METTL22

Summary

METTL22 (methyltransferase 22, Kin17 lysine, HGNC:28368) is a protein-coding gene on chromosome 16p13.2, encoding Methyltransferase-like protein 22 (Q9BUU2). Protein N-lysine methyltransferase.

This gene encodes a member of the non-histone lysine methyltransferases. It interacts with its substrate, Kin17, which is involved in DNA repair and replication and mRNA processing. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 79091 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 132 total
• MANE Select transcript: NM_024109

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28368
Approved symbol	METTL22
Name	methyltransferase 22, Kin17 lysine
Location	16p13.2
Locus type	gene with protein product
Status	Approved
Aliases	FLJ12433, MGC2654
Ensembl gene	ENSG00000067365
Ensembl biotype	protein_coding
OMIM	615261
Entrez	79091

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 20 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000163678, ENST00000381920, ENST00000561758, ENST00000561993, ENST00000562151, ENST00000562973, ENST00000563037, ENST00000563501, ENST00000563958, ENST00000564107, ENST00000564133, ENST00000564554, ENST00000564624, ENST00000565866, ENST00000567295, ENST00000568967, ENST00000569597, ENST00000572956, ENST00000900369, ENST00000900370, ENST00000900371, ENST00000900372, ENST00000900373, ENST00000900374, ENST00000912421, ENST00000912422, ENST00000912423, ENST00000912424, ENST00000957784, ENST00000957785, ENST00000957786, ENST00000957787

RefSeq mRNA: 1 — MANE Select: NM_024109 NM_024109

CCDS: CCDS10533

Canonical transcript exons

ENST00000381920 — 11 exons

Exon	Start	End
ENSE00000667694	8628730	8629110
ENSE00001010797	8621698	8621775
ENSE00001525704	8625496	8625798
ENSE00003488398	8641131	8641184
ENSE00003494571	8646108	8649654
ENSE00003504441	8635168	8635312
ENSE00003525732	8644557	8644725
ENSE00003589854	8639091	8639162
ENSE00003613881	8635039	8635079
ENSE00003617489	8642127	8642207
ENSE00003673119	8642463	8642565

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.3630 / max 143.7242, expressed in 1814 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152641	23.2790	1811
152642	1.2134	832
152647	0.6197	160
152648	0.2185	103
152645	0.0185	6
152646	0.0139	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	96.61	gold quality
left testis	UBERON:0004533	95.44	gold quality
right testis	UBERON:0004534	95.37	gold quality
gastrocnemius	UBERON:0001388	95.10	gold quality
gluteal muscle	UBERON:0002000	94.98	gold quality
monocyte	CL:0000576	94.87	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.80	gold quality
mononuclear cell	CL:0000842	94.64	gold quality
muscle of leg	UBERON:0001383	94.60	gold quality
mucosa of stomach	UBERON:0001199	94.44	gold quality
body of uterus	UBERON:0009853	94.36	gold quality
male germ cell	CL:0000015	93.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.97	gold quality
leukocyte	CL:0000738	93.94	gold quality
cerebellar hemisphere	UBERON:0002245	93.61	gold quality
left ovary	UBERON:0002119	93.36	gold quality
cerebellar cortex	UBERON:0002129	93.36	gold quality
lower esophagus mucosa	UBERON:0035834	93.14	gold quality
endocervix	UBERON:0000458	93.02	gold quality
muscle organ	UBERON:0001630	92.99	gold quality
testis	UBERON:0000473	92.93	gold quality
right ovary	UBERON:0002118	92.88	gold quality
apex of heart	UBERON:0002098	92.73	gold quality
muscle layer of sigmoid colon	UBERON:0035805	92.62	gold quality
ectocervix	UBERON:0012249	92.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.56	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.52	gold quality
lower esophagus	UBERON:0013473	92.51	gold quality
tibial nerve	UBERON:0001323	92.42	gold quality
skin of leg	UBERON:0001511	92.32	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-88	yes	20.50
E-ANND-3	yes	3.62
E-ENAD-27	no	3.44

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• METTL22 trimethylates Lys-135 in Kin17 (PMID:23349634)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mettl22	ENSDARG00000077863
mus_musculus	Mettl22	ENSMUSG00000039345
rattus_norvegicus	Mettl22	ENSRNOG00000002714
drosophila_melanogaster	CG10584	FBGN0037045

Protein

Protein identifiers

Methyltransferase-like protein 22 — Q9BUU2 (reviewed: Q9BUU2)

All UniProt accessions (9): Q9BUU2, H3BSA9, H3BTF5, H3BTI6, H3BTR2, H3BV20, I3L2J5, I3L3I8, I3L483

UniProt curated annotations — full annotation on UniProt →

Function. Protein N-lysine methyltransferase. Trimethylates KIN at Lys-135 (in vitro).

Subunit / interactions. Interacts with members of the heat shock protein 90 and 70 families; these proteins probably are methylation substrates.

Subcellular location. Nucleus.

Similarity. Belongs to the methyltransferase superfamily. METTL22 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9BUU2-1	1	yes
Q9BUU2-2	2
Q9BUU2-3	3

RefSeq proteins (1): NP_077014* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019410	Methyltransf_16	Family
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR038899	METTL22	Family

Pfam: PF10294

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + 3 S-adenosyl-L-methionine = N(6),N(6),N(6)-trimethyl-L-lysyl-[protein] + 3 S-adenosyl-L-homocysteine + 3 H(+) (RHEA:54192)

UniProt features (13 total): sequence variant 4, splice variant 3, region of interest 2, compositionally biased region 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BUU2-F1	78.07	0.56

Functional residue map

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

Post-translational modifications (1): 132

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-8876725	Protein methylation
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification

MSigDB gene sets: 75 (showing top): TGCGCANK_UNKNOWN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, MODULE_285, GOBP_METHYLATION, MODULE_69, GOCC_NUCLEOLUS, POS_RESPONSE_TO_HISTAMINE_DN, GOMF_HEAT_SHOCK_PROTEIN_BINDING, GOMF_N_METHYLTRANSFERASE_ACTIVITY, GOMF_PROTEIN_METHYLTRANSFERASE_ACTIVITY, GOMF_S_ADENOSYLMETHIONINE_DEPENDENT_METHYLTRANSFERASE_ACTIVITY, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_ONE_CARBON_GROUPS, GOMF_LYSINE_N_METHYLTRANSFERASE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

GO Biological Process (2): protein methylation (GO:0006479), methylation (GO:0032259)

GO Molecular Function (6): protein methyltransferase activity (GO:0008276), protein-lysine N-methyltransferase activity (GO:0016279), heat shock protein binding (GO:0031072), protein binding (GO:0005515), methyltransferase activity (GO:0008168), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Post-translational protein modification	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	2
protein alkylation	1
macromolecule methylation	1
metabolic process	1
methyltransferase activity	1
catalytic activity, acting on a protein	1
protein methyltransferase activity	1
lysine N-methyltransferase activity	1
protein binding	1
binding	1
transferase activity, transferring one-carbon groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1
intracellular membraneless organelle	1
cellular_component	1

Protein interactions and networks

STRING

472 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METTL22	METTL21A	Q8WXB1	797
METTL22	ETFBKMT	Q8IXQ9	796
METTL22	KIN	O60870	744
METTL22	METTL18	O95568	717
METTL22	VCPKMT	Q9H867	717
METTL22	METTL23	Q86XA0	702
METTL22	EEF2KMT	Q96G04	648
METTL22	CAMKMT	Q7Z624	647
METTL22	EEF1AKMT2	Q5JPI9	585
METTL22	EEF1AKMT1	Q8WVE0	548
METTL22	SLC25A53	Q5H9E4	523
METTL22	CSKMT	A8MUP2	513
METTL22	ATPSCKMT	Q6P4H8	495
METTL22	HAPSTR1	Q14CZ0	480
METTL22	ZC3H15	Q8WU90	480

IntAct

5 interactions, top by confidence:

A	B	Type	Score
METTL22	KIN	psi-mi:“MI:0914”(association)	0.500
METTL22	KIN	psi-mi:“MI:0915”(physical association)	0.500
RRAS	KIN	psi-mi:“MI:0914”(association)	0.350
wecF	METTL22	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): KIN (Affinity Capture-MS), IMPDH1 (Affinity Capture-MS), METTL22 (Affinity Capture-MS), KIN (Affinity Capture-MS), HNRNPL (Affinity Capture-MS), ILF2 (Affinity Capture-MS), RCN1 (Affinity Capture-MS), XPO1 (Affinity Capture-MS), PARP1 (Affinity Capture-MS), KIN (Biochemical Activity), KIN (Affinity Capture-Western), IMPDH1 (Affinity Capture-MS), METTL22 (Affinity Capture-MS), KIN (Affinity Capture-MS), METTL22 (Affinity Capture-RNA)

ESM2 similar proteins: A2AA28, A2RRH5, A4FV42, A6NDL7, A7MCT6, B0K012, B2RYG8, D3YWP0, D3ZRW8, E1B8U2, J3S6Y1, P21964, P50747, Q0V8R7, Q1JP61, Q2TBI8, Q3SZD4, Q3U2J5, Q4VBE8, Q58DC7, Q5E9Y6, Q5RJL2, Q5VZV1, Q6DJF8, Q6GQ33, Q6P9U1, Q7Z624, Q80WC9, Q86XA0, Q8BNV1, Q8C436, Q8CDZ2, Q8IZ69, Q8N371, Q8R1C6, Q8WU66, Q920N2, Q96AZ1, Q96CB9, Q96RR1

Diamond homologs: A2AA28, A4FV42, A4FV98, A4IGU3, A6NDL7, A6QP81, A7IQW5, D3YWP0, P0CU27, P53970, Q28IN4, Q2KIJ2, Q58DC7, Q5BLD8, Q5RE14, Q5RJL2, Q5VZV1, Q6DJF8, Q86XA0, Q8BLU2, Q8C436, Q8CDZ2, Q8R1C6, Q8WXB1, Q96AZ1, Q9BUU2, Q9CQL0, Q9H867, F4JNX3, O14118, O95568, P40389, P47163, Q4KM84, Q55DL2, Q9CZ09, A9ER52, Q4I2X5, Q5A013, Q5BAD0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	94
Likely benign	11
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2076 predictions. Top by Δscore:

Variant	Effect	Δscore
16:8621771:GGCGG:G	donor_gain	1.0000
16:8621772:GCGGG:G	donor_gain	1.0000
16:8621776:G:GG	donor_gain	1.0000
16:8635311:AG:A	donor_loss	1.0000
16:8635312:GG:G	donor_loss	1.0000
16:8635313:G:C	donor_loss	1.0000
16:8635314:T:G	donor_loss	1.0000
16:8641183:AGG:A	donor_loss	1.0000
16:8641184:GG:G	donor_loss	1.0000
16:8641185:G:T	donor_loss	1.0000
16:8641186:T:A	donor_loss	1.0000
16:8641758:G:GT	donor_gain	1.0000
16:8642123:TTA:T	acceptor_loss	1.0000
16:8642124:TA:T	acceptor_loss	1.0000
16:8642125:A:AC	acceptor_loss	1.0000
16:8642125:A:AG	acceptor_gain	1.0000
16:8642126:G:GA	acceptor_gain	1.0000
16:8642204:GAAG:G	donor_gain	1.0000
16:8642205:AAGGT:A	donor_loss	1.0000
16:8642207:GGTAA:G	donor_loss	1.0000
16:8642208:G:GG	donor_gain	1.0000
16:8642208:GTAAG:G	donor_loss	1.0000
16:8642209:T:G	donor_loss	1.0000
16:8642457:CCACA:C	acceptor_loss	1.0000
16:8642458:CACAG:C	acceptor_loss	1.0000
16:8642459:ACAG:A	acceptor_loss	1.0000
16:8642459:ACAGT:A	acceptor_gain	1.0000
16:8642460:CAGTG:C	acceptor_loss	1.0000
16:8642461:A:AG	acceptor_gain	1.0000
16:8642461:A:T	acceptor_loss	1.0000

AlphaMissense

2635 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:8635270:A:C	S220R	0.996
16:8635272:C:A	S220R	0.996
16:8635272:C:G	S220R	0.996
16:8644564:T:C	F340L	0.994
16:8644566:C:A	F340L	0.994
16:8644566:C:G	F340L	0.994
16:8635171:T:A	W187R	0.993
16:8635171:T:C	W187R	0.993
16:8635079:G:C	Q185H	0.992
16:8635079:G:T	Q185H	0.992
16:8628732:T:C	F46L	0.991
16:8628734:C:A	F46L	0.991
16:8628734:C:G	F46L	0.991
16:8642147:T:A	W283R	0.991
16:8642147:T:C	W283R	0.991
16:8639128:C:A	N246K	0.990
16:8639128:C:G	N246K	0.990
16:8635173:G:C	W187C	0.989
16:8635173:G:T	W187C	0.989
16:8635261:G:T	G217W	0.989
16:8635308:T:G	C232W	0.989
16:8642205:A:T	E302V	0.989
16:8644565:T:C	F340S	0.988
16:8642559:A:T	E335V	0.987
16:8635262:G:A	G217E	0.986
16:8635306:T:C	C232R	0.986
16:8639119:C:G	C243W	0.986
16:8642565:G:T	R337M	0.986
16:8642565:G:C	R337T	0.985
16:8644557:G:C	R337S	0.985

dbSNP variants (sampled 300 via entrez): RS1000042125 (16:8667214 C>CTT), RS1000081042 (16:8634373 A>G), RS1000167666 (16:8643763 G>A,C), RS1000240052 (16:8621154 C>G,T), RS1000263233 (16:8634650 GATT>G), RS1000290945 (16:8630110 T>C), RS1000367795 (16:8659713 G>A), RS1000379357 (16:8655353 C>T), RS1000437443 (16:8647761 C>A), RS1000443640 (16:8643580 G>C), RS1000453948 (16:8621417 G>A,T), RS1000466816 (16:8650533 A>G), RS1000523506 (16:8663593 A>C,T), RS1000717953 (16:8638060 T>C), RS1000749858 (16:8647573 C>G,T)

Disease associations

OMIM: gene MIM:615261 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST003901_11	Cognitive decline (age-related)	2.000000e-06
GCST005551_1	Systemic sclerosis (anti-topoisomerase-positive)	5.000000e-07
GCST009391_1421	Metabolite levels	2.000000e-06
GCST009391_1563	Metabolite levels	9.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008537	anti-topoisomerase-I-antibody-positive systemic scleroderma
EFO:0010452	adenosine diphosphate measurement
EFO:0009776	ornithine measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	6
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects methylation	1
beta-lapachone	increases expression	1
potassium chromate(VI)	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
cylindrospermopsin	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	increases methylation	1
Caffeine	increases phosphorylation	1
Carbamazepine	affects expression	1
Formaldehyde	increases expression	1
Lead	increases expression	1
Methyl Methanesulfonate	increases expression	1
Tunicamycin	increases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SY01	HAP1 METTL22 (-) 1	Cancer cell line	Male
CVCL_SY02	HAP1 METTL22 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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