Fanconi anemia complementation group N

disease

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Also known as FANCNFanconi anaemia caused by mutation in PALB2Fanconi anaemia complementation group type NFanconi anemia caused by mutation in PALB2Fanconi anemia complementation group type NFanconi anemia, complementation group NFanconi Anemia, complementation group type NPALB2 Fanconi anaemiaPALB2 Fanconi anemia

Summary

Fanconi anemia complementation group N (MONDO:0012565) is a disease caused by PALB2 (GenCC Definitive), with 2 cohort genes.

At a glance

Causal gene: PALB2 (GenCC Definitive)
Cohort genes: 2
ClinVar variants: 394

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group N
Mondo ID	MONDO:0012565
MeSH	C563657
OMIM	610832
DOID	DOID:0111094
UMLS	C1835817
MedGen	372133
GARD	0015500
Is cancer (heuristic)	no

Also known as: FANCN · Fanconi anaemia caused by mutation in PALB2 · Fanconi anaemia complementation group type N · Fanconi anemia caused by mutation in PALB2 · Fanconi anemia complementation group N · Fanconi anemia complementation group type N · Fanconi anemia, complementation group N · Fanconi Anemia, complementation group type N · PALB2 Fanconi anaemia · PALB2 Fanconi anemia

Data availability: 394 ClinVar variants · 4 GenCC gene-disease records · 4 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 N

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

394 retrieved; paginated sample, class counts are floors:

164 conflicting classifications of pathogenicity, 92 uncertain significance, 48 benign/likely benign, 38 pathogenic/likely pathogenic, 34 pathogenic, 8 likely benign, 7 likely pathogenic, 2 benign, 1 not provided

ClinVar	Variant (HGVS)	Gene	Classification	Review
126623	NM_024675.4(PALB2):c.172_175del (p.Gln60fs)	DCTN5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1050102	NM_024675.4(PALB2):c.892_893del (p.Val298fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1072355	NM_024675.4(PALB2):c.3351-1G>A	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1210162	NM_024675.4(PALB2):c.3114-16_3114-11del	PALB2	Pathogenic	criteria provided, single submitter
1243	NM_024675.4(PALB2):c.1653T>A (p.Tyr551Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1245	NM_024675.4(PALB2):c.3549C>G (p.Tyr1183Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1246	NM_024675.4(PALB2):c.2962C>T (p.Gln988Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126586	NM_024675.4(PALB2):c.1050_1053del (p.Thr351fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126614	NM_024675.4(PALB2):c.1676_1677delinsG (p.Gln559fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126629	NM_024675.4(PALB2):c.196C>T (p.Gln66Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126649	NM_024675.4(PALB2):c.2386G>T (p.Gly796Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126651	NM_024675.4(PALB2):c.2393_2394insCT (p.Thr799fs)	PALB2	Pathogenic	no assertion criteria provided
126675	NM_024675.4(PALB2):c.2718G>A (p.Trp906Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126688	NM_024675.4(PALB2):c.2835-1G>C	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126696	NM_024675.4(PALB2):c.2920_2921del (p.Lys974fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126707	NM_024675.4(PALB2):c.3048del (p.Phe1016fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126711	NM_024675.4(PALB2):c.3113G>A (p.Trp1038Ter)	PALB2	Pathogenic	reviewed by expert panel
126715	NM_024675.4(PALB2):c.3116del (p.Asn1039fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126729	NM_024675.4(PALB2):c.3256C>T (p.Arg1086Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126734	NM_024675.4(PALB2):c.3323del (p.Tyr1108fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126748	NM_024675.4(PALB2):c.395del (p.Val132fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126757	NM_024675.4(PALB2):c.509_510del (p.Arg170fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126766	NM_024675.4(PALB2):c.72del (p.Arg26fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
126767	NM_024675.4(PALB2):c.751C>T (p.Gln251Ter)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126768	NM_024675.4(PALB2):c.757_758del (p.Leu253fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
126769	NM_024675.4(PALB2):c.758dup (p.Ser254fs)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128117	NM_024675.4(PALB2):c.1240C>T (p.Arg414Ter)	PALB2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
128121	NM_024675.4(PALB2):c.1675_1676delinsTG	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
128142	NM_024675.4(PALB2):c.3456dup (p.Pro1153fs)	PALB2	Pathogenic	criteria provided, multiple submitters, no conflicts
128144	NM_024675.4(PALB2):c.3549C>A (p.Tyr1183Ter)	PALB2	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 9 · Orphanet: 5 · 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
PALB2	Definitive	Autosomal recessive	Fanconi anemia complementation group N	9

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
PALB2	Orphanet:1333	Familial pancreatic carcinoma
PALB2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
PALB2	Orphanet:178	Chordoma
PALB2	Orphanet:227535	Hereditary breast cancer
PALB2	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
PALB2	HGNC:26144	ENSG00000083093	Q86YC2	Partner and localizer of BRCA2	gencc,clinvar
DCTN5	HGNC:24594	ENSG00000166847	Q9BTE1	Dynactin subunit 5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
PALB2	Partner and localizer of BRCA2	Plays a critical role in homologous recombination repair (HRR) through its ability to recruit BRCA2 and RAD51 to DNA breaks.
DCTN5	Dynactin subunit 5	Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.

Protein-family classification

Druggable: 0 · Difficult: 1 · Unknown: 1 · 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
Scaffold/PPI	1	8.6×	0.225
Other/Unknown	1	0.9×	0.805

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
PALB2	Scaffold/PPI	no		WD40/YVTN_repeat-like_dom_sf, PALB2_WD40, WD40_repeat_dom_sf
DCTN5	Other/Unknown	no		Trimer_LpxA-like_sf, DCTN5

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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
oocyte	1
secondary oocyte	1
islet of Langerhans	1
rectum	1
stromal cell of endometrium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
PALB2	232	ubiquitous	yes	secondary oocyte, buccal mucosa cell, oocyte
DCTN5	288	ubiquitous	marker	islet of Langerhans, rectum, stromal cell of endometrium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
PALB2	5,641
DCTN5	1,910

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
PALB2	Q86YC2	4
DCTN5	Q9BTE1	3

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. 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
Impaired BRCA2 binding to PALB2	1	228.4×	0.012	PALB2
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	211.5×	0.012	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	211.5×	0.012	PALB2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	211.5×	0.012	PALB2
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	196.9×	0.012	PALB2
Homologous DNA Pairing and Strand Exchange	1	190.3×	0.012	PALB2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	150.3×	0.013	PALB2
COPI-independent Golgi-to-ER retrograde traffic	1	103.8×	0.015	DCTN5
HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand	1	96.8×	0.015	DCTN5
HDR through Homologous Recombination (HRR)	1	95.2×	0.015	PALB2
KEAP1-NFE2L2 pathway	1	60.1×	0.021	PALB2
COPI-mediated anterograde transport	1	54.9×	0.021	DCTN5
MHC class II antigen presentation	1	44.6×	0.024	DCTN5
Neddylation	1	23.7×	0.042	PALB2

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
inner cell mass cell proliferation	1	495.6×	0.008	PALB2
post-anal tail morphogenesis	1	366.4×	0.008	PALB2
coronary vasculature development	1	312.1×	0.008	DCTN5
aorta development	1	280.9×	0.008	DCTN5
mesoderm development	1	263.3×	0.008	PALB2
ventricular septum development	1	247.8×	0.008	DCTN5
embryonic organ development	1	240.7×	0.008	PALB2
somitogenesis	1	187.2×	0.009	PALB2
animal organ morphogenesis	1	95.8×	0.015	PALB2
double-strand break repair via homologous recombination	1	78.0×	0.017	PALB2
multicellular organism growth	1	68.5×	0.017	PALB2
negative regulation of apoptotic process	1	17.4×	0.061	PALB2
apoptotic process	1	14.3×	0.068	PALB2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2

Druggability breadth: 0 of 2 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
PALB2	0	0
DCTN5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

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	2	PALB2, DCTN5

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
PALB2	0	—
DCTN5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: PALB2, DCTN5