FAAP24

Summary

FAAP24 (FA core complex associated protein 24, HGNC:28467) is a protein-coding gene on chromosome 19q13.11, encoding Fanconi anemia core complex-associated protein 24 (Q9BTP7). Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. It is a selective cancer dependency (DepMap: 11.2% of cell lines).

FAAP24 is a component of the Fanconi anemia (FA) core complex (see MIM 227650), which plays a crucial role in DNA damage response (Ciccia et al., 2007 [PubMed 17289582]).

Source: NCBI Gene 91442 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency-associated lymphoproliferative disease (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 50 total
• Cancer dependency (DepMap): dependent in 11.2% of screened cell lines
• MANE Select transcript: NM_152266

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28467
Approved symbol	FAAP24
Name	FA core complex associated protein 24
Location	19q13.11
Locus type	gene with protein product
Status	Approved
Aliases	FLJ46828, MGC32020
Ensembl gene	ENSG00000131944
Ensembl biotype	protein_coding
OMIM	610884
Entrez	91442

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000254262, ENST00000588258, ENST00000589646, ENST00000590179, ENST00000590281, ENST00000591791, ENST00000699959, ENST00000699960, ENST00000699961

RefSeq mRNA: 2 — MANE Select: NM_152266 NM_001300978, NM_152266

CCDS: CCDS12426, CCDS74327

Canonical transcript exons

ENST00000588258 — 5 exons

Exon	Start	End
ENSE00000901907	32973184	32973302
ENSE00001161015	32972242	32972346
ENSE00002804378	32976431	32978229
ENSE00003528169	32974060	32974212
ENSE00003642072	32973426	32973562

Expression profiles

Bgee: expression breadth ubiquitous, 189 present calls, max score 89.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.6463 / max 88.6392, expressed in 1455 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175068	3.3784	1428
175069	0.2679	115

Top tissues by expression

256 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	89.58	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.51	gold quality
oocyte	CL:0000023	79.88	gold quality
gingival epithelium	UBERON:0001949	79.59	gold quality
tendon of biceps brachii	UBERON:0008188	79.43	gold quality
sperm	CL:0000019	79.37	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.32	gold quality
cerebellar vermis	UBERON:0004720	78.91	silver quality
secondary oocyte	CL:0000655	78.70	gold quality
male germ cell	CL:0000015	78.63	silver quality
triceps brachii	UBERON:0001509	77.74	gold quality
gluteal muscle	UBERON:0002000	77.46	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	75.97	gold quality
gingiva	UBERON:0001828	75.58	gold quality
nipple	UBERON:0002030	74.96	silver quality
ventricular zone	UBERON:0003053	74.56	gold quality
cervix squamous epithelium	UBERON:0006922	73.98	gold quality
embryo	UBERON:0000922	73.84	gold quality
squamous epithelium	UBERON:0006914	73.81	gold quality
ganglionic eminence	UBERON:0004023	73.77	gold quality
globus pallidus	UBERON:0001875	73.33	silver quality
medial globus pallidus	UBERON:0002477	73.29	silver quality
pharyngeal mucosa	UBERON:0000355	73.22	silver quality
pons	UBERON:0000988	73.12	silver quality
vena cava	UBERON:0004087	73.05	gold quality
vastus lateralis	UBERON:0001379	72.82	gold quality
lateral globus pallidus	UBERON:0002476	72.82	silver quality
cardia of stomach	UBERON:0001162	72.81	gold quality
quadriceps femoris	UBERON:0001377	72.77	gold quality
periodontal ligament	UBERON:0008266	72.73	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	31.55
E-ANND-3	no	2.38

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting FAAP24, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-605-3P	99.88	69.22	1833
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-8077	99.17	66.67	862
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-4768-3P	98.16	66.02	2330
HSA-MIR-3664-3P	97.85	67.62	1452
HSA-MIR-6866-5P	96.64	68.06	624
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-6775-3P	95.76	65.91	982
HSA-MIR-137-5P	94.03	60.01	43

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 11.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 10)

• FAAP24 targets FANCM to structures that mimic intermediates formed during the replication/repair of damaged DNA. (PMID:17289582)
• FANCM is an anchor required for recruitment of the FA core complex to chromatin, and the FANCM/FAAP24 interaction is essential for this chromatin-loading activity (PMID:18174376)
• FAAP24 is dispensable for DNA binding and branch migration activity of FANCM. (PMID:18206976)
• DNA damage recognition and remodeling activities of FANCM and FAAP24 cooperate to promote efficient activation of DNA damage checkpoints in Fanconi anemia. (PMID:18995830)
• FANCM/FAAP24 plays a role in ICL-induced checkpoint activation through regulating RPA recruiment at ICL-stalled replication forks. (PMID:20670894)
• FANCM and FAAP24 play multiple, while not fully epistatic, roles in maintaining genomic integrity. (PMID:23333308)
• Crystal structure of the FANCM-FAAP24 complex. (PMID:23932590)
• These results demonstrate dual roles of FAAP24 in DNA damage response against crosslinking lesions, one through the formation of FANCM/FAAP24 heterodimer and the other via its ssDNA-binding activity required in optimized checkpoint activation. (PMID:23999858)
• Results show that the first HhH motif of FAAP24 is a potential binding site for DNA, which plays a critical role in targeting FANCM-FAAP24 to chromatin. (PMID:24003026)
• This is the first report of an FAAP24 loss of function mutation found in human patients with EBV-associated lymphoproliferation. (PMID:27473539)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	faap24	ENSDARG00000051731
mus_musculus	Faap24	ENSMUSG00000030493
rattus_norvegicus	Faap24	ENSRNOG00000022393

Protein

Protein identifiers

Fanconi anemia core complex-associated protein 24 — Q9BTP7 (reviewed: Q9BTP7)

Alternative names: Fanconi anemia-associated protein of 24 kDa

All UniProt accessions (4): A0A0S2Z5V6, Q9BTP7, K7EKQ4, X6R368

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. Regulates FANCD2 monoubiquitination upon DNA damage. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed. Targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA.

Subunit / interactions. Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM and FAAP24. Interacts with FANCM.

Subcellular location. Nucleus.

Domain organisation. The C-terminal region is distantly related to RuvA domain 2, a DNA-binding domain.

RefSeq proteins (2): NP_001287907, NP_689479* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR010994	RuvA_2-like	Homologous_superfamily
IPR026985	FAAP24	Family
IPR040646	PND	Domain
IPR041663	DisA/LigA_HHH	Domain

Pfam: PF12826, PF17949

UniProt features (29 total): helix 13, strand 8, turn 3, sequence variant 3, chain 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
4BXO	X-RAY DIFFRACTION	2.15
9HJO	X-RAY DIFFRACTION	2.4
4M6W	X-RAY DIFFRACTION	2.9
2LYH	SOLUTION NMR
2M9M	SOLUTION NMR
2M9N	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BTP7-F1	90.12	0.80

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6783310	Fanconi Anemia Pathway
R-HSA-9833482	PKR-mediated signaling

MSigDB gene sets: 89 (showing top): PID_FANCONI_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_DNA_DAMAGE_RESPONSE, GOBP_INTERSTRAND_CROSS_LINK_REPAIR, FISCHER_DREAM_TARGETS, REACTOME_FANCONI_ANEMIA_PATHWAY, REACTOME_DNA_REPAIR, GOMF_CHROMATIN_BINDING, GOCC_FANCONI_ANAEMIA_NUCLEAR_COMPLEX, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOBP_DNA_METABOLIC_PROCESS, KIM_WT1_TARGETS_DN, GOBP_DNA_REPAIR, ARID5B_TARGET_GENES

GO Biological Process (3): interstrand cross-link repair (GO:0036297), DNA repair (GO:0006281), DNA damage response (GO:0006974)

GO Molecular Function (3): DNA binding (GO:0003677), chromatin binding (GO:0003682), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), Fanconi anaemia nuclear complex (GO:0043240), FANCM-MHF complex (GO:0071821), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
DNA Repair	1
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
binding	2
nuclear protein-containing complex	2
DNA repair	1
DNA metabolic process	1
DNA damage response	1
cellular response to stress	1
nucleic acid binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

759 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FAAP24	FANCM	Q8IYD8	999
FAAP24	FAAP100	Q0VG06	998
FAAP24	FANCA	O15360	997
FAAP24	CENPS	Q8N2Z9	994
FAAP24	CENPX	A8MT69	993
FAAP24	FANCB	Q8NB91	990
FAAP24	FANCC	Q00597	982
FAAP24	FANCF	Q9NPI8	973
FAAP24	F6S8H2	F6S8H2	970
FAAP24	FANCL	Q9NW38	965
FAAP24	FANCE	Q9HB96	958
FAAP24	FANCG	O15287	939
FAAP24	FANCD2	Q9BXW9	930
FAAP24	ERCC4	Q92889	907
FAAP24	RMI1	Q9H9A7	888

IntAct

37 interactions, top by confidence:

A	B	Type	Score
FANCA	FANCG	psi-mi:“MI:0914”(association)	0.960
FANCM	FAAP24	psi-mi:“MI:0915”(physical association)	0.810
FAAP24	FANCM	psi-mi:“MI:0915”(physical association)	0.810
CENPS	CENPX	psi-mi:“MI:0914”(association)	0.810
	FAAP24	psi-mi:“MI:0407”(direct interaction)	0.600
	FAAP24	psi-mi:“MI:0407”(direct interaction)	0.540
LYG2	TRAF2	psi-mi:“MI:0914”(association)	0.530
	FANCM	psi-mi:“MI:0915”(physical association)	0.520
FANCM	FAAP24	psi-mi:“MI:0407”(direct interaction)	0.520
FAAP24	RBBP6	psi-mi:“MI:0915”(physical association)	0.490
RBBP6	FAAP24	psi-mi:“MI:0915”(physical association)	0.490
FAAP24	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
	FANCM	psi-mi:“MI:0915”(physical association)	0.400
FANCM		psi-mi:“MI:0915”(physical association)	0.400
FAAP24	FANCM	psi-mi:“MI:0915”(physical association)	0.400
FANCM	FANCC	psi-mi:“MI:0914”(association)	0.350
FANCM	FANCG	psi-mi:“MI:0914”(association)	0.350
FAAP24	FANCG	psi-mi:“MI:0914”(association)	0.350

BioGRID (63): C19orf40 (Affinity Capture-MS), C19orf40 (Affinity Capture-Western), C19orf40 (Affinity Capture-Western), C19orf40 (Affinity Capture-MS), FANCM (Affinity Capture-Western), APITD1 (Affinity Capture-Western), STRA13 (Affinity Capture-Western), FANCA (Affinity Capture-Western), C19orf40 (Affinity Capture-MS), C19orf40 (Affinity Capture-MS), FANCM (Affinity Capture-MS), C19orf40 (Co-crystal Structure), C19orf40 (Reconstituted Complex), C19orf40 (Affinity Capture-Western), C19orf40 (Co-localization)

ESM2 similar proteins: A1A4M6, A2AGL3, B3DLA6, O65502, P14893, P26149, P27365, P42694, P48738, P48739, P53811, P53812, Q00169, Q0P5D8, Q0VBB0, Q28C34, Q2HJ54, Q32KN9, Q4R7G8, Q53H12, Q5BKH5, Q5F477, Q5IFP1, Q5R6F0, Q5R8P9, Q62878, Q6DFV5, Q6NRD0, Q6NTS7, Q6TV19, Q7RTV5, Q7ZUV0, Q7ZYD9, Q8CA95, Q8IX04, Q8N945, Q8R107, Q8VCM5, Q8VHQ9, Q8W4D4

Diamond homologs: A0AHX5, A0RJC3, A1V6A8, A2SA04, A3CNE1, A3MM33, A3NBR9, A3NXK5, A4XIQ3, A5N361, A8AWG9, A8FG01, A8YV13, A9VJI0, B1AJ20, B5ZBM7, B7HF33, B7HRG3, B7IJ18, B7JR24, B8DHZ8, B9J024, C0Z9I7, C1CJ89, C1CQA2, C1ETV9, C1L2D9, C3L7X5, C3PAA9, O84898, P14951, P47448, P75350, Q03F33, Q03K10, Q03QP1, Q043W2, Q04LQ9, Q0SW38, Q13VN8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
FAAP24	“form complex”	“Fanconi anemia core complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Fanconi Anemia Pathway	6	104.5×	2e-09
PKR-mediated signaling	6	52.9×	7e-08

GO biological processes:

GO term	Partners	Fold	FDR
interstrand cross-link repair	6	129.6×	1e-09
DNA damage response	6	16.1×	1e-04
DNA repair	5	16.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	7
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

502 predictions. Top by Δscore:

Variant	Effect	Δscore
19:32973299:CAAG:C	donor_loss	1.0000
19:32973300:AAGGT:A	donor_loss	1.0000
19:32973303:GTC:G	donor_loss	1.0000
19:32973304:T:G	donor_loss	1.0000
19:32973558:GAAAT:G	donor_gain	1.0000
19:32973559:AAATG:A	donor_loss	1.0000
19:32973560:AAT:A	donor_gain	1.0000
19:32973561:ATG:A	donor_loss	1.0000
19:32973562:TG:T	donor_loss	1.0000
19:32973563:G:GG	donor_gain	1.0000
19:32973563:GTA:G	donor_loss	1.0000
19:32973565:AA:A	donor_loss	1.0000
19:32974057:A:AG	acceptor_gain	1.0000
19:32974058:A:G	acceptor_gain	1.0000
19:32974059:G:GA	acceptor_gain	1.0000
19:32974059:GT:G	acceptor_gain	1.0000
19:32974059:GTC:G	acceptor_gain	1.0000
19:32974059:GTCC:G	acceptor_gain	1.0000
19:32974059:GTCCA:G	acceptor_gain	1.0000
19:32974209:GTTG:G	donor_gain	1.0000
19:32974213:G:GG	donor_gain	1.0000
19:32974213:GTGA:G	donor_loss	1.0000
19:32974214:TGA:T	donor_loss	1.0000
19:32974215:GAG:G	donor_loss	1.0000
19:32974216:AG:A	donor_loss	1.0000
19:32976419:ATTGT:A	acceptor_gain	1.0000
19:32976423:T:TA	acceptor_gain	1.0000
19:32976426:TTCA:T	acceptor_loss	1.0000
19:32976427:TCAG:T	acceptor_loss	1.0000
19:32976429:AGGTT:A	acceptor_loss	1.0000

AlphaMissense

1394 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:32973269:T:A	W25R	0.985
19:32973269:T:C	W25R	0.985
19:32974105:A:C	S97R	0.982
19:32974107:T:A	S97R	0.982
19:32974107:T:G	S97R	0.982
19:32974085:T:A	V90D	0.980
19:32976564:T:A	L177H	0.976
19:32974088:T:A	V91D	0.975
19:32976575:T:C	F181L	0.974
19:32976577:T:A	F181L	0.974
19:32976577:T:G	F181L	0.974
19:32974082:T:A	V89E	0.970
19:32973501:T:A	V61D	0.969
19:32973271:G:C	W25C	0.965
19:32973271:G:T	W25C	0.965
19:32976531:T:C	I166T	0.965
19:32976540:T:A	V169D	0.965
19:32976564:T:G	L177R	0.965
19:32976662:T:C	F210L	0.962
19:32976664:C:A	F210L	0.962
19:32976664:C:G	F210L	0.962
19:32973468:T:C	F50S	0.959
19:32974166:T:C	L117P	0.957
19:32974172:T:A	V119E	0.955
19:32976564:T:C	L177P	0.954
19:32976594:T:A	L187Q	0.954
19:32974189:G:C	A125P	0.953
19:32973258:C:A	A21D	0.952
19:32974131:G:C	Q105H	0.952
19:32974131:G:T	Q105H	0.952

dbSNP variants (sampled 300 via entrez): RS1000548613 (19:32972469 A>G), RS1000775887 (19:32977681 G>A), RS1002151268 (19:32978327 G>T), RS1002222581 (19:32973670 C>T), RS1002324061 (19:32972144 T>C), RS1002820253 (19:32975836 GTTGT>G), RS1003130275 (19:32975984 C>G,T), RS1003278322 (19:32971087 G>C,T), RS1003330736 (19:32970714 T>C,G), RS1003440312 (19:32970560 A>C), RS1003824913 (19:32974744 T>C), RS1004659785 (19:32974883 C>G,T), RS1005029936 (19:32971101 G>A,T), RS1005031008 (19:32974628 A>C), RS1005386327 (19:32971941 C>T)

Disease associations

OMIM: gene MIM:610884 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency-associated lymphoproliferative disease	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
lymphoproliferative syndrome	Disputed	AR

Mondo (1): immunodeficiency-associated lymphoproliferative disease (MONDO:0020083)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90002403_288	Red blood cell count	3.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

20 total (human), top 20 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Formaldehyde	increases expression	1
Methyl Methanesulfonate	increases expression	1
Parabens	affects cotreatment, decreases expression	1
Phthalic Acids	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.