MTHFS

Summary

MTHFS (methenyltetrahydrofolate synthetase, HGNC:7437) is a protein-coding gene on chromosome 15q25.1, encoding 5-formyltetrahydrofolate cyclo-ligase (P49914). Contributes to tetrahydrofolate metabolism.

The protein encoded by this gene is an enzyme that catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate, a precursor of reduced folates involved in 1-carbon metabolism. An increased activity of the encoded protein can result in an increased folate turnover rate and folate depletion. Three transcript variants encoding two different isoforms have been found for this gene.

Source: NCBI Gene 10588 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 55 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 34
• MANE Select transcript: NM_006441

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7437
Approved symbol	MTHFS
Name	methenyltetrahydrofolate synthetase
Location	15q25.1
Locus type	gene with protein product
Status	Approved
Aliases	HsT19268
Ensembl gene	ENSG00000136371
Ensembl biotype	protein_coding
OMIM	604197
Entrez	10588

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 nonsense_mediated_decay

ENST00000258874, ENST00000559722, ENST00000560261, ENST00000560919, ENST00000877637, ENST00000877638

RefSeq mRNA: 2 — MANE Select: NM_006441 NM_001199758, NM_006441

CCDS: CCDS10311

Canonical transcript exons

ENST00000258874 — 3 exons

Exon	Start	End
ENSE00000000071	79843547	79845442
ENSE00001228751	79896872	79897014
ENSE00003467484	79889093	79889354

Expression profiles

Bgee: expression breadth ubiquitous, 137 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.6728 / max 755.8205, expressed in 1820 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151183	23.6669	1819
151184	0.7183	415
151182	0.1727	59
207610	0.1149	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	98.38	gold quality
liver	UBERON:0002107	96.32	gold quality
adult mammalian kidney	UBERON:0000082	94.86	gold quality
monocyte	CL:0000576	93.08	gold quality
leukocyte	CL:0000738	93.06	gold quality
blood	UBERON:0000178	92.68	gold quality
kidney	UBERON:0002113	91.39	gold quality
duodenum	UBERON:0002114	91.12	gold quality
body of pancreas	UBERON:0001150	90.63	gold quality
cortex of kidney	UBERON:0001225	89.85	gold quality
pituitary gland	UBERON:0000007	89.15	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.05	gold quality
adenohypophysis	UBERON:0002196	88.95	gold quality
pancreas	UBERON:0001264	88.78	gold quality
omental fat pad	UBERON:0010414	88.64	gold quality
metanephros cortex	UBERON:0010533	88.45	gold quality
adipose tissue	UBERON:0001013	87.81	gold quality
granulocyte	CL:0000094	87.80	gold quality
substantia nigra	UBERON:0002038	87.80	gold quality
left adrenal gland cortex	UBERON:0035825	87.52	gold quality
upper lobe of left lung	UBERON:0008952	87.29	gold quality
left adrenal gland	UBERON:0001234	87.26	gold quality
mucosa of transverse colon	UBERON:0004991	87.25	gold quality
hypothalamus	UBERON:0001898	87.19	gold quality
prostate gland	UBERON:0002367	87.15	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.02	gold quality
body of stomach	UBERON:0001161	86.84	gold quality
right adrenal gland	UBERON:0001233	86.70	gold quality
islet of Langerhans	UBERON:0000006	86.51	gold quality
left lobe of thyroid gland	UBERON:0001120	86.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

81 targeting MTHFS, 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-7110-3P	100.00	73.18	2486
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-5680	99.91	69.83	3421

Literature-anchored findings (GeneRIF, showing 2)

• Methenyltetrahydrofolate synthetase regulates folate turnover and accumulation (PMID:12764149)
• The intronic Single nucleotide polymorphism in MTHFS had no significant effect on the risk of diabetic nephropathy in Taiwanese patients with T2D. (PMID:21895484)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	mthfs	ENSDARG00000104487
mus_musculus	Mthfs	ENSMUSG00000066442
mus_musculus	Mthfsl	ENSMUSG00000079427
rattus_norvegicus	Mthfs	ENSRNOG00000013229
drosophila_melanogaster	Mthfs	FBGN0085453
caenorhabditis_elegans	Y106G6E.4	WBGENE00013708

Paralogs (1): ATP5IF1 (ENSG00000130770)

Protein

Protein identifiers

5-formyltetrahydrofolate cyclo-ligase — P49914 (reviewed: P49914)

Alternative names: 5,10-methenyl-tetrahydrofolate synthetase

All UniProt accessions (4): A0A0U1RQM3, P49914, H3BMB9, H3BN04

UniProt curated annotations — full annotation on UniProt →

Function. Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm.

Disease relevance. Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (NEDMEHM) [MIM:618367] An autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy, and characterized by microcephaly, short stature, severe global developmental delay, progressive spasticity, and epilepsy. Brain imaging shows delayed myelination, hypomyelination, enlarged ventricles, and cerebellar atrophy. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.

Isoforms (2)

UniProt ID	Names	Canonical?
P49914-1	1	yes
P49914-2	2

RefSeq proteins (2): NP_001186687, NP_006432* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002698	FTHF_cligase	Family
IPR024185	FTHF_cligase-like_sf	Homologous_superfamily
IPR037171	NagB/RpiA_transferase-like	Homologous_superfamily

Pfam: PF01812

Enzyme classification (BRENDA):

• EC 6.3.3.2 — 5-formyltetrahydrofolate cyclo-ligase (BRENDA: 18 organisms, 55 substrates, 43 inhibitors, 81 Km, 28 kcat entries)

Substrate kinetics (BRENDA)

16 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0003–5	29
5-FORMYLTETRAHYDROFOLATE	0.0005–130	26
(6R,S)-5-FORMYLTETRAHYDROPTEROYL-GLU	0.0044–0.0047	3
CTP	0.0016–0.6	3
(6S)-5-FORMYLTETRAHYDROFOLATE	0.002–0.005	2
(6S)-5-FORMYLTETRAHYDROPTEROYL-PENTAGLUTAMATE	0.0006	2
UTP	0.0064–0.5	2
(6R,S)-5-FORMYLTETRAHYDROFOLATE	0.004	1
(6S)-5-FORMYLTETRAHYDROPTEROYL PENTAGLUTAMATE	0.0008	1
5-FORMYL-TETRAHYDROPTEROYL-PENTAGLUTAMATE	0.0002	1
ARAATP	0.0056	1
ATPGAMMAS	0.0002	1
DATP	0.0013	1
DTTP	0.0066	1
GTP	0.021	1

Catalyzed reactions (Rhea), 1 shown:

• (6S)-5-formyl-5,6,7,8-tetrahydrofolate + ATP = (6R)-5,10-methenyltetrahydrofolate + ADP + phosphate (RHEA:10488)

UniProt features (43 total): strand 9, binding site 8, helix 8, mutagenesis site 6, sequence variant 4, sequence conflict 2, turn 2, initiator methionine 1, chain 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3HY3	X-RAY DIFFRACTION	1.8
3HXT	X-RAY DIFFRACTION	1.9
3HY6	X-RAY DIFFRACTION	2.1
3HY4	X-RAY DIFFRACTION	2.79

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49914-F1	95.35	0.92

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 (8): 10–14; 14; 56; 61; 145–153; 148–152; 154; 189

Post-translational modifications (1): 2

Mutagenesis-validated functional residues (6):

Position	Phenotype
10	reduces activity by 93%.
14	reduces activity by 87%.
61	reduces activity by 94%.
145	reduces activity by 98%.
153	reduces activity by 97%.
154	reduces activity by 99%.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-196757	Metabolism of folate and pterines
R-HSA-1430728	Metabolism
R-HSA-196849	Metabolism of water-soluble vitamins and cofactors
R-HSA-196854	Metabolism of vitamins and cofactors

MSigDB gene sets: 242 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, GOBP_GLUTAMATE_METABOLIC_PROCESS, GOBP_MODIFIED_AMINO_ACID_CATABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_METABOLIC_PROCESS, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, KEGG_ONE_CARBON_POOL_BY_FOLATE, GOBP_PTERIDINE_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_FOLIC_ACID_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_PTERIDINE_CONTAINING_COMPOUND_METABOLIC_PROCESS, HOSHIDA_LIVER_CANCER_SUBCLASS_S3

GO Biological Process (7): glutamate metabolic process (GO:0006536), folic acid-containing compound biosynthetic process (GO:0009396), formate metabolic process (GO:0015942), tetrahydrofolate interconversion (GO:0035999), tetrahydrofolate metabolic process (GO:0046653), folic acid metabolic process (GO:0046655), folic acid catabolic process (GO:0046657)

GO Molecular Function (7): ATP binding (GO:0005524), folic acid binding (GO:0005542), 5-formyltetrahydrofolate cyclo-ligase activity (GO:0030272), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), protein binding (GO:0005515), ligase activity (GO:0016874)

GO Cellular Component (4): cytoplasm (GO:0005737), mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Metabolism of water-soluble vitamins and cofactors	1
Metabolism of vitamins and cofactors	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
folic acid-containing compound metabolic process	3
dicarboxylic acid metabolic process	2
heterocyclic compound binding	2
cellular anatomical structure	2
cytoplasm	2
amino acid metabolic process	1
modified amino acid biosynthetic process	1
pteridine-containing compound biosynthetic process	1
monocarboxylic acid metabolic process	1
one-carbon metabolic process	1
tetrahydrofolate metabolic process	1
folic acid-containing compound catabolic process	1
water-soluble vitamin catabolic process	1
dicarboxylic acid catabolic process	1
folic acid metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
vitamin binding	1
carboxylic acid binding	1
modified amino acid binding	1
cyclo-ligase activity	1
cation binding	1
nucleoside phosphate binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

946 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MTHFS	SHMT1	P34896	783
MTHFS	MTHFD1	P11586	662
MTHFS	FPGS	Q05932	625
MTHFS	MTHFR	P42898	622
MTHFS	MTHFSD	Q2M296	619
MTHFS	SHMT2	P34897	602
MTHFS	TYMS	P04818	587
MTHFS	ATIC	P31939	586
MTHFS	DHFR	P00374	579
MTHFS	GART	P22102	572
MTHFS	GNMT	Q14749	571
MTHFS	MTHFD2	P13995	531
MTHFS	FTCD	O95954	518
MTHFS	MTR	Q99707	506
MTHFS	DHFR2	Q86XF0	490
MTHFS	MTHFD2L	Q9H903	490

IntAct

9 interactions, top by confidence:

A	B	Type	Score
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
MTHFS	PLCL2	psi-mi:“MI:0915”(physical association)	0.590
MTHFS	SFPQ	psi-mi:“MI:0915”(physical association)	0.400
RGS4	MTHFS	psi-mi:“MI:0915”(physical association)	0.400
MTHFS	ACTA2	psi-mi:“MI:0915”(physical association)	0.400
MTHFS	TSC22D4	psi-mi:“MI:0915”(physical association)	0.370
NDUFS3	ACOT7	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): TSC22D4 (Two-hybrid), MTHFS (Affinity Capture-MS), PLCL2 (Affinity Capture-MS), MTHFS (Affinity Capture-MS), MTHFS (Affinity Capture-MS), SFPQ (Proximity Label-MS), PLCL2 (Affinity Capture-MS), ACTA2 (Affinity Capture-MS), MTHFS (Affinity Capture-MS), MTHFS (Proximity Label-MS), MTHFS (Affinity Capture-MS), RUVBL2 (Cross-Linking-MS (XL-MS)), MTHFS (Cross-Linking-MS (XL-MS)), MTHFS (Cross-Linking-MS (XL-MS)), MTHFS (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: B8M7D2, C4JWQ7, C5PBM5, K3VH30, O42895, O65583, P00927, P33312, P40099, P49914, P49915, P54886, P54889, P80405, Q08BY0, Q09509, Q0P464, Q0P4K0, Q22017, Q3THK7, Q42777, Q4V7C6, Q4V7F3, Q5BKM6, Q5R4M8, Q5R5P3, Q5RA96, Q5XI79, Q626I0, Q68EH8, Q6CJ61, Q6DJC2, Q6GQ37, Q6ING7, Q6PEB4, Q75AW4, Q7L592, Q8BH55, Q8L539, Q8LEA0

Diamond homologs: A0R3H2, P0AC28, P0AC29, P49914, P80405, Q8K9E3, Q8L539, Q9D110, Q9P7W2, Q9XWE6, P40099, P44905

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	27
Likely benign	12
Benign	5

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1344538	NM_006441.4(MTHFS):c.316A>T (p.Lys106Ter)	Pathogenic
2420564	NM_006441.4(MTHFS):c.220C>T (p.Arg74Ter)	Pathogenic
2875670	NM_006441.4(MTHFS):c.10_25dup (p.Ala9fs)	Pathogenic
624594	NM_006441.4(MTHFS):c.107T>C (p.Leu36Pro)	Pathogenic
3775227	NM_006441.4(MTHFS):c.9_18dup (p.Ser7fs)	Likely pathogenic
522830	NM_006441.4(MTHFS):c.484C>T (p.Gln162Ter)	Likely pathogenic

SpliceAI

1020 predictions. Top by Δscore:

Variant	Effect	Δscore
15:79845438:TCCCC:T	acceptor_gain	1.0000
15:79845439:CCCCC:C	acceptor_gain	1.0000
15:79845441:CCCTG:C	acceptor_loss	1.0000
15:79845443:C:A	acceptor_loss	1.0000
15:79845443:C:CC	acceptor_gain	1.0000
15:79845444:T:A	acceptor_loss	1.0000
15:79845439:CCCC:C	acceptor_gain	0.9900
15:79845440:CCC:C	acceptor_gain	0.9900
15:79845440:CCCC:C	acceptor_gain	0.9900
15:79845441:CC:C	acceptor_gain	0.9900
15:79845441:CCC:C	acceptor_gain	0.9900
15:79845442:CC:C	acceptor_gain	0.9900
15:79845443:CTGC:C	acceptor_loss	0.9900
15:79845446:C:CT	acceptor_gain	0.9900
15:79845447:G:T	acceptor_gain	0.9900
15:79889351:TCAC:T	acceptor_gain	0.9900
15:79889352:CACC:C	acceptor_gain	0.9900
15:79889353:ACC:A	acceptor_loss	0.9900
15:79889354:CCTAA:C	acceptor_loss	0.9900
15:79889356:T:C	acceptor_loss	0.9900
15:79896918:ATCG:A	donor_gain	0.9900
15:79854365:G:C	donor_gain	0.9800
15:79855273:A:AC	donor_gain	0.9800
15:79855274:C:CC	donor_gain	0.9800
15:79889085:ATACT:A	donor_loss	0.9800
15:79889088:CTCA:C	donor_loss	0.9800
15:79889089:TCA:T	donor_loss	0.9800
15:79889090:CA:C	donor_loss	0.9800
15:79889091:ACCTG:A	donor_loss	0.9800
15:79889092:C:A	donor_loss	0.9800

AlphaMissense

1334 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:79845405:A:C	F139L	0.996
15:79845405:A:T	F139L	0.996
15:79845407:A:G	F139L	0.996
15:79845409:C:T	G138E	0.994
15:79845430:A:G	L131P	0.994
15:79845388:C:G	R145P	0.993
15:79889235:G:C	F79L	0.992
15:79889235:G:T	F79L	0.992
15:79889237:A:G	F79L	0.992
15:79889307:A:C	F55L	0.990
15:79889307:A:T	F55L	0.990
15:79889309:A:G	F55L	0.990
15:79896892:A:G	S33P	0.990
15:79889336:A:C	Y46D	0.989
15:79845415:C:T	G136D	0.988
15:79845410:C:A	G138W	0.987
15:79896959:C:A	K10N	0.987
15:79896959:C:G	K10N	0.987
15:79845307:G:T	A172E	0.986
15:79845352:A:G	L157P	0.986
15:79845361:T:A	D154V	0.986
15:79845382:C:T	G147E	0.986
15:79845385:A:G	L146P	0.986
15:79845406:A:G	F139S	0.986
15:79889315:A:G	S53P	0.986
15:79845389:G:C	R145G	0.985
15:79889238:G:C	C78W	0.985
15:79896939:A:G	L17P	0.985
15:79845301:G:T	A174D	0.984
15:79845361:T:G	D154A	0.984

dbSNP variants (sampled 300 via entrez): RS1000009187 (15:79848487 T>G), RS1000012239 (15:79874104 C>T), RS1000076340 (15:79890269 G>A), RS1000084032 (15:79848817 T>G), RS1000165756 (15:79873797 C>G), RS1000226566 (15:79857170 AT>A,ATT), RS1000346053 (15:79867620 A>T), RS1000347575 (15:79850965 C>G), RS1000534828 (15:79889918 G>T), RS1000547345 (15:79885580 C>T), RS1000579145 (15:79843795 C>T), RS1000597024 (15:79857371 C>T), RS1000675438 (15:79867324 A>C,G), RS1000712886 (15:79878852 G>A), RS1000918270 (15:79874376 A>G)

Disease associations

OMIM: gene MIM:604197 | disease phenotypes: MIM:618367

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination	Strong	Autosomal recessive

Mondo (1): neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination (MONDO:0032705)

Orphanet (1): MTHFS-related developmental delay-microcephaly-short stature-epilepsy syndrome (Orphanet:597874)

HPO phenotypes

34 total (30 of 34 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000293	Full cheeks
HP:0000574	Thick eyebrow
HP:0000737	Irritability
HP:0000750	Delayed speech and language development
HP:0001182	Tapered finger
HP:0001196	Short umbilical cord
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001945	Fever
HP:0002015	Dysphagia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002188	Delayed CNS myelination
HP:0002267	Exaggerated startle response
HP:0002307	Drooling
HP:0003097	Short femur
HP:0003429	CNS hypomyelination
HP:0003593	Infantile onset
HP:0004322	Short stature
HP:0005792	Short humerus
HP:0006808	Cerebral hypomyelination
HP:0006956	Lateral ventricle dilatation
HP:0010819	Atonic seizure
HP:0010821	Focal emotional seizure with laughing
HP:0010845	EEG with generalized slow activity
HP:0011225	Epiblepharon

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002127_5	Periodontitis (Mean PAL)	4.000000e-06
GCST002847_1	Disease-free survival in breast cancer	3.000000e-07
GCST003486_6	Response to fenofibrate (LDL cholesterol levels)	5.000000e-06
GCST004070_8	Cerebrospinal P-tau181p levels	8.000000e-06
GCST006585_2900	Blood protein levels	6.000000e-35
GCST007676_7	3-month functional outcome in ischaemic stroke (modified Rankin score)	5.000000e-06
GCST009193_14	Pars opercularis volume	8.000000e-06
GCST009532_7	Circulating leptin levels in high cardiovascular risk	6.000000e-06
GCST012174_3	Diabetic retinopathy in type 2 diabetes	2.000000e-06

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0000409	disease free survival
EFO:0007804	LDL cholesterol change measurement
EFO:0004763	p-tau measurement
EFO:0009603	stroke outcome severity measurement
EFO:0005000	leptin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	3
Aflatoxin B1	decreases expression, decreases methylation	3
Cyclosporine	decreases expression	2
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
belinostat	decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Irinotecan	decreases expression	1
Temozolomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Tretinoin	increases expression	1
Tunicamycin	increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

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