FAAP24

protein-coding

FA core complex associated protein 24

Gene summary

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]).[supplied by OMIM, Mar 2008]

Previous symbols:

C19orf40

MANE transcript

NM_152266.5

Inheritance

ClinVar variants

U:31B:14

Top phenotype

FAAP24-related disorder

gnomAD constraint

pLI —, LoF o/e 1.16

Max pathogenic AF

—

Genomic locus

chr19:32,972,209-32,978,229

External References & Databases

Ensembl (ENSG00000131944)

Transcript & Mutation Effects

hg38 • Region Span ~6.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency-associated lymphoproliferative diseaseLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0020083

Submitter: PanelApp Australia

lymphoproliferative syndromeNO_KNOWN

Inheritance Pattern: AR

Disease ID:MONDO:0016537

Submitter: ClinGen

*FAAP24* was reported in relation to autosomal recessive lymphoproliferative syndrome in 2016 (Daschkey et al., PMID: 27473539). In this study, a homozygous missense variant in *FAAP24* was identified in two siblings from a consanguineous family with a fatal Epstein-Barr virus (EBV)-related lymphoproliferative disease. The allele frequency in the general population for the variant in these cases is higher than would be expected for disease-causing variants in this gene and was flagged as contradictory evidence. Given the allele frequency of the variant (particularly the presence of multiple homozygotes past the age of onset in the general population) in the only two patients with this disorder reported to date, there is convincing evidence disputing the relationship between *FAAP24* and autosomal recessive lymphoproliferative syndrome. This gene-disease association may be supported by in vitro functional assays. Experimental evidence assessing *FAAP24* expression and biochemical function supported this gene’s role in DNA damage repair pathways (PMID: 27473539, 23999858, 23333308). However, it is currently unclear if this role is consistent with the mechanism of disease and the data was insufficient for scoring. In summary, the evidence supporting the relationship between *FAAP24* and autosomal recessive lymphoproliferative syndrome has been disputed and no valid evidence remains to support the claim. More evidence is needed to either support or entirely refute the role *FAAP24* plays in this disease.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FAAP24 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 38

not providedTotal: 7

FAAP24-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_152266.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	6 clinvar	1 clinvar	8
missense			27 clinvar	5 clinvar	2 clinvar	34
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	31	11	3	45

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 14 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_152266.5	RefSeq	NP_689479.1	4	MANE Select
ENST00000588258.6	Ensembl	ENSP00000466121.1	4	MANE Select
NM_001300978.2	RefSeq	NP_001287907.1	2	Standard
ENST00000254262.9	Ensembl	ENSP00000254262.5	3	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fanconi anemia pathway - Homo sapiens (human)
Fanconi Anemia Pathway
DNA Repair
Fanconi anemia pathway

Biological Process

interstrand cross-link repair

Molecular Function

DNA binding
chromatin binding
protein binding

Cellular Component

nucleoplasm
intracellular membrane-bounded organelle
Fanconi anaemia nuclear complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000588258
Coding exons: 4
Length: 6014
Individuals with no LoFs: 125695
Homozygous LoFs: 0
Heterozygous LoFs: 52
Defined: 125747
p: 0.000207

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.164	118	123	0.958	0.00000693	1384
Missense (PolyPhen)		33	31.436	1.0497		403
Synonymous	-1.10	63	52.8	1.19	0.00000325	438
Loss of Function	-0.437	10	8.61	1.16	4.29e-7	100

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00031	0.00025	rare
Latino/Admixed American	0.00020	0.00020	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00027	0.00027	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: 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. {ECO:0000269|PubMed:17289582}.;

Recessive Scores

pRec: 0.134

Intolerance Scores

RVIS EVS: 0.99
RVIS percentile EVS: 90.56

Essentials

Essential (gene trap): N