FANCG

Summary

FANCG (FA complementation group G, HGNC:3588) is a protein-coding gene on chromosome 9p13.3, encoding Fanconi anemia group G protein (O15287). DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.

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 G.

Source: NCBI Gene 2189 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Fanconi anemia complementation group G (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 1,511 total — 83 pathogenic, 90 likely-pathogenic
• Phenotypes (HPO): 108
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_004629

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3588
Approved symbol	FANCG
Name	FA complementation group G
Location	9p13.3
Locus type	gene with protein product
Status	Approved
Aliases	FAG
Ensembl gene	ENSG00000221829
Ensembl biotype	protein_coding
OMIM	602956
Entrez	2189

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 15 protein_coding, 12 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000378643, ENST00000425676, ENST00000448890, ENST00000461149, ENST00000462124, ENST00000474894, ENST00000476212, ENST00000481254, ENST00000696700, ENST00000696701, ENST00000696702, ENST00000696703, ENST00000696706, ENST00000696707, ENST00000696708, ENST00000696709, ENST00000696710, ENST00000696711, ENST00000696712, ENST00000696713, ENST00000696714, ENST00000696715, ENST00000881804, ENST00000881805, ENST00000881806, ENST00000881807, ENST00000938586, ENST00000960438, ENST00000960439, ENST00000960440, ENST00000960441, ENST00000960442, ENST00000960443

RefSeq mRNA: 1 — MANE Select: NM_004629 NM_004629

CCDS: CCDS6574

Canonical transcript exons

ENST00000378643 — 14 exons

Exon	Start	End
ENSE00001091850	35078141	35078343
ENSE00001091851	35078605	35078736
ENSE00001091852	35079151	35079241
ENSE00001478288	35079441	35079942
ENSE00001812653	35073839	35074216
ENSE00003502137	35075465	35075754
ENSE00003526299	35076432	35076583
ENSE00003543692	35077264	35077399
ENSE00003594606	35074371	35074494
ENSE00003637791	35074927	35075082
ENSE00003648595	35075962	35076028
ENSE00003653157	35076724	35076870
ENSE00003656312	35076971	35077101
ENSE00003677034	35075279	35075325

Expression profiles

Bgee: expression breadth ubiquitous, 242 present calls, max score 94.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.2802 / max 115.0156, expressed in 1676 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100561	3.8468	1450
100560	2.1995	1075
100559	1.3775	774
100562	1.0420	603
100563	0.8145	400

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	94.00	gold quality
ganglionic eminence	UBERON:0004023	92.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	91.76	gold quality
cerebellar hemisphere	UBERON:0002245	91.56	gold quality
cerebellar cortex	UBERON:0002129	91.38	gold quality
embryo	UBERON:0000922	90.95	gold quality
lower esophagus mucosa	UBERON:0035834	89.86	gold quality
mucosa of transverse colon	UBERON:0004991	89.55	gold quality
cerebellum	UBERON:0002037	89.11	gold quality
granulocyte	CL:0000094	88.30	gold quality
body of pancreas	UBERON:0001150	88.30	gold quality
left testis	UBERON:0004533	88.00	gold quality
right testis	UBERON:0004534	87.72	gold quality
rectum	UBERON:0001052	87.25	gold quality
right frontal lobe	UBERON:0002810	86.97	gold quality
esophagus mucosa	UBERON:0002469	86.70	gold quality
ectocervix	UBERON:0012249	86.64	gold quality
endocervix	UBERON:0000458	86.19	gold quality
skin of abdomen	UBERON:0001416	86.04	gold quality
stromal cell of endometrium	CL:0002255	86.01	gold quality
skin of leg	UBERON:0001511	86.01	gold quality
cortical plate	UBERON:0005343	85.92	gold quality
left ovary	UBERON:0002119	85.78	gold quality
spleen	UBERON:0002106	85.75	gold quality
small intestine Peyer’s patch	UBERON:0003454	85.72	gold quality
body of uterus	UBERON:0009853	85.67	gold quality
right uterine tube	UBERON:0001302	85.58	gold quality
testis	UBERON:0000473	85.51	gold quality
right ovary	UBERON:0002118	85.24	gold quality
tibial nerve	UBERON:0001323	84.96	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.99

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting FANCG, 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-513A-5P	100.00	69.77	2465
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-5587-5P	99.07	68.58	838
HSA-MIR-4691-5P	98.41	66.77	1343
HSA-MIR-6792-3P	98.41	66.86	1359
HSA-MIR-4790-3P	96.63	67.08	806
HSA-MIR-6856-3P	96.47	66.27	781

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 31)

• Study of the molecular evolution of FA genes using database search methods such as PSI-BLAST suggested that FANCG may contain a known domain, and that this protein is a member of the family of tetratricopeptide repeat-containing proteins. (PMID:12432219)
• There is remarkably lage sequence variation in FANCG gene mutations and polymorphisms across ethnic and racial backgrounds found in the International Fanconi Anemia Registry they include IVS8-2A>G, IVS11+1G>c, 1794_1803del10, and IVS3+1G>C. (PMID:12552564)
• FANCG was able to mediate interaction between FANCA and FANCF, as well as between monomers of FANCA (PMID:12649160)
• FANCG is required for efficient homologous recombination-mediated repair of at least some types of DNA double-strand breaks (PMID:12861027)
• FANCG interacts directly with BRCA2. (PMID:12915460)
• A unique Fanconi-anemia-causing mutation, FANCG splice-site mutation IVS4+3A>G, showed exon 4 skipping. (PMID:15059067)
• FANCA and FANCG uniquely respond to oxidative damage by forming complexes via intermolecular disulfide linkages (PMID:15138265)
• FA proteins function at the level of chromatin during S phase to regulate and maintain genomic stability. (PMID:15256425)
• Primary fibroblasts from patients with Fanconi anemia with reduced FANCG expression show no signs of telomere dysfunction. (PMID:15319283)
• FANCG, in addition to stabilising the FA core complex, may have a role in building multiprotein complexes that facilitate homologous recombination repair. (PMID:16621732)
• Four human FANCG polymorphic variants show normal biological function. (PMID:17010390)
• FANCG promotes formation of a newly identified protein complex containing BRCA2, FANCD2 and XRCC3. (PMID:18212739)
• sites of interaction of FANCG with ERCC1, which is different from the region of ERCC1 that binds to XPF (PMID:20518486)
• Areca nut extracts-induced miR-23a was correlated with a reduced FANCG expression and DSB repair, which might contribute to ANE-associated human malignancies. (PMID:21750350)
• FANCA and FANCG are the major Fanconi anemia genes in the Korean population. (PMID:23067021)
• Three novel single base pair deletions, resulting in frameshift mutations (c.247delA, c.179delT and c.899delT) were identified in patients with Fanconi anaemia (PMID:24300640)
• A new role of FANCG in Homologous recombination repair of interstrand crosslinks through K63Ub-mediated interaction with the Rap80-BRCA1 complex. (PMID:25132264)
• Patients, homozygous for the FANCG founder mutation, present with severe cytopenia but progress to bone marrow failure at similar ages to other individuals affected with Fanconi anemia of heterogeneous genotype. (PMID:25477267)
• founder haplotype analysis of FANCG for the Korean Fanconi anemia population (PMID:25703136)
• a systems biology approach for elucidating the therapeutic potential of curcumin against FA and leukemia is investigated by analyzing the computational molecular interactions of curcumin ligand with FANC G of FA and seven other key disease targets of leukemia (PMID:27608133)
• studied the impact of mutations on the function and structure of FANCG (PMID:28024295)
• LOH may predominantly indicate copy number gains in FANCF and losses in FANCG and BRIP1. Integration of copy number data and gene expression proved difficult as the available sample sets did not overlap. (PMID:28440438)
• In >80% of black patients with Fanconi anaemia , a homozygous seven basepair deletion mutation in the FANCG gene (NM_004629.1 g.35077270_35077264del p.Tyr213Lysfs)[2] has been confirmed as the cause of the disease. (PMID:29843852)
• FANCG stimulates FANCA-mediated strand annealing and strand exchange. (PMID:30057198)
• Endocrine profiling in patients with Fanconi anemia, homozygous for a FANCG founder mutation. (PMID:32529760)
• Clinical and Genetic Features of Patients With Fanconi Anemia in Lebanon and Report on Novel Mutations in the FANCA and FANCG Genes. (PMID:32947577)
• Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase. (PMID:32989015)
• Severe telomere shortening in Fanconi anemia complementation group L. (PMID:33394227)
• Frequent internuclear bridging in a Fanconi anemia patient with FANCG mutation. (PMID:34436527)
• In silico study of missense variants of FANCA, FANCC and FANCG genes reveals high risk deleterious alleles predisposing to Fanconi anemia pathogenesis. (PMID:34864095)
• A comprehensive study evaluating germline FANCG variants in predisposition to breast and ovarian cancer. (PMID:39149814)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fancg	ENSDARG00000024967
mus_musculus	Fancg	ENSMUSG00000028453
rattus_norvegicus	Fancg	ENSRNOG00000057945

Protein

Protein identifiers

Fanconi anemia group G protein — O15287 (reviewed: O15287)

Alternative names: DNA repair protein XRCC9

All UniProt accessions (8): A0A0S2Z3R2, A0A8Q3SJ04, A0A8Q3WLH9, A0A8Q3WMK6, C9JSE3, F8WC08, O15287, Q53XM5

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. Candidate tumor suppressor gene.

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 FANCF, FANCA 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. The complex with FANCC and FANCG may also include EIF2AK2 and HSP70. When phosphorylated at Ser-7, forms a complex with BRCA2, FANCD2 and XRCC3.

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in testis and thymus. Found in lymphoblasts.

Disease relevance. Fanconi anemia complementation group G (FANCG) [MIM:614082] 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_004620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR039684	FANCG	Family

UniProt features (19 total): sequence variant 9, repeat 4, mutagenesis site 4, chain 1, modified residue 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
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-O15287-F1	83.39	0.53

Functional residue map

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

Post-translational modifications (1): 7

Mutagenesis-validated functional residues (4):

Position	Phenotype
7	loss of brca2-, fancd2- and xrcc3-binding. no effect on complex formation with fanca and fancf.
383	no effect on brca2-, fanca-, fancf-, nor xrcc3-binding.
387	no effect on brca2-, fanca-, fancf-, nor xrcc3-binding.
546	no effect on hes1-, nor fanca-binding.

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: 433 (showing top): PID_FANCONI_PATHWAY, MORF_RAGE, E2F_Q4_01, E2F4DP1_01, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, FISCHER_G1_S_CELL_CYCLE, MORF_ATRX, MITSIADES_RESPONSE_TO_APLIDIN_DN, GOBP_MALE_GAMETE_GENERATION, MODULE_308, KAUFFMANN_DNA_REPAIR_GENES, PATIL_LIVER_CANCER, KOKKINAKIS_METHIONINE_DEPRIVATION_96HR_UP, GOBP_OVARIAN_FOLLICLE_DEVELOPMENT, E2F1DP1_01

GO Biological Process (7): ovarian follicle development (GO:0001541), DNA repair (GO:0006281), DNA damage response (GO:0006974), mitochondrion organization (GO:0007005), spermatid development (GO:0007286), response to radiation (GO:0009314), interstrand cross-link repair (GO:0036297)

GO Molecular Function (2): damaged DNA binding (GO:0003684), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), nucleoplasm (GO:0005654), mitochondrion (GO:0005739), cytosol (GO:0005829), nuclear speck (GO:0016607), Fanconi anaemia nuclear complex (GO:0043240), nucleus (GO:0005634), cytoplasm (GO:0005737)

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	4
cytoplasm	2
intracellular membrane-bounded organelle	2
female gonad development	1
anatomical structure development	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
organelle organization	1
germ cell development	1
spermatid differentiation	1
response to abiotic stimulus	1
DNA repair	1
DNA binding	1
binding	1
chromosome	1
nuclear lumen	1
nuclear ribonucleoprotein granule	1
nuclear protein-containing complex	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1209 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FANCG	FANCE	Q9HB96	999
FANCG	FANCM	Q8IYD8	999
FANCG	FANCC	Q00597	999
FANCG	FANCF	Q9NPI8	999
FANCG	FANCA	O15360	999
FANCG	FANCB	Q8NB91	999
FANCG	FANCL	Q9NW38	999
FANCG	FAAP100	Q0VG06	997
FANCG	FANCD2	Q9BXW9	995
FANCG	F6S8H2	F6S8H2	994
FANCG	BRCA2	P51587	991
FANCG	FANCI	Q9NVI1	953
FANCG	CYP2E1	P05181	952
FANCG	XRCC3	O43542	948
FANCG	FAAP24	Q9BTP7	939

IntAct

239 interactions, top by confidence:

A	B	Type	Score
FANCA	FANCG	psi-mi:“MI:0914”(association)	0.960
FANCG	FANCA	psi-mi:“MI:0915”(physical association)	0.960
FANCA	FANCG	psi-mi:“MI:0915”(physical association)	0.960
FANCG	FANCA	psi-mi:“MI:0914”(association)	0.960
FANCA	FANCG	psi-mi:“MI:2364”(proximity)	0.960
FANCG	FANCA	psi-mi:“MI:2364”(proximity)	0.960
FANCF	FANCG	psi-mi:“MI:0915”(physical association)	0.750
FANCG	FANCF	psi-mi:“MI:0915”(physical association)	0.750
PRPF18	FANCG	psi-mi:“MI:0915”(physical association)	0.560
ZNF329	FANCG	psi-mi:“MI:0915”(physical association)	0.560
CCHCR1	FANCG	psi-mi:“MI:0915”(physical association)	0.560
SUOX	FANCG	psi-mi:“MI:0915”(physical association)	0.560
FANCG	PRPF18	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (289): UIMC1 (Affinity Capture-Western), FANCG (Reconstituted Complex), BRCC3 (Affinity Capture-Western), FAM175A (Affinity Capture-Western), FANCG (FRET), FANCA (Affinity Capture-Western), FANCG (Biochemical Activity), FANCG (Affinity Capture-MS), FANCG (Affinity Capture-Western), FANCG (Affinity Capture-Western), FANCG (Affinity Capture-MS), CTNNB1 (Affinity Capture-Western), FANCG (Affinity Capture-Western), FANCG (Affinity Capture-MS), FANCG (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI67, A0JMF6, A1L3T7, A2BGG1, A4FU01, A6NE52, D4A929, O15287, O35827, O75064, O95398, O95704, P58660, P97680, Q13671, Q3U1Y4, Q3V1L6, Q400C9, Q562E7, Q58EX7, Q5ND34, Q5PQS0, Q5RA67, Q5XIS1, Q68EF8, Q6IRN0, Q6P4K6, Q6ZNJ1, Q6ZQA0, Q76MJ5, Q7TSI1, Q80VA5, Q8CFK6, Q8IV53, Q8K330, Q8NCE2, Q8R2S1, Q8R5G7, Q8TE77, Q8VCC8

Diamond homologs: O15287, Q9EQR6

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CDK1	up-regulates	FANCG	phosphorylation
FANCG	“form complex”	“Fanconi anemia core complex”	binding
FANCG	“form complex”	“D1-D2-G-X3 complex”	binding
FANCG	“up-regulates quantity by stabilization”	SPTAN1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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	8	34.8×	2e-08
PKR-mediated signaling	7	15.4×	7e-05

GO biological processes:

GO term	Partners	Fold	FDR
interstrand cross-link repair	8	40.2×	2e-08
intermediate filament organization	5	14.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

1511 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	83
Likely pathogenic	90
Uncertain significance	636
Likely benign	582
Benign	19

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068804	NM_004629.2(FANCG):c.395dup (p.Pro133fs)	Pathogenic
1070503	NM_004629.2(FANCG):c.365G>A (p.Trp122Ter)	Pathogenic
1072435	NM_004629.2(FANCG):c.1652dup (p.Tyr551Ter)	Pathogenic
1073453	NM_004629.2(FANCG):c.1309_1310dup (p.Asp437fs)	Pathogenic
1075003	NM_004629.2(FANCG):c.1033C>T (p.Gln345Ter)	Pathogenic
1075707	NM_004629.2(FANCG):c.1216C>T (p.Gln406Ter)	Pathogenic
1076277	NM_004629.2(FANCG):c.689del (p.Ser230fs)	Pathogenic
1224529	NM_004629.2(FANCG):c.346C>T (p.Gln116Ter)	Pathogenic
1224534	NM_004629.2(FANCG):c.1468G>T (p.Glu490Ter)	Pathogenic
1224535	NM_004629.2(FANCG):c.1572G>A (p.Trp524Ter)	Pathogenic
1224536	NM_004629.2(FANCG):c.1501C>T (p.Gln501Ter)	Pathogenic
1322888	NM_004629.2(FANCG):c.910G>T (p.Glu304Ter)	Pathogenic
1362165	NM_004629.2(FANCG):c.1007C>A (p.Ser336Ter)	Pathogenic
1368148	NM_004629.2(FANCG):c.336del (p.Arg113fs)	Pathogenic
1418010	NM_004629.2(FANCG):c.1585C>T (p.Gln529Ter)	Pathogenic
1436762	NM_004629.2(FANCG):c.1062C>A (p.Cys354Ter)	Pathogenic
1442713	NM_004629.2(FANCG):c.214_217del (p.Thr72fs)	Pathogenic
1452560	NM_004629.2(FANCG):c.560del (p.Pro187fs)	Pathogenic
1454833	NM_004629.2(FANCG):c.832dup (p.Ala278fs)	Pathogenic
1456052	NM_004629.2(FANCG):c.76C>T (p.Gln26Ter)	Pathogenic
1456128	NM_004629.2(FANCG):c.604G>T (p.Gly202Ter)	Pathogenic
1459835	NM_004629.2(FANCG):c.1246_1247del (p.Leu416fs)	Pathogenic
1695249	NM_004629.2(FANCG):c.1400del (p.Gly467fs)	Pathogenic
2008902	NM_004629.2(FANCG):c.825_828del (p.Glu275fs)	Pathogenic
2030792	NM_004629.2(FANCG):c.643C>T (p.Gln215Ter)	Pathogenic
2057340	NM_004629.2(FANCG):c.1428del (p.Phe476fs)	Pathogenic
2080001	NM_004629.2(FANCG):c.1474G>T (p.Glu492Ter)	Pathogenic
2088008	NM_004629.2(FANCG):c.1144-2A>G	Pathogenic
216091	NM_004629.2(FANCG):c.156dup (p.Leu53fs)	Pathogenic
2162333	NM_004629.2(FANCG):c.182del (p.Pro61fs)	Pathogenic

SpliceAI

2194 predictions. Top by Δscore:

Variant	Effect	Δscore
9:35078705:C:CT	acceptor_gain	1.0000
9:35078706:A:T	acceptor_gain	1.0000
9:35075326:C:A	acceptor_loss	0.9900
9:35075326:C:CC	acceptor_gain	0.9900
9:35075327:T:A	acceptor_loss	0.9900
9:35075339:C:CT	acceptor_gain	0.9900
9:35075567:T:TA	donor_gain	0.9900
9:35075960:AC:A	donor_gain	0.9900
9:35075961:CC:C	donor_gain	0.9900
9:35077230:A:C	donor_gain	0.9900
9:35077259:CTGA:C	donor_loss	0.9900
9:35077260:TGA:T	donor_loss	0.9900
9:35077261:GA:G	donor_loss	0.9900
9:35077262:A:C	donor_loss	0.9900
9:35077263:C:CG	donor_loss	0.9900
9:35077296:T:TA	donor_gain	0.9900
9:35077395:CCACT:C	acceptor_gain	0.9900
9:35077396:CACT:C	acceptor_gain	0.9900
9:35077396:CACTC:C	acceptor_gain	0.9900
9:35077398:CT:C	acceptor_gain	0.9900
9:35077400:C:CC	acceptor_gain	0.9900
9:35078599:CCTCA:C	donor_loss	0.9900
9:35078600:CTCAC:C	donor_loss	0.9900
9:35078601:TCACC:T	donor_loss	0.9900
9:35078602:CA:C	donor_loss	0.9900
9:35078603:A:C	donor_loss	0.9900
9:35078604:C:CA	donor_loss	0.9900
9:35078604:CCT:C	donor_gain	0.9900
9:35078604:CCTCT:C	donor_gain	0.9900
9:35078705:C:T	acceptor_gain	0.9900

AlphaMissense

3961 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:35076742:A:C	S302R	0.981
9:35076742:A:T	S302R	0.981
9:35076744:T:G	S302R	0.981
9:35076456:G:T	A351E	0.978
9:35078684:G:C	N76K	0.978
9:35078684:G:T	N76K	0.978
9:35076792:C:G	A286P	0.973
9:35075004:C:G	R520P	0.966
9:35077360:A:G	W184R	0.966
9:35077360:A:T	W184R	0.966
9:35075519:C:T	G460D	0.964
9:35075470:A:C	F476L	0.962
9:35075470:A:T	F476L	0.962
9:35075472:A:G	F476L	0.962
9:35075520:C:G	G460R	0.960
9:35076780:A:C	Y290D	0.960
9:35077264:C:G	G216R	0.957
9:35075002:C:G	G521R	0.956
9:35075002:C:T	G521R	0.956
9:35075700:C:G	A400P	0.956
9:35075996:A:G	L370P	0.956
9:35078287:A:G	W122R	0.956
9:35078287:A:T	W122R	0.956
9:35074943:A:C	S540R	0.954
9:35074943:A:T	S540R	0.954
9:35074945:T:G	S540R	0.954
9:35075324:A:G	C479R	0.954
9:35076017:G:T	A363D	0.951
9:35076018:C:G	A363P	0.950
9:35074957:C:G	D536H	0.949

dbSNP variants (sampled 300 via entrez): RS1000355215 (9:35074946 G>A,C), RS1000754593 (9:35081709 C>G), RS1001208056 (9:35081010 A>C,G,T), RS1001653235 (9:35077997 C>T), RS1002110834 (9:35080737 A>T), RS1002242077 (9:35076277 A>C,G), RS1003316167 (9:35073431 T>C), RS1003373828 (9:35079801 G>A,T), RS1003595944 (9:35075067 C>T), RS1003928149 (9:35073625 T>A,C), RS1004003629 (9:35073405 T>C), RS1004272420 (9:35080502 G>A), RS1004442775 (9:35080135 C>T), RS1005169963 (9:35078782 T>G), RS1005869651 (9:35080734 T>G)

Disease associations

OMIM: gene MIM:602956 | disease phenotypes: MIM:614082, MIM:227650, MIM:167000

GenCC curated gene-disease

Disease	Classification	Inheritance
Fanconi anemia complementation group G	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 G	Definitive	AR

Mondo (6): Fanconi anemia complementation group G (MONDO:0013565), Fanconi anemia (MONDO:0019391), ovarian cancer (MONDO:0008170), exocrine pancreatic carcinoma (MONDO:0005192), Fanconi anemia complementation group A (MONDO:0009215), pituitary stalk interruption syndrome (MONDO:0019828)

Orphanet (5): Fanconi anemia (Orphanet:84), Rare ovarian cancer (Orphanet:213500), Familial pancreatic carcinoma (Orphanet:1333), Rare carcinoma of pancreas (Orphanet:217074), Pituitary stalk interruption syndrome (Orphanet:95496)

HPO phenotypes

108 total (30 of 108 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000035	Abnormal testis morphology
HP:0000047	Hypospadias
HP:0000072	Hydroureter
HP:0000079	Abnormality of the urinary system
HP:0000083	Renal insufficiency
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:0000453	Choanal atresia
HP:0000478	Abnormality of the eye
HP:0000483	Astigmatism
HP:0000486	Strabismus
HP:0000492	Abnormal eyelid morphology
HP:0000504	Abnormality of vision
HP:0000505	Visual impairment

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST90002396_404	Mean reticulocyte volume	9.000000e-18
GCST90002397_681	Mean spheric corpuscular volume	3.000000e-20
GCST90002402_57	Platelet count	3.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D005199	Fanconi Anemia	C15.378.050.085.080.280; C15.378.190.223.500.500.280; C16.320.077.280; C18.452.284.280
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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	increases expression, increases response to substance	3
Fluorouracil	affects response to substance, increases expression	3
Cyclosporine	decreases expression, decreases methylation	3
bisphenol A	decreases expression	2
(+)-JQ1 compound	decreases expression	2
Cadmium Chloride	decreases expression	2
pradimicin-IRD	affects expression, affects response to substance	1
methylmercuric chloride	decreases expression	1
lasiocarpine	increases expression	1
4-biphenylamine	decreases expression	1
geraniol	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
zinc chromate	decreases expression, increases abundance	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
chromium hexavalent ion	decreases expression, increases abundance	1
CGP 52608	affects binding, increases reaction	1
CPG-oligonucleotide	decreases expression	1
4(2’-aminoethyl)amino-1,8-dimethylimidazo(1,2-a)quinoxaline	decreases expression	1
abrine	decreases expression	1
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
brevetoxin 2	increases expression	1
riccardin D	decreases expression	1
NSC 689534	affects binding, decreases expression	1
Irinotecan	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1

Cellosaurus cell lines

40 cell lines: 20 transformed cell line, 15 finite cell line, 3 cancer cell line, 2 telomerase immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_2896	FA9JTO	Finite cell line	Male
CVCL_2897	FA9JTOTERT	Telomerase immortalized cell line	Male
CVCL_B2WY	Abcam HEK293T FANCG KO	Transformed cell line	Female
CVCL_D254	FA9JTO hTERT-1	Telomerase immortalized cell line	Male
CVCL_G057	EUFA143	Transformed cell line	Male
CVCL_G063	EUFA316	Transformed cell line	Female
CVCL_G064	EUFA349	Transformed cell line	Male
CVCL_HE21	RKO FANCG(+/-)	Cancer cell line	Sex unspecified
CVCL_HE22	RKO FANCG(-/-)	Cancer cell line	Sex unspecified
CVCL_SN08	HAP1 FANCG (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00190697	PHASE4	COMPLETED	A Study of LY353381 (Arzoxifene) for Patients Who Benefitted From This Drug in Other Oncology Trials and Wished to Continue Treatment
NCT00277160	PHASE4	COMPLETED	A Study of Primary Prophylaxis With Neulasta (Pegfilgrastim) Versus Secondary Prophylaxis After Chemotherapy in Elderly Subjects (>/= 65 Years Old) With Cancer
NCT00727961	PHASE4	COMPLETED	A Study to Evaluate Efficacy and Tolerance of Caelyx in Patients With Epithelial Ovarian Cancer. (Study P04072)(COMPLETED)
NCT00740116	PHASE4	COMPLETED	Tranexamic Acid in Surgery of Advanced Ovarian Cancer
NCT00817479	PHASE4	COMPLETED	Tumor Gene Expression in Women With Ovarian Cancer
NCT01432015	PHASE4	COMPLETED	Fosaprepitant Versus Aprepitant in the Prevention of Chemotherapy Induced Nausea and Vomiting
NCT01706120	PHASE4	UNKNOWN	Study of Clinical and Biological Prognostic Factors in Patients With Ovarian Cancer Receiving Carboplatin +Paclitaxel With Bevacizumab
NCT01932125	PHASE4	COMPLETED	An Interventional Study of Avastin (Bevacizumab) in Patients With Advanced/Metastatic Epithelial Ovarian Cancer, Fallopian Tube Cancer or Primary Peritoneal Cancer
NCT01953107	PHASE4	COMPLETED	Oral Iron vs. Placebo in Newly Diagnosed Gynecologic Oncology Patients Who Are Surgical Candidates.
NCT02035345	PHASE4	TERMINATED	Slowed Carboplatin Infusion for Ovarian Cancer Patients Receiving Carboplatin Re-Treatment
NCT02243059	PHASE4	WITHDRAWN	Magnetic Resonance Imaging for Lymph Node Staging in Ovarian Cancer
NCT03164980	PHASE4	TERMINATED	QoL-Comparison Between Trabectedin/PLD and Pt-based Therapy in Patients With Pt-sensitive Recurrent Ovarian Cancer
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03543462	PHASE4	COMPLETED	Diaphragmatic Resection And Gynecological Ovarian Neoplasm
NCT03752216	PHASE4	COMPLETED	NIraparib and Quality of LifE is a Longitudinal Study Evaluating in Real Life the Tolerability of Niraparib.
NCT03858166	PHASE4	TERMINATED	Efficacy and Safety of PEG-rhG-CSF Secondary Prophylaxis vs. Therapeutic Administration in Patients With Ovarian Cancer
NCT04024254	PHASE4	COMPLETED	A Study of Serum Folate Levels in Patients Treated With Olaparib
NCT04330040	PHASE4	COMPLETED	Prospective Multicentre Phase-IV Clinical Trial of Olaparib in Indian Patients With Ovarian and Metastatic Breast Cancer
NCT04352439	PHASE4	COMPLETED	Aspirin for Prevention of Venous Thromboembolism Among Ovarian Cancer Patients Receiving Neoadjuvant Chemotherapy
NCT05187208	PHASE4	UNKNOWN	PARP Inhibitor Oral Maintenance in Low-Risk Ovarian Cancer
NCT05606692	PHASE4	RECRUITING	Influences of Propofol and Sevoflurane Anesthesia in Ovarian Cancer (Anesthetics)
NCT05926336	PHASE4	RECRUITING	The Effects of Using Different Anesthetics on the Prognosis of Primary Tumors and Its Mechanism of Action
NCT06412120	PHASE4	RECRUITING	Study Evaluating Safety, Tolerability, and Metabolism of Niraparib
NCT06871787	PHASE4	NOT_YET_RECRUITING	Near-Infrared Fluorescence Imaging With Indocyanine Green to Evaluate Bowel Anastomoses in Gynecologic Oncology Surgery
NCT06887933	PHASE4	NOT_YET_RECRUITING	A Trial to Evaluate the Safety of Niraparib Tablets in Adult Female Participants With Advanced or Relapsed Epithelial Ovarian Cancer
NCT07469202	PHASE4	NOT_YET_RECRUITING	CYTALUX Dose Extension Study
NCT06519786	PHASE3	UNKNOWN	Safety and Efficacy of Metformin for Treatment of Cytopenia in Children and Adolescents With Fanconi Anemia
NCT00001806	PHASE3	COMPLETED	Methods in Education for Breast Cancer Genetics
NCT00002477	PHASE3	UNKNOWN	Adjuvant Chemotherapy Compared With Observation in Treating Patients With Resected Early Stage Ovarian Epithelial Cancer
NCT00002568	PHASE3	COMPLETED	Combination Chemotherapy With or Without Surgery in Treating Patients With Stage III Ovarian Epithelial Cancer
NCT00002641	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Soft Tissue Sarcoma
NCT00002717	PHASE3	COMPLETED	Paclitaxel and Cisplatin in Treating Patients With Stage III or Stage IV Ovarian Cancer or Primary Peritoneal Cancer
NCT00002764	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Lung Metastases From Soft Tissue Sarcoma
NCT00002819	PHASE3	TERMINATED	Chemotherapy With or Without Peripheral Stem Cell Transplantation in Treating Patients With Persistent Ovarian Epithelial Cancer
NCT00002894	PHASE3	COMPLETED	Platinum-based Chemotherapy With or Without Paclitaxel in Treating Patients With Relapsed Ovarian Cancer
NCT00002895	PHASE3	COMPLETED	Early Chemotherapy Based on CA 125 Level Alone Compared With Delayed Chemotherapy in Treating Patients With Recurrent Ovarian Epithelial , Fallopian Tube, or Primary Peritoneal Cancer
NCT00003120	PHASE3	COMPLETED	S9701 Paclitaxel in Treating Patients With Advanced Ovarian, Fallopian Tube, or Primary Peritoneal Cancer in Remission
NCT00003214	PHASE3	COMPLETED	Chemosensitivity Testing to Assign Treatment for Patients With Stage III or Stage IV Ovarian Cancer
NCT00003322	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Primary Peritoneal or Stage III Epithelial Ovarian Cancer
NCT00003636	PHASE3	COMPLETED	Chemotherapy Plus Surgery in Treating Patients With Stage III or Stage IV Ovarian, Peritoneal, or Fallopian Tube Cancer