FANCD2 (Fanconi anemia, complementation group D2)

2002-06-01 Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Identity

HGNC

FANCD2

LOCATION

3p25.3

IMAGE

LEGEND

Probe(s) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics

LOCUSID

2177

ALIAS

FA-D2,FA4,FACD,FAD,FAD2,FANCD

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

44 exons; 4356 bp open reading frame; the first exon is non-coding.

Proteins

Expression

weak

Localisation

nucleus

Function

the FA complex is comprised of : FANCA, FANCC, FANCE, FANCF, and FANCG; this complex is only found in the nucleus.

FANCA and FANCG form a complex in the cytoplasm, through a N-term FANCA (involving the nuclear localization signal) - FANCG interaction; FANCC join the complex; phosphorylation of FANCA would induce its translocation into the nucleus.This FA complex translocates into the nucleus, where FANCE and FANCF are present; FANCE and FANCF join the complex. The FA complex subsequently interacts with FANCD2 by monoubiquitination of FANCD2 during S phase or following DNA damage. Activated (ubiquinated ) FANCD2 (i.e. FANCD2-L), downstream in the FA pathway, will then interact with other proteins involved in DNA repair, possibly BRCA1; after DNA repair, FANCD2 return to the non-ubiquinated form (FANCD2-S).

FANCD2co-localizes with BRCA1 in DNA damaged-induced loci and in the synaptonemal complex of meotic chromosomes as well.

Homology

significant homologies can be found with proteins from various species

Implicated in

Entity name

Fanconi anaemia (FA); FANCD2 is implicated in the FA complementation group D, a heterogeneous group, with at least 2 genes: FANCD2, and a yet undiscovered FANCD1. FA complementation group D represents about 1% of FA cases. In FA complementation group D patients, the FA complex is normal, in contrast with results found in group A, B (with a yet unknown gene), C, E, F, and G patients.

Disease

Fanconi anaemia is a chromosome instability syndrome/cancer prone disease (at risk of leukaemia and squamous cell carcinoma)

Prognosis

Fanconi anaemias prognosis is poor; mean survival is 20 years: patients die of bone marrow failure (infections, haemorrhages), leukaemia, or solid cancer.

It has recently been shown that significant phenotypic differences were found between the various complementation groups. Patients from the rare groups FA-D, FA-E, and FA-F had somatic abnormalities more frequently.

Cytogenetics

Spontaneously enhanced chromatid-type aberrations (breaks, gaps, interchanges; increased rate of breaks compared to control, when induced by specific clastogens known as DNA cross-linking agents (e.g. mitomycin C, diepoxybutane).

Bibliography

Pubmed ID	Last Year	Title	Authors

Other Information

Locus ID:

NCBI: 2177
MIM: 613984
HGNC: 3585
Ensembl: ENSG00000144554

Variants:

dbSNP: 2177
ClinVar: 2177
TCGA: ENSG00000144554
COSMIC: FANCD2

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000144554	ENST00000287647	Q9BXW9
ENSG00000144554	ENST00000383807	Q9BXW9
ENSG00000144554	ENST00000383807	A0A024R2G2
ENSG00000144554	ENST00000419585	Q9BXW9
ENSG00000144554	ENST00000419585	A0A024R2G2
ENSG00000144554	ENST00000421731	H7BZJ7
ENSG00000144554	ENST00000431693	Q9BXW9
ENSG00000144554	ENST00000435522	F8WE37
ENSG00000144554	ENST00000625535	F8WE37

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Fanconi anemia pathway	KEGG	ko03460
Fanconi anemia pathway	KEGG	hsa03460
Gene Expression	REACTOME	R-HSA-74160
Generic Transcription Pathway	REACTOME	R-HSA-212436
Transcriptional Regulation by TP53	REACTOME	R-HSA-3700989
DNA Repair	REACTOME	R-HSA-73894
Fanconi Anemia Pathway	REACTOME	R-HSA-6783310
TP53 Regulates Transcription of DNA Repair Genes	REACTOME	R-HSA-6796648

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
38229567	2024	FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.	1
38443946	2024	Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival.	3
38229567	2024	FANCD2 deficiency sensitizes SHH medulloblastoma to radiotherapy via ferroptosis.	1
38443946	2024	Pancancer analysis of the prognostic and immunological role of FANCD2: a potential target for carcinogenesis and survival.	3
36814203	2023	FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma.	8
37526271	2023	FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.	5
37591242	2023	FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress.	0
37599085	2023	LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma.	4
37777152	2023	Mitotic DNA Synthesis in Untransformed Human Cells Preserves Common Fragile Site Stability via a FANCD2-Driven Mechanism That Requires HELQ.	1
37821996	2023	FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.	2
38060446	2023	FANCD2-dependent mitotic DNA synthesis relies on PCNA K164 ubiquitination.	3
36814203	2023	FANCD2 inhibits ferroptosis by regulating the JAK2/STAT3 pathway in osteosarcoma.	8
37526271	2023	FANCD2 and RAD51 recombinase directly inhibit DNA2 nuclease at stalled replication forks and FANCD2 acts as a novel RAD51 mediator in strand exchange to promote genome stability.	5
37591242	2023	FBXL12 degrades FANCD2 to regulate replication recovery and promote cancer cell survival under conditions of replication stress.	0
37599085	2023	LncRNA SNHG1 upregulates FANCD2 and G6PD to suppress ferroptosis by sponging miR-199a-5p/3p in hepatocellular carcinoma.	4

Citation

Jean-Loup Huret

FANCD2 (Fanconi anemia, complementation group D2)

Atlas Genet Cytogenet Oncol Haematol. 2002-06-01

Online version: http://atlasgeneticsoncology.org/gene/103/css/css/lib/css/card-gene.css

Historical Card

1998-04-01 FANCD2 (Fanconi anemia, complementation group D2) by Jean-Loup Huret Affiliation

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France