PEMT

Summary

PEMT (phosphatidylethanolamine N-methyltransferase, HGNC:8830) is a protein-coding gene on chromosome 17p11.2, encoding Phosphatidylethanolamine N-methyltransferase (Q9UBM1). Catalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure.

Phosphatidylcholine (PC) is the most abundant mammalian phospholipid. This gene encodes an enzyme which converts phosphatidylethanolamine to phosphatidylcholine by sequential methylation in the liver. Another distinct synthetic pathway in nucleated cells converts intracellular choline to phosphatidylcholine by a three-step process. The protein isoforms encoded by this gene localize to the endoplasmic reticulum and mitochondria-associated membranes. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 10400 — RefSeq curated summary.

At a glance

• GWAS associations: 60
• Clinical variants (ClinVar): 40 total
• MANE Select transcript: NM_148172

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8830
Approved symbol	PEMT
Name	phosphatidylethanolamine N-methyltransferase
Location	17p11.2
Locus type	gene with protein product
Status	Approved
Aliases	PEMPT, PEMT2
Ensembl gene	ENSG00000133027
Ensembl biotype	protein_coding
OMIM	602391
Entrez	10400

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000255389, ENST00000395781, ENST00000395782, ENST00000395783, ENST00000421096, ENST00000435340, ENST00000461404, ENST00000472446, ENST00000477595, ENST00000484838, ENST00000490392, ENST00000580147, ENST00000582268, ENST00000900341, ENST00000900342, ENST00000900343, ENST00000900344

RefSeq mRNA: 5 — MANE Select: NM_148172 NM_001267551, NM_001267552, NM_007169, NM_148172, NM_148173

CCDS: CCDS11186, CCDS11187, CCDS58520

Canonical transcript exons

ENST00000255389 — 7 exons

Exon	Start	End
ENSE00002267547	17591531	17591708
ENSE00003473367	17505563	17505848
ENSE00003545082	17576920	17577027
ENSE00003588977	17512509	17512654
ENSE00003624470	17506227	17506301
ENSE00003628393	17509434	17509545
ENSE00003684258	17522280	17522395

Expression profiles

Bgee: expression breadth ubiquitous, 259 present calls, max score 99.05.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.4153 / max 1039.8395, expressed in 1800 samples.

FANTOM5 promoters (25 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164784	20.2039	1795
164773	3.1770	88
164782	2.5088	1323
164783	1.8590	1218
164775	1.5417	101
164769	0.5929	61
164781	0.5236	14
164772	0.4793	72
164774	0.2674	49
164788	0.2511	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.05	gold quality
right lobe of liver	UBERON:0001114	98.70	gold quality
type B pancreatic cell	CL:0000169	98.63	gold quality
right uterine tube	UBERON:0001302	97.40	gold quality
liver	UBERON:0002107	96.55	gold quality
adenohypophysis	UBERON:0002196	96.15	gold quality
endocervix	UBERON:0000458	95.84	gold quality
caput epididymis	UBERON:0004358	95.28	gold quality
pituitary gland	UBERON:0000007	95.16	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.10	gold quality
adipose tissue	UBERON:0001013	94.94	gold quality
right testis	UBERON:0004534	94.48	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.30	gold quality
omental fat pad	UBERON:0010414	94.30	gold quality
peritoneum	UBERON:0002358	94.24	gold quality
left testis	UBERON:0004533	94.09	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
connective tissue	UBERON:0002384	93.73	gold quality
decidua	UBERON:0002450	93.68	gold quality
cauda epididymis	UBERON:0004360	93.65	gold quality
left lobe of thyroid gland	UBERON:0001120	93.60	gold quality
ectocervix	UBERON:0012249	93.43	gold quality
skin of abdomen	UBERON:0001416	93.07	gold quality
skin of leg	UBERON:0001511	92.98	gold quality
lower esophagus mucosa	UBERON:0035834	92.66	gold quality
tibial nerve	UBERON:0001323	92.52	gold quality
islet of Langerhans	UBERON:0000006	92.47	gold quality
left ovary	UBERON:0002119	92.39	gold quality
body of uterus	UBERON:0009853	92.38	gold quality
right ovary	UBERON:0002118	92.37	gold quality

Single-cell (SCXA)

Detected in 8 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-81547	yes	1100.33
E-GEOD-134144	yes	40.44
E-HCAD-31	yes	37.87
E-MTAB-5061	yes	32.59
E-GEOD-83139	yes	11.29
E-ENAD-27	yes	10.73
E-GEOD-125970	yes	6.25
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, YY1

miRNA regulators (miRDB)

9 targeting PEMT, 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-10401-5P	99.99	65.79	948
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3187-3P	97.38	65.80	904

Literature-anchored findings (GeneRIF, showing 36)

• an examination of the membrane topography of this enzyme (PMID:12431977)
• PEMT2 mRNA expression was inversely related to tumor proliferation and to histologic grade. (PMID:12931022)
• PEMT-mediated Hcy secretion correlated with the methyltransferase activity of the enzyme, independently of subcellular localization (PMID:15927961)
• Val175Met variant of PEMT could be a susceptibility candidate to nonalcoholic steatohepatitis (NASH), because it is more frequently observed in NASH patients and non-obese persons with Val175Met variant of PEMT are facilitated to develop NASH (PMID:17391797)
• Human PEMT genes have three unique transcription start sites, which are indicative of either multiple promoters and/or alternative splicing. (PMID:17456783)
• The present results suggest that the PEMT gene may contribute to the etiology of schizophrenia. (PMID:17720317)
• single nucleotide polymorphisms of choline-metabolizing genes, PEMT -774G>C (rs12325817) and CHDH +432G>T (rs12676), were found be related to breast cancer risk (PMID:18230680)
• These data suggest that polymorphisms in PEMT genes relevant to choline metabolism modulate parameters of choline status when folate intake is restricted. (PMID:19167960)
• in folate-deplete men, several factors with roles in 1-carbon metabolism interact with the MTHFR C677T genotype to affect plasma homocysteine (PMID:19211833)
• The allele frequency of PEMT did not show a significant difference between normal control group and fatty liver patients (P=0.222). (PMID:19262398)
• No association of the rs4646396 SNP in the PEMT locus with schizophrenia in a Chinese case-control sample. (PMID:19647326)
• Total intake of choline and genotype can influence the concentrations of choline and its metabolites in the breast milk and blood of lactating women and thereby affect the amount of choline available to the developing infant. (PMID:20534746)
• Choline requirements for both women are increased by the genetic polymorphism rs12325817 in phosphatidylethanolamine-N-methyltransferase. (PMID:20861172)
• allele-specific ablation of estrogen receptor-DNA interaction in the PEMT locus prevents hormone-inducible PEMT expression, conferring risk of choline deficiency in women (PMID:21059658)
• nvestigation of factors affecting liver PEMT activity: PEMT activity is lower in liver samples from women who are homozygous for an SNP in PEMT (rs12325817) (PMID:21411618)
• genetic association studies on endometriosis in a population of women in Poland: Data suggest interaction between an SNP in PEMT (rs4244593) and an SNP in MTHFR (Ala222Val; rs1801133) in infertile women with some indication of endometriosis. (PMID:21429654)
• PEMT is a functional single nucleotide polymorphism (rs7946) in PEMT with sporadic Alzheimer’s disease risk in a Han Chinese population. (PMID:21881829)
• the PEMT -774G>C and CHDH +432G>T polymorphisms were associated with sperm concentration. This finding suggests a possible influence of these genes on sperm quality (PMID:22387881)
• The GG genotype of the PEMT G774C polymorphism, higher levels of serum homocysteine and lower levels of serum betaine are associated with an increased risk of microangiopathy in patients with diabetes. (PMID:23794489)
• MTHFR rs1801131 C allele and PEMT rs4646356 T allele were associated with a high risk of type 2 diabetes in Han Chinese. (PMID:25074646)
• Data suggest that maternal dietary intake during lactation (here, choline intake exceeding dietary recommendations) can alter hepatic PEMT activity and increase choline content of breast milk. (PMID:26025328)
• a significant association between the PEMT rs7946 A-allele and a risk of nonalcoholic fatty liver disease, with the effect being more prominent in East-Asians, but not in non-Asians (Meta-Analysis) (PMID:26636496)
• Data show that phosphatidylethanolamineN-methyltransferase (PEMT) rs12325817 polymorphism only marginally changed the association value with academic achievement. (PMID:26728177)
• Results showed that PEMT mRNA expression in liver tissues of non-alcoholic steatohepatitis (NASH) patients was significantly lower than those with simple steatosis suggesting a distinct clinical entity of lean NASH with insufficiency of PEMT activities. (PMID:26883167)
• In genotypic combination analysis considering PEMT -744GG/CHDH +432GG/BHMT +742GG as the reference combination, PEMT -744GC/CHDH +432GG/BHMT +742GG genotypic combination was significantly higher in mothers of a down syndrome child compared with that in control mothers with an odds ratio of 2.061 (95% CI: 1.10-3.86, P=0.0342). (PMID:27677362)
• Study found three gene variants (CLOCK-rs4864548, PEMT-rs936108, and GHRELIN-rs696217) that exhibited uncorrected gene-by-sleep duration interactions in relation to BMI z-scores in a cohort of New Zealand European children. However, no interactions were identified in percentage body fat differences. Notably, these interactions are evident without detectable effects on sleep duration. (PMID:28899534)
• Our study shows that choline intake in Polish pregnant women is inadequate and that polymorphisms of PEMT rs12325817 and PCYT1A rs7639752 are associated with betaine but not choline concentrations. (PMID:30055775)
• PEMT polymorphisms may be associated with the susceptibility to intrauterine fetal death in the Polish population (PMID:30321787)
• Associations between folate and choline intake, homocysteine metabolism, and genetic polymorphism of MTHFR, BHMT and PEMT in healthy pregnant Polish women. (PMID:31044529)
• Total liver phosphatidylcholine content associates with non-alcoholic steatohepatitis and glycine N-methyltransferase expression. (PMID:31199045)
• Genetic variations in PEMT and MTHFR were associated with different PUFA levels in erythrocyte membranes and are estimators for PUFA species in erythrocytes. Further research is needed to establish whether these genotype-specific alterations are specific to overweight children. (PMID:31671528)
• Dietary Choline Intake during Pregnancy and PEMT rs7946 Polymorphism on Risk of Preterm Birth: A Case-Control Study. (PMID:33503637)
• Hepatic PEMT Expression Decreases with Increasing NAFLD Severity. (PMID:36012560)
• PEMT variants are associated with nonsyndromic cleft lip with or without cleft palate in Chile. (PMID:36154674)
• The Role of Phosphatidylethanolamine N-Methyltransferase (PEMT) and Its Waist-Hip-Ratio-Associated Locus rs4646404 in Obesity-Related Metabolic Traits and Liver Disease. (PMID:38069170)
• Association between PEMT rs7946 and blood pressure levels in Chinese adolescents. (PMID:38502043)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pemt	ENSDARG00000103614
mus_musculus	Pemt	ENSMUSG00000000301
rattus_norvegicus	Pemt	ENSRNOG00000054423

Protein

Protein identifiers

Phosphatidylethanolamine N-methyltransferase — Q9UBM1 (reviewed: Q9UBM1)

Alternative names: PEMT2, Phospholipid methyltransferase

All UniProt accessions (4): D3YTC7, Q9UBM1, J3KTR2, J3QLU8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure. Uses S-adenosylmethionine (S-adenosyl-L-methionine, SAM or AdoMet) as the methyl group donor for the methylation of phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE) to phosphatidylmonomethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine, PMME), PMME to phosphatidyldimethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine, PDME), and PDME to phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), producing S-adenosyl-L-homocysteine in each step. Responsible for approximately 30% of hepatic PC with the CDP-choline pathway accounting for the other 70%. Catalyzes the three sequential steps of the methylation of 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine (PMME) to 1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine (PDME) more efficiently than isoform 2. Induces increase in PC species with longer polyunsaturated chains than isoform 2. Produces a higher increase in the level of PC species containing long chains with three double bonds than isoform 1.

Subcellular location. Endoplasmic reticulum Endoplasmic reticulum membrane. Mitochondrion membrane Endoplasmic reticulum membrane.

Tissue specificity. Primarily expressed in liver (at protein level).

Post-translational modifications. Isoform 2 is N-glycosylated with high-mannose oligosaccharides.

Activity regulation. The first methylation is rate-limiting.

Pathway. Phospholipid metabolism; phosphatidylcholine biosynthesis.

Similarity. Belongs to the class VI-like SAM-binding methyltransferase superfamily. PEMT/PEM2 methyltransferase family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBM1-1	1, PEMT-S	yes
Q9UBM1-2	2, PEMT-L
Q9UBM1-3	3

RefSeq proteins (5): NP_001254480, NP_001254481, NP_009100, NP_680477, NP_680478 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007318	Phopholipid_MeTrfase	Domain
IPR024960	PEMT/MFAP	Family

Pfam: PF04191

Enzyme classification (BRENDA):

• EC 2.1.1.17 — phosphatidylethanolamine N-methyltransferase (BRENDA: 19 organisms, 33 substrates, 16 inhibitors, 23 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

5 substrates with measured Km, best-characterized 5. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
S-ADENOSYLMETHIONINE	0.0019–0.11	13
PHOSPHATIDYL-N-METHYLETHANOLAMINE	0.0175–0.74	4
PHOSPHATIDYLETHANOLAMINE	0.0336–5	3
PHOSPHATIDYL-N,N-DIMETHYLETHANOLAMINE	0.45–2.12	2
S-ADENOSYL-L-METHIONINE	0.02	1

Catalyzed reactions (Rhea), 12 shown:

• a 1,2-diacyl-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-methionine = a 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:11164)
• a 1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-methionine = a 1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:32735)
• a 1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-methionine = a 1,2-diacyl-sn-glycero-3-phosphocholine + S-adenosyl-L-homocysteine + H(+) (RHEA:32739)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:46112)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:70619)
• 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + S-adenosyl-L-homocysteine + H(+) (RHEA:70623)
• 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:70739)
• 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:70743)
• 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine + S-adenosyl-L-homocysteine + H(+) (RHEA:70747)
• 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphoethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:70751)
• 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N-methylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-homocysteine + H(+) (RHEA:70755)
• 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phospho-N,N-dimethylethanolamine + S-adenosyl-L-methionine = 1,2-di-(9Z,12Z,15Z-octadecatrienoyl)-sn-glycero-3-phosphocholine + S-adenosyl-L-homocysteine + H(+) (RHEA:70759)

UniProt features (25 total): sequence variant 6, topological domain 5, mutagenesis site 4, transmembrane region 3, binding site 2, splice variant 2, chain 1, intramembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBM1-F1	93.45	0.89

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): 98–100; 180–181

Mutagenesis-validated functional residues (4):

Position	Phenotype
98	impairs binding to s-adenosyl-l-methionine.
100	abolishes binding to s-adenosyl-l-methionine.
180	abolishes binding to s-adenosyl-l-methionine.
181	impairs binding to s-adenosyl-l-methionine.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1483191	Synthesis of PC

MSigDB gene sets: 188 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLCHOLINE_BIOSYNTHETIC_PROCESS, GNF2_GSTM1, GNF2_HPN, GOBP_SPHINGOMYELIN_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_SPHINGOLIPID_METABOLIC_PROCESS, GOBP_AMIDE_METABOLIC_PROCESS

GO Biological Process (7): blastocyst hatching (GO:0001835), phosphatidylcholine biosynthetic process (GO:0006656), sphingomyelin biosynthetic process (GO:0006686), methylation (GO:0032259), positive regulation of cold-induced thermogenesis (GO:0120162), lipid metabolic process (GO:0006629), phospholipid biosynthetic process (GO:0008654)

GO Molecular Function (6): phosphatidyl-N-methylethanolamine N-methyltransferase activity (GO:0000773), phosphatidylethanolamine N-methyltransferase activity (GO:0004608), protein binding (GO:0005515), methyltransferase activity (GO:0008168), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757), transferase activity (GO:0016740)

GO Cellular Component (6): mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), mitochondrial membrane (GO:0031966), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Glycerophospholipid biosynthesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
N-methyltransferase activity	2
S-adenosylmethionine-dependent methyltransferase activity	2
intracellular membrane-bounded organelle	2
organelle membrane	2
cellular anatomical structure	2
blastocyst development	1
hatching	1
phosphatidylcholine metabolic process	1
glycerophospholipid biosynthetic process	1
sphingomyelin metabolic process	1
phospholipid biosynthetic process	1
sphingolipid biosynthetic process	1
metabolic process	1
positive regulation of multicellular organismal process	1
cold-induced thermogenesis	1
regulation of cold-induced thermogenesis	1
primary metabolic process	1
phospholipid metabolic process	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
binding	1
transferase activity, transferring one-carbon groups	1
methyltransferase activity	1
catalytic activity	1
endomembrane system	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
mitochondrion	1
mitochondrial envelope	1

Protein interactions and networks

STRING

1168 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PEMT	PISD	Q9UG56	775
PEMT	BHMT	Q93088	734
PEMT	CEPT1	Q9Y6K0	733
PEMT	CHPT1	Q8WUD6	714
PEMT	PCYT1A	P49585	683
PEMT	PCYT2	Q99447	681
PEMT	CHKA	P35790	670
PEMT	CDIPT	O14735	643
PEMT	MTHFR	P42898	643
PEMT	GAMT	Q14353	643
PEMT	CHDH	Q8NE62	636
PEMT	MTR	Q99707	628
PEMT	PCYT1B	Q9Y5K3	625
PEMT	GNMT	Q14749	608
PEMT	PTDSS1	P48651	603

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PEMT	FABP7	psi-mi:“MI:0914”(association)	0.350

BioGRID (39): PEMT (Two-hybrid), STOM (Two-hybrid), FCER1G (Two-hybrid), PEMT (Affinity Capture-MS), PADI3 (Affinity Capture-MS), TGM3 (Affinity Capture-MS), PKP1 (Affinity Capture-MS), ARL8B (Affinity Capture-MS), LRRC15 (Affinity Capture-MS), H2AFY (Affinity Capture-MS), CALML3 (Affinity Capture-MS), ATG9B (Affinity Capture-MS), PMEL (Affinity Capture-MS), ACPP (Affinity Capture-MS), DNASE1L2 (Affinity Capture-MS)

ESM2 similar proteins: A2XX73, A3F5L3, A5PJS2, C8VRV0, O05883, O12947, O18765, O60725, O88455, P18405, P24008, P31214, Q08388, Q0II71, Q28891, Q41131, Q4KLV1, Q4V7R2, Q564G3, Q5PRC0, Q61907, Q66H21, Q68FF9, Q6NV38, Q6QHC5, Q6RS95, Q71KT5, Q7S5W9, Q7SXF1, Q7XSR9, Q7YRH6, Q7ZW02, Q7ZXH1, Q84UB8, Q84UB9, Q84UC0, Q8C025, Q8GZC2, Q8L586, Q8R2F2

Diamond homologs: C8VRV0, O74827, P05375, Q08388, Q54H80, Q54SD5, Q61907, Q7S5W9, Q7YRH6, Q9UBM1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	23
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2194 predictions. Top by Δscore:

Variant	Effect	Δscore
17:17506223:TCACT:T	donor_loss	1.0000
17:17506224:CACTC:C	donor_loss	1.0000
17:17506225:A:AC	donor_gain	1.0000
17:17506225:ACT:A	donor_gain	1.0000
17:17506225:ACTCT:A	donor_loss	1.0000
17:17506226:C:CG	donor_gain	1.0000
17:17506226:CT:C	donor_gain	1.0000
17:17506226:CTC:C	donor_gain	1.0000
17:17506226:CTCTT:C	donor_gain	1.0000
17:17509429:CTCA:C	donor_loss	1.0000
17:17509430:TCA:T	donor_loss	1.0000
17:17509431:CACAT:C	donor_loss	1.0000
17:17509432:A:AC	donor_gain	1.0000
17:17509432:ACA:A	donor_loss	1.0000
17:17509433:C:CC	donor_gain	1.0000
17:17512504:CTTAC:C	donor_loss	1.0000
17:17512505:TTA:T	donor_loss	1.0000
17:17512506:TAC:T	donor_loss	1.0000
17:17512508:C:CG	donor_loss	1.0000
17:17512652:AAGC:A	acceptor_loss	1.0000
17:17512653:AG:A	acceptor_gain	1.0000
17:17512653:AGCT:A	acceptor_loss	1.0000
17:17512655:C:CC	acceptor_gain	1.0000
17:17512655:CTGTG:C	acceptor_loss	1.0000
17:17512656:T:C	acceptor_loss	1.0000
17:17522274:GCTTA:G	donor_loss	1.0000
17:17522275:CTTAC:C	donor_loss	1.0000
17:17522276:TTACC:T	donor_loss	1.0000
17:17522277:TA:T	donor_loss	1.0000
17:17522278:A:AC	donor_gain	1.0000

AlphaMissense

1523 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:17509496:G:C	F135L	0.986
17:17509496:G:T	F135L	0.986
17:17509498:A:G	F135L	0.986
17:17512543:G:C	S107R	0.983
17:17512543:G:T	S107R	0.983
17:17512545:T:G	S107R	0.983
17:17509463:G:C	S146R	0.973
17:17509463:G:T	S146R	0.973
17:17509465:T:G	S146R	0.973
17:17512513:G:C	F117L	0.972
17:17512513:G:T	F117L	0.972
17:17512515:A:G	F117L	0.972
17:17509535:G:C	F122L	0.969
17:17509535:G:T	F122L	0.969
17:17509537:A:G	F122L	0.969
17:17522318:G:C	S57R	0.961
17:17522318:G:T	S57R	0.961
17:17522320:T:G	S57R	0.961
17:17509446:C:T	G152D	0.953
17:17505842:G:C	F183L	0.952
17:17505842:G:T	F183L	0.952
17:17505844:A:G	F183L	0.952
17:17522381:T:A	E36D	0.945
17:17522381:T:G	E36D	0.945
17:17509502:G:C	F133L	0.944
17:17509502:G:T	F133L	0.944
17:17509504:A:G	F133L	0.944
17:17506284:C:T	G162D	0.937
17:17522290:G:T	R67S	0.934
17:17509468:C:G	G145R	0.931

dbSNP variants (sampled 300 via entrez): RS1000047498 (17:17582322 A>T), RS1000062010 (17:17518180 C>A), RS1000134939 (17:17553676 C>G), RS1000142868 (17:17576551 G>A), RS1000145412 (17:17592031 T>C), RS1000175189 (17:17513989 C>T), RS1000213085 (17:17558720 G>A,C), RS1000216383 (17:17522139 T>C), RS1000328389 (17:17571004 G>A), RS1000358631 (17:17533026 C>CA), RS1000392158 (17:17593826 C>T), RS1000450804 (17:17519578 C>G), RS1000483522 (17:17513721 G>T), RS1000487642 (17:17540532 G>A,T), RS1000496778 (17:17524766 A>C)

Disease associations

OMIM: gene MIM:602391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

60 associations (top):

Study	Trait	p-value
GCST000998_30	Coronary heart disease	4.000000e-10
GCST002287_3	Coronary artery disease or ischemic stroke	2.000000e-08
GCST002289_7	Coronary artery disease	2.000000e-07
GCST002290_12	Coronary artery disease or large artery stroke	2.000000e-10
GCST002782_137	Waist-to-hip ratio adjusted for body mass index	5.000000e-11
GCST002782_138	Waist-to-hip ratio adjusted for body mass index	1.000000e-11
GCST002782_139	Waist-to-hip ratio adjusted for body mass index	4.000000e-11
GCST002782_140	Waist-to-hip ratio adjusted for body mass index	1.000000e-11
GCST003434_9	Obsessive-compulsive symptoms	7.000000e-06
GCST004064_26	Waist-hip ratio	3.000000e-09
GCST004064_69	Waist-hip ratio	4.000000e-07
GCST004505_92	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	9.000000e-06
GCST004787_65	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	3.000000e-06
GCST006613_99	Triglycerides	8.000000e-13
GCST007484_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	4.000000e-11
GCST007491_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	1.000000e-10
GCST007493_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	1.000000e-06
GCST007496_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	1.000000e-06
GCST007501_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	3.000000e-06
GCST007503_1	Waist-to-hip ratio adjusted for BMI (recessive genetic model)	2.000000e-06
GCST008155_19	Waist-hip ratio	8.000000e-06
GCST010173_67	Triglyceride levels	2.000000e-15
GCST010241_410	Apolipoprotein A1 levels	2.000000e-10
GCST010242_34	HDL cholesterol levels	1.000000e-15
GCST010243_82	Apolipoprotein B levels	1.000000e-10
GCST010244_255	Triglyceride levels	2.000000e-21
GCST012227_396	Hip circumference adjusted for BMI	2.000000e-10
GCST012228_510	Waist-hip index	1.000000e-09
GCST012228_511	Waist-hip index	3.000000e-15
GCST012228_512	Waist-hip index	4.000000e-10

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007802	obsessive-compulsive symptom measurement
EFO:0004343	waist-hip ratio
EFO:0004318	smoking behavior
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004615	apolipoprotein B measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0006925	lipoprotein A measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7946	PEMT		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
bisphenol A	decreases methylation, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	decreases expression	2
Benzo(a)pyrene	decreases expression	2
Progesterone	affects cotreatment, increases expression	2
Tretinoin	decreases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, increases reaction	1
mono-(2-ethylhexyl)phthalate	increases expression	1
cobaltous chloride	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	increases expression	1
aflatoxin B2	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Troglitazone	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects response to substance	1
Cadmium	increases abundance, increases expression	1
Choline	affects response to substance	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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