Fanconi anemia, complementation group W

disease

On this page

Also known as FANCW

Summary

Fanconi anemia, complementation group W (MONDO:0044325) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 15

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia, complementation group W
Mondo ID	MONDO:0044325
OMIM	617784
DOID	DOID:0060978
UMLS	C4521564
MedGen	1621245
GARD	0025895
Is cancer (heuristic)	no

Also known as: Fanconi anemia, complementation group W · FANCW

Data availability: 15 ClinVar variants · 3 GenCC gene-disease records.

Disease family

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

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

15 retrieved; paginated sample, class counts are floors:

9 uncertain significance, 3 benign, 2 likely benign, 1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
446412	NM_018124.4(RFWD3):c.1916T>A (p.Ile639Lys)	RFWD3	Pathogenic	no assertion criteria provided
1185032	NM_018124.4(RFWD3):c.1189G>C (p.Val397Leu)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2073923	NM_018124.4(RFWD3):c.1731G>T (p.Gln577His)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2197913	NM_018124.4(RFWD3):c.443C>T (p.Pro148Leu)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2441970	NM_018124.4(RFWD3):c.1577G>A (p.Ser526Asn)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2807145	NM_018124.4(RFWD3):c.1968T>C (p.Pro656=)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
2867878	NM_018124.4(RFWD3):c.2195C>G (p.Ala732Gly)	RFWD3	Uncertain significance	criteria provided, multiple submitters, no conflicts
3377801	NM_018124.4(RFWD3):c.1579C>A (p.Leu527Met)	RFWD3	Uncertain significance	criteria provided, single submitter
446411	NM_018124.4(RFWD3):c.204_205dup (p.Leu69fs)	RFWD3	Uncertain significance	criteria provided, single submitter
973889	NM_018124.4(RFWD3):c.1367G>C (p.Cys456Ser)	RFWD3	Uncertain significance	criteria provided, single submitter
1185033	NM_018124.4(RFWD3):c.2205G>A (p.Ser735=)	RFWD3	Likely benign	criteria provided, multiple submitters, no conflicts
1327952	NM_018124.4(RFWD3):c.1755-33G>A	RFWD3	Benign	criteria provided, multiple submitters, no conflicts
1327953	NM_018124.4(RFWD3):c.1212G>A (p.Thr404=)	RFWD3	Benign	criteria provided, multiple submitters, no conflicts
1327954	NM_018124.4(RFWD3):c.269C>A (p.Thr90Asn)	RFWD3	Benign	criteria provided, multiple submitters, no conflicts
2064152	NM_018124.4(RFWD3):c.2299A>G (p.Met767Val)	RFWD3	Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

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

Gene	Classification	Inheritance	Disease	Records
RFWD3	Moderate	Autosomal recessive	Fanconi anemia, complementation group W	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
RFWD3	Orphanet:84	Fanconi anemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
RFWD3	HGNC:25539	ENSG00000168411	Q6PCD5	E3 ubiquitin-protein ligase RFWD3	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
RFWD3	E3 ubiquitin-protein ligase RFWD3	E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.0

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	1	8.3×	0.121

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
RFWD3	Transcription factor	no		WD40_rpt, Znf_RING, Znf_RING/FYVE/PHD

Expression context

Cohort genes with no expression data: 0.

1 cohort gene 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)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	1
oocyte	1
secondary oocyte	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
RFWD3	216	ubiquitous	marker	oocyte, secondary oocyte, male germ line stem cell (sensu Vertebrata) in testis

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
RFWD3	1,267

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
RFWD3	Q6PCD5	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of DNA damage checkpoint	1	1123.5×	0.004	RFWD3
mitotic G1 DNA damage checkpoint signaling	1	1053.2×	0.004	RFWD3
interstrand cross-link repair	1	432.1×	0.004	RFWD3
replication fork processing	1	421.3×	0.004	RFWD3
response to ionizing radiation	1	411.0×	0.004	RFWD3
double-strand break repair via homologous recombination	1	156.0×	0.009	RFWD3
DNA damage response	1	53.5×	0.021	RFWD3
protein ubiquitination	1	41.4×	0.024	RFWD3

Therapeutics

Drug target analysis

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

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
RFWD3	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

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

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	RFWD3

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
RFWD3	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: RFWD3