ENOSF1

Summary

ENOSF1 (enolase superfamily member 1, HGNC:30365) is a protein-coding gene on chromosome 18p11.32, encoding Mitochondrial enolase superfamily member 1 (Q7L5Y1). Plays a role in the catabolism of L-fucose, a sugar that is part of the carbohydrates that are attached to cellular glycoproteins.

This gene can encode a mitochondrial enzyme that is thought to convert L-fuconate to 2-keto-3-deoxy-L-fuconate. This locus was originally identified as the source of antisense RNAs of the adjacent thymidylate synthase gene. Splice variants at this locus may contain an alternate 3’ exon that is complementary to the 3’UTR and terminal intron of the thymidylate synthase (TS) RNA and may downregulate TS expression.

Source: NCBI Gene 55556 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 149 total — 4 pathogenic
• MANE Select transcript: NM_017512

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30365
Approved symbol	ENOSF1
Name	enolase superfamily member 1
Location	18p11.32
Locus type	gene with protein product
Status	Approved
Aliases	HSRTSBETA, rTS, TYMSAS, FUCD
Ensembl gene	ENSG00000132199
Ensembl biotype	protein_coding
OMIM	607427
Entrez	55556

Gene structure

Transcript identifiers

Ensembl transcripts: 63 — 46 protein_coding, 10 retained_intron, 4 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

ENST00000340116, ENST00000383578, ENST00000577334, ENST00000578647, ENST00000578651, ENST00000579053, ENST00000580605, ENST00000580982, ENST00000581332, ENST00000581475, ENST00000581906, ENST00000581928, ENST00000582745, ENST00000583771, ENST00000583973, ENST00000584259, ENST00000584453, ENST00000584646, ENST00000584706, ENST00000585004, ENST00000585128, ENST00000647584, ENST00000891877, ENST00000891878, ENST00000891879, ENST00000891880, ENST00000891881, ENST00000891882, ENST00000891883, ENST00000891884, ENST00000891885, ENST00000891886, ENST00000891887, ENST00000891888, ENST00000891889, ENST00000891890, ENST00000891891, ENST00000891892, ENST00000891893, ENST00000891894, ENST00000891895, ENST00000891896, ENST00000891897, ENST00000891898, ENST00000891899, ENST00000891900, ENST00000891901, ENST00000891902, ENST00000891903, ENST00000891904, ENST00000891905, ENST00000917860, ENST00000917861, ENST00000917862, ENST00000917863, ENST00000969782, ENST00000969783, ENST00000969784, ENST00000969785, ENST00000969786, ENST00000969787, ENST00000969788, ENST00000969789

RefSeq mRNA: 7 — MANE Select: NM_017512 NM_001318760, NM_001354065, NM_001354066, NM_001354067, NM_001354068, NM_017512, NM_202758

CCDS: CCDS11822, CCDS11823, CCDS45821

Canonical transcript exons

ENST00000647584 — 16 exons

Exon	Start	End
ENSE00002706097	712504	712630
ENSE00003458840	677743	677872
ENSE00003464465	693882	693908
ENSE00003492549	685921	686008
ENSE00003538447	706470	706578
ENSE00003577611	677345	677444
ENSE00003597814	683246	683380
ENSE00003612810	688574	688608
ENSE00003635062	691204	691276
ENSE00003645224	697240	697355
ENSE00003647992	691068	691106
ENSE00003656758	678696	678737
ENSE00003658009	694248	694334
ENSE00003669138	675321	675402
ENSE00003676556	690549	690631
ENSE00003837508	670318	674406

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 99.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5758 / max 244.7140, expressed in 1774 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170948	11.3136	1763
170947	2.2592	1153
170945	0.0030	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	99.08	gold quality
mucosa of stomach	UBERON:0001199	98.34	gold quality
right lobe of thyroid gland	UBERON:0001119	98.32	gold quality
left lobe of thyroid gland	UBERON:0001120	98.03	gold quality
adenohypophysis	UBERON:0002196	97.87	gold quality
thyroid gland	UBERON:0002046	97.83	gold quality
nephron tubule	UBERON:0001231	97.75	gold quality
metanephros cortex	UBERON:0010533	97.75	gold quality
pituitary gland	UBERON:0000007	97.66	gold quality
left adrenal gland cortex	UBERON:0035825	97.49	gold quality
right lobe of liver	UBERON:0001114	97.46	gold quality
left adrenal gland	UBERON:0001234	97.40	gold quality
right adrenal gland cortex	UBERON:0035827	97.39	gold quality
right adrenal gland	UBERON:0001233	97.35	gold quality
adrenal cortex	UBERON:0001235	97.30	gold quality
endocervix	UBERON:0000458	97.28	gold quality
body of pancreas	UBERON:0001150	97.14	gold quality
minor salivary gland	UBERON:0001830	97.13	gold quality
right ovary	UBERON:0002118	97.00	gold quality
left ovary	UBERON:0002119	97.00	gold quality
adrenal gland	UBERON:0002369	96.80	gold quality
cortex of kidney	UBERON:0001225	96.74	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.64	gold quality
lower esophagus mucosa	UBERON:0035834	96.49	gold quality
saliva-secreting gland	UBERON:0001044	96.47	gold quality
ectocervix	UBERON:0012249	96.39	gold quality
lower esophagus	UBERON:0013473	96.37	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.36	gold quality
mouth mucosa	UBERON:0003729	96.28	gold quality
body of stomach	UBERON:0001161	96.27	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	17.73
E-MTAB-6379	no	119.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

101 targeting ENOSF1, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-26A-5P	99.78	73.52	2303
HSA-MIR-26B-5P	99.78	73.51	2305

Literature-anchored findings (GeneRIF, showing 6)

• The toxicity polymorphism in the TYMS region may actually act through ENOSF1 (PMID:24647007)
• A reverse thymidylate synthase gamma is an l-fuconate dehydratase and its high-resolution crystal structure was determined. (PMID:24697329)
• The suitability of the present method for gastric serum proteomic analysis was demonstrated and led to the identification of two peptide regions the expression of the SERPINA1 and ENOSF1 (PMID:25677901)
• No significant association has been found between rs495139 in the TYMS-ENOSF1 region and risk of ovarian carcinoma of mucinous histology. (Meta-analysis) (PMID:30134598)
• Evaluating the role of ENOSF1 and TYMS variants as predictors in fluoropyrimidine-related toxicities: An IPD meta-analysis. (PMID:31838077)
• Evaluation of TS and ENOSF1 Variants as a Biomarker in Response to Neoadjuvant Chemotherapy based on 5FU in Gastric Cancer Patients. (PMID:36172660)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	enosf1	ENSDARG00000038359

Protein

Protein identifiers

Mitochondrial enolase superfamily member 1 — Q7L5Y1 (reviewed: Q7L5Y1)

Alternative names: Antisense RNA to thymidylate synthase, L-fuconate dehydratase

All UniProt accessions (7): Q7L5Y1, A0A3F2YNX7, J3QL81, J3QL99, J3QSB6, R4GNF8, X6RM24

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in the catabolism of L-fucose, a sugar that is part of the carbohydrates that are attached to cellular glycoproteins. Catalyzes the dehydration of L-fuconate to 2-keto-3-deoxy-L-fuconate by the abstraction of the 2-proton to generate an enediolate intermediate that is stabilized by the magnesium ion.

Subcellular location. Mitochondrion.

Post-translational modifications. Could be sumoylated.

Disease relevance. Dyskeratosis congenita, digenic (DKCD) [MIM:620040] A form of dyskeratosis congenita, a rare multisystem disorder caused by defective telomere maintenance. It is characterized by progressive bone marrow failure, and the clinical triad of reticulated skin hyperpigmentation, nail dystrophy, and mucosal leukoplakia. Common but variable features include premature graying, aplastic anemia, low platelets, osteoporosis, pulmonary fibrosis, and liver fibrosis among others. Early mortality is often associated with bone marrow failure, infections, fatal pulmonary complications, or malignancy. DKCD transmission pattern is consistent with digenic inheritance. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. A common ENOSF1 haplotype (defined by rs699517, rs2790 and rs1512643) in the presence of TYMS germline variants result in severe thymidylate synthase deficiency and disease. The pathogenic mechanism involves increased expression of ENOSF1 relative to TYMS, and post-transcriptional inhibition of TYMS translation through ENOSF1-TYMS RNA-RNA interactions.

Cofactor. Binds 1 Mg(2+) ion per subunit.

Similarity. Belongs to the mandelate racemase/muconate lactonizing enzyme family. ENOSF1 subfamily.

Isoforms (7)

UniProt ID	Names	Canonical?
Q7L5Y1-1	1, rTSgamma	yes
Q7L5Y1-2	2, rTSalpha
Q7L5Y1-3	3
Q7L5Y1-4	4
Q7L5Y1-5	5
Q7L5Y1-6	6
Q7L5Y1-7	7

RefSeq proteins (7): NP_001305689, NP_001340994, NP_001340995, NP_001340996, NP_001340997, NP_059982, NP_974487 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR013341	Mandelate_racemase_N	Domain
IPR013342	Mandelate_racemase_C	Domain
IPR018110	Mandel_Rmase/mucon_lact_enz_CS	Conserved_site
IPR029017	Enolase-like_N	Homologous_superfamily
IPR029065
IPR034610	L-fuconate_dehydratase	Family
IPR036849	Enolase-like_C_sf	Homologous_superfamily
IPR046945	RHMD-like	Family

Pfam: PF02746, PF13378

Catalyzed reactions (Rhea), 1 shown:

• L-fuconate = 2-dehydro-3-deoxy-L-fuconate + H2O (RHEA:22772)

UniProt features (71 total): helix 23, strand 14, binding site 11, splice variant 9, turn 6, sequence variant 3, active site 2, chain 1, modified residue 1, mutagenesis site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4A35	X-RAY DIFFRACTION	1.74

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7L5Y1-F1	97.47	0.98

Functional residue map

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

Catalytic / active sites (2): 222 (proton donor/acceptor); 355

Ligand- & substrate-binding residues (11): 305; 305; 355–357; 386; 24–26; 34; 220; 250; 252; 276; 276

Post-translational modifications (1): 148

Mutagenesis-validated functional residues (1):

Position	Phenotype
1–27	impairs protein solubility. abolishes catalytic activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 138 (showing top): ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CARBOHYDRATE_METABOLIC_PROCESS, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, TURASHVILI_BREAST_DUCTAL_CARCINOMA_VS_DUCTAL_NORMAL_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_CARBOHYDRATE_CATABOLIC_PROCESS, TIEN_INTESTINE_PROBIOTICS_24HR_UP, FLECHNER_BIOPSY_KIDNEY_TRANSPLANT_REJECTED_VS_OK_DN, GOBP_AMINO_ACID_CATABOLIC_PROCESS, GOMF_HYDRO_LYASE_ACTIVITY, WALLACE_PROSTATE_CANCER_RACE_DN

GO Biological Process (2): amino acid catabolic process (GO:0009063), carbohydrate catabolic process (GO:0016052)

GO Molecular Function (7): magnesium ion binding (GO:0000287), hydro-lyase activity (GO:0016836), isomerase activity (GO:0016853), L-fuconate dehydratase activity (GO:0050023), catalytic activity (GO:0003824), lyase activity (GO:0016829), metal ion binding (GO:0046872)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
catabolic process	2
catalytic activity	2
amino acid metabolic process	1
carbohydrate metabolic process	1
metal ion binding	1
carbon-oxygen lyase activity	1
hydro-lyase activity	1
molecular_function	1
cation binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

850 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ENOSF1	TYMS	P04818	957
ENOSF1	CLUL1	Q15846	621
ENOSF1	DPH5	Q9H2P9	579
ENOSF1	TMEM14C	Q9P0S9	570
ENOSF1	AKAIN1	P0CW23	516
ENOSF1	DPYD	Q12882	515
ENOSF1	COLEC12	Q5KU26	507
ENOSF1	ARMC9	Q7Z3E5	497
ENOSF1	THOC1	Q96FV9	479
ENOSF1	CETN1	Q12798	476
ENOSF1	FUOM	A2VDF0	472
ENOSF1	MAN2B2	Q9Y2E5	456
ENOSF1	LRRC23	Q53EV4	433
ENOSF1	HPS3	Q969F9	429
ENOSF1	KIAA1958	Q8N8K9	423

IntAct

9 interactions, top by confidence:

A	B	Type	Score
PWP2	FBL	psi-mi:“MI:0914”(association)	0.610
VENTX	TLE1	psi-mi:“MI:0914”(association)	0.550
LRRC10	CCT2	psi-mi:“MI:0914”(association)	0.530
ANO4	ANO6	psi-mi:“MI:0914”(association)	0.530
SNX20	DIRAS1	psi-mi:“MI:0914”(association)	0.350
CIP2A	ALDH3A2	psi-mi:“MI:0914”(association)	0.350
thrC	ENOSF1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-RNA), ENOSF1 (Affinity Capture-RNA), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-MS), ENOSF1 (Co-fractionation), ENOSF1 (Affinity Capture-MS), ENOSF1 (Affinity Capture-RNA)

ESM2 similar proteins: A1L4Y1, A7M6E7, A7M6E8, B8BJ39, B8BM17, B9I2J6, G7IFI7, O04397, O23653, O65502, O80574, O82782, O89000, P21218, P24846, P24847, P35433, Q01289, Q06203, Q0JL73, Q12882, Q28007, Q28943, Q2QXR8, Q2RAK2, Q41249, Q42536, Q52QW2, Q52QW3, Q56Y42, Q5R6R5, Q5R895, Q5RAT4, Q67W29, Q6DHV7, Q6STH5, Q6ZHE5, Q7L5Y1, Q8CHR6, Q8CIH9

Diamond homologs: A9B055, B5EFW2, B6EJ59, B9I2J6, C0QM06, F7ZLS5, O34508, Q11T61, Q30PM2, Q6INX4, Q7L5Y1, Q834W6, Q8P3K2, Q97MK4, Q97U96, Q9RYA6, Q9WXM1, A0A0P0ZBS7, A0NXQ8, A1B198, A6TFZ4, A8MA91, A9MWL9, B0RTW1, B1A612, B4SY97, B4TA81, B5BIK9, B5FN00, B5QUN9, C4LDK0, D7A0Y2, Q0FPQ4, Q2KIA9, Q3BUN6, Q4UTT5, Q57I11, Q5L1G9, Q5RAT4, Q8P9V1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	107
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1693537	NM_001071.4(TYMS):c.486_487del (p.Arg163fs)	Pathogenic
1693539	NM_001071.4(TYMS):c.556+1G>A	Pathogenic
1693540	NM_001071.4(TYMS):c.811C>T (p.Arg271Ter)	Pathogenic
560039	Single allele	Pathogenic

SpliceAI

3482 predictions. Top by Δscore:

Variant	Effect	Δscore
18:671369:C:A	acceptor_gain	1.0000
18:671370:G:A	acceptor_gain	1.0000
18:671378:A:T	acceptor_loss	1.0000
18:671379:GC:G	acceptor_gain	1.0000
18:671379:GCCA:G	acceptor_gain	1.0000
18:671448:TCAGG:T	donor_loss	1.0000
18:671449:CAGG:C	donor_loss	1.0000
18:671450:AGGTA:A	donor_loss	1.0000
18:671451:GGT:G	donor_loss	1.0000
18:671453:T:A	donor_loss	1.0000
18:674407:C:CC	acceptor_gain	1.0000
18:674408:T:G	acceptor_loss	1.0000
18:674411:C:CT	acceptor_gain	1.0000
18:674418:C:CT	acceptor_gain	1.0000
18:675315:GCTTA:G	donor_loss	1.0000
18:675316:CTTA:C	donor_loss	1.0000
18:675317:TTACC:T	donor_loss	1.0000
18:675318:TACCT:T	donor_loss	1.0000
18:675319:ACC:A	donor_loss	1.0000
18:675320:C:CA	donor_loss	1.0000
18:675399:CACC:C	acceptor_gain	1.0000
18:677741:A:AC	donor_gain	1.0000
18:677742:C:CC	donor_gain	1.0000
18:677744:TTCAA:T	donor_gain	1.0000
18:683240:TCCTA:T	donor_loss	1.0000
18:683241:CCTAC:C	donor_loss	1.0000
18:683242:CTACC:C	donor_loss	1.0000
18:683243:TAC:T	donor_loss	1.0000
18:683244:ACCTT:A	donor_loss	1.0000
18:706469:CCAA:C	donor_gain	1.0000

AlphaMissense

2913 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:677789:A:C	S334R	0.998
18:677789:A:T	S334R	0.998
18:677791:T:G	S334R	0.998
18:693902:A:G	W135R	0.997
18:693902:A:T	W135R	0.997
18:697242:A:G	W103R	0.997
18:697242:A:T	W103R	0.997
18:694277:A:G	W123R	0.996
18:694277:A:T	W123R	0.996
18:677804:A:C	S329R	0.995
18:677804:A:T	S329R	0.995
18:677806:T:G	S329R	0.995
18:677849:C:A	K314N	0.995
18:677849:C:G	K314N	0.995
18:706495:G:C	F56L	0.995
18:706495:G:T	F56L	0.995
18:706497:A:G	F56L	0.995
18:686002:T:A	K220N	0.993
18:686002:T:G	K220N	0.993
18:712540:G:C	F16L	0.992
18:712540:G:T	F16L	0.992
18:712542:A:G	F16L	0.992
18:706505:C:T	G53E	0.991
18:677781:T:A	E337V	0.990
18:677851:T:C	K314E	0.990
18:677799:C:G	R331T	0.989
18:683294:C:A	E276D	0.989
18:683294:C:G	E276D	0.989
18:694294:G:T	A117D	0.989
18:674337:A:G	W434R	0.988

dbSNP variants (sampled 300 via entrez): RS1000103586 (18:703146 A>G), RS1000136158 (18:703342 G>T), RS1000334068 (18:691962 G>A), RS1000372743 (18:708570 A>C,G), RS1000374003 (18:712602 G>A,C,T), RS1000391153 (18:677564 G>C), RS1000443694 (18:677299 T>A,C), RS1000615726 (18:682592 G>A), RS1000645239 (18:682421 C>T), RS1000738363 (18:712335 G>A,C,T), RS1000778221 (18:678526 A>C,G), RS1000910651 (18:671014 T>C), RS1000931877 (18:687079 A>C), RS1000938745 (18:672802 G>A,T), RS1000969791 (18:707300 C>T)

Disease associations

OMIM: gene MIM:607427 | disease phenotypes: MIM:127550, MIM:620040

GenCC curated gene-disease

Mondo (2): dyskeratosis congenita (MONDO:0015780), dyskeratosis congenita, digenic (MONDO:0031057)

Orphanet (1): Dyskeratosis congenita (Orphanet:1775)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004635_37	Testicular germ cell tumor	4.000000e-10
GCST012020_150	Serum metabolite levels	2.000000e-12

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D019871	Dyskeratosis Congenita	C15.378.190.223.500.750; C16.131.831.150; C16.320.322.108; C16.320.850.235; C17.800.804.150; C17.800.827.235

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

4 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11280056	Toxicity	3	methotrexate	Acute lymphoblastic leukemia;Gastrointestinal toxicity;Mucositis;Neutropenia
rs11280056	Efficacy	3	methotrexate	Acute lymphoblastic leukemia;Rheumatoid arthritis
rs2612091	Toxicity	3	capecitabine	Neoplasms
rs2741171	Toxicity	3	capecitabine	Colorectal Neoplasms

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2612091	ENOSF1	3	2.50	1	capecitabine
rs2741171	ENOSF1	3	4.00	1	capecitabine
rs699517	ENOSF1, TYMS	3	5.50	1	capecitabine
rs11280056	ENOSF1, TYMS	3	3.50	6	methotrexate;fluorouracil;fluorouracil;FOLFOX;pemetrexed
rs2790	ENOSF1, TYMS		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	6
trichostatin A	affects cotreatment, increases expression	3
cobaltous chloride	decreases expression	2
methacrylaldehyde	affects cotreatment, affects expression, increases expression, increases abundance	2
Acetaminophen	decreases expression	2
Acrolein	affects cotreatment, affects expression, increases expression, increases abundance	2
Benzo(a)pyrene	affects methylation	2
Fluorouracil	affects response to substance, decreases response to substance	2
Ozone	affects cotreatment, affects expression, increases expression, increases abundance	2
Tretinoin	decreases expression, increases expression	2
Cyclosporine	decreases expression	2
GSK-J4	decreases expression	1
bisphenol F	increases expression	1
chloroacetaldehyde	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
beta-lapachone	decreases expression	1
sodium arsenite	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	increases expression, affects cotreatment	1
manumycin	decreases expression, affects localization	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
MRK 003	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Cidofovir	decreases expression	1
Air Pollutants	affects cotreatment, affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00004787	PHASE2	COMPLETED	Phase II Pilot Study of Granulocyte Colony-Stimulating Factor for Inherited Bone Marrow Failure Syndromes
NCT01659606	PHASE2	ACTIVE_NOT_RECRUITING	Radiation- and Alkylator-free Bone Marrow Transplantation Regimen for Patients With Dyskeratosis Congenita
NCT03579875	PHASE2	RECRUITING	Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
NCT04232085	PHASE2	RECRUITING	Regenerative Medicine to Restore Hematopoiesis and Immune Function in Immunodeficiencies and Inherited Bone Marrow Failures
NCT04638517	PHASE2	TERMINATED	The TELO-SCOPE Study: Attenuating Telomere Attrition With Danazol. Is There Scope to Dramatically Improve Health Outcomes for Adults and Children With Pulmonary Fibrosis
NCT01917708	PHASE1	COMPLETED	Bone Marrow Transplant With Abatacept for Non-Malignant Diseases
NCT06477614	PHASE1	RECRUITING	Anti-cancer DC Cell Vaccination to Treat Solid Tumors
NCT06817590	PHASE1	RECRUITING	Nucleoside Therapy in Patients With Telomere Biology Disorders
NCT00455312	PHASE2/PHASE3	COMPLETED	Stem Cell Transplant (SCT) for Dyskeratosis Congenita or SAA
NCT01001598	PHASE1/PHASE2	TERMINATED	Safety and Efficacy Trial of Danazol in Patients With Fanconi Anemia or Dyskeratosis Congenita
NCT00027274	Not specified	RECRUITING	Cancer in Inherited Bone Marrow Failure Syndromes
NCT00499070	Not specified	COMPLETED	Assessing Immune Function in Young Patients With Cytopenia That Did Not Respond to Treatment
NCT01319851	Not specified	TERMINATED	Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
NCT02162420	Not specified	COMPLETED	Hematopoietic Stem Cell Transplant for Dyskeratosis Congenita or Severe Aplastic Anemia
NCT02720679	Not specified	RECRUITING	Investigation of the Genetics of Hematologic Diseases
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT04959188	Not specified	COMPLETED	Needs Assessment for Individuals and Families Affected by Dyskeratosis Congenita (DC) and Related Telomere Biology Disorders (TBD)
NCT06731036	Not specified	AVAILABLE	Expanded Access to CD34+ Selection Utilizing Miltenyi CliniMACS Prodigy® for Patients Receiving Peripheral Blood Stem Cell Transplantations and Stem Cell Boosts