Fanconi anemia complementation group L

disease

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Also known as FANCLFANCL Fanconi anaemiaFANCL Fanconi anemiaFanconi anaemia caused by mutation in FANCLFanconi anaemia complementation group type LFanconi anemia caused by mutation in FANCLFanconi anemia complementation group type LFanconi anemia, complementation group LFanconi Anemia, complementation group type 50

Summary

Fanconi anemia complementation group L (MONDO:0013566) is a disease caused by FANCL (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: FANCL (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 216

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group L
Mondo ID	MONDO:0013566
OMIM	614083
DOID	DOID:0111082
UMLS	C3469528
MedGen	854018
GARD	0015754
Is cancer (heuristic)	no

Also known as: FANCL · FANCL Fanconi anaemia · FANCL Fanconi anemia · Fanconi anaemia caused by mutation in FANCL · Fanconi anaemia complementation group type L · Fanconi anemia caused by mutation in FANCL · Fanconi anemia complementation group L · Fanconi anemia complementation group type L · Fanconi anemia, complementation group L · Fanconi Anemia, complementation group type 50

Data availability: 216 ClinVar variants · 5 GenCC gene-disease records · 1 cell line.

Disease family

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

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

216 retrieved; paginated sample, class counts are floors:

108 uncertain significance, 34 likely pathogenic, 20 pathogenic/likely pathogenic, 20 conflicting classifications of pathogenicity, 11 likely benign, 9 benign, 9 benign/likely benign, 5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1066864	NM_018062.4(FANCL):c.472-1G>C	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1076769	NM_018062.4(FANCL):c.202C>T (p.Arg68Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1332720	NM_018062.4(FANCL):c.746_756del (p.Pro249fs)	FANCL	Pathogenic	criteria provided, single submitter
1691887	NM_018062.4(FANCL):c.1A>G (p.Met1Val)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1704583	NM_018062.4(FANCL):c.223C>T (p.Gln75Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1951904	NM_018062.4(FANCL):c.28del (p.Arg10fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
209076	NM_018062.4(FANCL):c.268del (p.Leu90fs)	FANCL	Pathogenic	criteria provided, single submitter
209077	NM_018062.4(FANCL):c.430del (p.Ser144fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2535	NM_018062.3(FANCL):c.822-15_822-9delins177	FANCL	Pathogenic	no assertion criteria provided
2675660	NM_018062.4(FANCL):c.822G>A (p.Trp274Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675666	NM_018062.4(FANCL):c.89C>A (p.Ser30Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675669	NM_018062.4(FANCL):c.1029dup (p.Gly344fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675673	NM_018062.4(FANCL):c.64A>T (p.Lys22Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675675	NM_018062.4(FANCL):c.1023_1031del (p.Trp341_Gly344delinsTer)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675679	NM_018062.4(FANCL):c.636G>A (p.Trp212Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2716231	NM_018062.4(FANCL):c.933T>G (p.Tyr311Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2896923	NM_018062.4(FANCL):c.378del (p.Val127fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2982183	NM_018062.4(FANCL):c.13del (p.Glu5fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3241613	NM_018062.4(FANCL):c.1017_1018insA (p.Glu340fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
336654	NM_018062.4(FANCL):c.932dup (p.Tyr311Ter)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
456247	NM_018062.4(FANCL):c.759_762del (p.Phe253fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
566870	NM_018062.4(FANCL):c.2T>C (p.Met1Thr)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
871168	NM_018062.4(FANCL):c.739_740dup (p.Met247fs)	FANCL	Pathogenic	criteria provided, multiple submitters, no conflicts
929823	NM_018062.4(FANCL):c.1092G>A (p.Lys364=)	FANCL	Pathogenic	criteria provided, multiple submitters, no conflicts
958767	NM_018062.4(FANCL):c.40del (p.Leu14fs)	FANCL	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1027625	NM_018062.4(FANCL):c.1051_1052dup (p.Ser351fs)	FANCL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1705600	NM_018062.4(FANCL):c.1_22dup (p.Leu8fs)	FANCL	Likely pathogenic	criteria provided, single submitter
2018512	NM_018062.4(FANCL):c.903+1_903+2del	FANCL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2194330	NM_018062.4(FANCL):c.903+1del	FANCL	Likely pathogenic	criteria provided, multiple submitters, no conflicts
2675661	NM_018062.4(FANCL):c.1092+1G>C	FANCL	Likely pathogenic	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
FANCL	Definitive	Autosomal recessive	Fanconi anemia complementation group L	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FANCL	Orphanet:84	Fanconi anemia

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FANCL	HGNC:20748	ENSG00000115392	Q9NW38	E3 ubiquitin-protein ligase FANCL	gencc,clinvar
VRK2	HGNC:12719	ENSG00000028116	Q86Y07	Serine/threonine-protein kinase VRK2	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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.
VRK2	Serine/threonine-protein kinase VRK2	Serine/threonine kinase that regulates several signal transduction pathways.

Protein-family classification

Druggable: 1 · Difficult: 1 · Unknown: 0 · Druggable fraction: 0.5

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
Kinase	1	13.9×	0.142
Transcription factor	1	4.1×	0.228

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FANCL	Transcription factor	no	2.3.2.27	Znf_RING/FYVE/PHD, UBQ-conjugating_enzyme/RWD, FancL_WD-rpt_cont_dom
VRK2	Kinase	yes		Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf

Expression context

Cohort genes with no expression data: 0.

2 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
calcaneal tendon	2
adenohypophysis	1
pituitary gland	1
monocyte	1
mononuclear cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FANCL	293	ubiquitous	marker	pituitary gland, adenohypophysis, calcaneal tendon
VRK2	280	ubiquitous	marker	monocyte, mononuclear cell, calcaneal tendon

Protein interactions among cohort

Intra-cohort edges: 1.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
VRK2	2,000
FANCL	1,621

Intra-cohort edges

A	B	Sources
FANCL	VRK2	string_interaction

Structural data

PDB: 2 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FANCL	Q9NW38	8
VRK2	Q86Y07	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 9. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Initiation of Nuclear Envelope (NE) Reformation	1	300.5×	0.019	VRK2
Nuclear Envelope Breakdown	1	228.4×	0.019	VRK2
Fanconi Anemia Pathway	1	139.3×	0.019	FANCL
RHOD GTPase cycle	1	102.0×	0.019	VRK2
RHOG GTPase cycle	1	74.2×	0.019	VRK2
PKR-mediated signaling	1	70.5×	0.019	FANCL
RAC2 GTPase cycle	1	63.4×	0.019	VRK2
RAC3 GTPase cycle	1	59.5×	0.019	VRK2
RAC1 GTPase cycle	1	30.5×	0.032	VRK2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of interleukin-1-mediated signaling pathway	1	4213.0×	0.002	VRK2
DNA damage response	2	53.5×	0.002	FANCL, VRK2
gamete generation	1	443.5×	0.009	FANCL
regulation of MAPK cascade	1	227.7×	0.011	VRK2
interstrand cross-link repair	1	216.1×	0.011	FANCL
protein monoubiquitination	1	172.0×	0.012	FANCL
cellular response to oxidative stress	1	77.3×	0.021	VRK2
protein autophosphorylation	1	72.6×	0.021	VRK2
regulation of cell population proliferation	1	57.7×	0.023	FANCL
protein phosphorylation	1	34.0×	0.034	VRK2
DNA repair	1	31.9×	0.034	FANCL
signal transduction	1	8.0×	0.121	VRK2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 2 evidence-associated genes (50%) 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
VRK2	RUXOLITINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
VRK2	4	4
FANCL	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
RUXOLITINIB	4	VRK2
BOSUTINIB	4	VRK2
DASATINIB	4	VRK2
ALVOCIDIB	3	VRK2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
VRK2	146	Binding:146

Cohort enzymes (BRENDA EC)

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

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
VRK2	146

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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)
RUXOLITINIB	4	VRK2
BOSUTINIB	4	VRK2
DASATINIB	4	VRK2
ALVOCIDIB	3	VRK2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	VRK2
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	FANCL

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)
FANCL	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: FANCL, VRK2