A1CF

Summary

A1CF (APOBEC1 complementation factor, HGNC:24086) is a protein-coding gene on chromosome 10q11.23, encoding APOBEC1 complementation factor (Q9NQ94). Essential component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in APOB mRNA.

Mammalian apolipoprotein B mRNA undergoes site-specific C to U deamination, which is mediated by a multi-component enzyme complex containing a minimal core composed of APOBEC-1 and a complementation factor encoded by this gene. The gene product has three non-identical RNA recognition motifs and belongs to the hnRNP R family of RNA-binding proteins. It has been proposed that this complementation factor functions as an RNA-binding subunit and docks APOBEC-1 to deaminate the upstream cytidine. Studies suggest that the protein may also be involved in other RNA editing or RNA processing events. Several transcript variants encoding a few different isoforms have been found for this gene.

Source: NCBI Gene 29974 — RefSeq curated summary.

At a glance

• GWAS associations: 27
• Clinical variants (ClinVar): 82 total — 7 pathogenic, 1 likely-pathogenic
• MANE Select transcript: NM_014576

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24086
Approved symbol	A1CF
Name	APOBEC1 complementation factor
Location	10q11.23
Locus type	gene with protein product
Status	Approved
Aliases	ACF, ASP, ACF64, ACF65, APOBEC1CF
Ensembl gene	ENSG00000148584
Ensembl biotype	protein_coding
OMIM	618199
Entrez	29974

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 70 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000373993, ENST00000373995, ENST00000373997, ENST00000374001, ENST00000395489, ENST00000395495, ENST00000414883, ENST00000473480, ENST00000493415, ENST00000855019, ENST00000855020, ENST00000855021, ENST00000855022, ENST00000855023, ENST00000855024, ENST00000855025, ENST00000855026, ENST00000855027, ENST00000855028, ENST00000855029, ENST00000855030, ENST00000855031, ENST00000855032, ENST00000855033, ENST00000855034, ENST00000855035, ENST00000855036, ENST00000855037, ENST00000855038, ENST00000855039, ENST00000855040, ENST00000855041, ENST00000855042, ENST00000855043, ENST00000855044, ENST00000855045, ENST00000855046, ENST00000855047, ENST00000855048, ENST00000855049, ENST00000855050, ENST00000855051, ENST00000855052, ENST00000855053, ENST00000855054, ENST00000855055, ENST00000855056, ENST00000855057, ENST00000855058, ENST00000855059, ENST00000855060, ENST00000855061, ENST00000855062, ENST00000855063, ENST00000855064, ENST00000855065, ENST00000855066, ENST00000855067, ENST00000855068, ENST00000855069, ENST00000855070, ENST00000855071, ENST00000855072, ENST00000855073, ENST00000855074, ENST00000855075, ENST00000855076, ENST00000855077, ENST00000855078, ENST00000855079, ENST00000855080, ENST00000855081

RefSeq mRNA: 8 — MANE Select: NM_014576 NM_001198818, NM_001198819, NM_001198820, NM_001370130, NM_001370131, NM_014576, NM_138932, NM_138933

CCDS: CCDS7241, CCDS7242, CCDS7243, CCDS73133

Canonical transcript exons

ENST00000373997 — 13 exons

Exon	Start	End
ENSE00001093113	50811040	50811176
ENSE00001142847	50809894	50810042
ENSE00001345617	50864033	50864080
ENSE00003459832	50828131	50828295
ENSE00003539976	50859842	50859985
ENSE00003543429	50816006	50816279
ENSE00003554113	50820552	50820649
ENSE00003579604	50841862	50841992
ENSE00003683587	50813857	50814038
ENSE00003688232	50843988	50844122
ENSE00003708651	50799409	50806880
ENSE00003788749	50836074	50836312
ENSE00003848896	50885581	50885627

Expression profiles

Bgee: expression breadth broad, 78 present calls, max score 96.81.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.2914 / max 211.3556, expressed in 71 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109368	0.6543	58
109367	0.6371	45

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
liver	UBERON:0002107	96.81	gold quality
jejunal mucosa	UBERON:0000399	96.80	gold quality
ileal mucosa	UBERON:0000331	95.59	gold quality
right lobe of liver	UBERON:0001114	94.10	gold quality
buccal mucosa cell	CL:0002336	92.44	gold quality
duodenum	UBERON:0002114	91.56	gold quality
colonic mucosa	UBERON:0000317	91.44	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.04	gold quality
oocyte	CL:0000023	88.80	gold quality
pancreatic ductal cell	CL:0002079	88.23	gold quality
nephron tubule	UBERON:0001231	87.41	gold quality
secondary oocyte	CL:0000655	87.18	gold quality
mucosa of transverse colon	UBERON:0004991	85.52	gold quality
kidney epithelium	UBERON:0004819	84.80	gold quality
islet of Langerhans	UBERON:0000006	83.79	gold quality
rectum	UBERON:0001052	81.84	gold quality
pancreas	UBERON:0001264	79.45	gold quality
adult mammalian kidney	UBERON:0000082	79.02	gold quality
body of pancreas	UBERON:0001150	78.42	gold quality
renal glomerulus	UBERON:0000074	78.11	gold quality
kidney	UBERON:0002113	77.81	gold quality
jejunum	UBERON:0002115	77.61	gold quality
metanephric glomerulus	UBERON:0004736	76.92	gold quality
diaphragm	UBERON:0001103	76.85	gold quality
epithelial cell of pancreas	CL:0000083	75.21	silver quality
small intestine	UBERON:0002108	74.98	gold quality
colonic epithelium	UBERON:0000397	73.74	gold quality
renal medulla	UBERON:0000362	73.44	gold quality
gall bladder	UBERON:0002110	73.26	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-81608	yes	16.11
E-ENAD-27	yes	10.82
E-GEOD-83139	yes	9.90
E-MTAB-5061	no	3.72
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

358 targeting A1CF, 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-1252-5P	100.00	69.80	2774
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 11)

• results suggested both AID and APOBEC-1 are equally likely to bind single-stranded DNA or RNA, which has implications for the identification of natural AID targets (PMID:15148397)
• ACF plays a crucial role, which is independent of apobec-1 expression, in cell survival, particularly during early embryonic development (PMID:16055734)
• The data presented in this report suggested that similar regulatory mechanisms controlling the functional interaction of APOBEC-1 with ACF might be operational during enterocyte differentiation. (PMID:19932086)
• hnRNP K and hnRNP L may serve as A1CF-like cofactors in AID-mediated class switch recombination and somatic hypermutation (PMID:25902538)
• Study reported that the deleted 8aa, EIYMNVPV, was just localized in the internal region of A1CF nuclear translocation signal. Also, A1CF (-8aa), but not its full-length counterpart, can promote proliferation of MDA-MB-231 cells accompanied with increased level of IL-6 mRNA. (PMID:27231908)
• Interaction of any alcohol exposure with GCKR (rs780094) and A1CF (rs10821905) influenced the risk of gout in Europeans (PMID:28679452)
• A1CF-Axin2 signal axis regulates Wilms tumor-derived cells’ apoptosis and migration through Axin2. (PMID:30825095)
• this study revealed that A1CF can upregulate the expression of FAM224A via strengthening its stability, which in turn, influenced the negative modulation of miR-590-3p on transcription factor ZNF143. (PMID:31186064)
• High APOBEC1 Complementation Factor Expression Positively Modulates the Proliferation, Invasion, and Migration of Endometrial Cancer Cells Through Regulating P53/P21 Signaling Pathway. (PMID:32818382)
• Both variants of A1CF and BAZ1B genes are associated with gout susceptibility: a replication study and meta-analysis in a Japanese population. (PMID:33517564)
• A1CF Binding to the p65 Interaction Site on NKRF Decreased IFN-beta Expression and p65 Phosphorylation (Ser536) in Renal Carcinoma Cells. (PMID:38612387)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	a1cf	ENSDARG00000002968
mus_musculus	A1cf	ENSMUSG00000052595
rattus_norvegicus	A1cf	ENSRNOG00000033195

Paralogs (36): DAZAP1 (ENSG00000071626), CIRBP (ENSG00000099622), RBM23 (ENSG00000100461), RBM3 (ENSG00000102317), NCL (ENSG00000115053), TIA1 (ENSG00000116001), HNRNPA2B1 (ENSG00000122566), RBM19 (ENSG00000122965), RBM39 (ENSG00000131051), MSI1 (ENSG00000135097), HNRNPA1 (ENSG00000135486), HNRNPD (ENSG00000138668), HNRNPA1L2 (ENSG00000139675), RBMX (ENSG00000147274), TIAL1 (ENSG00000151923), RBM46 (ENSG00000151962), HNRNPDL (ENSG00000152795), MSI2 (ENSG00000153944), RBM47 (ENSG00000163694), RBMY1F (ENSG00000169800), HNRNPA3 (ENSG00000170144), RBMXL2 (ENSG00000170748), RBM4B (ENSG00000173914), RBM4 (ENSG00000173933), RBMXL3 (ENSG00000175718), HNRNPA0 (ENSG00000177733), TRNAU1AP (ENSG00000180098), HNRNPAB (ENSG00000197451), RBMXL1 (ENSG00000213516), HNRNPA1L3 (ENSG00000224578), RBMY1J (ENSG00000226941), RBMY1A1 (ENSG00000234414), RBMY1E (ENSG00000242389), RBMY1B (ENSG00000242875), RBMY1D (ENSG00000244395), DND1 (ENSG00000256453)

Protein

Protein identifiers

APOBEC1 complementation factor — Q9NQ94 (reviewed: Q9NQ94)

Alternative names: APOBEC1-stimulating protein

All UniProt accessions (3): Q9NQ94, F8W9F8, Q5T0W7

UniProt curated annotations — full annotation on UniProt →

Function. Essential component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in APOB mRNA. Binds to APOB mRNA and is probably responsible for docking the catalytic subunit, APOBEC1, to the mRNA to allow it to deaminate its target cytosine. The complex also protects the edited APOB mRNA from nonsense-mediated decay.

Subunit / interactions. Part of the apolipoprotein B mRNA editing complex with APOBEC1. Interacts with TNPO2; TNPO2 may be responsible for transport of A1CF into the nucleus. Interacts with SYNCRIP. Interacts with CELF2/CUGBP2. Interacts with RBM47.

Subcellular location. Nucleus. Endoplasmic reticulum. Cytoplasm.

Tissue specificity. Widely expressed with highest levels in brain, liver, pancreas, colon and spleen.

Domain organisation. The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity.

Miscellaneous. Major isoform found in 66-78% of cDNA clones. Does not exhibit APOBEC1 complementation activity. Does not exhibit APOBEC1 complementation activity. Minor isoform found in 2-3% of cDNA clones.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9NQ94-1	1	yes
Q9NQ94-2	2
Q9NQ94-3	3
Q9NQ94-4	4
Q9NQ94-5	5
Q9NQ94-6	6

RefSeq proteins (8): NP_001185747, NP_001185748, NP_001185749, NP_001357059, NP_001357060, NP_055391, NP_620310, NP_620311 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000504	RRM_dom	Domain
IPR006535	HnRNP_R/Q_splicing_fac	Family
IPR012677	Nucleotide-bd_a/b_plait_sf	Homologous_superfamily
IPR034538	ACF_RRM1	Domain
IPR035979	RBD_domain_sf	Homologous_superfamily
IPR044461	A1CF_DSRM	Domain

Pfam: PF00076, PF14709

UniProt features (28 total): mutagenesis site 6, splice variant 5, strand 5, domain 3, sequence variant 2, sequence conflict 2, helix 2, chain 1, region of interest 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2CPD	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NQ94-F1	69.70	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 499

Mutagenesis-validated functional residues (6):

Position	Phenotype
59	greatly reduced rna binding.
100	greatly reduced rna binding.
139	greatly reduced rna binding.
183	greatly reduced rna binding.
234	slightly reduced rna binding.
270	slightly reduced rna binding.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-72200	mRNA Editing: C to U Conversion
R-HSA-75094	Formation of the Editosome
R-HSA-75072	mRNA Editing
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 210 (showing top): MODULE_97, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_182, GGGTGGRR_PAX4_03, GOBP_MRNA_MODIFICATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_RNA_MODIFICATION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_PROTEIN_STABILIZATION, PPAR_DR1_Q2, GOBP_REGULATION_OF_PROTEIN_STABILITY, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, HNF1_C

GO Biological Process (10): mRNA processing (GO:0006397), embryo implantation (GO:0007566), mRNA localization resulting in post-transcriptional regulation of gene expression (GO:0010609), cytidine to uridine editing (GO:0016554), mRNA modification (GO:0016556), protein stabilization (GO:0050821), chromosomal 5-methylcytosine DNA demethylation pathway (GO:0141166), negative regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:2000623), low-density lipoprotein particle clearance (GO:0034383), negative regulation of mRNA catabolic process (GO:1902373)

GO Molecular Function (6): single-stranded RNA binding (GO:0003727), mRNA binding (GO:0003729), enzyme-substrate adaptor activity (GO:0140767), nucleic acid binding (GO:0003676), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), apolipoprotein B mRNA editing enzyme complex (GO:0030895), mRNA editing complex (GO:0045293)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
mRNA Editing	1
mRNA Editing: C to U Conversion	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
mRNA metabolic process	2
RNA binding	2
binding	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
RNA processing	1
multicellular organism development	1
female pregnancy	1
reproductive process	1
intracellular mRNA localization	1
post-transcriptional regulation of gene expression	1
base conversion or substitution editing	1
RNA modification	1
regulation of protein stability	1
DNA metabolic process	1
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
negative regulation of mRNA catabolic process	1
regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	1
plasma lipoprotein particle clearance	1
low-density lipoprotein particle disassembly	1
mRNA catabolic process	1
positive regulation of gene expression	1
regulation of mRNA catabolic process	1
negative regulation of RNA catabolic process	1
negative regulation of mRNA metabolic process	1
protein-macromolecule adaptor activity	1
nucleic acid binding	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
endomembrane system	1
mRNA editing complex	1
nuclear protein-containing complex	1
catalytic complex	1

Protein interactions and networks

STRING

1426 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
A1CF	APOBEC1	P41238	995
A1CF	APOB	P04114	779
A1CF	CDA	P32320	677
A1CF	B3GNT4	Q9C0J1	568
A1CF	TMEM171	Q8WVE6	567
A1CF	APOBEC4	Q8WW27	560
A1CF	HNF4G	Q14541	525
A1CF	SLC17A1	Q14916	524
A1CF	UBE2Q2	Q8WVN8	520
A1CF	APOBEC2	Q9Y235	518
A1CF	TRIM46	Q7Z4K8	513
A1CF	HNRNPK	P61978	491
A1CF	SLC2A9	Q9NRM0	476
A1CF	APOBEC3F	Q8IUX4	462
A1CF	RBM41	Q96IZ5	460
A1CF	SLC16A9	Q7RTY1	460

IntAct

69 interactions, top by confidence:

A	B	Type	Score
A1CF	TRAF1	psi-mi:“MI:0915”(physical association)	0.720
TRAF1	A1CF	psi-mi:“MI:0915”(physical association)	0.720
A1CF	REL	psi-mi:“MI:0915”(physical association)	0.560
A1CF	FHL3	psi-mi:“MI:0915”(physical association)	0.560
FHL3	A1CF	psi-mi:“MI:0915”(physical association)	0.560
FHL2	A1CF	psi-mi:“MI:0915”(physical association)	0.560
KRT34	A1CF	psi-mi:“MI:0915”(physical association)	0.560
A1CF	RIMBP3	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	A1CF	psi-mi:“MI:0915”(physical association)	0.560
PLEKHG4	A1CF	psi-mi:“MI:0915”(physical association)	0.560
KLHDC7B	A1CF	psi-mi:“MI:0915”(physical association)	0.560
OIP5	A1CF	psi-mi:“MI:0915”(physical association)	0.560
SPMIP6	A1CF	psi-mi:“MI:0915”(physical association)	0.560
ECM1	A1CF	psi-mi:“MI:0915”(physical association)	0.560
POGZ	A1CF	psi-mi:“MI:0915”(physical association)	0.560
HSPB2	A1CF	psi-mi:“MI:0915”(physical association)	0.560
METTL27	A1CF	psi-mi:“MI:0915”(physical association)	0.560
DOK3	A1CF	psi-mi:“MI:0915”(physical association)	0.560
EIF4G1	A1CF	psi-mi:“MI:0915”(physical association)	0.560
KRT31	A1CF	psi-mi:“MI:0915”(physical association)	0.560
ACTMAP	A1CF	psi-mi:“MI:0915”(physical association)	0.560
A1CF	PSMG2	psi-mi:“MI:0915”(physical association)	0.400
P		psi-mi:“MI:0914”(association)	0.350
	POLRMT	psi-mi:“MI:0914”(association)	0.350

BioGRID (49): A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), PSMG2 (Affinity Capture-MS), PSMG3 (Affinity Capture-MS), A1CF (Reconstituted Complex), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid), A1CF (Two-hybrid)

ESM2 similar proteins: A0A0R4IEW8, A4QNI8, B5DF91, O01671, O09032, O17310, O61374, O64380, O95758, O97018, P16914, P19339, P26378, P26599, P42731, P70372, P86049, Q12926, Q14576, Q15717, Q1JQ73, Q24668, Q28FX0, Q28GD4, Q29099, Q5R9H4, Q5R9Z6, Q5U259, Q5YD48, Q60899, Q60900, Q61701, Q6DEY7, Q6GLB5, Q6GR16, Q6YZW2, Q7SZT7, Q8CH84, Q8GZ26, Q8LFS6

Diamond homologs: A0A8M1NHK4, A0AV96, A0JM51, A4FV72, A4QUF0, A8WLV5, O01671, O04425, O43040, O43390, O60506, P28659, P33240, P86049, Q08BH5, Q08E07, Q0P4R6, Q0V9L3, Q10B98, Q14498, Q28HE9, Q2HJG2, Q2UK72, Q3UEB3, Q4QQT3, Q4R2Z0, Q4R535, Q5B630, Q5EA36, Q5R469, Q5R5P4, Q5R723, Q5R9H4, Q5RC41, Q5RC80, Q5RDA3, Q5SZQ8, Q5YD48, Q66H68, Q6DCB7

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
A1CF	“form complex”	“C-to-U editosome complex”	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	1
Uncertain significance	59
Likely benign	2
Benign	4

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
144977	GRCh38/hg38 10q11.21-21.1(chr10:42884294-52265317)x3	Pathogenic
148945	GRCh38/hg38 10q11.23-23.2(chr10:50729367-87147204)x3	Pathogenic
154900	GRCh38/hg38 10q11.21-21.3(chr10:42112187-67400675)x3	Pathogenic
2574696	GRCh37/hg19 10p14-q26.3(chr10:11138692-135427143)	Pathogenic
2685375	GRCh37/hg19 10q11.23-22.1(chr10:51735638-70791246)x1	Pathogenic
441986	GRCh37/hg19 10p15.3-q26.3(chr10:100027-135427143)x3	Pathogenic
815342	GRCh37/hg19 10q11.23-21.3(chr10:50250603-69256083)x1	Pathogenic
624468	GRCh37/hg19 10q11.22-21.1(chr10:49390457-60061643)x1	Likely pathogenic

SpliceAI

1334 predictions. Top by Δscore:

Variant	Effect	Δscore
10:50810043:C:CC	acceptor_gain	1.0000
10:50820546:CCTTA:C	donor_loss	1.0000
10:50820547:CTTA:C	donor_loss	1.0000
10:50820550:A:C	donor_loss	1.0000
10:50820551:C:CT	donor_loss	1.0000
10:50828125:TCCTA:T	donor_loss	1.0000
10:50828126:CCTA:C	donor_loss	1.0000
10:50828127:CTACC:C	donor_loss	1.0000
10:50828128:TA:T	donor_loss	1.0000
10:50828130:C:G	donor_loss	1.0000
10:50841855:AGCTT:A	donor_loss	1.0000
10:50841856:GCTTA:G	donor_loss	1.0000
10:50841857:CTTA:C	donor_loss	1.0000
10:50841858:TTA:T	donor_loss	1.0000
10:50841859:TAC:T	donor_loss	1.0000
10:50843981:GACT:G	donor_loss	1.0000
10:50843982:ACT:A	donor_loss	1.0000
10:50843984:TCACT:T	donor_loss	1.0000
10:50843985:CACTT:C	donor_loss	1.0000
10:50843986:A:AC	donor_gain	1.0000
10:50843986:A:C	donor_loss	1.0000
10:50843987:C:CA	donor_gain	1.0000
10:50843987:C:T	donor_loss	1.0000
10:50843987:CT:C	donor_gain	1.0000
10:50844132:C:CT	acceptor_gain	1.0000
10:50844132:C:T	acceptor_gain	1.0000
10:50844133:A:T	acceptor_gain	1.0000
10:50844137:CAGG:C	acceptor_gain	1.0000
10:50844138:A:T	acceptor_gain	1.0000
10:50844140:G:C	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000105385 (10:50801243 C>T), RS1000113730 (10:50846363 C>A), RS1000124337 (10:50841440 C>T), RS1000143023 (10:50853674 T>C,G), RS1000145540 (10:50867007 G>A), RS1000197434 (10:50821927 G>A), RS1000289167 (10:50808854 T>G), RS1000298677 (10:50874020 A>G), RS1000351123 (10:50860980 T>A), RS1000355470 (10:50803279 T>G), RS1000369367 (10:50874007 C>A,T), RS1000381744 (10:50854766 A>C), RS1000387610 (10:50861315 C>A), RS1000430001 (10:50886368 T>A,C), RS1000446418 (10:50846689 G>T)

Disease associations

OMIM: gene MIM:618199 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): distal trisomy 10q (MONDO:0019884), hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (2): Distal duplication 10q syndrome (Orphanet:96102), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

27 associations (top):

Study	Trait	p-value
GCST001791_38	Urate levels	7.000000e-17
GCST002666_2	Interferon alpha levels in systemic lupus erythematosus	3.000000e-08
GCST002830_13	Urate levels in lean individuals	1.000000e-06
GCST002912_3	Narcolepsy with cataplexy	5.000000e-06
GCST003401_9	Glomerular filtration rate in non diabetics (creatinine)	1.000000e-12
GCST004292_26	Glomerular filtration rate (creatinine)	5.000000e-09
GCST006612_44	LDL cholesterol	6.000000e-10
GCST006613_72	Triglycerides	4.000000e-09
GCST006614_118	Total cholesterol levels	6.000000e-13
GCST007672_15	3-month functional outcome in ischaemic stroke (modified Rankin score)	2.000000e-06
GCST007733_50	Serum uric acid levels	3.000000e-13
GCST007856_40	Colorectal cancer or advanced adenoma	5.000000e-10
GCST007876_132	Estimated glomerular filtration rate	1.000000e-10
GCST008058_62	Estimated glomerular filtration rate	5.000000e-26
GCST008059_60	Estimated glomerular filtration rate	2.000000e-24
GCST008074_130	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	1.000000e-09
GCST008074_160	Triglyceride levels x alcohol consumption (regular vs non-regular drinkers) interaction (2df)	4.000000e-09
GCST008087_35	Triglyceride levels in current drinkers	7.000000e-07
GCST008087_98	Triglyceride levels in current drinkers	2.000000e-07
GCST008745_74	Estimated glomerular filtration rate in non-diabetics	1.000000e-08
GCST008747_45	Estimated glomerular filtration rate	1.000000e-14
GCST008971_44	Urate levels	1.000000e-36
GCST008972_181	Urate levels	7.000000e-42
GCST010173_26	Triglyceride levels	4.000000e-19
GCST010204_179	Low density lipoprotein cholesterol levels	4.000000e-13
GCST010637_16	Urate levels	1.000000e-12
GCST011349_14	Gamma glutamyl transferase levels	3.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0006517	interferon alpha measurement
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004574	total cholesterol measurement
EFO:0009603	stroke outcome severity measurement
EFO:0004761	uric acid measurement
EFO:0004532	serum gamma-glutamyl transferase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C538087	Distal Trisomy 10q Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Silicon Dioxide	decreases expression	2
Valproic Acid	affects expression, decreases expression, decreases methylation	2
Cyclosporine	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
periodate-oxidized adenosine	affects expression	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Arsenic Trioxide	affects binding, decreases reaction	1
Acetaminophen	decreases expression	1
Air Pollutants	decreases expression	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	decreases expression	1
Quercetin	decreases expression	1
Urethane	decreases expression	1
Uric Acid	affects abundance	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome