CTIF

Summary

CTIF (cap binding complex dependent translation initiation factor, HGNC:23925) is a protein-coding gene on chromosome 18q21.1, encoding CBP80/20-dependent translation initiation factor (O43310). Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC).

CTIF is a component of the CBP80 (NCBP1; MIM 600469)/CBP20 (NCBP2; MIM 605133) translation initiation complex that binds cotranscriptionally to the cap end of nascent mRNA. The CBP80/CBP20 complex is involved in a simultaneous editing and translation step that recognizes premature termination codons (PTCs) in mRNAs and directs PTC-containing mRNAs toward nonsense-mediated decay (NMD). On mRNAs without PTCs, the CBP80/CBP20 complex is replaced with cytoplasmic mRNA cap-binding proteins, including EIF4G (MIM 600495), and steady-state translation of the mRNAs resumes in the cytoplasm (Kim et al., 2009 [PubMed 19648179]).

Source: NCBI Gene 9811 — RefSeq curated summary.

At a glance

• GWAS associations: 23
• Clinical variants (ClinVar): 125 total
• GTEx eGene: eQTL in 30 tissues, sQTL in 35 (q < 0.05)
• Constraint (gnomAD): pLI 0.99 (loss-of-function intolerant), LOEUF 0.49 (moderately constrained)
• MANE Select transcript: NM_014772
• Notable: 125 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23925
Approved symbol	CTIF
Name	cap binding complex dependent translation initiation factor
Location	18q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000134030
Ensembl biotype	protein_coding
OMIM	613178
Entrez	9811

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 40 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000256413

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 3, TSL 3: 3, TSL 4: 2, TSL 5: 1

ENST00000256413, ENST00000382998, ENST00000587752, ENST00000587769, ENST00000587860, ENST00000588345, ENST00000589585, ENST00000590422, ENST00000591387, ENST00000591412, ENST00000592658, ENST00000865528, ENST00000865529, ENST00000865530, ENST00000865531, ENST00000865532, ENST00000865533, ENST00000865534, ENST00000865535, ENST00000865536, ENST00000865537, ENST00000865538, ENST00000865539, ENST00000912180, ENST00000912181, ENST00000912182, ENST00000959041, ENST00000959042, ENST00000959043, ENST00000959044, ENST00000959045, ENST00000959046, ENST00000959047, ENST00000959048, ENST00000959049, ENST00000959050, ENST00000959051, ENST00000959052, ENST00000959053, ENST00000959054, ENST00000959055, ENST00001113728, ENST00001125270, ENST00001130769, ENST00001132449

RefSeq mRNA: 2 — MANE Select: NM_014772 NM_001142397, NM_014772

CCDS: CCDS11935, CCDS45864

Canonical transcript exons

ENST00000256413 — 12 exons

Exon	Start	End
ENSE00001111108	48757919	48758405
ENSE00001111112	48761390	48761689
ENSE00001297798	48619538	48619745
ENSE00001855968	48859344	48863217
ENSE00001940052	48539031	48539312
ENSE00003458321	48670669	48670744
ENSE00003492805	48817221	48817376
ENSE00003548969	48663752	48663825
ENSE00003575429	48857588	48857641
ENSE00003635752	48664447	48664551
ENSE00003665944	48636614	48636685
ENSE00003784792	48711619	48711695

Expression profiles

Bgee: expression breadth ubiquitous, 136 present calls, max score 97.86.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0305 / max 300.1958, expressed in 1793 samples.

Highest expression (Bgee): primary visual cortex, superior frontal gyrus, Brodmann (1909) area 9, hypothalamus, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CTIF is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 30 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 65 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Adipose Subcutaneous	sqtl	7.2e-66	-1.04	18:48854987:TG:T
Nerve Tibial	sqtl	3.3e-39	-0.91	18:48854987:TG:T
Skin Sun Exposed Lower leg	sqtl	6.3e-35	-0.73	18:48806024:A:G
Adipose Visceral Omentum	sqtl	3.1e-31	-0.85	18:48854987:TG:T
Brain Cerebellum	sqtl	1.8e-24	+1.01	18:48854987:TG:T
Breast Mammary Tissue	sqtl	1.2e-22	-0.80	18:48855520:T:C
Brain Cerebellar Hemisphere	sqtl	5.3e-20	+1.02	18:48854987:TG:T
Skin Not Sun Exposed Suprapubic	sqtl	6.9e-20	-0.65	18:48806024:A:G
Thyroid	sqtl	9.3e-19	-0.63	18:48854987:TG:T
Testis	sqtl	3.5e-18	+0.73	18:48806024:A:G
Esophagus Mucosa	sqtl	4.9e-18	-0.68	18:48806024:A:G
Brain Cortex	sqtl	4.2e-16	-0.93	18:48854987:TG:T
Esophagus Muscularis	sqtl	1.7e-14	-0.56	18:48758469:T:C
Artery Tibial	sqtl	3.0e-14	-0.63	18:48862073:C:T
Colon Sigmoid	sqtl	4.3e-14	-0.72	18:48854987:TG:T
Adrenal Gland	sqtl	1.3e-13	-0.91	18:48855131:T:C
Pituitary	eqtl	2.1e-12	+0.35	18:48758469:T:C
Pituitary	sqtl	1.2e-10	-0.97	18:48854987:TG:T
Esophagus Gastroesophageal Junction	sqtl	1.6e-10	-0.67	18:48855954:C:T
Brain Caudate basal ganglia	sqtl	4.4e-10	-0.81	18:48855954:C:T

FANTOM5 promoters

8 alternative TSS:

Promoter ID	TPM avg	Samples expressed
170201	14.2386	1769
170203	8.1564	1503
170204	3.6569	1188
170202	0.6461	353
170208	0.5579	255
170205	0.3199	170
170206	0.2528	123
170207	0.2020	92

Top tissues by expression

showing 100 of 136 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primary visual cortex	UBERON:0002436	97.86	gold quality
superior frontal gyrus	UBERON:0002661	96.22	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.87	gold quality
hypothalamus	UBERON:0001898	95.74	gold quality
cortical plate	UBERON:0005343	95.60	gold quality
putamen	UBERON:0001874	95.46	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.38	gold quality
sural nerve	UBERON:0015488	95.36	gold quality
right frontal lobe	UBERON:0002810	95.34	gold quality
cerebral cortex	UBERON:0000956	94.82	gold quality
frontal cortex	UBERON:0001870	94.76	gold quality
anterior cingulate cortex	UBERON:0009835	94.75	gold quality
Ammon’s horn	UBERON:0001954	94.56	gold quality
substantia nigra	UBERON:0002038	94.40	gold quality
prefrontal cortex	UBERON:0000451	94.25	gold quality
temporal lobe	UBERON:0001871	94.09	gold quality
caudate nucleus	UBERON:0001873	94.09	gold quality
amygdala	UBERON:0001876	94.06	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.88	gold quality
nucleus accumbens	UBERON:0001882	93.76	gold quality
brain	UBERON:0000955	93.74	gold quality
cerebellum	UBERON:0002037	93.69	gold quality
cerebellar cortex	UBERON:0002129	93.66	gold quality
cerebellar hemisphere	UBERON:0002245	93.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.47	gold quality
lower esophagus	UBERON:0013473	93.44	gold quality
right coronary artery	UBERON:0001625	92.97	gold quality
popliteal artery	UBERON:0002250	92.92	gold quality
tibial artery	UBERON:0007610	92.91	gold quality
apex of heart	UBERON:0002098	92.83	gold quality
subcutaneous adipose tissue	UBERON:0002190	92.58	gold quality
stromal cell of endometrium	CL:0002255	92.41	gold quality
adipose tissue	UBERON:0001013	91.74	gold quality
ascending aorta	UBERON:0001496	91.60	gold quality
corpus callosum	UBERON:0002336	91.55	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	91.52	gold quality
thoracic aorta	UBERON:0001515	91.48	gold quality
left coronary artery	UBERON:0001626	91.07	gold quality
ganglionic eminence	UBERON:0004023	90.95	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.95	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.74	gold quality
omental fat pad	UBERON:0010414	90.68	gold quality
left ovary	UBERON:0002119	90.67	gold quality
ovary	UBERON:0000992	90.54	gold quality
heart left ventricle	UBERON:0002084	90.34	gold quality
right ovary	UBERON:0002118	90.18	gold quality
myometrium	UBERON:0001296	90.04	gold quality
descending thoracic aorta	UBERON:0002345	89.94	gold quality
mucosa of stomach	UBERON:0001199	89.92	gold quality
right lobe of liver	UBERON:0001114	89.80	gold quality
fundus of stomach	UBERON:0001160	89.74	gold quality
lower esophagus mucosa	UBERON:0035834	89.73	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.71	gold quality
calcaneal tendon	UBERON:0003701	89.25	gold quality
heart	UBERON:0000948	89.17	gold quality
urinary bladder	UBERON:0001255	88.99	gold quality
thoracic mammary gland	UBERON:0005200	88.84	gold quality
liver	UBERON:0002107	88.42	gold quality
left adrenal gland cortex	UBERON:0035825	88.39	gold quality
left adrenal gland	UBERON:0001234	88.25	gold quality
right adrenal gland	UBERON:0001233	88.21	gold quality
right atrium auricular region	UBERON:0006631	88.19	gold quality
adrenal gland	UBERON:0002369	88.13	gold quality
skeletal muscle tissue	UBERON:0001134	88.02	gold quality
body of stomach	UBERON:0001161	87.86	gold quality
tibial nerve	UBERON:0001323	87.82	gold quality
esophagus	UBERON:0001043	87.76	gold quality
muscle tissue	UBERON:0002385	87.72	gold quality
right adrenal gland cortex	UBERON:0035827	87.58	gold quality
body of uterus	UBERON:0009853	87.33	gold quality
stomach	UBERON:0000945	87.26	gold quality
material anatomical entity	UBERON:0000465	86.85	gold quality
multicellular organism	UBERON:0000468	86.85	gold quality
anatomical system	UBERON:0000467	86.84	gold quality
gall bladder	UBERON:0002110	86.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.41	gold quality
cortex of kidney	UBERON:0001225	86.15	gold quality
right lung	UBERON:0002167	86.14	gold quality
left uterine tube	UBERON:0001303	86.12	gold quality
prostate gland	UBERON:0002367	85.99	gold quality
colonic epithelium	UBERON:0000397	85.98	gold quality
muscle of leg	UBERON:0001383	85.91	gold quality
gastrocnemius	UBERON:0001388	85.55	gold quality
metanephros cortex	UBERON:0010533	85.41	gold quality
smooth muscle tissue	UBERON:0001135	85.34	gold quality
uterine cervix	UBERON:0000002	85.24	gold quality
endocervix	UBERON:0000458	85.21	gold quality
adult mammalian kidney	UBERON:0000082	84.88	gold quality
pituitary gland	UBERON:0000007	84.79	gold quality
colon	UBERON:0001155	84.78	gold quality
skin of leg	UBERON:0001511	84.71	gold quality
ectocervix	UBERON:0012249	84.57	gold quality
upper lobe of left lung	UBERON:0008952	84.54	gold quality
adrenal tissue	UBERON:0018303	84.26	gold quality
kidney	UBERON:0002113	84.04	gold quality
lung	UBERON:0002048	84.00	gold quality
zone of skin	UBERON:0000014	83.71	gold quality
placenta	UBERON:0001987	83.61	gold quality
adenohypophysis	UBERON:0002196	83.60	gold quality
intestine	UBERON:0000160	83.15	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.09

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Locus coeruleus	tissue	71.9
Postcentral gyrus	tissue	63.2
Pons	tissue	52.1
Thalamus	tissue	49.1
Superior colliculi	tissue	47.3
Hippocampus	tissue	47.3	medium
Cerebral cortex	tissue	46.0	medium
Somatosensory cortex	tissue	46.0
Cerebellum	tissue	44.7	low
Midbrain	tissue	42.7
Substantia nigra	tissue	42.7
Hypothalamus	tissue	41.5
Occipital cortex	tissue	41.5
Motor cortex	tissue	40.0
Prefrontal cortex	tissue	38.6
Nucleus accumbens	tissue	38.6
Medulla oblongata	tissue	37.8
Temporal cortex	tissue	36.0
Spinal cord	tissue	35.5
Insular cortex	tissue	35.5
Hippocampal formation	tissue	35.4
Entorhinal cortex	tissue	35.4
Retrosplenial and cingulate cortex	tissue	35.3
Retrosplenial cortex	tissue	33.8
Periaqueductal gray	tissue	33.7
Olfactory bulb	tissue	32.7
Septum	tissue	31.7
Ventral forebrain	tissue	31.1
Amygdala	tissue	27.5
Basal ganglia	tissue	24.8	low
Putamen	tissue	24.5
Frontal cortex	tissue	23.1
Adipose tissue	tissue	20.4	not detected
Corpus callosum	tissue	18.6
Choroid plexus	tissue	18.5
Caudate putamen	tissue	16.6
Ovary	tissue	12.6	low
Pituitary gland	tissue	11.8
Vagina	tissue	11.6	not detected
Heart muscle	tissue	8.2	not detected
Esophagus	tissue	8.1	low
Skeletal muscle	tissue	7.7	low
Gallbladder	tissue	7.0	medium
Retina	tissue	6.9
Smooth muscle	tissue	6.5	low
Adrenal gland	tissue	6.3	medium
Lung	tissue	5.3	medium
Seminal vesicle	tissue	5.1	low
Salivary gland	tissue	5.1	low
Stomach 1	tissue	4.8	medium
Endometrium 1	tissue	4.4	low
Parathyroid gland	tissue	4.3	medium
Urinary bladder	tissue	4.2	low
Tongue	tissue	4.0
Placenta	tissue	4.0	low
Thyroid gland	tissue	3.8	medium
Cervix	tissue	3.7	medium
Pancreas	tissue	3.6	medium
Prostate	tissue	3.5	low
Breast	tissue	3.4	medium

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Precentral gyrus (69.1), Nucleus raphe magnus (64.6), Nuclei of the trapezoid body (62.2), Parvicellular reticular nuclei, medullary (61.3), Ventral posterolateral thalamic nucleus (61.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ESR2

miRNA regulators (miRDB)

Targeting CTIF by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 84 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3120-5P	100.00	65.56	965
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-22-3P	99.93	68.13	917
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-532-3P	99.34	65.76	1195

Functional genomics

gnomAD constraint: pLI 0.99, LOEUF 0.487, missense Z 1.11 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000256413 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
18:48,619,566–48,761,475	529 / 520.3	1.02	no
18:48,761,476–48,859,556	210 / 292.3	0.72	no

Literature-anchored findings (GeneRIF, showing 6)

• a new MIF4G domain-containing protein, CTIF that interacts directly with CBP80 and is part of the CBP80/20-dependent translation initiation complex [CBP80/20-dependent translation initiation factor, CTIF] (PMID:19648179)
• Study reveals that Ago2, but not Ago2F2V2, inhibits the binding of CBP80/20 to cap structure. (PMID:21840310)
• association of SNPs in LCP1 and CTIF with hearing (PMID:26264041)
• CTIF was identified as a novel PARylation target of the TNKS2 in the centrosomal region of cells, which plays a role in the distribution of the centrosomal satellites. (PMID:29789535)
• CBP80/20-dependent translation initiation factor (CTIF) inhibits HIV-1 Gag synthesis by targeting the function of the viral protein Rev. (PMID:33103564)
• Translation mediated by the nuclear cap-binding complex is confined to the perinuclear region via a CTIF-DDX19B interaction. (PMID:34232997)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctif	ENSDARG00000090617
mus_musculus	Ctif	ENSMUSG00000052928
rattus_norvegicus	Ctif	ENSRNOG00000018342
drosophila_melanogaster	CG13124	FBGN0032156
caenorhabditis_elegans		WBGENE00018405

Paralogs (2): MIF4GD (ENSG00000125457), PAIP1 (ENSG00000172239)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2685518) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal coat/hair pigmentation	1
increased heart rate	1
improved glucose tolerance	1
shortened RR interval	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q3ZC21	97.7%	Diamond
Xenopus laevis	A3KND5	92.8%	Diamond
Xenopus tropicalis	Q28H63	92.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR4743	ncRNA	100616366
ZBTB7C	protein-coding	201501
SMAD7	protein-coding	4092
CTIF-AS1	ncRNA	105372105
DYM-AS1	ncRNA	100129878
DYM	protein-coding	54808

Protein

Protein identifiers

CBP80/20-dependent translation initiation factor — O43310 (reviewed: O43310)

All UniProt accessions (5): K7EK08, K7EPK6, K7EQS5, K7EQS9, O43310

UniProt curated annotations — full annotation on UniProt →

Function. Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC). Acts via its interaction with the NCBP1/CBP80 component of the CBC complex and recruits the 40S small subunit of the ribosome via eIF3. In contrast, it is not involved in steady state translation, that takes place when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. Also required for nonsense-mediated mRNA decay (NMD), the pioneer round of mRNA translation mediated by the cap-binding complex playing a central role in nonsense-mediated mRNA decay (NMD).

Subunit / interactions. Interacts with NCBP1/CBP80; the interaction is direct. Associates with the eukaryotic translation initiation factor 3 (eIF-3) complex.

Subcellular location. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed.

Similarity. Belongs to the CTIF family.

Isoforms (2)

UniProt ID	Names	Canonical?
O43310-1	1	yes
O43310-2	2

RefSeq proteins (2): NP_001135869, NP_055587* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003890	MIF4G-like_typ-3	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR051367	mRNA_TranslReg/HistoneTransl	Family

Pfam: PF02854

UniProt features (20 total): compositionally biased region 6, modified residue 4, region of interest 4, sequence variant 3, chain 1, domain 1, splice variant 1

Structure

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43310-F1	63.13	0.34

Human Protein Atlas

Protein class: Transporters, Transporter channels and pores, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): cytosol

Antibody reliability (HPA): IH uncertain · IF supported

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 (4)

Type	Positions
N-acetylmethionine	1
Phosphoserine	18, 299
Phosphothreonine	289

Function

Pathways and Gene Ontology

Reactome pathways

0 curated (TAS) of 0; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

MSigDB gene sets: 99 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_XPCS_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TRANSLATIONAL_INITIATION, USF_C, GOBP_TRANSLATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOMF_TRANSLATION_REGULATOR_ACTIVITY, CAGCAGG_MIR370, MYCMAX_01, DACOSTA_UV_RESPONSE_VIA_ERCC3_TTD_DN, GOBP_NUCLEAR_TRANSCRIBED_MRNA_CATABOLIC_PROCESS_NONSENSE_MEDIATED_DECAY, SENESE_HDAC3_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_TRANSLATION, YAGI_AML_WITH_11Q23_REARRANGED

GO Biological Process (4): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), regulation of translational initiation (GO:0006446), regulation of translation (GO:0006417), positive regulation of translation (GO:0045727)

GO Molecular Function (3): RNA binding (GO:0003723), translation activator activity (GO:0008494), protein binding (GO:0005515)

GO Cellular Component (2): cytosol (GO:0005829), perinuclear region of cytoplasm (GO:0048471)

GO top-level categories

14 GO namespaces:

Category	Terms
regulation of translation	2
translation	2
cytoplasm	2
cellular anatomical structure	2
nuclear-transcribed mRNA catabolic process	1
translational initiation	1
post-transcriptional regulation of gene expression	1
regulation of protein metabolic process	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
nucleic acid binding	1
translation regulator activity	1
positive regulation of translation	1
binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 9 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
nuclear-transcribed mRNA catabolic process, nonsense-mediated decay	BP	mutant phenotype
regulation of translational initiation	BP	mutant phenotype
cytosol	CC	direct assay
perinuclear region of cytoplasm	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 786 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTIF	NCBP1	Q09161	938
CTIF	NCBP2	P52298	917
CTIF	DYM	Q7RTS9	623
CTIF	SKA1	Q96BD8	524
CTIF	TSPAN4	O14817	463
CTIF	SLBP	Q14493	452
CTIF	SNCAIP	Q9Y6H5	446
CTIF	DCTN1	Q14203	446
CTIF	PNRC2	Q9NPJ4	427
CTIF	ZBTB44	Q8NCP5	418
CTIF	SLC25A41	Q8N5S1	416
CTIF	RAB11FIP3	O75154	413
CTIF	EIF3G	O75821	412
CTIF	EIF4E	P06730	406
CTIF	UPF1	Q92900	406

IntAct

Human interaction partners of CTIF in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

1 partners by confidence:

Partner	Interaction type	MIscore	Records
MIF4GD	association	0.350	2

BioGRID (100 interactions; top human partners by supporting records): MIF4GD (Affinity Capture-MS; 6 records), SLBP (Affinity Capture-Western; 5 records), DDX19A (Affinity Capture-MS; 4 records), DDX19B (Two-hybrid; 4 records), TRIM28 (Affinity Capture-MS; 4 records), DCTN1 (Reconstituted Complex; 2 records), EEF1A1 (Affinity Capture-MS; 2 records), HOOK1 (Proximity Label-MS; 2 records), HOOK3 (Two-hybrid; 2 records), TDRD3 (Proximity Label-MS; 2 records), ACLY (Affinity Capture-MS), AGO1 (Proximity Label-MS), AGO2 (Proximity Label-MS), AGO3 (Proximity Label-MS), AHCYL1 (Proximity Label-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
CBP80/20- dependent translation complex	6	NCBP2, UPF3B, CTIF, EIF3B, EIF4A3, NCBP1

Disease & clinical

Genetic variants

Variant evidence for CTIF: 125 ClinVar records (0 pathogenic / likely pathogenic); 23 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	102
Likely benign	3
Benign	3

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 38 predictions of 2,111):

Position(s)	Effect	Δscore	Sites
18:48619536–48619537	acceptor_loss	1.0000	5
18:48619746–48619747	donor_loss	1.0000	5
18:48663742	acceptor_gain	1.0000
18:48663750–48663751	acceptor_loss	1.0000	5
18:48663826–48663827	donor_loss	1.0000	4
18:48664445–48664446	acceptor_loss	1.0000	5
18:48664552	donor_loss	1.0000	2
18:48670661	acceptor_gain	1.0000
18:48670667–48670668	acceptor_loss	1.0000	5
18:48670745–48670746	donor_loss	1.0000	5

AlphaMissense

1,494 missense substitutions predicted likely pathogenic (of 3,972 scored), across 324 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M438	9	0.944	0.999
M543	9	0.942	0.995
M554	9	0.907	0.997
M488	9	0.845	0.991
D29	8	0.996	0.999
F448	8	0.990	1.000
F27	8	0.983	1.000
F480	8	0.980	0.999
F496	8	0.977	0.997
D519	8	0.972	0.995
F187	8	0.967	0.996
F427	8	0.965	0.997
F396	8	0.962	0.998
F485	8	0.947	0.992
D114	8	0.943	0.980
F441	8	0.941	0.994
D459	8	0.935	0.982
F477	8	0.933	0.995
S450	8	0.921	0.999
D424	8	0.911	0.983

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Glioblastoma Multiforme (validation)	favorable	4.25e-05
Kidney Renal Papillary Cell Carcinoma (TCGA)	favorable	0.00025
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000286

Disease associations

OMIM: gene MIM:613178 | disease phenotypes:

GWAS associations

23 associations:

Study	Trait	p-value
GCST90002384_335	Hemoglobin	2e-19
GCST90002383_387	Hematocrit	3e-19
GCST90002403_92	Red blood cell count	2e-15
GCST90002384_336	Hemoglobin	2e-13
GCST90002386_153	High light scatter reticulocyte percentage of red cells	3e-11
GCST90002383_388	Hematocrit	5e-11
GCST90002403_93	Red blood cell count	5e-11
GCST004601_155	Red blood cell count	2e-10
GCST90002387_74	Immature fraction of reticulocytes	3e-10
GCST90002385_276	High light scatter reticulocyte count	6e-10
GCST90002407_481	White blood cell count	4e-9
GCST005455_7	Mean diameter of HDL particles	7e-9
GCST007843_27	Rheumatoid arthritis	7e-9
GCST005497_4	Large HDL particle concentration	9e-9
GCST005499_12	Phospholipid levels in large HDL	1e-8
GCST008839_405	Height	2e-8
GCST007329_40	Automobile speeding propensity	4e-8
GCST007015_7	Lumbar spine bone mineral density (integral)	2e-6
GCST010121_13	Ceramide levels (C24:0)	3e-6
GCST001692_11	Response to taxane treatment (docetaxel)	4e-6
GCST003440_1	Response to carboplatin in ovarian cancer (MTT IC50)	9e-6
GCST007742_22	Iris heterochromicity	9e-6
GCST010122_6	Ceramide levels (C22:0)	9e-6

EFO canonical traits (from GWAS)

9 canonical traits:

EFO ID	Trait name
EFO:0006952	cytotoxicity measurement
EFO:0004305	erythrocyte count
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0007620	volumetric bone mineral density
EFO:0008579	risk-taking behaviour
EFO:0009764	eye colour measurement
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	4
Aflatoxin B1	decreases expression, increases methylation	3
sodium arsenite	decreases expression, increases expression	2
Cisplatin	affects cotreatment, decreases expression	2
Estradiol	affects expression, affects cotreatment, increases expression	2
aristolochic acid I	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	decreases methylation	1
beta-lapachone	decreases expression, increases expression	1
benzo(e)pyrene	decreases methylation, increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	decreases methylation	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
tamibarotene	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Doxorubicin	decreases expression	1
Methapyrilene	decreases methylation, increases methylation	1
Nickel	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SK08	HAP1 CTIF (-) 1	Cancer cell line	Male
CVCL_SK09	HAP1 CTIF (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.