FYTTD1

Summary

FYTTD1 (forty-two-three domain containing 1, HGNC:25407) is a protein-coding gene on chromosome 3q29, encoding UAP56-interacting factor (Q96QD9). Required for mRNA export from the nucleus to the cytoplasm.

Enables mRNA binding activity. Involved in mRNA export from nucleus. Located in cytosol; nuclear speck; and nucleolus.

Source: NCBI Gene 84248 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_032288

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25407
Approved symbol	FYTTD1
Name	forty-two-three domain containing 1
Location	3q29
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761B1514, UIF
Ensembl gene	ENSG00000122068
Ensembl biotype	protein_coding
OMIM	616933
Entrez	84248

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 8 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000241502, ENST00000412924, ENST00000415708, ENST00000418169, ENST00000424384, ENST00000426031, ENST00000428738, ENST00000492360, ENST00000494309, ENST00000899456, ENST00000966385, ENST00000966386

RefSeq mRNA: 2 — MANE Select: NM_032288 NM_001011537, NM_032288

CCDS: CCDS3329, CCDS43196

Canonical transcript exons

ENST00000241502 — 9 exons

Exon	Start	End
ENSE00000827636	197778338	197778464
ENSE00001930158	197781811	197787596
ENSE00002275948	197749883	197750074
ENSE00003466226	197768439	197768587
ENSE00003513947	197773403	197773499
ENSE00003609551	197770132	197770244
ENSE00003622237	197774149	197774210
ENSE00003660110	197756426	197756557
ENSE00003790141	197776927	197777001

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 59.0072 / max 731.2733, expressed in 1824 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
40775	56.0062	1823
40774	1.4710	902
40773	0.5893	350
40776	0.3824	136
203082	0.2879	119
203081	0.2172	70
40777	0.0531	20

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	99.31	gold quality
left ventricle myocardium	UBERON:0006566	98.74	gold quality
deltoid	UBERON:0001476	98.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.49	gold quality
quadriceps femoris	UBERON:0001377	98.18	gold quality
myocardium	UBERON:0002349	98.16	gold quality
biceps brachii	UBERON:0001507	98.07	gold quality
vastus lateralis	UBERON:0001379	98.03	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.02	gold quality
upper arm skin	UBERON:0004263	97.84	gold quality
cartilage tissue	UBERON:0002418	97.79	gold quality
skeletal muscle tissue	UBERON:0001134	97.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.57	gold quality
ileal mucosa	UBERON:0000331	97.38	gold quality
ileum	UBERON:0002116	97.28	silver quality
muscle tissue	UBERON:0002385	97.05	gold quality
heart right ventricle	UBERON:0002080	96.53	gold quality
calcaneal tendon	UBERON:0003701	96.07	gold quality
upper leg skin	UBERON:0004262	95.99	gold quality
penis	UBERON:0000989	95.88	gold quality
skin of hip	UBERON:0001554	95.78	gold quality
oral cavity	UBERON:0000167	95.72	gold quality
cauda epididymis	UBERON:0004360	95.44	gold quality
cortical plate	UBERON:0005343	95.40	gold quality
thymus	UBERON:0002370	95.33	gold quality
skeletal muscle organ	UBERON:0014892	95.32	gold quality
esophagus squamous epithelium	UBERON:0006920	95.08	gold quality
body of tongue	UBERON:0011876	95.05	gold quality
superficial temporal artery	UBERON:0001614	95.00	gold quality
palpebral conjunctiva	UBERON:0001812	94.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-9467	yes	11.78
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting FYTTD1, 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-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-9-5P	100.00	72.28	2361
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 2)

• FYTTD1 was named UIF for UAP56 Interacting Factor. UIF is an mRNA export adaptor, recruited to mRNA by SSRP1 of the FACT complex. It also binds mRNA and NXF1. It is required for efficient nuclear export of mRNA in vertebrates and other animals. (PMID:19836239)
• In both ORF57 and ICP27 the interaction sites for ALYREF and UIF partially overlap, suggestive of mutually exclusive binding. The data provide a map of the binding sites responsible for promoting herpes virus mRNA export, enabling future studies to accurately probe these interactions and reveal the functional consequences for UIF and ALYREF redundancy (PMID:30301920)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Fyttd1	ENSMUSG00000022800
rattus_norvegicus	Fyttd1	ENSRNOG00000034233

Protein

Protein identifiers

UAP56-interacting factor — Q96QD9 (reviewed: Q96QD9)

Alternative names: Forty-two-three domain-containing protein 1

All UniProt accessions (5): Q96QD9, H9KVC1, H9KVC6, H9KVD1, H9KVD5

UniProt curated annotations — full annotation on UniProt →

Function. Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the DDX39B/UAP56-NFX1 pathway to ensure efficient mRNA export and delivering to the nuclear pore. Associates with spliced and unspliced mRNAs simultaneously with ALYREF/THOC4.

Subunit / interactions. Interacts with CHTOP. Interacts with DDX39B/UAP56 and NXF1; interaction with DDX39B/UAP56 and NXF1 are mutually exclusive. Interacts with SSRP1; required for its recruitment to mRNAs.

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle.

Tissue specificity. Expressed in a wide variety of cancer types.

Similarity. Belongs to the UIF family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q96QD9-1	1	yes
Q96QD9-2	2
Q96QD9-3	3
Q96QD9-4	4

RefSeq proteins (2): NP_001011537, NP_115664* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009782	FYTTD1	Family

Pfam: PF07078

UniProt features (20 total): modified residue 6, splice variant 4, region of interest 2, cross-link 2, sequence conflict 2, chain 1, sequence variant 1, short sequence motif 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96QD9-F1	57.88	0.03

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 (8): 118, 140, 261, 1, 14, 16, 23, 61

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-159236	Transport of Mature mRNA derived from an Intron-Containing Transcript
R-HSA-72187	mRNA 3’-end processing
R-HSA-73856	RNA Polymerase II Transcription Termination

MSigDB gene sets: 191 (showing top): MODULE_97, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, MODULE_182, GOBP_NUCLEAR_TRANSPORT, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, REACTOME_MRNA_3_END_PROCESSING, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_NUCLEOBASE_CONTAINING_COMPOUND_TRANSPORT, ATF4_Q2, GOBP_NUCLEAR_EXPORT, ATGTCAC_MIR489, GOBP_RNA_LOCALIZATION, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, MODULE_47

GO Biological Process (2): mRNA export from nucleus (GO:0006406), mRNA transport (GO:0051028)

GO Molecular Function (3): RNA binding (GO:0003723), mRNA binding (GO:0003729), protein binding (GO:0005515)

GO Cellular Component (5): nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytosol (GO:0005829), nuclear speck (GO:0016607), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Transport of Mature Transcript to Cytoplasm	1
Processing of Capped Intron-Containing Pre-mRNA	1
RNA Polymerase II Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
cellular anatomical structure	2
RNA export from nucleus	1
gene expression	1
mRNA transport	1
RNA transport	1
nucleic acid binding	1
RNA binding	1
binding	1
intracellular membraneless organelle	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FYTTD1	DDX39B	Q13838	972
FYTTD1	SARNP	P82979	963
FYTTD1	NXF1	Q9UBU9	960
FYTTD1	POLDIP3	Q9BY77	907
FYTTD1	CHTOP	Q9Y3Y2	861
FYTTD1	ALYREF	Q86V81	841
FYTTD1	THOC5	Q13769	789
FYTTD1	NXT1	Q9UKK6	789
FYTTD1	DDX39A	O00148	763
FYTTD1	THOC1	Q96FV9	740
FYTTD1	THOC2	Q8NI27	733
FYTTD1	THOC3	Q96J01	665
FYTTD1	THOC6	Q86W42	660
FYTTD1	MCM3AP	O60318	632
FYTTD1	THOC7	Q6I9Y2	624

IntAct

136 interactions, top by confidence:

A	B	Type	Score
SARNP	DDX39A	psi-mi:“MI:0914”(association)	0.740
DDX39B	FYTTD1	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
	FYTTD1	psi-mi:“MI:0915”(physical association)	0.650
FYTTD1		psi-mi:“MI:0403”(colocalization)	0.650
FYTTD1		psi-mi:“MI:0407”(direct interaction)	0.650
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
RPL14	RRP8	psi-mi:“MI:0914”(association)	0.640
NOP53	RRP8	psi-mi:“MI:0914”(association)	0.640
NOL12	RRP8	psi-mi:“MI:0914”(association)	0.640
	ALYREF	psi-mi:“MI:0915”(physical association)	0.620
SARNP	ZC3H11A	psi-mi:“MI:0914”(association)	0.610
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
Smc3	RAD21	psi-mi:“MI:0914”(association)	0.600
FYTTD1	HNRNPC	psi-mi:“MI:0915”(physical association)	0.560
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
H1-4	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
RPL37A	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530

BioGRID (225): FYTTD1 (Affinity Capture-RNA), FYTTD1 (Affinity Capture-RNA), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), FYTTD1 (Affinity Capture-MS), PALM (Affinity Capture-MS), PLS1 (Affinity Capture-MS), ERICH5 (Affinity Capture-MS), GNG10 (Affinity Capture-MS), PTPRG (Affinity Capture-MS), GNAZ (Affinity Capture-MS)

ESM2 similar proteins: A0JMU8, A1L1K8, A1L2F3, B5X3V2, C1C488, E1B7L7, G3CHK5, H6D7E6, O60293, O95104, Q14444, Q17QU6, Q1ECZ4, Q1LZB6, Q28IB3, Q2YDJ0, Q3SYW9, Q498T2, Q4KME6, Q4V7Q7, Q5BKG8, Q5CZI8, Q5JVS0, Q5U236, Q5ZJ20, Q60865, Q63623, Q68FG3, Q6DGN6, Q6DID3, Q6P4R8, Q6Y7W6, Q6Y7W8, Q6ZPK0, Q7K3L1, Q7TPM1, Q7TQ84, Q8CHI8, Q91Z49, Q96EV2

Diamond homologs: B5X3V2, C1C488, Q17QU6, Q28IB3, Q4V7Q7, Q5ZJ20, Q7TQ84, Q91Z49, Q96QD9

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 141 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	8	36.7×	2e-09
mRNA 3’-end processing	15	35.6×	1e-17
Transport of Mature mRNA derived from an Intron-Containing Transcript	18	33.0×	1e-20
RNA Polymerase II Transcription Termination	8	21.2×	1e-07
Processing of Capped Intron-Containing Pre-mRNA	16	15.8×	3e-13
Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC)	13	15.3×	1e-10
Peptide chain elongation	9	13.8×	4e-07
Viral mRNA Translation	9	13.8×	4e-07

GO biological processes:

GO term	Partners	Fold	FDR
mRNA export from nucleus	17	41.2×	9e-21
negative regulation of mRNA splicing, via spliceosome	6	37.7×	1e-06
poly(A)+ mRNA export from nucleus	6	33.1×	2e-06
ribosomal large subunit biogenesis	6	21.8×	2e-05
cytoplasmic translation	9	13.7×	2e-06
RNA splicing	17	12.3×	1e-11
regulation of alternative mRNA splicing, via spliceosome	6	12.0×	6e-04
regulation of translation	6	10.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	49
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1262 predictions. Top by Δscore:

Variant	Effect	Δscore
3:197756422:A:AG	acceptor_gain	1.0000
3:197756423:T:G	acceptor_gain	1.0000
3:197756423:TA:T	acceptor_loss	1.0000
3:197756424:A:AG	acceptor_gain	1.0000
3:197756424:A:AT	acceptor_loss	1.0000
3:197756424:AGAT:A	acceptor_gain	1.0000
3:197756425:G:GT	acceptor_gain	1.0000
3:197756425:GA:G	acceptor_gain	1.0000
3:197756425:GAT:G	acceptor_gain	1.0000
3:197756425:GATG:G	acceptor_gain	1.0000
3:197756425:GATGA:G	acceptor_gain	1.0000
3:197756553:TTCTG:T	donor_gain	1.0000
3:197756554:TCTG:T	donor_gain	1.0000
3:197756556:TG:T	donor_gain	1.0000
3:197756557:GG:G	donor_gain	1.0000
3:197756558:G:GG	donor_gain	1.0000
3:197768426:T:TA	acceptor_gain	1.0000
3:197768435:ATAG:A	acceptor_gain	1.0000
3:197768436:T:G	acceptor_gain	1.0000
3:197768436:TA:T	acceptor_loss	1.0000
3:197768437:A:AG	acceptor_gain	1.0000
3:197768437:AG:A	acceptor_gain	1.0000
3:197768437:AGGTT:A	acceptor_loss	1.0000
3:197768438:G:GA	acceptor_gain	1.0000
3:197768438:GG:G	acceptor_gain	1.0000
3:197768438:GGT:G	acceptor_gain	1.0000
3:197768438:GGTT:G	acceptor_gain	1.0000
3:197768438:GGTTT:G	acceptor_gain	1.0000
3:197768550:G:GT	donor_gain	1.0000
3:197768583:ACAAG:A	donor_gain	1.0000

AlphaMissense

2072 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:197778438:T:C	F278L	1.000
3:197778440:T:A	F278L	1.000
3:197778440:T:G	F278L	1.000
3:197750072:T:C	L34S	0.999
3:197756432:T:A	I37N	0.999
3:197756432:T:G	I37S	0.999
3:197756435:T:A	I38N	0.999
3:197756435:T:C	I38T	0.999
3:197756435:T:G	I38S	0.999
3:197776959:T:C	L230S	0.999
3:197778433:T:C	L276P	0.999
3:197778439:T:C	F278S	0.999
3:197781835:T:C	F295L	0.999
3:197781836:T:C	F295S	0.999
3:197781836:T:G	F295C	0.999
3:197781837:T:A	F295L	0.999
3:197781837:T:G	F295L	0.999
3:197781896:T:A	V315D	0.999
3:197750066:T:C	M32T	0.998
3:197750069:C:T	S33F	0.998
3:197750074:G:C	D35H	0.998
3:197756426:A:T	D35V	0.998
3:197756432:T:C	I37T	0.998
3:197776959:T:G	L230W	0.998
3:197776965:T:A	V232E	0.998
3:197776967:T:C	S233P	0.998
3:197778423:G:C	G273R	0.998
3:197778433:T:A	L276Q	0.998
3:197778439:T:G	F278C	0.998
3:197778454:T:A	V283D	0.998

dbSNP variants (sampled 300 via entrez): RS1000033572 (3:197751239 C>G,T), RS1000046794 (3:197749714 C>G,T), RS1000057104 (3:197762813 C>G,T), RS1000100932 (3:197781189 C>T), RS1000143102 (3:197757178 A>G), RS1000175382 (3:197764524 A>G), RS1000200292 (3:197763570 A>G), RS1000238587 (3:197781472 C>T), RS1000268402 (3:197764753 A>G), RS1000406642 (3:197768893 A>C), RS1000613856 (3:197774643 A>C), RS1000670813 (3:197781709 A>G), RS1000718357 (3:197757232 T>C), RS1000761828 (3:197787818 AC>A), RS1000827491 (3:197747871 A>G)

Disease associations

OMIM: gene MIM:616933 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Hydrogen Peroxide	affects expression	2
Valproic Acid	affects expression, increases expression	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
afimoxifene	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
jinfukang	decreases expression	1
Temozolomide	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Dexamethasone	affects cotreatment, decreases expression	1
Estradiol	increases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Ribonucleotides	affects binding	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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