METTL24

Summary

METTL24 (methyltransferase like 24, HGNC:21566) is a protein-coding gene on chromosome 6q21, encoding Probable methyltransferase-like protein 24 (Q5JXM2). Probable methyltransferase.

Predicted to enable methyltransferase activity. Predicted to be involved in methylation. Predicted to be located in extracellular region.

Source: NCBI Gene 728464 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 74 total
• MANE Select transcript: NM_001123364

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21566
Approved symbol	METTL24
Name	methyltransferase like 24
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	dJ71D21.2
Ensembl gene	ENSG00000053328
Ensembl biotype	protein_coding
Entrez	728464

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000338882, ENST00000490043, ENST00000969421

RefSeq mRNA: 2 — MANE Select: NM_001123364 NM_001123364, NM_001354594

CCDS: CCDS43489

Canonical transcript exons

ENST00000338882 — 5 exons

Exon	Start	End
ENSE00001365442	110322774	110322872
ENSE00001372474	110298922	110299150
ENSE00001372732	110315342	110315481
ENSE00001448299	110357955	110358349
ENSE00001923736	110243940	110246260

Expression profiles

Bgee: expression breadth ubiquitous, 125 present calls, max score 84.79.

FANTOM5 (CAGE): breadth broad, TPM avg 0.6672 / max 19.2965, expressed in 256 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75046	0.6672	256

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
smooth muscle tissue	UBERON:0001135	84.79	gold quality
calcaneal tendon	UBERON:0003701	79.06	gold quality
muscle layer of sigmoid colon	UBERON:0035805	77.23	gold quality
popliteal artery	UBERON:0002250	77.06	gold quality
thoracic aorta	UBERON:0001515	77.05	gold quality
tibial artery	UBERON:0007610	77.03	gold quality
ascending aorta	UBERON:0001496	77.01	gold quality
right coronary artery	UBERON:0001625	76.90	gold quality
descending thoracic aorta	UBERON:0002345	76.81	gold quality
gall bladder	UBERON:0002110	76.17	gold quality
left coronary artery	UBERON:0001626	75.13	gold quality
lower esophagus muscularis layer	UBERON:0035833	74.87	gold quality
lower esophagus	UBERON:0013473	74.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	74.03	gold quality
myometrium	UBERON:0001296	73.93	gold quality
body of uterus	UBERON:0009853	73.76	gold quality
fallopian tube	UBERON:0003889	72.47	gold quality
rectum	UBERON:0001052	72.12	gold quality
urinary bladder	UBERON:0001255	71.82	gold quality
left uterine tube	UBERON:0001303	70.54	gold quality
left ovary	UBERON:0002119	69.76	gold quality
ovary	UBERON:0000992	69.57	gold quality
islet of Langerhans	UBERON:0000006	69.28	gold quality
endocervix	UBERON:0000458	68.88	gold quality
colon	UBERON:0001155	68.57	gold quality
right ovary	UBERON:0002118	68.47	gold quality
mucosa of stomach	UBERON:0001199	68.33	gold quality
pituitary gland	UBERON:0000007	66.93	gold quality
intestine	UBERON:0000160	66.75	gold quality
endometrium	UBERON:0001295	66.66	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.76

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 2)

• The strongest DNA methylation changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. (PMID:29729188)
• A comprehensive investigation discovered the novel methyltransferase METTL24 as one presumably prognostic gene for kidney renal clear cell carcinoma potentially modulating tumor immune microenvironment. (PMID:36311770)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	mettl24	ENSDARG00000075817
mus_musculus	Mettl24	ENSMUSG00000045555
rattus_norvegicus	Mettl24	ENSRNOG00000024221
caenorhabditis_elegans		WBGENE00000599
caenorhabditis_elegans	col-35	WBGENE00000612
caenorhabditis_elegans	col-47	WBGENE00000624
caenorhabditis_elegans	col-50	WBGENE00000627
caenorhabditis_elegans		WBGENE00000661
caenorhabditis_elegans		WBGENE00000700
caenorhabditis_elegans		WBGENE00000701
caenorhabditis_elegans		WBGENE00000717
caenorhabditis_elegans		WBGENE00000718
caenorhabditis_elegans		WBGENE00000721
caenorhabditis_elegans		WBGENE00000757
caenorhabditis_elegans		WBGENE00000760

Paralogs (2): CTHRC1 (ENSG00000164932), SCARA3 (ENSG00000168077)

Protein

Protein identifiers

Probable methyltransferase-like protein 24 — Q5JXM2 (reviewed: Q5JXM2)

All UniProt accessions (1): Q5JXM2

UniProt curated annotations — full annotation on UniProt →

Function. Probable methyltransferase.

Subcellular location. Secreted.

Similarity. Belongs to the methyltransferase superfamily.

RefSeq proteins (2): NP_001116836, NP_001341523 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR025714	Methyltranfer_dom	Domain
IPR026913	METTL24	Family

Pfam: PF13383

UniProt features (7 total): compositionally biased region 2, signal peptide 1, chain 1, region of interest 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5JXM2-F1	79.63	0.62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 23 (showing top): GOBP_METHYLATION, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, DESCARTES_MAIN_FETAL_MESANGIAL_CELLS, DESCARTES_FETAL_ADRENAL_STROMAL_CELLS, DESCARTES_FETAL_KIDNEY_MESANGIAL_CELLS, MYOCD_TARGET_GENES, OSMAN_BLOOD_CHAD63_KH_AGE_18_50YO_HIGH_DOSE_SUBJECTS_24HR_DN, GSE27786_BCELL_VS_CD8_TCELL_DN, GSE2405_0H_VS_3H_A_PHAGOCYTOPHILUM_STIM_NEUTROPHIL_DN, GSE1566_WT_VS_EZH2_KO_LN_TCELL_UP, GSE22601_IMMATURE_CD4_SINGLE_POSITIVE_VS_DOUBLE_POSITIVE_THYMOCYTE_UP, GSE22601_DOUBLE_NEGATIVE_VS_CD8_SINGLE_POSITIVE_THYMOCYTE_UP, GSE2585_CTEC_VS_THYMIC_DC_UP, GSE2585_CTEC_VS_MTEC_THYMUS_DN

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

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

GO Cellular Component (1): extracellular region (GO:0005576)

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
cellular anatomical structure	1

Protein interactions and networks

STRING

146 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METTL24	METTL2B	Q6P1Q9	654
METTL24	METTL13	Q8N6R0	649
METTL24	EEF1AKMT2	Q5JPI9	599
METTL24	METTL9	Q9H1A3	572
METTL24	METTL25	Q8N6Q8	557
METTL24	METTL16	Q86W50	525
METTL24	METTL21C	Q5VZV1	487
METTL24	RNF151	Q2KHN1	474
METTL24	SHCBP1L	Q9BZQ2	442
METTL24	DDO	Q99489	433
METTL24	TMT1B	Q6UX53	413
METTL24	METTL26	Q96S19	411
METTL24	RFLNA	Q6ZTI6	395
METTL24	A4GNT	Q9UNA3	394
METTL24	METTL27	Q8N6F8	393

IntAct

0 interactions, top by confidence:

BioGRID (2): METTL24 (Affinity Capture-RNA), METTL24 (Cross-Linking-MS (XL-MS))

ESM2 similar proteins: A2RRU4, A4Q9F3, A6NFA1, A6QM06, B1ATG9, D4A6L0, E1BBQ2, E7F4V6, E7F6V0, E9Q6C8, F1LQY6, F6PTN1, O02695, O09010, O35245, P0DJQ9, P56726, P97260, P97698, Q12770, Q13563, Q3TMX7, Q58CS8, Q5BK01, Q5GH57, Q5JXM2, Q5MNU5, Q5QQ49, Q5QQ50, Q5QQ51, Q5T848, Q6GQT6, Q6NW40, Q6ZRP7, Q7TQ33, Q86V40, Q8C419, Q8CCB5, Q8IZP7, Q8TCT7

Diamond homologs: B1WB06, Q5BK01, Q5JXM2, Q8CCB5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1544 predictions. Top by Δscore:

Variant	Effect	Δscore
6:110246257:CAAT:C	acceptor_gain	1.0000
6:110246260:TCTG:T	acceptor_loss	1.0000
6:110298916:CCTCA:C	donor_loss	1.0000
6:110298917:CTCA:C	donor_loss	1.0000
6:110298918:TCAC:T	donor_loss	1.0000
6:110298919:CACCT:C	donor_loss	1.0000
6:110298920:A:T	donor_loss	1.0000
6:110298921:C:CT	donor_loss	1.0000
6:110299146:CTAGC:C	acceptor_gain	1.0000
6:110299151:C:CA	acceptor_loss	1.0000
6:110299151:C:CC	acceptor_gain	1.0000
6:110322704:T:TA	donor_gain	1.0000
6:110246256:TCAAT:T	acceptor_gain	0.9900
6:110246257:CAATC:C	acceptor_gain	0.9900
6:110246258:AAT:A	acceptor_gain	0.9900
6:110246259:AT:A	acceptor_gain	0.9900
6:110246261:C:CC	acceptor_gain	0.9900
6:110246262:T:A	acceptor_loss	0.9900
6:110246267:C:CT	acceptor_gain	0.9900
6:110246268:A:T	acceptor_gain	0.9900
6:110246272:C:CT	acceptor_gain	0.9900
6:110298920:A:AC	donor_gain	0.9900
6:110298921:C:CC	donor_gain	0.9900
6:110298952:T:TA	donor_gain	0.9900
6:110298953:C:A	donor_gain	0.9900
6:110299147:TAGC:T	acceptor_gain	0.9900
6:110299149:GC:G	acceptor_gain	0.9900
6:110299150:CCTA:C	acceptor_gain	0.9900
6:110315340:AC:A	donor_gain	0.9900
6:110315341:CC:C	donor_gain	0.9900

AlphaMissense

2410 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:110246224:A:G	W275R	0.999
6:110246224:A:T	W275R	0.999
6:110246222:C:A	W275C	0.997
6:110246222:C:G	W275C	0.997
6:110245969:A:G	W360R	0.996
6:110245969:A:T	W360R	0.996
6:110246090:G:C	S319R	0.996
6:110246090:G:T	S319R	0.996
6:110246092:T:G	S319R	0.996
6:110246135:A:C	F304L	0.996
6:110246135:A:T	F304L	0.996
6:110246137:A:G	F304L	0.996
6:110246098:A:G	W317R	0.995
6:110246098:A:T	W317R	0.995
6:110246169:A:G	L293P	0.995
6:110246250:A:G	L266P	0.995
6:110246231:A:C	S272R	0.994
6:110246231:A:T	S272R	0.994
6:110246233:T:G	S272R	0.994
6:110299085:A:G	F208S	0.993
6:110315408:C:G	C164S	0.993
6:110315409:A:G	C164R	0.993
6:110315409:A:T	C164S	0.993
6:110246088:A:G	L320P	0.992
6:110299012:C:A	W232C	0.992
6:110299012:C:G	W232C	0.992
6:110315352:A:C	Y183D	0.992
6:110245985:G:C	S354R	0.991
6:110245985:G:T	S354R	0.991
6:110245987:T:G	S354R	0.991

dbSNP variants (sampled 300 via entrez): RS1000025499 (6:110288246 C>A), RS1000058780 (6:110292889 T>C), RS1000195755 (6:110281564 G>A,C), RS1000208010 (6:110296331 GT>G), RS1000213348 (6:110326291 A>G,T), RS1000379847 (6:110274970 T>A), RS1000402646 (6:110333183 A>G), RS1000414503 (6:110245413 G>C), RS1000436255 (6:110289788 GTTC>G), RS1000436361 (6:110333006 C>G), RS1000438101 (6:110303077 CT>C), RS1000477510 (6:110327921 C>G,T), RS1000513156 (6:110276096 C>A), RS1000574994 (6:110283106 G>T), RS1000585776 (6:110283274 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

3 associations (top):

Study	Trait	p-value
GCST003518_86	Daytime sleep phenotypes	3.000000e-07
GCST006585_1727	Blood protein levels	7.000000e-10
GCST012146_14	Hemoglobin levels	6.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007828	daytime rest measurement
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	increases methylation	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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