Fanconi anemia complementation group A

disease

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Also known as Estren-Dameshek variant of Fanconi AnaemiaFANCAFANCA Fanconi anaemiaFANCA Fanconi anemiaFanconi AnaemiaFanconi anaemia caused by mutation in FANCAFanconi anaemia complementation group type AFanconi anemia caused by mutation in FANCAFanconi anemia complementation group type AFanconi anemia, complementation group AFanconi Anemia, complementation group type a

Summary

Fanconi anemia complementation group A (MONDO:0009215) is a disease caused by FANCA (GenCC Definitive), with 13 cohort genes and 5 clinical trials. The dominant Reactome pathway is Fanconi Anemia Pathway (9 cohort genes). Top therapeutic interventions include mozafancogene autotemcel.

At a glance

Causal gene: FANCA (GenCC Definitive)
Cohort genes: 13
ClinVar variants: 1,922
Clinical trials: 5

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group A
Mondo ID	MONDO:0009215
OMIM	227650
DOID	DOID:0111095
NCIT	C125702
UMLS	C3469521
MedGen	483333
GARD	0015170
Is cancer (heuristic)	no

Also known as: Estren-Dameshek variant of Fanconi Anaemia · FANCA · FANCA Fanconi anaemia · FANCA Fanconi anemia · Fanconi Anaemia · Fanconi anaemia caused by mutation in FANCA · Fanconi anaemia complementation group type A · Fanconi anemia caused by mutation in FANCA · Fanconi anemia complementation group A · Fanconi anemia complementation group type A · Fanconi anemia, complementation group A · Fanconi Anemia, complementation group type a

Data availability: 1,922 ClinVar variants · 7 GenCC gene-disease records · 97 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 A

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

600 retrieved; paginated sample, class counts are floors:

184 uncertain significance, 98 conflicting classifications of pathogenicity, 75 likely pathogenic, 56 likely benign, 53 pathogenic/likely pathogenic, 51 benign, 43 pathogenic, 39 benign/likely benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
209105	NM_007294.4(BRCA1):c.594_597delTGTG	BRCA1	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1029499	NM_000135.4(FANCA):c.189+1G>T	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1064631	NM_000135.4(FANCA):c.1307A>G (p.Gln436Arg)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1066827	NM_000135.4(FANCA):c.3791_3793del (p.Ser1264del)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1068013	NM_000135.4(FANCA):c.426+1G>A	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1071066	NM_000135.4(FANCA):c.2832dup (p.Ala945fs)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1071067	NM_000135.4(FANCA):c.1144C>T (p.Gln382Ter)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1072568	NM_000135.4(FANCA):c.1294del (p.Leu432fs)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076167	NM_000135.4(FANCA):c.3189G>A (p.Trp1063Ter)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179127	NM_000135.4(FANCA):c.560_561insGAGT (p.Gln188fs)	FANCA	Pathogenic	criteria provided, single submitter
1179145	NM_000135.4(FANCA):c.1850_1859del (p.Leu617fs)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1224515	NM_000135.4(FANCA):c.2265dup (p.Arg756fs)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1319527	NM_000135.4(FANCA):c.1827-2A>G	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322867	NM_000135.4(FANCA):c.2143G>T (p.Glu715Ter)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1322868	NM_000135.4(FANCA):c.206_207del (p.Leu68_Cys69insTer)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322869	NM_000135.4(FANCA):c.580C>T (p.Gln194Ter)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322871	NM_000135.4(FANCA):c.3234C>G (p.Tyr1078Ter)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1322872	NM_000135.4(FANCA):c.1567-1G>C	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1322873	NM_000135.4(FANCA):c.3931_3932del (p.Glu1310_Ser1311insTer)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1331378	NM_000135.4(FANCA):c.991del (p.Ser331fs)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1338313	NM_000135.4(FANCA):c.4096C>T (p.Gln1366Ter)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1338565	NM_000135.4(FANCA):c.3146_3147del (p.Leu1048_Phe1049insTer)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
134239	NM_000135.4(FANCA):c.862G>T (p.Glu288Ter)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1350875	NM_000135.4(FANCA):c.3064C>T (p.Gln1022Ter)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts
1389482	NM_000135.4(FANCA):c.1226-1G>C	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1397477	NM_000135.4(FANCA):c.283+1G>A	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1413965	NM_000135.4(FANCA):c.2001dup (p.Ser668fs)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1419699	NM_000135.4(FANCA):c.3973del (p.Asp1325fs)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1420592	NM_000135.4(FANCA):c.1213C>T (p.Gln405Ter)	FANCA	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1430115	NM_000135.4(FANCA):c.3439_3440del (p.Asp1147fs)	FANCA	Pathogenic	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 8 · Orphanet: 21 · 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
FANCA	Definitive	Autosomal recessive	Fanconi anemia complementation group A	8

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FANCA	Orphanet:84	Fanconi anemia
BRCA1	Orphanet:1331	Familial prostate cancer
BRCA1	Orphanet:1333	Familial pancreatic carcinoma
BRCA1	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA1	Orphanet:168829	Primary peritoneal carcinoma
BRCA1	Orphanet:227535	Hereditary breast cancer
BRCA1	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA1	Orphanet:694963	Inflammatory breast cancer
BRCA1	Orphanet:70567	Cholangiocarcinoma
BRCA1	Orphanet:84	Fanconi anemia
FANCL	Orphanet:84	Fanconi anemia
FANCM	Orphanet:399805	Male infertility with azoospermia or oligozoospermia due to single gene mutation
FANCM	Orphanet:84	Fanconi anemia
ZNF469	Orphanet:90354	Brittle cornea syndrome
SLX4	Orphanet:84	Fanconi anemia
FANCI	Orphanet:84	Fanconi anemia
FANCB	Orphanet:3412	VACTERL with hydrocephalus
FANCB	Orphanet:84	Fanconi anemia
FANCC	Orphanet:84	Fanconi anemia
FANCD2	Orphanet:84	Fanconi anemia
FANCG	Orphanet:84	Fanconi anemia

Cohort genes → proteins

13 cohort genes, 13 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	13

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FANCA	HGNC:3582	ENSG00000187741	O15360	Fanconi anemia group A protein	gencc,clinvar
BRCA1	HGNC:1100	ENSG00000012048	P38398	Breast cancer type 1 susceptibility protein	clinvar
AOPEP	HGNC:1361	ENSG00000148120	Q8N6M6	Aminopeptidase O	clinvar
FANCL	HGNC:20748	ENSG00000115392	Q9NW38	E3 ubiquitin-protein ligase FANCL	clinvar
FANCM	HGNC:23168	ENSG00000187790	Q8IYD8	Fanconi anemia group M protein	clinvar
ZNF469	HGNC:23216	ENSG00000225614	Q96JG9	Zinc finger protein 469	clinvar
ZNF276	HGNC:23330	ENSG00000158805	Q8N554	Zinc finger protein 276	clinvar
SLX4	HGNC:23845	ENSG00000188827	Q8IY92	Structure-specific endonuclease subunit SLX4	clinvar
FANCI	HGNC:25568	ENSG00000140525	Q9NVI1	Fanconi anemia group I protein	clinvar
FANCB	HGNC:3583	ENSG00000181544	Q8NB91	Fanconi anemia group B protein	clinvar
FANCC	HGNC:3584	ENSG00000158169	Q00597	Fanconi anemia group C protein	clinvar
FANCD2	HGNC:3585	ENSG00000144554	Q9BXW9	Fanconi anemia group D2 protein	clinvar
FANCG	HGNC:3588	ENSG00000221829	O15287	Fanconi anemia group G protein	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
FANCA	Fanconi anemia group A protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
BRCA1	Breast cancer type 1 susceptibility protein	E3 ubiquitin-protein ligase that specifically mediates the formation of ‘Lys-6’-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage.
AOPEP	Aminopeptidase O	Aminopeptidase which catalyzes the hydrolysis of amino acid residues from the N-terminus of peptide or protein substrates.
FANCL	E3 ubiquitin-protein ligase FANCL	Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway.
FANCM	Fanconi anemia group M protein	DNA-dependent ATPase component of the Fanconi anemia (FA) core complex.
ZNF469	Zinc finger protein 469	May be involved in transcriptional regulation.
ZNF276	Zinc finger protein 276	May be involved in transcriptional regulation.
SLX4	Structure-specific endonuclease subunit SLX4	Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases.
FANCI	Fanconi anemia group I protein	Plays an essential role in the repair of DNA double-strand breaks by homologous recombination and in the repair of interstrand DNA cross-links (ICLs) by promoting FANCD2 monoubiquitination by FANCL and participating in recruitment to DNA r…
FANCB	Fanconi anemia group B protein	DNA repair protein required for FANCD2 ubiquitination.
FANCC	Fanconi anemia group C protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.
FANCD2	Fanconi anemia group D2 protein	Required for maintenance of chromosomal stability.
FANCG	Fanconi anemia group G protein	DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function.

Protein-family classification

Druggable: 1 · Difficult: 4 · Unknown: 8 · Druggable fraction: 0.08

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
Transcription factor	4	2.5×	0.188
Protease	1	2.8×	0.451
Other/Unknown	8	1.1×	0.451

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FANCA	Other/Unknown	no		FANCA, Fanconi_A_N, Fanconi_A_C
BRCA1	Transcription factor	no	2.3.2.27	BRCT_dom, Znf_RING, BRCA1
AOPEP	Protease	yes		Peptidase_M1_dom, Peptidase_M1_C, ARM-type_fold
FANCL	Transcription factor	no	2.3.2.27	Znf_RING/FYVE/PHD, UBQ-conjugating_enzyme/RWD, FancL_WD-rpt_cont_dom
FANCM	Other/Unknown	no		Helicase_C-like, ERCC4_domain, RuvA_2-like
ZNF469	Transcription factor	no		Znf_C2H2_type, Znf_C2H2_sf, ZNF469
ZNF276	Transcription factor	no		Znf_AD, Znf_C2H2_type, Znf_C2H2_sf
SLX4	Other/Unknown	no		BTB/POZ_dom, Rad18_UBZ4, SKP1/BTB/POZ_sf
FANCI	Other/Unknown	no		FANCI, FANCI_S1-cap, FANCI_S1
FANCB	Other/Unknown	no		FANCB
FANCC	Other/Unknown	no		FANCC
FANCD2	Other/Unknown	no		FANCD2
FANCG	Other/Unknown	no		TPR-like_helical_dom_sf, TPR_rpt, FANCG

Expression context

Cohort genes with no expression data: 0.

12 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)	13
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	6
ventricular zone	5
right hemisphere of cerebellum	3
primordial germ cell in gonad	2
secondary oocyte	2
left testis	1
right testis	1
apex of heart	1
ascending aorta	1
right coronary artery	1
adenohypophysis	1
calcaneal tendon	1
pituitary gland	1
oocyte	1
sperm	1
cartilage tissue	1
tibia	1
upper arm skin	1
granulocyte	1
sural nerve	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FANCA	185	ubiquitous	marker	right testis, ventricular zone, left testis
BRCA1	208	ubiquitous	marker	ventricular zone, male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad
AOPEP	224	ubiquitous	marker	apex of heart, right coronary artery, ascending aorta
FANCL	293	ubiquitous	marker	pituitary gland, adenohypophysis, calcaneal tendon
FANCM	203	ubiquitous	marker	sperm, oocyte, male germ line stem cell (sensu Vertebrata) in testis
ZNF469	211	broad	yes	tibia, upper arm skin, cartilage tissue
ZNF276	233	ubiquitous	marker	granulocyte, sural nerve, right hemisphere of cerebellum
SLX4	175	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex
FANCI	221	ubiquitous	marker	ventricular zone, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis
FANCB	160	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, primordial germ cell in gonad, buccal mucosa cell
FANCC	195	ubiquitous	marker	pancreatic ductal cell, right lobe of liver, male germ line stem cell (sensu Vertebrata) in testis
FANCD2	200	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, ventricular zone, secondary oocyte
FANCG	242	ubiquitous	marker	ventricular zone, ganglionic eminence, right hemisphere of cerebellum

Protein interactions among cohort

Intra-cohort edges: 36.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA1	9,064
FANCD2	3,820
SLX4	3,122
FANCA	3,036
FANCM	2,764
FANCI	2,312
FANCG	1,737
FANCL	1,621
FANCC	1,470
FANCB	1,097

Intra-cohort edges

A	B	Sources
BRCA1	FANCA	intact, string_interaction
BRCA1	FANCD2	string_interaction
BRCA1	FANCI	string_interaction
FANCA	FANCB	biogrid_interaction, intact, string_interaction
FANCA	FANCC	biogrid_interaction, intact, string_interaction
FANCA	FANCD2	string_interaction
FANCA	FANCG	biogrid_interaction, intact, string_interaction
FANCA	FANCI	string_interaction
FANCA	FANCL	biogrid_interaction, intact, string_interaction
FANCA	FANCM	biogrid_interaction, intact, string_interaction
FANCA	SLX4	string_interaction
FANCA	ZNF276	string_interaction
FANCB	FANCC	biogrid_interaction, intact, string_interaction
FANCB	FANCD2	string_interaction
FANCB	FANCG	biogrid_interaction, intact, string_interaction
FANCB	FANCI	string_interaction
FANCB	FANCL	biogrid_interaction, string_interaction
FANCB	FANCM	intact, string_interaction
FANCC	FANCD2	biogrid_interaction, string_interaction
FANCC	FANCG	biogrid_interaction, string_interaction
FANCC	FANCI	string_interaction
FANCC	FANCL	string_interaction
FANCC	FANCM	string_interaction
FANCD2	FANCG	string_interaction
FANCD2	FANCI	biogrid_interaction, intact, string_interaction
FANCD2	FANCL	string_interaction
FANCD2	FANCM	string_interaction
FANCD2	SLX4	string_interaction
FANCG	FANCI	string_interaction
FANCG	FANCL	biogrid_interaction, string_interaction
FANCG	FANCM	biogrid_interaction, string_interaction
FANCI	FANCL	string_interaction
FANCI	FANCM	string_interaction
FANCI	SLX4	string_interaction
FANCL	FANCM	biogrid_interaction, string_interaction
FANCM	SLX4	string_interaction

Structural data

PDB: 10 · AlphaFold-only: 3 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA1	P38398	33
FANCD2	Q9BXW9	13
FANCL	Q9NW38	8
FANCI	Q9NVI1	8
FANCM	Q8IYD8	7
SLX4	Q8IY92	7
FANCA	O15360	6
FANCB	Q8NB91	6
FANCC	Q00597	6
FANCG	O15287	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
AOPEP	Q8N6M6	83.36
ZNF276	Q8N554	56.21
ZNF469	Q96JG9

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. Enrichment computed across 13 evidence-associated genes (10 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 10 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	9	250.7×	2e-20	FANCA, FANCL, FANCM, SLX4, FANCI, FANCB, FANCC, FANCD2 (+1 more)
PKR-mediated signaling	6	84.6×	7e-10	FANCA, FANCL, FANCM, FANCB, FANCC, FANCG
TP53 Regulates Transcription of DNA Repair Genes	4	72.5×	4e-06	BRCA1, FANCI, FANCC, FANCD2
Resolution of D-Loop Structures	2	126.9×	0.002	BRCA1, SLX4
Homology Directed Repair	2	61.7×	0.004	BRCA1, SLX4
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	2	61.7×	0.004	BRCA1, SLX4
Resolution of D-loop Structures through Holliday Junction Intermediates	2	60.1×	0.004	BRCA1, SLX4
DNA Double-Strand Break Repair	2	49.6×	0.005	BRCA1, SLX4
HDR through Homologous Recombination (HRR)	2	38.1×	0.008	BRCA1, SLX4
Defective DNA double strand break response due to BRCA1 loss of function	1	571.0×	0.010	BRCA1
Defective DNA double strand break response due to BARD1 loss of function	1	571.0×	0.010	BRCA1
DNA Repair	2	19.7×	0.022	BRCA1, SLX4
Regulation of MITF-M-dependent genes involved in DNA replication, damage repair and senescence	1	163.1×	0.029	BRCA1
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	95.2×	0.046	BRCA1
Diseases of DNA Double-Strand Break Repair	1	81.6×	0.046	BRCA1
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	81.6×	0.046	BRCA1
Diseases of DNA repair	1	57.1×	0.062	BRCA1
DNA Double Strand Break Response	1	47.6×	0.065	BRCA1
Impaired BRCA2 binding to PALB2	1	45.7×	0.065	BRCA1
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	42.3×	0.065	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	42.3×	0.065	BRCA1
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	42.3×	0.065	BRCA1
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	39.4×	0.066	BRCA1
Homologous DNA Pairing and Strand Exchange	1	38.1×	0.066	BRCA1
Impaired BRCA2 binding to RAD51	1	30.9×	0.073	BRCA1
Metalloprotease DUBs	1	30.1×	0.073	BRCA1
HDR through Single Strand Annealing (SSA)	1	29.3×	0.073	BRCA1
Transcriptional Regulation by E2F6	1	29.3×	0.073	BRCA1
Meiosis	1	28.6×	0.073	BRCA1
Presynaptic phase of homologous DNA pairing and strand exchange	1	27.2×	0.074	BRCA1

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 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	8	265.9×	4e-17	FANCA, FANCL, FANCM, FANCI, FANCB, FANCC, FANCD2, FANCG
DNA repair	6	29.5×	9e-07	FANCA, BRCA1, FANCL, SLX4, FANCC, FANCG
regulation of CD40 signaling pathway	2	648.1×	9e-05	FANCA, FANCD2
regulation of regulatory T cell differentiation	2	288.1×	4e-04	FANCA, FANCD2
resolution of meiotic recombination intermediates	2	144.0×	0.001	FANCM, SLX4
gamete generation	2	136.4×	0.001	FANCL, FANCD2
nucleotide-excision repair	2	58.9×	0.006	SLX4, FANCC
regulation of germ cell proliferation	1	648.1×	0.015	FANCA
DNA damage response	3	12.3×	0.015	BRCA1, FANCL, FANCG
double-strand break repair via synthesis-dependent strand annealing	1	324.1×	0.017	FANCM
response to intra-S DNA damage checkpoint signaling	1	324.1×	0.017	SLX4
positive regulation of t-circle formation	1	324.1×	0.017	SLX4
regulation of inflammatory response	2	25.9×	0.017	FANCA, FANCD2
double-strand break repair via homologous recombination	2	24.0×	0.017	BRCA1, SLX4
cellular response to oxidative stress	2	23.8×	0.017	FANCC, FANCD2
cellular response to indole-3-methanol	1	259.3×	0.019	BRCA1
positive regulation of protein monoubiquitination	1	259.3×	0.019	FANCM
chordate embryonic development	1	216.1×	0.021	BRCA1
replication-born double-strand break repair via sister chromatid exchange	1	216.1×	0.021	FANCB
negative regulation of centriole replication	1	185.2×	0.023	BRCA1
protein-containing complex assembly	2	17.5×	0.023	FANCA, FANCC
DNA double-strand break processing involved in repair via single-strand annealing	1	162.0×	0.023	SLX4
DNA strand resection involved in replication fork processing	1	162.0×	0.023	BRCA1
telomeric D-loop disassembly	1	144.0×	0.024	SLX4
regulation of extracellular matrix organization	1	144.0×	0.024	ZNF469
DNA damage tolerance	1	129.6×	0.025	BRCA1
homologous recombination	1	108.0×	0.027	BRCA1
t-circle formation	1	108.0×	0.027	SLX4
negative regulation of telomere maintenance via telomere lengthening	1	108.0×	0.027	SLX4
double-strand break repair involved in meiotic recombination	1	99.7×	0.028	FANCD2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 12

Druggability breadth: 4 of 13 evidence-associated genes (31%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
BRCA1	RIBOFLAVIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA1	12	4
FANCA	0	0
AOPEP	0	0
FANCL	0	0
FANCM	0	0
ZNF469	0	0
ZNF276	0	0
SLX4	0	0
FANCI	0	0
FANCB	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

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

Symbol	Assays	Type breakdown
BRCA1	13	Binding:9, Functional:4
FANCD2	2	Binding:2
AOPEP	1	ADMET:1
FANCI	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
BRCA1	2.3.2.27	RING-type E3 ubiquitin transferase
FANCL	2.3.2.27	RING-type E3 ubiquitin transferase

Pharmacogenomics

Cohort genes with a PharmGKB record: 13; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

12 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.

Compound	Max phase	Cohort target (bioactivity)
RIBOFLAVIN	4	BRCA1
DAUNORUBICIN HYDROCHLORIDE	4	BRCA1
TOPOTECAN HYDROCHLORIDE	4	BRCA1
DAUNORUBICIN	4	BRCA1
DOXORUBICIN HYDROCHLORIDE	4	BRCA1
MESALAMINE	4	BRCA1
DIPYRIDAMOLE	4	BRCA1
CURCUMIN	3	BRCA1
SURAMIN	3	BRCA1
SURAMIN HEXASODIUM	3	BRCA1
SODIUM TANSHINONE IIA SULFONATE	2	BRCA1
HOMIDIUM BROMIDE	2	BRCA1

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	BRCA1
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	11	FANCA, FANCL, FANCM, ZNF469, ZNF276, SLX4, FANCI, FANCB, FANCC, FANCD2 (+1 more)

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
FANCD2	2	BRCA1
FANCA	0	—
AOPEP	1	—
FANCL	0	—
FANCM	0	—
ZNF469	0	—
ZNF276	0	—
SLX4	0	—
FANCI	1	—
FANCB	0	—
FANCC	0	—
FANCG	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 5.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	2
Not specified	2
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT04069533	PHASE2	ACTIVE_NOT_RECRUITING	Lentiviral-mediated Gene Therapy for Pediatric Patients With Fanconi Anemia Subtype A
NCT04248439	PHASE2	ACTIVE_NOT_RECRUITING	Gene Therapy for Fanconi Anemia, Complementation Group A
NCT03814408	PHASE1	UNKNOWN	A Clinical Trial to Evaluate the Safety of RP-L102 in Pediatric Subjects With Fanconi Anemia Subtype A
NCT04437771	Not specified	ACTIVE_NOT_RECRUITING	Long-Term Follow-up of Subjects With Fanconi Anaemia Subtype A Treated With ex Vivo Gene Therapy
NCT07242261	Not specified	NOT_YET_RECRUITING	Non-invasive Characterisation of Oral Carcinomas in Patients With Fanconi Anaemia

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
MOZAFANCOGENE AUTOTEMCEL	2	3

Cohort genes: FANCA, BRCA1, AOPEP, FANCL, FANCM, ZNF469, ZNF276, SLX4, FANCI, FANCB, FANCC, FANCD2, FANCG