FANCF

Summary

FANCF (FA complementation group F, HGNC:3587) is a protein-coding gene on chromosome 11p14.3, encoding Fanconi anemia group F protein (Q9NPI8). DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. It is a selective cancer dependency (DepMap: 15.6% of cell lines).

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 F.

Source: NCBI Gene 2188 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fanconi anemia complementation group F (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 533 total — 28 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 132
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 15.6% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_022725

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3587
Approved symbol	FANCF
Name	FA complementation group F
Location	11p14.3
Locus type	gene with protein product
Status	Approved
Aliases	FAF
Ensembl gene	ENSG00000183161
Ensembl biotype	protein_coding
OMIM	613897
Entrez	2188

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000327470

RefSeq mRNA: 1 — MANE Select: NM_022725 NM_022725

CCDS: CCDS7857

Canonical transcript exons

ENST00000327470 — 1 exons

Exon	Start	End
ENSE00001308799	22622533	22625823

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 88.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.7358 / max 56.7846, expressed in 1732 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119013	9.5422	1714
119011	1.0002	676
119010	0.1221	33
119012	0.0712	22

Top tissues by expression

274 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	88.30	gold quality
endothelial cell	CL:0000115	87.73	gold quality
bronchial epithelial cell	CL:0002328	87.33	gold quality
ganglionic eminence	UBERON:0004023	87.12	gold quality
corpus epididymis	UBERON:0004359	85.26	gold quality
choroid plexus epithelium	UBERON:0003911	85.22	gold quality
caput epididymis	UBERON:0004358	84.43	gold quality
epithelium of bronchus	UBERON:0002031	84.30	gold quality
bronchus	UBERON:0002185	83.03	gold quality
cortical plate	UBERON:0005343	82.94	gold quality
oocyte	CL:0000023	81.79	gold quality
hair follicle	UBERON:0002073	81.01	silver quality
islet of Langerhans	UBERON:0000006	80.87	gold quality
ventricular zone	UBERON:0003053	80.84	gold quality
body of pancreas	UBERON:0001150	80.12	gold quality
colonic mucosa	UBERON:0000317	79.93	gold quality
jejunal mucosa	UBERON:0000399	79.93	gold quality
germinal epithelium of ovary	UBERON:0001304	79.91	gold quality
palpebral conjunctiva	UBERON:0001812	79.89	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.85	gold quality
pancreas	UBERON:0001264	79.64	gold quality
embryo	UBERON:0000922	79.01	gold quality
esophagus squamous epithelium	UBERON:0006920	79.00	gold quality
epithelium of nasopharynx	UBERON:0001951	78.96	gold quality
right uterine tube	UBERON:0001302	78.02	gold quality
mucosa of transverse colon	UBERON:0004991	77.98	gold quality
endometrium	UBERON:0001295	77.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	77.42	gold quality
duodenum	UBERON:0002114	76.77	gold quality
parietal pleura	UBERON:0002400	76.71	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.98
E-GEOD-83139	no	2.87

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IRF8

miRNA regulators (miRDB)

106 targeting FANCF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-380-3P	99.89	70.18	1978
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-8067	99.86	69.59	2260

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 15.6% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 17)

• inactivation of the FANC-BRCA pathway is relatively common in solid tumors and may be related to tobacco and alcohol exposure and survival (PMID:14647419)
• Inactivation of genes in the FA-BRCA pathway by epigenetic alterations have been found in a high proportion of cervix cancer patients, suggesting a major role for this pathway in the development of cervical cancer. (PMID:15126331)
• FANCF acts as a flexible adaptor protein that plays a key role in the proper assembly of the FA core complex. (PMID:15262960)
• results showed that FANCF methylation regulates the expression of FANCF at both mRNA and protein levels; methylation-induced inactivation of FANCF plays an important role in the occurrence of ovarian cancers via disrupting the FA-BRCA pathway (PMID:16418574)
• human FANCF protein has specific structural components that function in the assembly of a DNA damage signaling complex (PMID:17082180)
• FANCF methylation was rare in breast tumors (PMID:17932744)
• This study does not support methylation-dependent silencing of FANCF as a mechanism of sensitisation to platinum-based chemotherapy in ovarian cancer. (PMID:18414472)
• Data identify the gene encoding Fanconi F (FANCF) as an ICSBP target gene. (PMID:19801548)
• FANCF methylation is a rare event in Japanese primary invasive breast cancer. (PMID:19813073)
• Silencing of FANCF enhanced the antiproliferative effect of ADM in OVCAR3 cells. (PMID:23440494)
• Data suggest that the Fanconi anemia group F protein/BRCA1/2 proteins pathway may be a new target to reverse adriamycin (ADR) resistance in leukemia treatment. (PMID:24996439)
• careful examination of three electively aborted fetuses in one family and one affected girl in the other indicated an association of the FANCF loss-of-function mutation with a severe phenotype characterized by multiple malformations (PMID:26033879)
• CpG island methylation of FANCF gene promoter region is strongly associated with the susceptibility and clinicopathologic features of epithelial ovarian cancer. (PMID:26507869)
• we report three patients who illustrate the clinical variability within the FA-F group. This analysis suggests a more severe phenotype for those with the common c.484_485delCT mutation. (PMID:27714961)
• LOH in FA genes appears to be a common feature of head and neck squamous cell carcinomas development seen here in 57% of patients and other mutation types may increase this mutation frequency. We suggest larger patient cohorts would be needed to test the observed association of LOH in FANCF and patient survival comprehensively (PMID:28440438)
• A mutation in the FANCF gene in Iranian patients with Fanconi anemia. This new mutation correlates with a hematological problem (pancytopenia), short stature, and microcephaly and skin hyperpigmentation. Until now, no evidence of malignancy was detected. (PMID:31288759)
• FANCF hypomethylation is associated with colorectal cancer in Han Chinese. (PMID:32915143)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fancf	ENSDARG00000019250
mus_musculus	Fancf	ENSMUSG00000092118
rattus_norvegicus	Fancf	ENSRNOG00000023968

Protein

Protein identifiers

Fanconi anemia group F protein — Q9NPI8 (reviewed: Q9NPI8)

All UniProt accessions (2): A3KME0, Q9NPI8

UniProt curated annotations — full annotation on UniProt →

Function. DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability.

Subunit / interactions. Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. The complex is not found in FA patients. In complex with FANCA, FANCG and FANCL, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins.

Subcellular location. Nucleus.

Disease relevance. Fanconi anemia complementation group F (FANCF) [MIM:603467] A disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_073562* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR035428	FANCF	Family
IPR038505	FANCF_C_sf	Homologous_superfamily

Pfam: PF11107

UniProt features (24 total): helix 11, mutagenesis site 7, sequence variant 2, strand 2, chain 1, turn 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2IQC	X-RAY DIFFRACTION	2.4
7KZP	ELECTRON MICROSCOPY	3.1
7KZS	ELECTRON MICROSCOPY	4.2
7KZT	ELECTRON MICROSCOPY	4.2
7KZV	ELECTRON MICROSCOPY	4.2
7KZQ	ELECTRON MICROSCOPY	4.3
7KZR	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NPI8-F1	78.87	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Mutagenesis-validated functional residues (7):

Position	Phenotype
209	reduced monoubiquitination of fancd2.
251	reduced monoubiquitination of fancd2.
287	strongly reduced monoubiquitination of fancd2; when associated with a-289; a-339; a-341 and a-344.
289	strongly reduced monoubiquitination of fancd2; when associated with a-287; a-339; a-341 and a-344.
339	strongly reduced monoubiquitination of fancd2; when associated with a-287; a-289; a-341 and a-344.
341	strongly reduced monoubiquitination of fancd2; when associated with a-287; a-289; a-339 and a-344.
344	strongly reduced monoubiquitination of fancd2; when associated with a-287; a-289; a-339 and a-341.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-9833482	PKR-mediated signaling

MSigDB gene sets: 397 (showing top): PID_FANCONI_PATHWAY, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, BHATI_G2M_ARREST_BY_2METHOXYESTRADIOL_DN, KAUFFMANN_DNA_REPAIR_GENES, OHM_METHYLATED_IN_ADULT_CANCERS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_DN, MATHEW_FANCONI_ANEMIA_GENES, MODULE_301, GOBP_DNA_DAMAGE_RESPONSE, GOBP_INTERSTRAND_CROSS_LINK_REPAIR, REACTOME_FANCONI_ANEMIA_PATHWAY, REACTOME_DNA_REPAIR, MODULE_188, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS

GO Biological Process (3): DNA damage response (GO:0006974), interstrand cross-link repair (GO:0036297), DNA repair (GO:0006281)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), Fanconi anaemia nuclear complex (GO:0043240), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
DNA Repair	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
cellular response to stress	1
DNA repair	1
DNA metabolic process	1
DNA damage response	1
binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
nuclear protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

590 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FANCF	FANCE	Q9HB96	999
FANCF	FANCM	Q8IYD8	999
FANCF	FANCC	Q00597	999
FANCF	FANCG	O15287	999
FANCF	FANCA	O15360	999
FANCF	FANCB	Q8NB91	999
FANCF	FANCL	Q9NW38	999
FANCF	FAAP100	Q0VG06	997
FANCF	F6S8H2	F6S8H2	988
FANCF	FAAP24	Q9BTP7	973
FANCF	FANCD2	Q9BXW9	971
FANCF	FANCI	Q9NVI1	954
FANCF	BRCA2	P51587	908
FANCF	BRIP1	Q9BX63	883
FANCF	UBE2T	Q9NPD8	854

IntAct

43 interactions, top by confidence:

A	B	Type	Score
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
FANCF	FANCG	psi-mi:“MI:0915”(physical association)	0.750
FANCG	FANCF	psi-mi:“MI:0915”(physical association)	0.750
FANCF	FANCA	psi-mi:“MI:0915”(physical association)	0.570
FANCA	FANCF	psi-mi:“MI:0915”(physical association)	0.570
TCP11	FANCF	psi-mi:“MI:0915”(physical association)	0.560
HTT	FANCF	psi-mi:“MI:0915”(physical association)	0.560
SPTAN1	FANCF	psi-mi:“MI:0915”(physical association)	0.400
Hacd3	FANCF	psi-mi:“MI:0915”(physical association)	0.400
PPP5C	FANCF	psi-mi:“MI:0915”(physical association)	0.400
FANCM	FANCC	psi-mi:“MI:0914”(association)	0.350
FANCE	FANCG	psi-mi:“MI:0914”(association)	0.350
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	FANCF	psi-mi:“MI:2364”(proximity)	0.270
FANCF	FBXW7	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	FANCF	psi-mi:“MI:2364”(proximity)	0.270
FANCF	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SPOP	FANCF	psi-mi:“MI:2364”(proximity)	0.270
FANCF	SPOP	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (107): FANCF (Affinity Capture-MS), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-MS), FANCF (Affinity Capture-MS), FANCF (Affinity Capture-MS), FANCF (Affinity Capture-MS), FANCE (Affinity Capture-Western), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-Western), CTBP1 (Two-hybrid), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-Western), FANCF (Affinity Capture-Western)

ESM2 similar proteins: A0A140LIA7, A0A2Y9GDB5, A0JNN2, A6NJJ6, A6QNY1, E1BLZ4, E1C7U0, E9PXB6, O88324, P01586, P06740, P08700, P16772, P20109, P35225, P42203, P51748, Q08648, Q08E62, Q0MUT8, Q13790, Q1HVF6, Q1JQE1, Q28809, Q3KSS3, Q4KM46, Q5EAA5, Q5JTB6, Q5M889, Q5R7E2, Q5U2R2, Q5XIF1, Q63072, Q6P0A1, Q6PDA7, Q6UJB9, Q6UW10, Q7TSF4, Q86XT9, Q8N6T0

Diamond homologs: E9Q5Z5, Q9NPI8

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
FANCM	up-regulates	FANCF	binding
FANCF	“form complex”	“Fanconi anemia core complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 25 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Fanconi Anemia Pathway	5	69.6×	1e-06
PKR-mediated signaling	6	42.3×	1e-06

GO biological processes:

GO term	Partners	Fold	FDR
interstrand cross-link repair	5	93.9×	1e-06
DNA repair	5	13.9×	2e-03
positive regulation of gene expression	6	10.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

533 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	28
Likely pathogenic	23
Uncertain significance	323
Likely benign	102
Benign	15

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1075622	NM_022725.4(FANCF):c.24_25insA (p.Asp9fs)	Pathogenic
1169397	NM_022725.4(FANCF):c.438_451del (p.Leu146_Arg147insTer)	Pathogenic
1169400	NM_022725.4(FANCF):c.534del (p.Lys179fs)	Pathogenic
1224528	NM_022725.4(FANCF):c.594_595del (p.Asn199fs)	Pathogenic
1432834	NM_022725.4(FANCF):c.326dup (p.Tyr109Ter)	Pathogenic
1456016	NM_022725.4(FANCF):c.3G>A (p.Met1Ile)	Pathogenic
1677115	NC_000011.9:g.(?22644078)(22647388_?)del	Pathogenic
1691096	NM_022725.4(FANCF):c.283_284del (p.Leu95fs)	Pathogenic
2029770	NM_022725.4(FANCF):c.63del (p.Tyr22fs)	Pathogenic
2067569	NM_022725.4(FANCF):c.236del (p.Gly79fs)	Pathogenic
2084424	NM_022725.4(FANCF):c.538del (p.Ala180fs)	Pathogenic
2096716	NM_022725.4(FANCF):c.88dup (p.Thr30fs)	Pathogenic
2121109	NM_022725.4(FANCF):c.535A>T (p.Lys179Ter)	Pathogenic
2894603	NM_022725.4(FANCF):c.667G>T (p.Glu223Ter)	Pathogenic
3244533	NC_000011.9:g.(?22646232)(22647356_?)del	Pathogenic
3640232	NM_022725.4(FANCF):c.320_321insATGC (p.Arg108fs)	Pathogenic
3724996	NM_022725.4(FANCF):c.512del (p.Leu171fs)	Pathogenic
4713243	NM_022725.4(FANCF):c.53C>G (p.Ser18Ter)	Pathogenic
4737422	NM_022725.4(FANCF):c.224del (p.Gly75fs)	Pathogenic
4754855	NM_022725.4(FANCF):c.327C>A (p.Tyr109Ter)	Pathogenic
6340	NM_022725.4(FANCF):c.230_252del (p.Val77fs)	Pathogenic
6342	NM_022725.4(FANCF):c.16C>T (p.Gln6Ter)	Pathogenic
6343	NM_022725.4(FANCF):c.484_485del (p.Leu162fs)	Pathogenic
6344	NM_022725.4(FANCF):c.327C>G (p.Tyr109Ter)	Pathogenic
847349	NM_022725.4(FANCF):c.123dup (p.Arg42fs)	Pathogenic
929561	NM_022725.4(FANCF):c.84del (p.Ala29fs)	Pathogenic
929562	NM_022725.4(FANCF):c.219del (p.Arg74fs)	Pathogenic
929563	NM_022725.4(FANCF):c.496C>T (p.Gln166Ter)	Pathogenic
1691924	NM_022725.4(FANCF):c.1A>C (p.Met1Leu)	Likely pathogenic
1691925	NM_022725.4(FANCF):c.1A>T (p.Met1Leu)	Likely pathogenic

SpliceAI

121 predictions. Top by Δscore:

Variant	Effect	Δscore
11:22625538:G:GT	donor_gain	0.9300
11:22625482:T:TA	donor_gain	0.7900
11:22625483:G:GA	donor_gain	0.7800
11:22625463:A:T	donor_gain	0.7600
11:22625524:C:CT	acceptor_gain	0.7500
11:22625562:G:GT	donor_gain	0.7400
11:22625479:AGGT:A	donor_gain	0.7300
11:22625484:G:GG	donor_gain	0.7300
11:22625481:G:GT	donor_gain	0.6800
11:22625617:T:A	acceptor_gain	0.6700
11:22625480:GGTG:G	donor_gain	0.6400
11:22625487:A:AG	donor_gain	0.6400
11:22625579:G:GT	donor_gain	0.6200
11:22625423:G:GT	donor_gain	0.6100
11:22625482:T:A	donor_gain	0.6100
11:22625486:AACG:A	donor_gain	0.6100
11:22625502:G:GC	acceptor_gain	0.6000
11:22625562:G:T	donor_gain	0.6000
11:22625402:C:T	donor_gain	0.5500
11:22625488:C:G	donor_gain	0.5300
11:22625546:A:AG	donor_gain	0.5000
11:22625547:G:GG	donor_gain	0.5000
11:22625518:A:T	acceptor_gain	0.4900
11:22625074:T:TA	donor_gain	0.4800
11:22625750:T:TA	donor_gain	0.4800
11:22625751:A:AA	donor_gain	0.4800
11:22625580:A:T	donor_gain	0.4700
11:22625526:C:CT	acceptor_gain	0.4500
11:22625679:G:GT	donor_gain	0.4500
11:22622589:T:TG	acceptor_gain	0.4400

AlphaMissense

2394 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:22625735:A:G	W26R	0.987
11:22625735:A:T	W26R	0.987
11:22624929:C:A	W294C	0.984
11:22624929:C:G	W294C	0.984
11:22625733:C:A	W26C	0.984
11:22625733:C:G	W26C	0.984
11:22624931:A:G	W294R	0.983
11:22624931:A:T	W294R	0.983
11:22624776:G:C	S345R	0.981
11:22624776:G:T	S345R	0.981
11:22624778:T:G	S345R	0.981
11:22624794:A:C	F339L	0.981
11:22624794:A:T	F339L	0.981
11:22624796:A:G	F339L	0.981
11:22624812:T:A	K333N	0.974
11:22624812:T:G	K333N	0.974
11:22625702:A:G	W37R	0.973
11:22625702:A:T	W37R	0.973
11:22624772:A:G	W347R	0.972
11:22624772:A:T	W347R	0.972
11:22625700:C:A	W37C	0.971
11:22625700:C:G	W37C	0.971
11:22625667:A:C	F48L	0.970
11:22625667:A:T	F48L	0.970
11:22625669:A:G	F48L	0.970
11:22624768:G:A	T348I	0.966
11:22624899:C:A	W304C	0.965
11:22624899:C:G	W304C	0.965
11:22624770:C:A	W347C	0.963
11:22624770:C:G	W347C	0.963

dbSNP variants (sampled 300 via entrez): RS1000985563 (11:22625217 C>A,G), RS1001386843 (11:22624221 T>G), RS1002269655 (11:22623342 A>G), RS1002463466 (11:22623665 G>A,C), RS1003042380 (11:22622596 A>G), RS1003212913 (11:22626755 G>A), RS1004706680 (11:22624996 G>A,C), RS1005449037 (11:22626766 T>A,G), RS1005481496 (11:22626562 G>A), RS1006095116 (11:22627774 C>A), RS1006908460 (11:22623210 T>G), RS1007108124 (11:22623430 T>C), RS1007846974 (11:22622289 GA>G), RS1008018216 (11:22625901 C>G), RS1009249827 (11:22623710 T>C)

Disease associations

OMIM: gene MIM:613897 | disease phenotypes: MIM:603467, MIM:227650, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
Fanconi anemia complementation group F	Definitive	Autosomal recessive
Fanconi anemia	Supportive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Fanconi anemia complementation group F	Definitive	AR

Mondo (6): Fanconi anemia complementation group F (MONDO:0011325), Fanconi anemia (MONDO:0019391), breast cancer (MONDO:0007254), ovarian cancer (MONDO:0008170), hereditary neoplastic syndrome (MONDO:0015356), breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (3): Fanconi anemia (Orphanet:84), Inherited cancer-predisposing syndrome (Orphanet:140162), Rare ovarian cancer (Orphanet:213500)

HPO phenotypes

132 total (30 of 132 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000076	Vesicoureteral reflux
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000125	Pelvic kidney
HP:0000130	Abnormality of the uterus
HP:0000135	Hypogonadism
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000340	Sloping forehead
HP:0000347	Micrognathia
HP:0000364	Hearing abnormality
HP:0000365	Hearing impairment
HP:0000377	Abnormal pinna morphology
HP:0000405	Conductive hearing impairment
HP:0000453	Choanal atresia
HP:0000478	Abnormality of the eye

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90000014_5	Parkinson’s disease motor subtype (tremor dominant vs postural instability/gait difficulty)	4.000000e-06

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
D009386	Neoplastic Syndromes, Hereditary	C04.700; C16.320.700
D010051	Ovarian Neoplasms	C04.588.322.455; C12.050.351.500.056.630.705; C12.050.351.937.418.685; C12.100.250.056.630.705; C12.900.418.685; C19.344.410; C19.391.630.705

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2157856 (SINGLE PROTEIN), CHEMBL3885567 (PROTEIN-PROTEIN INTERACTION)

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4442551	FANCF, GAS2		0.00	0
rs3740615	FANCF, GAS2		0.00	0

ChEMBL bioactivities

1 potent at pChembl≥5 of 3 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.28	Kd	530	nM	CHEMBL2159398

PubChem BioAssay actives

1 with measured affinity, of 5 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-N-[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]hexanamide	696199: Binding affinity to human thymus flag-tagged full-length FANCF expressed in HEK293T cells assessed as dissociation constant by surface plasmon resonance assay	kd	0.5300	uM

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	2
manganese chloride	increases abundance, increases expression, affects cotreatment, decreases expression	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Formaldehyde	decreases expression	2
Manganese	increases abundance, increases expression, decreases expression, affects cotreatment	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4(2’-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline	decreases expression	1
abrine	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Lycopene	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Asbestos	affects response to substance	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression	1
Carbamazepine	affects expression	1
Diclofenac	affects expression	1
Dimethyl Sulfoxide	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Ouabain	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Rotenone	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2160582	Binding	Binding affinity to human thymus flag-tagged full-length FANCF expressed in HEK293T cells after 10 mins by pull-down assay	The antitumor agent doxorubicin binds to Fanconi anemia group F protein. — Bioorg Med Chem

Cellosaurus cell lines

3 cell lines: 2 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E1WZ	HAP1 FANCF (-) 1	Cancer cell line	Male
CVCL_E1X0	HAP1 FANCF (-) 2	Cancer cell line	Male
CVCL_G040	EUFA121	Transformed cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00014638	PHASE4	COMPLETED	Letrozole in Treating Postmenopausal Women With Metastatic Breast Cancer
NCT00022386	PHASE4	COMPLETED	Epoetin Alfa in Treating Chemotherapy-Related Anemia in Women With Stage I, Stage II, or Stage III Breast Cancer
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00030758	PHASE4	UNKNOWN	Filgrastim or Pegfilgrastim in Preventing Neutropenia in Women Receiving Chemotherapy Following Surgery for Breast Cancer
NCT00082277	PHASE4	COMPLETED	Anastrozole Biphosphonate Study in Postmenopausal Women With Hormone-Receptor-Positive Early Breast Cancer
NCT00087620	PHASE4	TERMINATED	A Study of Capecitabine In Combination With Docetaxel vs Capecitabine Followed by Docetaxel As First-Line Treatment For Metastatic Breast Cancer
NCT00121836	PHASE4	COMPLETED	A Study of Xeloda (Capecitabine) in Women With HER2-Negative Metastatic Breast Cancer
NCT00126360	PHASE4	UNKNOWN	STARS Breast Trial (Study of Anastrozole and Radiotherapy Sequencing Pilot)
NCT00127933	PHASE4	COMPLETED	XeNA Study - A Study of Xeloda (Capecitabine) in Patients With Invasive Breast Cancer
NCT00128297	PHASE4	COMPLETED	Pamidronate Administration in Breast Cancer Patients With Bone Metastases
NCT00129597	PHASE4	UNKNOWN	Effect of Ketalar to Prevent Postoperative Chronic Pain After Mastectomy
NCT00131170	PHASE4	COMPLETED	Paravertebral Block for Breast Surgery
NCT00156039	PHASE4	COMPLETED	Randomized Trial of Follow-up Strategies in Breast Cancer
NCT00160901	PHASE4	COMPLETED	Complementary Therapies for the Reduction of Side Effects During Chemotherapy for Breast Cancer
NCT00171847	PHASE4	TERMINATED	Study of the Efficacy and Safety of Letrozole Combined With Trastuzumab in Patients With Metastatic Breast Cancer
NCT00176046	PHASE4	COMPLETED	Mistletoe Extract in Early or Advanced Breast Cancer, A Feasibility Study
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00234195	PHASE4	COMPLETED	Wellbutrin XL, Major Depressive Disorder and Breast Cancer
NCT00237133	PHASE4	COMPLETED	Treatment of Locally Advanced Breast Cancer With Letrozole in Postmenopausal Women
NCT00237224	PHASE4	COMPLETED	Open Label Study of Postmenopausal Women With ER and /or PgR Positive Breast Cancer Treated With Letrozole
NCT00241046	PHASE4	TERMINATED	Letrozole in the Treatment of 1st and 2nd Line Hormone Receptor Positive Breast Cancer: Pre-therapeutic Risk Assessment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00323479	PHASE4	COMPLETED	Arthralgia During Anastrozole Therapy for Breast Cancer
NCT00334139	PHASE4	COMPLETED	Effect of Zoledronic Acid on Bone Metabolism in Patients With Bone Metastasis and Prostate or Breast Cancer
NCT00356148	PHASE4	COMPLETED	The Efficacy of Prophylactic Antibiotic Administration During Breast Cancer Surgery in Overweight Patients.
NCT00372476	PHASE4	COMPLETED	Efficacy and Safety of Imatinib and Vinorelbine in Patients With Advanced Breast Cancer
NCT00413491	PHASE4	UNKNOWN	National Screening in Denmark With MR Versus Mammography and Ultrasound of Women With BRCA1 or BRCA2 Mutations
NCT00484614	PHASE4	UNKNOWN	Study the Role of Positron Emission Mammography in Pre-surgical Planning for Breast Cancer
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00496678	PHASE4	COMPLETED	Trial of Patient Navigation-Activation
NCT00531973	PHASE4	UNKNOWN	A Study of Liposomal Doxorubicin in Women With Breast Cancer Exploiting Tissue Doppler Imaging
NCT00537771	PHASE4	COMPLETED	Liver Safety Under Upfront Arimidex vs Tamoxifen
NCT00544986	PHASE4	COMPLETED	A Prospective,Open-label Study of Anastrozole in Post-menopausal Women With Hormone Sensitive Advanced Breast Cancer
NCT00613275	PHASE4	COMPLETED	Patient Navigation in the Safety Net:CONNECTeDD
NCT00638599	PHASE4	COMPLETED	Comparison of Laryngeal Mask Airway (LMA®) and Tracheal Tube in Modified Radical Mastectomy on Breast Cancer
NCT00647075	PHASE4	UNKNOWN	Yunzhi as Dietary Supplement in Breast Cancer
NCT00688909	PHASE4	COMPLETED	Rheumatological Evaluation of Anastrozole and Letrozole as Adjuvant Treatment in Post-menopausal Women With Breast Cancer
NCT00699101	PHASE4	TERMINATED	Using the Conture® Multi-Lumen Balloon to Deliver Accelerated Partial Breast Brachytherapy
NCT00742222	PHASE4	COMPLETED	Electronic Xoft Intersociety Brachytherapy Trial: Electronic Brachytherapy (EBT) For Treatment of Early Stage Breast Cancer
NCT00754767	PHASE4	TERMINATED	L-Carnitine L-Tartrate in Preventing Peripheral Neuropathy Caused By Chemotherapy in Women With Metastatic Breast Cancer