Fanconi anemia complementation group P

Summary

Fanconi anemia complementation group P (MONDO:0013499) is a disease caused by SLX4 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: SLX4 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 807

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	Fanconi anemia complementation group P
Mondo ID	MONDO:0013499
OMIM	613951
DOID	DOID:0111092
UMLS	C3469542
MedGen	854020
GARD	0015731
Is cancer (heuristic)	no

Also known as: Fanconi anaemia caused by mutation in SLX4 · Fanconi anaemia caused by mutation in Slx4 · Fanconi anaemia complementation group type P · Fanconi anemia caused by mutation in SLX4 · Fanconi anemia caused by mutation in Slx4 · Fanconi anemia complementation group type P · Fanconi anemia, complementation group P · Fanconi Anemia, complementation group type P · FANCP · SLX4 Fanconi anaemia · Slx4 Fanconi anaemia · SLX4 Fanconi anemia · Slx4 Fanconi anemia

Data availability: 807 ClinVar variants · 4 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 P

Related subtypes (21): Fanconi anemia complementation group C, Fanconi anemia complementation group D2, Fanconi anemia complementation group A, Fanconi anemia complementation group B, Fanconi anemia complementation group E, Fanconi anemia complementation group F, Fanconi anemia complementation group D1, Fanconi anemia complementation group I, Fanconi anemia complementation group J, Fanconi anemia complementation group N, Fanconi anemia complementation group O, Fanconi anemia complementation group G, Fanconi anemia complementation group L, Fanconi anemia complementation group Q, Fanconi anemia complementation group T, Fanconi anemia complementation group V, Fanconi anemia complementation group R, Fanconi anemia complementation group U, Fanconi anemia, complementation group W, Fanconi anemia, complementation group S, fanconi anemia, complementation group 10

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:

393 uncertain significance, 66 conflicting classifications of pathogenicity, 39 benign, 36 likely benign, 34 benign/likely benign, 17 likely pathogenic, 10 pathogenic/likely pathogenic, 5 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1070771	NM_032444.4(SLX4):c.3895_3896del (p.Arg1299fs)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1179203	NM_032444.4(SLX4):c.1163+2dup	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1323619	NM_032444.4(SLX4):c.4625T>A (p.Leu1542Ter)	SLX4	Pathogenic	criteria provided, single submitter
1366481	NM_032444.4(SLX4):c.2469G>A (p.Trp823Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1454486	NM_032444.4(SLX4):c.2808_2809del (p.Ala938fs)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1675611	NM_032444.4(SLX4):c.3619_3643del (p.Pro1207fs)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2177902	NM_032444.4(SLX4):c.4283G>A (p.Trp1428Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2420933	NM_032444.4(SLX4):c.4523C>A (p.Ser1508Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2664892	NM_032444.4(SLX4):c.106G>T (p.Glu36Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
31021	NM_032444.4(SLX4):c.286del (p.Thr96fs)	SLX4	Pathogenic	no assertion criteria provided
31022	NM_032444.4(SLX4):c.1093del (p.Gln365fs)	SLX4	Pathogenic	criteria provided, multiple submitters, no conflicts
31024	NM_032444.4(SLX4):c.1163+2T>A	SLX4	Pathogenic	no assertion criteria provided
31025	NM_032444.4(SLX4):c.514del (p.Leu172fs)	SLX4	Pathogenic	criteria provided, multiple submitters, no conflicts
3580453	NM_032444.4(SLX4):c.4761dup (p.Lys1588Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3775304	NM_032444.4(SLX4):c.3601C>T (p.Gln1201Ter)	SLX4	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
1034145	NM_032444.4(SLX4):c.5120_5121del (p.Val1707fs)	SLX4	Likely pathogenic	criteria provided, single submitter
1325101	NM_032444.4(SLX4):c.951-1G>T	SLX4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
1982926	NM_032444.4(SLX4):c.1684-1G>A	SLX4	Likely pathogenic	criteria provided, multiple submitters, no conflicts
3235726	NM_032444.4(SLX4):c.838G>T (p.Gly280Ter)	SLX4	Likely pathogenic	criteria provided, single submitter
3580460	NM_032444.4(SLX4):c.4541G>A (p.Trp1514Ter)	SLX4	Likely pathogenic	criteria provided, single submitter
3580470	NM_032444.4(SLX4):c.4091_4104dup (p.Phe1369fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3580481	NM_032444.4(SLX4):c.3638del (p.Val1213fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3580490	NM_032444.4(SLX4):c.3366_3367delinsC (p.Ser1123fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3580498	NM_032444.4(SLX4):c.3003_3006del (p.Glu1003fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3580502	NM_032444.4(SLX4):c.2848G>T (p.Glu950Ter)	SLX4	Likely pathogenic	criteria provided, single submitter
3580513	NM_032444.4(SLX4):c.2424C>A (p.Cys808Ter)	SLX4	Likely pathogenic	criteria provided, single submitter
3580555	NM_032444.4(SLX4):c.634C>T (p.Arg212Ter)	SLX4	Likely pathogenic	criteria provided, single submitter
3580564	NM_032444.4(SLX4):c.279del (p.Lys94fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3580572	NM_032444.4(SLX4):c.58_59del (p.Leu20fs)	SLX4	Likely pathogenic	criteria provided, single submitter
3780642	NM_032444.4(SLX4):c.3638dup (p.Leu1214fs)	SLX4	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
SLX4	Definitive	Autosomal recessive	Fanconi anemia complementation group P	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SLX4	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
SLX4	HGNC:23845	ENSG00000188827	Q8IY92	Structure-specific endonuclease subunit SLX4	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SLX4	Structure-specific endonuclease subunit SLX4	Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases.

Protein-family classification

Druggable: 0 · Difficult: 0 · 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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SLX4	Other/Unknown	no		BTB/POZ_dom, Rad18_UBZ4, SKP1/BTB/POZ_sf

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SLX4	175	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SLX4	3,122

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
SLX4	Q8IY92	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 8. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Resolution of D-Loop Structures	1	634.4×	0.005	SLX4
Homology Directed Repair	1	308.6×	0.005	SLX4
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.005	SLX4
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.005	SLX4
Fanconi Anemia Pathway	1	278.5×	0.005	SLX4
DNA Double-Strand Break Repair	1	248.3×	0.005	SLX4
HDR through Homologous Recombination (HRR)	1	190.3×	0.006	SLX4
DNA Repair	1	98.5×	0.010	SLX4

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
response to intra-S DNA damage checkpoint signaling	1	4213.0×	0.001	SLX4
positive regulation of t-circle formation	1	4213.0×	0.001	SLX4
DNA double-strand break processing involved in repair via single-strand annealing	1	2106.5×	0.001	SLX4
telomeric D-loop disassembly	1	1872.4×	0.001	SLX4
t-circle formation	1	1404.3×	0.001	SLX4
negative regulation of telomere maintenance via telomere lengthening	1	1404.3×	0.001	SLX4
resolution of meiotic recombination intermediates	1	936.2×	0.002	SLX4
positive regulation of telomere maintenance	1	510.7×	0.003	SLX4
nucleotide-excision repair	1	383.0×	0.003	SLX4
DNA replication	1	165.2×	0.007	SLX4
double-strand break repair via homologous recombination	1	156.0×	0.007	SLX4
DNA repair	1	63.8×	0.016	SLX4

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
SLX4	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	SLX4

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)
SLX4	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.