germ cell in gonad, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DCLRE1B	1,528
FANCC	1,470
AOPEP	991

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FANCC	Q00597	6
DCLRE1B	Q9H816	5

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AOPEP	Q8N6M6	83.36

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 3 evidence-associated genes (2 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Fanconi Anemia Pathway	2	278.5×	4e-05	FANCC, DCLRE1B
TP53 Regulates Transcription of DNA Repair Genes	1	90.6×	0.014	FANCC
PKR-mediated signaling	1	70.5×	0.014	FANCC

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
interstrand cross-link repair	2	288.1×	2e-04	FANCC, DCLRE1B
telomeric loop formation	1	2808.7×	0.002	DCLRE1B
telomeric 3’ overhang formation	1	1404.3×	0.003	DCLRE1B
protection from non-homologous end joining at telomere	1	802.5×	0.004	DCLRE1B
telomere maintenance via telomere lengthening	1	624.1×	0.004	DCLRE1B
telomere capping	1	432.1×	0.005	DCLRE1B
double-strand break repair via nonhomologous end joining	1	140.4×	0.013	DCLRE1B
nucleotide-excision repair	1	127.7×	0.013	FANCC
telomere maintenance	1	89.2×	0.016	DCLRE1B
cellular response to oxidative stress	1	51.5×	0.025	FANCC
protein-containing complex assembly	1	38.0×	0.031	FANCC
DNA repair	1	21.3×	0.050	FANCC
proteolysis	1	11.4×	0.085	AOPEP

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 3

Druggability breadth: 2 of 3 evidence-associated genes (67%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FANCC	0	0
AOPEP	0	0
DCLRE1B	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
AOPEP	1	ADMET:1
DCLRE1B	1	Binding:1

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	AOPEP
E	Difficult family or no structure, no drug	2	FANCC, DCLRE1B

Undrugged target profiles

3 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
FANCC	0	—
AOPEP	1	—
DCLRE1B	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.