METTL25

Summary

METTL25 (methyltransferase like 25, HGNC:26228) is a protein-coding gene on chromosome 12q21.31, encoding Probable methyltransferase-like protein 25 (Q8N6Q8). Probable methyltransferase.

Predicted to enable methyltransferase activity. Predicted to be involved in methylation.

Source: NCBI Gene 84190 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 94 total
• MANE Select transcript: NM_032230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26228
Approved symbol	METTL25
Name	methyltransferase like 25
Location	12q21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22789
Ensembl gene	ENSG00000127720
Ensembl biotype	protein_coding
Entrez	84190

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 2 retained_intron

ENST00000248306, ENST00000547357, ENST00000547985, ENST00000548200, ENST00000548432, ENST00000548569, ENST00000550058, ENST00000550298, ENST00000551645, ENST00000551722, ENST00000552741, ENST00000872357, ENST00000872358, ENST00000872359, ENST00000935491

RefSeq mRNA: 3 — MANE Select: NM_032230 NM_001319675, NM_001347934, NM_032230

CCDS: CCDS9024

Canonical transcript exons

ENST00000248306 — 12 exons

Exon	Start	End
ENSE00000910621	82358529	82358824
ENSE00003463804	82398795	82399394
ENSE00003481514	82430893	82430987
ENSE00003483236	82476644	82476718
ENSE00003534997	82456727	82456820
ENSE00003560476	82386803	82386967
ENSE00003561003	82402983	82403130
ENSE00003595422	82438718	82438791
ENSE00003604653	82389816	82389922
ENSE00003614876	82477281	82477352
ENSE00003621319	82434695	82434724
ENSE00003645472	82478932	82479239

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 92.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.6958 / max 73.8873, expressed in 1649 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
127144	5.3494	1619
127145	0.3373	160
206824	0.0091	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	92.41	gold quality
epithelial cell of pancreas	CL:0000083	90.82	silver quality
endothelial cell	CL:0000115	90.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.11	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	88.78	gold quality
parietal pleura	UBERON:0002400	88.52	gold quality
tibia	UBERON:0000979	87.75	gold quality
oviduct epithelium	UBERON:0004804	87.39	gold quality
calcaneal tendon	UBERON:0003701	86.94	gold quality
epithelium of nasopharynx	UBERON:0001951	86.72	gold quality
nasopharynx	UBERON:0001728	86.70	gold quality
upper arm skin	UBERON:0004263	85.02	gold quality
adrenal tissue	UBERON:0018303	84.76	gold quality
corpus callosum	UBERON:0002336	84.59	gold quality
esophagus squamous epithelium	UBERON:0006920	84.34	gold quality
cerebellar hemisphere	UBERON:0002245	84.06	gold quality
cerebellar cortex	UBERON:0002129	83.91	gold quality
oocyte	CL:0000023	83.79	gold quality
visceral pleura	UBERON:0002401	83.75	gold quality
sperm	CL:0000019	83.64	silver quality
right hemisphere of cerebellum	UBERON:0014890	83.56	gold quality
cerebellum	UBERON:0002037	83.04	gold quality
metanephros	UBERON:0000081	82.85	gold quality
colonic epithelium	UBERON:0000397	82.81	gold quality
pituitary gland	UBERON:0000007	82.62	gold quality
tendon	UBERON:0000043	82.60	gold quality
mucosa of paranasal sinus	UBERON:0005030	82.45	gold quality
palpebral conjunctiva	UBERON:0001812	82.40	gold quality
adenohypophysis	UBERON:0002196	82.03	gold quality
monocyte	CL:0000576	81.94	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	223.25
E-ANND-3	yes	4.48

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting METTL25, 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-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-5000-3P	98.79	65.63	1251
HSA-MIR-1237-3P	98.55	67.65	1423
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-4436A	98.05	64.83	1140
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-4700-3P	97.74	68.64	1014
HSA-MIR-675-3P	95.77	69.27	675

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mettl25	ENSDARG00000045754
mus_musculus	Mettl25	ENSMUSG00000036009
rattus_norvegicus	Mettl25	ENSRNOG00000027451
drosophila_melanogaster	CG2906	FBGN0033240
caenorhabditis_elegans	F25H2.12	WBGENE00009123

Paralogs (1): METTL25B (ENSG00000143303)

Protein

Protein identifiers

Probable methyltransferase-like protein 25 — Q8N6Q8 (reviewed: Q8N6Q8)

All UniProt accessions (4): Q8N6Q8, F8VZA8, H0YIN2, H0YIW7

UniProt curated annotations — full annotation on UniProt →

Function. Probable methyltransferase.

RefSeq proteins (3): NP_001306604, NP_001334863, NP_115606* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025714	Methyltranfer_dom	Domain
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR052220	METTL25	Family

Pfam: PF13679

UniProt features (5 total): sequence conflict 2, chain 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6Q8-F1	76.70	0.61

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 85 (showing top): chr12q21, GOBP_METHYLATION, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, CEBPZ_TARGET_GENES, CHAF1B_TARGET_GENES, CIITA_TARGET_GENES, DIDO1_TARGET_GENES, FOXD2_TARGET_GENES, FOXE1_TARGET_GENES, GLI4_TARGET_GENES, HHEX_TARGET_GENES, HMG20B_TARGET_GENES, IGLV5_37_TARGET_GENES, KAT2A_TARGET_GENES, KAT5_TARGET_GENES

GO Biological Process (1): methylation (GO:0032259)

GO Molecular Function (2): methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
metabolic process	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1

Protein interactions and networks

STRING

314 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METTL25	EEF1AKMT2	Q5JPI9	800
METTL25	METTL8	Q9H825	783
METTL25	METTL2B	Q6P1Q9	756
METTL25	TMT1B	Q6UX53	749
METTL25	METTL9	Q9H1A3	734
METTL25	METTL13	Q8N6R0	681
METTL25	METTL16	Q86W50	624
METTL25	METTL21C	Q5VZV1	581
METTL25	METTL5	Q9NRN9	559
METTL25	METTL24	Q5JXM2	557
METTL25	METTL26	Q96S19	553
METTL25	FGD6	Q6ZV73	540
METTL25	METTL27	Q8N6F8	537
METTL25	TMEM126A	Q9H061	531
METTL25	METTL2A	Q96IZ6	528

IntAct

10 interactions, top by confidence:

A	B	Type	Score
RPGRIP1	NEK4	psi-mi:“MI:0914”(association)	0.620
METTL25	H1-5	psi-mi:“MI:0915”(physical association)	0.400
METTL25	NRDC	psi-mi:“MI:0915”(physical association)	0.400
HTR3C	TMEM223	psi-mi:“MI:0914”(association)	0.350
METTL25	NRDC	psi-mi:“MI:0914”(association)	0.350
S100B	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
HTR3C	GET1	psi-mi:“MI:0914”(association)	0.350
NRAS	IGKV2D-24	psi-mi:“MI:0914”(association)	0.350
METTL25	RPGRIP1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (18): METTL25 (Affinity Capture-MS), METTL25 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), PCBP3 (Affinity Capture-MS), RPGRIP1 (Affinity Capture-MS), METTL25 (Proximity Label-MS), METTL25 (Affinity Capture-MS), METTL25 (Affinity Capture-MS), NRD1 (Affinity Capture-MS), METTL25 (Affinity Capture-MS), METTL25 (Cross-Linking-MS (XL-MS)), METTL25 (Cross-Linking-MS (XL-MS)), METTL25 (Cross-Linking-MS (XL-MS)), METTL25 (Cross-Linking-MS (XL-MS)), METTL25 (Affinity Capture-RNA)

ESM2 similar proteins: A0JM24, A1A5R7, A2AKG8, A2CI34, D3YWQ0, F1MAB7, F6S215, O08653, O43149, O54705, O62699, P29477, P35608, P59438, P97499, Q06518, Q08DB2, Q20CR4, Q27995, Q28314, Q4R856, Q4TVR5, Q4VSN2, Q4VSN3, Q4VSN4, Q4VSN5, Q5BIW4, Q5EB20, Q5R6T6, Q5SSH7, Q5TEA3, Q5VW36, Q6NV72, Q6NXH8, Q6NXP6, Q6P996, Q6XUX0, Q6XUX1, Q6XUX2, Q6XUX3

Diamond homologs: Q6NXH8, Q8N6Q8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2501 predictions. Top by Δscore:

Variant	Effect	Δscore
12:82358754:G:GT	donor_gain	1.0000
12:82358806:G:GT	donor_gain	1.0000
12:82388913:GACCA:G	donor_gain	1.0000
12:82389805:A:AG	acceptor_gain	1.0000
12:82389806:T:G	acceptor_gain	1.0000
12:82389811:A:AG	acceptor_gain	1.0000
12:82389811:ATTAG:A	acceptor_gain	1.0000
12:82389812:T:G	acceptor_gain	1.0000
12:82389812:TTAGG:T	acceptor_loss	1.0000
12:82389813:TAG:T	acceptor_loss	1.0000
12:82389814:A:AG	acceptor_gain	1.0000
12:82389814:AG:A	acceptor_gain	1.0000
12:82389814:AGGT:A	acceptor_gain	1.0000
12:82389815:G:GA	acceptor_gain	1.0000
12:82389815:GG:G	acceptor_gain	1.0000
12:82389815:GGT:G	acceptor_gain	1.0000
12:82389815:GGTG:G	acceptor_gain	1.0000
12:82389815:GGTGA:G	acceptor_gain	1.0000
12:82389918:AGCAG:A	donor_gain	1.0000
12:82389919:GCAG:G	donor_gain	1.0000
12:82389919:GCAGG:G	donor_gain	1.0000
12:82389923:G:GG	donor_gain	1.0000
12:82389924:T:A	donor_loss	1.0000
12:82402975:T:G	acceptor_gain	1.0000
12:82402979:AAAG:A	acceptor_gain	1.0000
12:82402982:GGATT:G	acceptor_gain	1.0000
12:82403067:G:GT	donor_gain	1.0000
12:82434693:A:G	acceptor_gain	1.0000
12:82456721:TTACA:T	acceptor_loss	1.0000
12:82456722:TACA:T	acceptor_loss	1.0000

AlphaMissense

3946 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:82438742:C:A	R477S	0.997
12:82438749:T:A	V479D	0.997
12:82438752:T:C	L480P	0.997
12:82398828:A:C	S189R	0.996
12:82398830:C:A	S189R	0.996
12:82398830:C:G	S189R	0.996
12:82403004:C:G	H385D	0.996
12:82438743:G:C	R477P	0.996
12:82478987:G:C	R592T	0.996
12:82403002:T:C	L384P	0.995
12:82438745:G:C	A478P	0.995
12:82438746:C:A	A478D	0.995
12:82477330:G:C	R566P	0.995
12:82478965:T:C	F585L	0.995
12:82478967:T:A	F585L	0.995
12:82478967:T:G	F585L	0.995
12:82389855:A:T	K155I	0.994
12:82389864:A:T	E158V	0.994
12:82389865:A:C	E158D	0.994
12:82389865:A:T	E158D	0.994
12:82398911:A:C	R216S	0.994
12:82398911:A:T	R216S	0.994
12:82403085:T:C	C412R	0.994
12:82478987:G:T	R592I	0.994
12:82389856:A:C	K155N	0.993
12:82389856:A:T	K155N	0.993
12:82398819:G:C	G186R	0.993
12:82398826:T:C	L188P	0.993
12:82403020:T:C	L390P	0.993
12:82430980:C:A	A456E	0.993

dbSNP variants (sampled 300 via entrez): RS1000083930 (12:82446260 C>A,T), RS1000091090 (12:82455086 C>T), RS1000115993 (12:82433538 A>G), RS1000130534 (12:82403628 A>G,T), RS1000136362 (12:82445941 G>A), RS1000195598 (12:82392423 A>G), RS1000211459 (12:82386728 A>C,G), RS1000236822 (12:82432680 C>A), RS1000250464 (12:82386157 G>A,C), RS1000279924 (12:82469954 T>C,G), RS1000281052 (12:82380275 T>C), RS1000321028 (12:82437505 T>G), RS1000327539 (12:82473392 A>C), RS1000345777 (12:82386354 T>C), RS1000384288 (12:82440002 G>T)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006417_3	Plasma factor VII activating protease levels	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Air Pollutants	increases abundance, decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
abrine	decreases expression	1
Temozolomide	increases expression	1
Decitabine	affects expression	1
Caffeine	increases phosphorylation	1
Cisplatin	affects expression	1
Estradiol	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	increases expression	1

Clinical trials (associated diseases)

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