ABCF1

Summary

ABCF1 (ATP binding cassette subfamily F member 1, HGNC:70) is a protein-coding gene on chromosome 6p21.33, encoding ATP-binding cassette sub-family F member 1 (Q8NE71). Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. It is a common-essential gene (DepMap: required in 97.7% of cancer cell lines).

The protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the GCN20 subfamily. Unlike other members of the superfamily, this protein lacks the transmembrane domains which are characteristic of most ABC transporters. This protein may be regulated by tumor necrosis factor-alpha and play a role in enhancement of protein synthesis and the inflammation process.

Source: NCBI Gene 23 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 126 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 97.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001025091

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:70
Approved symbol	ABCF1
Name	ATP binding cassette subfamily F member 1
Location	6p21.33
Locus type	gene with protein product
Status	Approved
Aliases	EST123147
Ensembl gene	ENSG00000204574
Ensembl biotype	protein_coding
OMIM	603429
Entrez	23

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 17 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000326195, ENST00000376545, ENST00000441867, ENST00000468958, ENST00000475993, ENST00000479542, ENST00000542772, ENST00000896196, ENST00000896197, ENST00000896198, ENST00000896199, ENST00000915355, ENST00000915356, ENST00000915357, ENST00000915358, ENST00000915359, ENST00000971696, ENST00000971697, ENST00000971698, ENST00000971699

RefSeq mRNA: 2 — MANE Select: NM_001025091 NM_001025091, NM_001090

CCDS: CCDS34380, CCDS34381

Canonical transcript exons

ENST00000326195 — 25 exons

Exon	Start	End
ENSE00001592750	30585260	30585343
ENSE00001603491	30580406	30580519
ENSE00001613197	30584192	30584331
ENSE00001614180	30585558	30585682
ENSE00001621859	30583066	30583188
ENSE00001625359	30577409	30577455
ENSE00001627388	30578470	30578577
ENSE00001629189	30579931	30580005
ENSE00001631627	30586134	30586305
ENSE00001638686	30584418	30584566
ENSE00001646370	30578348	30578385
ENSE00001658742	30585879	30585991
ENSE00001664739	30586474	30586548
ENSE00001705637	30586641	30586711
ENSE00001727199	30583805	30583890
ENSE00001754126	30582394	30582507
ENSE00001787262	30589806	30589974
ENSE00001790050	30589688	30589720
ENSE00001924537	30571442	30571560
ENSE00002321921	30590535	30591522
ENSE00003549661	30577818	30577913
ENSE00003589061	30590149	30590213
ENSE00003591250	30578076	30578202
ENSE00003634765	30590306	30590378
ENSE00003785200	30583608	30583708

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.18.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 95.9275 / max 1228.4589, expressed in 1826 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66740	95.2148	1825
66742	0.7127	390

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.18	gold quality
gastrocnemius	UBERON:0001388	96.03	gold quality
muscle of leg	UBERON:0001383	95.72	gold quality
skeletal muscle tissue	UBERON:0001134	95.52	gold quality
muscle tissue	UBERON:0002385	94.90	gold quality
islet of Langerhans	UBERON:0000006	94.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.98	gold quality
placenta	UBERON:0001987	93.08	gold quality
ventricular zone	UBERON:0003053	92.90	gold quality
mucosa of transverse colon	UBERON:0004991	92.83	gold quality
stromal cell of endometrium	CL:0002255	92.81	gold quality
granulocyte	CL:0000094	92.68	gold quality
skin of abdomen	UBERON:0001416	92.46	gold quality
zone of skin	UBERON:0000014	92.41	gold quality
apex of heart	UBERON:0002098	92.40	gold quality
skin of leg	UBERON:0001511	92.36	gold quality
pancreas	UBERON:0001264	92.32	gold quality
smooth muscle tissue	UBERON:0001135	91.89	gold quality
lymph node	UBERON:0000029	91.86	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.84	gold quality
body of stomach	UBERON:0001161	91.81	gold quality
ganglionic eminence	UBERON:0004023	91.80	gold quality
lower esophagus	UBERON:0013473	91.80	gold quality
heart left ventricle	UBERON:0002084	91.71	gold quality
vermiform appendix	UBERON:0001154	91.65	gold quality
muscle layer of sigmoid colon	UBERON:0035805	91.64	gold quality
testis	UBERON:0000473	91.59	gold quality
bone marrow	UBERON:0002371	91.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.52	gold quality
left testis	UBERON:0004533	91.48	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

37 targeting ABCF1, 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-8068	99.98	73.85	2376
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-202-5P	99.78	67.65	991
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-4427	99.34	70.33	1854
HSA-MIR-5001-5P	99.05	66.76	1972
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-625-5P	99.02	68.64	2031
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-502-5P	98.77	66.51	906
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-6842-3P	98.07	66.33	1325
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4665-5P	97.91	67.69	1536
HSA-MIR-1271-3P	97.56	64.85	865
HSA-MIR-550A-3-5P	97.56	65.35	823

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 27)

• The data demonstrate a specific over-expression phenotype for hsp22 and suggest that hsp22 interacts with heat and oxidative stress resistance pathways. (PMID:15491684)
• We conclude that histone acetylation stimulates the transcription initiation and promotes the transcription elongation, thereby up-regulating both basal and inducible expression of hsp22 in D. melanogaster. (PMID:15607742)
• Hsp22 and Hsp23 play important roles in the recovery from chill coma in adult males, and suggest that these contribute to adaptive responses to fluctuating thermal conditions. (PMID:21112994)
• Small heat shock proteins determine synapse number and neuronal activity during development. (PMID:32437379)
• Genomic knockout of hsp23 both decreases and increases fitness under opposing thermal extremes in Drosophila melanogaster. (PMID:34562590)
• N terminus of the head protein of T4 bacteriophage directs proteins to the GroEL chaperonin (PMID:15571729)
• time-resolved fluorescence properties of the bacteriophage T4 capsid protein gp23 are investigated (PMID:15629249)
• folding of the T4 major capsid protein gp23 requires a gp31-dependent cis-folding mechanism likely inside an enlarged “Anfinsen cage” provided by GroEL and gp31 (PMID:15919824)
• structures of gp23-chaperonin complexes, showing both the initial captured state and the final, close-to-native state with gp23 encapsulated in the folding chamber (PMID:19122642)
• The distribution of g23 of T4-type bacteriophages was distinctly different among natural environments of marines, lakes and paddy fields. (PMID:21866696)
• The two critical HLA regions for susceptibility to autoimmune pancreatitis are limited to the HLA-DRB1*0405-DQB1*0401 in the class II and the ABCF1in the class I regions. (PMID:17119950)
• ABC50 N-terminal region interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2 (PMID:17894550)
• ABC50 plays a key role in translation initiation and has functions that are distinct from those of other non-membrane ABC proteins. (PMID:19570978)
• ABCF1 is a critical protein that associates with viral double-stranded DNA. (PMID:23263557)
• ABCF1 showed a significant increase in expression after escitalopram treatment. (PMID:23719290)
• A rare copy number variation of the ABCF1 gene was detected among dengue patients from Malaysia. (PMID:24634119)
• The results suggested that SNPs at PRR3 and ABCF1 genes and the haplotype composed by SNPs at GNL1 and PRR3 between the HLA-A and HLA-C genes tended to predict Graves ophthalmology in a gender-dependent manner in patients with Graves disease in Taiwan. (PMID:24908204)
• expression of ABC50 mutants, which cannot hydrolyse ATP, decreases general translation and relaxes the discrimination against the use of non-AUG codons at translation start sites. (PMID:25597744)
• ABCF1 extrinsically regulates retinal pigment epithelial cell phagocytosis of shed photoreceptor outer segments. (PMID:25904329)
• Elevated microRNA-23a Expression Enhances the Chemoresistance of Colorectal Cancer Cells with Microsatellite Instability to 5-Fluorouracil by Directly Targeting ABCF1 (PMID:25929864)
• The high copy number variant in the ABCF1 gene was the strongest risk factor for gout. (PMID:28405828)
• The combined assessment of IGF2BP3 and ABCF1 predicts recurrence in Ewing sarcoma patients. (PMID:29703820)
• Study solves the crystal structure of an ATP-bound wild-type human ABCF1 at 2.3-A resolution. The comparative studies indicate that the structure is in a pre-activation intermediate conformation. This conformation is stabilized by the interaction between ATP and protein suggesting that this conformation is an important step in the activation of ABCF1. (PMID:30017566)
• The ATP-binding cassette transporter ABCF1 is a hepatic oncofetal protein that promotes chemoresistance, epithelial mesenchymal transformation and cancer stemness in hepatocellular carcinoma cells. (PMID:31100412)
• ABCF1 Regulates dsDNA-induced Immune Responses in Human Airway Epithelial Cells. (PMID:33042865)
• ABCF1 functions as a transcriptional coactivator for OCT4 and SOX2 to stimulate transciption of pluripotency-associated genes in embryonic stem cells. (PMID:34714667)
• ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway. (PMID:37757768)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	abcf1	ENSDARG00000031795
mus_musculus	Abcf1	ENSMUSG00000038762
rattus_norvegicus	Abcf1	ENSRNOG00000000799
drosophila_melanogaster	CG1703	FBGN0030321
caenorhabditis_elegans		WBGENE00006512

Paralogs (2): ABCF2 (ENSG00000033050), ABCF3 (ENSG00000161204)

Protein

Protein identifiers

ATP-binding cassette sub-family F member 1 — Q8NE71 (reviewed: Q8NE71)

Alternative names: ATP-binding cassette 50, TNF-alpha-stimulated ABC protein

All UniProt accessions (6): A0A1U9X609, Q8NE71, F5GYK6, H0YGW7, Q2L6I2, Q5STZ8

UniProt curated annotations — full annotation on UniProt →

Function. Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis.

Subunit / interactions. Isoform 2 interacts (via N-terminus) with EIF2S1; the interaction is independent of its phosphorylated status. Isoform 2 associates (via both ABC transporter domains) with the ribosomes.

Subcellular location. Cytoplasm. Nucleus. Nucleoplasm. Nucleus envelope.

Tissue specificity. Ubiquitous.

Post-translational modifications. Isoform 2 is phosphorylated at phosphoserine and phosphothreonine. Isoform 2 phosphorylation on Ser-109 and Ser-140 by CK2 inhibits association of EIF2 with ribosomes.

Induction. By TNF in cultured synoviocytes.

Similarity. Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NE71-1	1	yes
Q8NE71-2	2

RefSeq proteins (2): NP_001020262, NP_001081 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003439	ABC_transporter-like_ATP-bd	Domain
IPR003593	AAA+_ATPase	Domain
IPR017871	ABC_transporter-like_CS	Conserved_site
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050611	ABCF	Family

Pfam: PF00005

UniProt features (79 total): helix 21, strand 18, mutagenesis site 12, modified residue 9, compositionally biased region 7, domain 2, binding site 2, region of interest 2, turn 2, chain 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
5ZXD	X-RAY DIFFRACTION	2.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NE71-F1	71.68	0.35

Functional residue map

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

Ligand- & substrate-binding residues (2): 336–343; 658–665

Post-translational modifications (9): 22, 24, 105, 108, 109, 140, 166, 228, 595

Mutagenesis-validated functional residues (12):

Position	Phenotype
109	reduces phosphorylation. inhibits strongly phosphorylation by ck2; when associated with s-140. does not inhibit interact
140	reduces phosphorylation. inhibits strongly phosphorylation by ck2; when associated with s-109. does not inhibits interac
342	does not inhibit ribosome binding. reduces atp-binding. inhibits atp-binding and reduces protein synthesis; when associa
367	does not inhibit ribosome binding.
454	does not inhibit ribosome binding.
477	does not inhibit ribosome binding. reduces protein synthesis; when associated with q-768.
506	does not inhibit ribosome binding.
664	does not inhibit ribosome binding. reduces atp-binding. inhibits atp-binding and reduces protein synthesis; when associa
695	does not inhibit ribosome binding.
745	does not inhibit ribosome binding.
768	does not inhibit ribosome binding. reduces protein synthesis; when associated with q-477.
797	does not inhibit ribosome binding.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-382556	ABC-family protein mediated transport
R-HSA-382551	Transport of small molecules

MSigDB gene sets: 156 (showing top): GOBP_RIBOSOME_BIOGENESIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_TRANSLATIONAL_INITIATION, MORF_HDAC2, PATIL_LIVER_CANCER, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, MORF_RFC4, MORF_PRKDC, GRASEMANN_RETINOBLASTOMA_WITH_6P_AMPLIFICATION, GOMF_TRANSLATION_FACTOR_ACTIVITY_RNA_BINDING, MODULE_18, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, MODULE_62

GO Biological Process (4): translation (GO:0006412), translational initiation (GO:0006413), inflammatory response (GO:0006954), positive regulation of translation (GO:0045727)

GO Molecular Function (8): RNA binding (GO:0003723), ATP binding (GO:0005524), translation factor activity, RNA binding (GO:0008135), translation activator activity (GO:0008494), ATP hydrolysis activity (GO:0016887), ribosome binding (GO:0043022), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (6): nuclear envelope (GO:0005635), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
translation	3
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
formation of translation initiation ternary complex	1
metabolic process	1
defense response	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
RNA binding	1
translation factor activity	1
translation regulator activity	1
positive regulation of translation	1
ribonucleoside triphosphate phosphatase activity	1
ATP-dependent activity	1
ribonucleoprotein complex binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
nucleus	1
endomembrane system	1
organelle envelope	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3126 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABCF1	ABCE1	P61221	727
ABCF1	ABCB7	O75027	593
ABCF1	POLR1C	O15160	574
ABCF1	POLR1B	Q9H9Y6	570
ABCF1	OAZ1	P54368	521
ABCF1	POLR1D	P0DPB6	520
ABCF1	EEF1G	P26641	505
ABCF1	ABCD4	O14678	502
ABCF1	TOLLIP	Q9H0E2	497
ABCF1	ABCA2	Q9BZC7	490
ABCF1	ABCC10	Q5T3U5	489
ABCF1	TUBB	P05218	482
ABCF1	C6orf136	Q5SQH8	477
ABCF1	GNL1	P36915	476
ABCF1	ABCA5	Q8WWZ7	475

IntAct

83 interactions, top by confidence:

A	B	Type	Score
NCK1	NCK2	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
EED	EPOP	psi-mi:“MI:0914”(association)	0.530
MAPT	KIF2A	psi-mi:“MI:0914”(association)	0.530
ERBB2	HAX1	psi-mi:“MI:0914”(association)	0.530
ENG	ABCF1	psi-mi:“MI:0407”(direct interaction)	0.440
ABCF1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PCSK4	ABCF1	psi-mi:“MI:0915”(physical association)	0.400
ABCF1	HMGN2	psi-mi:“MI:0915”(physical association)	0.400
ABCF1	H2AZ1	psi-mi:“MI:0915”(physical association)	0.400
ABCF1	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
ABCF1	H3-4	psi-mi:“MI:0915”(physical association)	0.400
CCDC181	ABCF1	psi-mi:“MI:0915”(physical association)	0.400
S	ABCF1	psi-mi:“MI:0915”(physical association)	0.400
OTUB1		psi-mi:“MI:0914”(association)	0.350
CNOT1	IBTK	psi-mi:“MI:0914”(association)	0.350
Fbl	COPS8	psi-mi:“MI:0914”(association)	0.350
TIGD6	ZRANB2	psi-mi:“MI:0914”(association)	0.350
Rrbp1	PIPSL	psi-mi:“MI:0914”(association)	0.350
NOP56	C12orf43	psi-mi:“MI:0914”(association)	0.350
EMC2	TBL2	psi-mi:“MI:0914”(association)	0.350
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
Xpo1	IFT56	psi-mi:“MI:0914”(association)	0.350
RPGRIP1L	NPHP1	psi-mi:“MI:0914”(association)	0.350
KDM1A	KIF2A	psi-mi:“MI:0914”(association)	0.350
RRP1B	ZNF785	psi-mi:“MI:0914”(association)	0.350
MAPT	MEX3A	psi-mi:“MI:0914”(association)	0.350
MAPT	C11orf98	psi-mi:“MI:0914”(association)	0.350
MAPT	POTEF	psi-mi:“MI:0914”(association)	0.350

BioGRID (261): ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Co-fractionation), ABCF1 (Co-fractionation), HMGN1P30 (Co-fractionation), ABCF1 (Affinity Capture-MS), ABCF1 (Reconstituted Complex), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS), ABCF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0D1CLQ4, A0A139AVY4, A9X4T1, B9FK36, C5E4D9, D0MYB4, G5EES6, J9VQZ9, O14134, O42943, O59672, O93796, O94489, P06625, P08240, P16521, P16638, P25997, P29551, P40024, P43535, P53396, P53585, P53978, Q08972, Q2KJA2, Q2TCH3, Q32PF2, Q3MHE8, Q4HY71, Q5KIM6, Q5R9Z5, Q66H39, Q6MG08, Q75EV6, Q767L0, Q7YR37, Q8H0V6, Q8K268, Q8NE71

Diamond homologs: A0A0H2VBH0, A0A0H2VFI8, A0KPH6, A1AC19, A1B9H9, A1JRI2, A1U776, O05519, O06476, O31716, O34512, O34631, O42943, O59672, P0A9U3, P0A9U4, P0A9U5, P0A9W3, P0A9W4, P0A9W5, P0A9X1, P0A9X2, P0A9X3, P12622, P25256, P40024, P43535, P43672, P44808, P45127, P57403, P63389, P63390, P9WQK2, P9WQK3, Q0I4A9, Q0T3U8, Q0TGX4, Q0VTB6, Q1C1S0

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
CSNK2A1	unknown	ABCF1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	83
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
974733	NC_000006.11:g.28005012_31683185del	Likely pathogenic

SpliceAI

2612 predictions. Top by Δscore:

Variant	Effect	Δscore
6:30571562:T:G	donor_loss	1.0000
6:30577816:A:AC	acceptor_loss	1.0000
6:30577816:A:AG	acceptor_gain	1.0000
6:30577817:G:GT	acceptor_gain	1.0000
6:30577817:GT:G	acceptor_gain	1.0000
6:30577817:GTT:G	acceptor_gain	1.0000
6:30577817:GTTC:G	acceptor_gain	1.0000
6:30577909:AGCAG:A	donor_loss	1.0000
6:30577910:GCAG:G	donor_gain	1.0000
6:30577911:CAG:C	donor_loss	1.0000
6:30577912:AGG:A	donor_loss	1.0000
6:30577914:G:T	donor_loss	1.0000
6:30577915:T:G	donor_loss	1.0000
6:30578064:T:A	acceptor_gain	1.0000
6:30578067:TCTCA:T	acceptor_loss	1.0000
6:30578068:CTCAG:C	acceptor_loss	1.0000
6:30578069:TCAG:T	acceptor_loss	1.0000
6:30578070:CAG:C	acceptor_loss	1.0000
6:30578071:A:AG	acceptor_gain	1.0000
6:30578072:G:GA	acceptor_gain	1.0000
6:30578072:GC:G	acceptor_gain	1.0000
6:30578072:GCA:G	acceptor_gain	1.0000
6:30578072:GCAGC:G	acceptor_gain	1.0000
6:30578073:CAGCA:C	acceptor_loss	1.0000
6:30578074:A:T	acceptor_loss	1.0000
6:30578075:G:GA	acceptor_gain	1.0000
6:30578075:GC:G	acceptor_gain	1.0000
6:30578075:GCA:G	acceptor_gain	1.0000
6:30578075:GCAA:G	acceptor_gain	1.0000
6:30578193:G:GT	donor_gain	1.0000

AlphaMissense

5558 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:30583618:T:C	F309S	1.000
6:30583620:A:C	S310R	1.000
6:30583622:C:A	S310R	1.000
6:30583622:C:G	S310R	1.000
6:30583624:T:A	I311N	1.000
6:30583645:T:C	L318P	1.000
6:30583656:G:C	A322P	1.000
6:30583663:T:C	L324P	1.000
6:30583689:G:A	G333R	1.000
6:30583689:G:C	G333R	1.000
6:30583689:G:T	G333W	1.000
6:30583690:G:A	G333E	1.000
6:30583693:T:C	L334P	1.000
6:30583698:G:A	G336R	1.000
6:30583698:G:C	G336R	1.000
6:30583699:G:A	G336E	1.000
6:30583706:T:A	N338K	1.000
6:30583706:T:G	N338K	1.000
6:30583707:G:C	G339R	1.000
6:30583707:G:T	G339C	1.000
6:30583708:G:A	G339D	1.000
6:30583708:G:T	G339V	1.000
6:30583809:G:A	G341S	1.000
6:30583809:G:C	G341R	1.000
6:30583809:G:T	G341C	1.000
6:30583810:G:A	G341D	1.000
6:30583810:G:T	G341V	1.000
6:30583812:A:C	K342Q	1.000
6:30583814:G:C	K342N	1.000
6:30583814:G:T	K342N	1.000

dbSNP variants (sampled 300 via entrez): RS1000030264 (6:30588487 G>A), RS1000177520 (6:30570431 A>G), RS1000225697 (6:30575025 G>A,C), RS1000479465 (6:30586002 G>A,T), RS1000821115 (6:30573207 C>T), RS1001077320 (6:30575777 C>T), RS1001169975 (6:30573766 G>T), RS1001537737 (6:30584785 C>A,T), RS1001592652 (6:30591676 G>A,C), RS1001616546 (6:30578597 C>G), RS1001902395 (6:30583498 C>T), RS1001921893 (6:30587059 A>G), RS1001954979 (6:30576964 A>C,G), RS1002028728 (6:30577347 G>A,C), RS1002145908 (6:30579346 C>T)

Disease associations

OMIM: gene MIM:603429 | disease phenotypes:

GenCC curated gene-disease

Mondo (2): long QT syndrome (MONDO:0002442), megacolon (MONDO:0001273)

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003124_1	Mild influenza (H1N1) infection	1.000000e-08
GCST004521_114	Autism spectrum disorder or schizophrenia	3.000000e-17
GCST004521_117	Autism spectrum disorder or schizophrenia	3.000000e-15
GCST004521_121	Autism spectrum disorder or schizophrenia	3.000000e-13
GCST004521_132	Autism spectrum disorder or schizophrenia	2.000000e-09
GCST004521_171	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_2	Autism spectrum disorder or schizophrenia	2.000000e-16
GCST004521_209	Autism spectrum disorder or schizophrenia	5.000000e-16
GCST004521_210	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_211	Autism spectrum disorder or schizophrenia	5.000000e-15
GCST004521_263	Autism spectrum disorder or schizophrenia	7.000000e-17
GCST004521_265	Autism spectrum disorder or schizophrenia	7.000000e-14
GCST004521_269	Autism spectrum disorder or schizophrenia	7.000000e-11
GCST004521_295	Autism spectrum disorder or schizophrenia	6.000000e-18
GCST004521_3	Autism spectrum disorder or schizophrenia	2.000000e-15
GCST004521_56	Autism spectrum disorder or schizophrenia	1.000000e-22
GCST004521_70	Autism spectrum disorder or schizophrenia	8.000000e-20
GCST004521_79	Autism spectrum disorder or schizophrenia	1.000000e-16
GCST006269_1165	General cognitive ability	3.000000e-08
GCST008575_4	IgM levels	3.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:1001488	influenza A (H1N1)
EFO:0004337	intelligence

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D008531	Megacolon	C06.405.469.158.701

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724742 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases methylation, increases expression, decreases expression	3
bisphenol F	increases expression, affects cotreatment, decreases expression	2
bisphenol S	affects cotreatment, increases methylation, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation, affects methylation	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
tetrahydropalmatine	decreases expression	1
sodium arsenite	decreases expression, increases activity	1
ferrous sulfate	increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
coumarin	decreases phosphorylation	1
cupric oxide	decreases expression	1
1-nitropyrene	increases expression	1
beta-methylcholine	affects expression	1
arsenic trisulfide	affects expression	1
di-n-butylphosphoric acid	affects expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
bisphenol B	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
LDN 193189	decreases expression, affects cotreatment	1
bisphenol AF	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Carbamazepine	affects expression	1
Coumestrol	affects cotreatment, increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5650812	Binding	Binding affinity to human ABCF1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)
NCT00399412	Not specified	COMPLETED	ECG Signal Collection From Long QT Syndrome, Wide QRS Complexes, Heart Failure, and Cardiac Resynchronization Patients
NCT00488254	Not specified	COMPLETED	The Long QT Syndrome in Pregnancy
NCT00588965	Not specified	COMPLETED	Effect of Beta-blocker Therapy on QTc Response in Exercise and Recovery in Normal Subjects
NCT01705925	Not specified	COMPLETED	Multicenter Evaluation of Children and Young Adults With Genotype Positive Long QT Syndrome
NCT01903564	Not specified	COMPLETED	Fetal and Neonatal Magnetophysiology
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02413450	Not specified	ENROLLING_BY_INVITATION	Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias
NCT02425189	Not specified	COMPLETED	The Canadian National Long QT Syndrome Registry
NCT02439645	Not specified	TERMINATED	A Registry to Determine the Clinical and Genetic Risk Factors for Torsade De Pointes
NCT02439658	Not specified	UNKNOWN	Genetics of QT Prolongation With Antiarrhythmics
NCT02549664	Not specified	COMPLETED	Exercise in Genetic Cardiovascular Conditions
NCT02581241	Not specified	COMPLETED	Abnormal QT-Response to the Sudden Tachycardia Provoked by Standing in Individuals With Drug-induced Long QT Syndrome
NCT02680080	Not specified	COMPLETED	Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
NCT02775513	Not specified	UNKNOWN	Metabolism of Patients With Genetically Caused Cardiac Arrhythmia
NCT02814981	Not specified	UNKNOWN	Hydroxyzine and Risk of Prolongation of QT Interval
NCT02876380	Not specified	COMPLETED	Prospective Identification of Long QT Syndrome in Fetal Life
NCT03182777	Not specified	COMPLETED	Safety of Local Dental Anesthesia in Patients With Cardiac Channelopathies
NCT03544918	Not specified	COMPLETED	Prevalence of Congenital Long QT Syndrome and Acquired QT Prolongation in a Hospital Cohort
NCT03642405	Not specified	UNKNOWN	Drug-induced Repolarization ECG Changes
NCT03678311	Not specified	COMPLETED	Long QT Syndrome and Sleep Apnea