METTL27

Summary

METTL27 (methyltransferase like 27, HGNC:19068) is a protein-coding gene on chromosome 7q11.23, encoding Methyltransferase-like protein 27 (Q8N6F8).

This gene encodes a protein belonging to ubiE/COQ5 methyltransferase family. The gene is deleted in Williams syndrome, a multisystem developmental disorder caused by the deletion of contiguous genes at 7q11.22-q11.23.

Source: NCBI Gene 155368 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total — 3 pathogenic
• Phenotypes (HPO): 186
• MANE Select transcript: NM_152559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19068
Approved symbol	METTL27
Name	methyltransferase like 27
Location	7q11.23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000165171
Ensembl biotype	protein_coding
OMIM	612546
Entrez	155368

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000297873, ENST00000458679, ENST00000493174, ENST00000866837, ENST00000866838, ENST00000866839, ENST00000920429, ENST00000959569

RefSeq mRNA: 1 — MANE Select: NM_152559 NM_152559

CCDS: CCDS5561

Canonical transcript exons

ENST00000297873 — 6 exons

Exon	Start	End
ENSE00001090946	73840414	73840549
ENSE00001719058	73842490	73842516
ENSE00001736786	73834590	73835002
ENSE00003525291	73841070	73841198
ENSE00003551334	73840031	73840120
ENSE00003661399	73842018	73842144

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 91.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.3805 / max 104.7305, expressed in 1232 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
84336	4.2734	1215
84335	0.1071	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	91.96	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.30	gold quality
endocervix	UBERON:0000458	77.99	gold quality
body of pancreas	UBERON:0001150	77.82	gold quality
body of uterus	UBERON:0009853	75.29	gold quality
ectocervix	UBERON:0012249	73.64	gold quality
mucosa of transverse colon	UBERON:0004991	73.36	gold quality
right coronary artery	UBERON:0001625	72.77	gold quality
pancreas	UBERON:0001264	72.57	gold quality
adult mammalian kidney	UBERON:0000082	72.18	gold quality
bronchial epithelial cell	CL:0002328	71.98	gold quality
right lobe of thyroid gland	UBERON:0001119	71.95	gold quality
metanephros cortex	UBERON:0010533	71.86	gold quality
left lobe of thyroid gland	UBERON:0001120	71.81	gold quality
minor salivary gland	UBERON:0001830	71.42	gold quality
left ovary	UBERON:0002119	71.37	gold quality
right ovary	UBERON:0002118	70.85	gold quality
left uterine tube	UBERON:0001303	70.60	gold quality
bronchus	UBERON:0002185	70.56	gold quality
thyroid gland	UBERON:0002046	70.36	gold quality
adenohypophysis	UBERON:0002196	70.33	gold quality
transverse colon	UBERON:0001157	70.15	gold quality
cortex of kidney	UBERON:0001225	70.13	gold quality
uterine cervix	UBERON:0000002	69.75	gold quality
descending thoracic aorta	UBERON:0002345	68.32	gold quality
saliva-secreting gland	UBERON:0001044	68.13	gold quality
lower esophagus mucosa	UBERON:0035834	68.06	gold quality
pituitary gland	UBERON:0000007	67.82	gold quality
prostate gland	UBERON:0002367	67.79	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

15 targeting METTL27, 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-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-4717-5P	98.19	67.97	894
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6726-5P	95.97	63.72	841
HSA-MIR-920	95.97	63.95	811
HSA-MIR-4300	95.85	64.56	1003
HSA-MIR-5591-5P	95.85	64.76	1002

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	mettl27	ENSDARG00000069507
mus_musculus	Mettl27	ENSMUSG00000040557
rattus_norvegicus	Mettl27	ENSRNOG00000046700
caenorhabditis_elegans		WBGENE00019675
caenorhabditis_elegans		WBGENE00019961
caenorhabditis_elegans		WBGENE00019963
caenorhabditis_elegans		WBGENE00019968

Paralogs (4): COQ5 (ENSG00000110871), TMT1B (ENSG00000170439), TMT1A (ENSG00000185432), AS3MT (ENSG00000214435)

Protein

Protein identifiers

Methyltransferase-like protein 27 — Q8N6F8 (reviewed: Q8N6F8)

Alternative names: Williams-Beuren syndrome chromosomal region 27 protein

All UniProt accessions (2): B4DWM3, Q8N6F8

UniProt curated annotations — full annotation on UniProt →

Disease relevance. METTL27 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of METTL27 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.

RefSeq proteins (1): NP_689772* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029063	SAM-dependent_MTases_sf	Homologous_superfamily
IPR041698	Methyltransf_25	Domain

Pfam: PF13649

UniProt features (4 total): sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N6F8-F1	83.31	0.74

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 497 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, chr7q11, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MARTENS_TRETINOIN_RESPONSE_UP, LEE_BMP2_TARGETS_UP, DELACROIX_RAR_BOUND_ES, MTOR_UP.V1_DN, ESC_J1_UP_EARLY.V1_UP, ESC_J1_UP_LATE.V1_UP, TERF1_TARGET_GENES, ZNF322_TARGET_GENES, GSE13229_IMM_VS_INTMATURE_NKCELL_UP, GSE13485_CTRL_VS_DAY21_YF17D_VACCINE_PBMC_DN

GO Biological Process (0):

GO Molecular Function (2): protein binding (GO:0005515), S-adenosylmethionine-dependent methyltransferase activity (GO:0008757)

GO Cellular Component (0):

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
methyltransferase activity	1

Protein interactions and networks

STRING

1382 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
METTL27	DRC10	Q96DY2	597
METTL27	TMEM270	Q6UE05	586
METTL27	METTL17	Q9H7H0	584
METTL27	METTL18	O95568	561
METTL27	METTL9	Q9H1A3	558
METTL27	NTMT1	Q9BV86	539
METTL27	METTL25	Q8N6Q8	537
METTL27	NTMT2	Q5VVY1	534
METTL27	BCL7B	Q9BQE9	512
METTL27	TMEM126A	Q9H061	508
METTL27	METTL26	Q96S19	506
METTL27	METTL1	Q9UBP6	501
METTL27	SCGB1D4	Q6XE38	493
METTL27	METTL5	Q9NRN9	488
METTL27	CLLU1-AS1	Q5K130	479

IntAct

168 interactions, top by confidence:

A	B	Type	Score
ATXN1	METTL27	psi-mi:“MI:0915”(physical association)	0.720
PIK3R3	METTL27	psi-mi:“MI:0915”(physical association)	0.570
METTL27	PIK3R3	psi-mi:“MI:0915”(physical association)	0.570
SNRPC	METTL27	psi-mi:“MI:0915”(physical association)	0.560
NOXA1	METTL27	psi-mi:“MI:0915”(physical association)	0.560
HGS	METTL27	psi-mi:“MI:0915”(physical association)	0.560
DOK6	METTL27	psi-mi:“MI:0915”(physical association)	0.560
PITX1	METTL27	psi-mi:“MI:0915”(physical association)	0.560
CSTF2	METTL27	psi-mi:“MI:0915”(physical association)	0.560
PRKAB2	METTL27	psi-mi:“MI:0915”(physical association)	0.560
LMO4	METTL27	psi-mi:“MI:0915”(physical association)	0.560
GLYCTK	METTL27	psi-mi:“MI:0915”(physical association)	0.560
TBX6	METTL27	psi-mi:“MI:0915”(physical association)	0.560
METTL27	CCDC120	psi-mi:“MI:0915”(physical association)	0.560
VPS37C	METTL27	psi-mi:“MI:0915”(physical association)	0.560
METTL27	FOXC2	psi-mi:“MI:0915”(physical association)	0.560
ZIC1	METTL27	psi-mi:“MI:0915”(physical association)	0.560
EFHC1	METTL27	psi-mi:“MI:0915”(physical association)	0.560
ZNF77	METTL27	psi-mi:“MI:0915”(physical association)	0.560
PROP1	METTL27	psi-mi:“MI:0915”(physical association)	0.560
METTL27	TEKT3	psi-mi:“MI:0915”(physical association)	0.560
SAXO4	METTL27	psi-mi:“MI:0915”(physical association)	0.560
GPANK1	METTL27	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (41): WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), PIK3R3 (Affinity Capture-Luminescence), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid), WBSCR27 (Two-hybrid)

ESM2 similar proteins: A0A061IR73, A5YM72, A6NE52, A7MBM2, A8MYJ7, D3KCC4, D3Z7H8, G3MZC5, O95382, P0C263, P0DPD7, P10938, P51657, P54777, Q0V8J4, Q13608, Q14296, Q3U5Q7, Q53GL7, Q561R2, Q5BK61, Q643R3, Q6MG64, Q6PAT0, Q6ZPS2, Q6ZS72, Q76MJ5, Q8BH02, Q8BH83, Q8CG70, Q8IVL6, Q8IZY2, Q8N2G8, Q8N6F8, Q8N9W5, Q8VIM9, Q95K25, Q96BM1, Q96EY9, Q96IR7

Diamond homologs: A5GA37, B9LZA9, Q6ANL3, Q8N6F8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	35
Likely benign	10
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1071515	NC_000007.13:g.(?73150889)(73604636_?)del	Pathogenic
443516	GRCh37/hg19 7q11.23(chr7:72643631-74142190)x1	Pathogenic
563394	GRCh37/hg19 7q11.23(chr7:72700524-74069858)x3	Pathogenic

SpliceAI

764 predictions. Top by Δscore:

Variant	Effect	Δscore
7:73840129:G:GC	acceptor_gain	1.0000
7:73842395:ATCTT:A	donor_gain	1.0000
7:73842399:T:TA	donor_gain	1.0000
7:73840025:CCTCA:C	donor_loss	0.9900
7:73840026:CTCA:C	donor_loss	0.9900
7:73840027:TCACC:T	donor_loss	0.9900
7:73840028:CA:C	donor_loss	0.9900
7:73840029:A:AG	donor_loss	0.9900
7:73840030:C:A	donor_loss	0.9900
7:73840030:CCTGG:C	donor_gain	0.9900
7:73840125:G:C	acceptor_gain	0.9900
7:73840125:G:GC	acceptor_gain	0.9900
7:73840127:G:C	acceptor_gain	0.9900
7:73840127:G:GC	acceptor_gain	0.9900
7:73840129:G:C	acceptor_gain	0.9900
7:73841064:CCTCA:C	donor_loss	0.9900
7:73841065:CTCAC:C	donor_loss	0.9900
7:73841066:TCACC:T	donor_loss	0.9900
7:73841067:CACCT:C	donor_loss	0.9900
7:73841068:A:C	donor_loss	0.9900
7:73841069:CCTCG:C	donor_loss	0.9900
7:73840119:CCCTG:C	acceptor_gain	0.9800
7:73840120:CCTG:C	acceptor_gain	0.9800
7:73840131:G:C	acceptor_gain	0.9800
7:73840131:G:GC	acceptor_gain	0.9800
7:73842322:CA:C	donor_gain	0.9800
7:73842322:CACT:C	donor_gain	0.9800
7:73842395:AT:A	donor_gain	0.9800
7:73842400:C:A	donor_gain	0.9800
7:73840119:CC:C	acceptor_gain	0.9700

AlphaMissense

1559 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:73840113:G:C	F132L	0.927
7:73840113:G:T	F132L	0.927
7:73840115:A:G	F132L	0.927
7:73840532:G:C	F90L	0.896
7:73840532:G:T	F90L	0.896
7:73840534:A:G	F90L	0.896
7:73840505:G:C	S99R	0.860
7:73840505:G:T	S99R	0.860
7:73840507:T:G	S99R	0.860
7:73834950:C:A	K177N	0.857
7:73834950:C:G	K177N	0.857
7:73841110:A:G	I71T	0.836
7:73840497:A:G	M102T	0.831
7:73840057:A:T	I151K	0.825
7:73840496:C:A	M102I	0.818
7:73840496:C:G	M102I	0.818
7:73840496:C:T	M102I	0.818
7:73842048:G:C	F31L	0.803
7:73842048:G:T	F31L	0.803
7:73842050:A:G	F31L	0.803
7:73842036:C:A	W35C	0.801
7:73842036:C:G	W35C	0.801
7:73841092:C:A	G77V	0.799
7:73842038:A:G	W35R	0.780
7:73842038:A:T	W35R	0.780
7:73834991:A:G	C164R	0.754
7:73840083:A:C	S142R	0.748
7:73840083:A:T	S142R	0.748
7:73840085:T:G	S142R	0.748
7:73841110:A:T	I71N	0.745

dbSNP variants (sampled 300 via entrez): RS1000083575 (7:73838999 C>A,T), RS1002087256 (7:73841730 G>C), RS1002184993 (7:73834553 G>A,T), RS1002544397 (7:73841431 C>G,T), RS1002643186 (7:73837337 A>G), RS1003807329 (7:73842862 G>A,C), RS1004202663 (7:73843204 T>G), RS1004244233 (7:73841403 A>G), RS1004422329 (7:73834528 G>A,T), RS1004599835 (7:73835359 G>A,C), RS1004720937 (7:73841703 C>T), RS1004755582 (7:73835466 C>T), RS1004983845 (7:73842809 C>A), RS1006252164 (7:73844419 C>A), RS1006680572 (7:73838526 G>A)

Disease associations

OMIM: gene MIM:612546 | disease phenotypes: MIM:185500

GenCC curated gene-disease

Mondo (1): supravalvular aortic stenosis (MONDO:0008504)

Orphanet (1): Supravalvular aortic stenosis (Orphanet:3193)

HPO phenotypes

186 total (30 of 186 shown, HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000014	Abnormality of the bladder
HP:0000015	Bladder diverticulum
HP:0000023	Inguinal hernia
HP:0000025	Functional abnormality of male internal genitalia
HP:0000028	Cryptorchidism
HP:0000044	Hypogonadotropic hypogonadism
HP:0000075	Renal duplication
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000089	Renal hypoplasia
HP:0000093	Proteinuria
HP:0000121	Nephrocalcinosis
HP:0000125	Pelvic kidney
HP:0000147	Polycystic ovaries
HP:0000154	Wide mouth
HP:0000158	Macroglossia
HP:0000179	Thick lower lip vermilion
HP:0000212	Gingival overgrowth
HP:0000232	Everted lower lip vermilion
HP:0000252	Microcephaly
HP:0000275	Narrow face
HP:0000280	Coarse facial features
HP:0000286	Epicanthus
HP:0000307	Pointed chin
HP:0000337	Broad forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000358	Posteriorly rotated ears

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Smoke	decreases expression, increases abundance, increases expression	2
pirinixic acid	affects binding, decreases expression, increases activity	1
bisphenol A	increases expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
terbufos	increases methylation	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous chloride	decreases expression	1
perfluorooctane sulfonic acid	increases expression	1
K 7174	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Temozolomide	increases expression	1
Arsenic Trioxide	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Parathion	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Rotenone	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02706639	Not specified	COMPLETED	Williams Syndrome (WS) and Supravalvar Aortic Stenosis (SVAS) DNA and Tissue Bank
NCT02840448	Not specified	COMPLETED	Impact of Elastin Mediated Vascular Stiffness on End Organs
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns