METTL5

protein-coding

methyltransferase 5, N6-adenosine, the group of 7BS N6-adenosine DNA/RNA methyltransferases

Gene summary

Enables S-adenosyl-L-methionine binding activity and rRNA (adenine-N6-)-methyltransferase activity. Involved in positive regulation of translation and rRNA methylation. Located in several cellular components, including fibrillar center; postsynapse; and presynapse. Implicated in autosomal recessive intellectual developmental disorder 72. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_014168.4

Inheritance

ClinVar variants

P:11U:43B:3

Top phenotype

Intellectual developmental disorder, autosomal recessive 72

gnomAD constraint

pLI —, LoF o/e 0.7

Max pathogenic AF

—

Genomic locus

chr2:169,810,081-169,824,931

External References & Databases

Ensembl (ENSG00000138382)

Transcript & Mutation Effects

hg38 • Region Span ~14.9 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

intellectual developmental disorder, autosomal recessive 72STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032860

Submitter: G2P

autosomal recessive primary microcephalySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0016660

Submitter: Orphanet

intellectual developmental disorder, autosomal recessive 72STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032860

Submitter: PanelApp Australia

intellectual developmental disorder, autosomal recessive 72STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032860

Submitter: Labcorp Genetics (formerly Invitae)

intellectual developmental disorder, autosomal recessive 72MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032860

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Intellectual developmental disorder, autosomal recessive 72AR

Manifestation: Craniofacial; Neurologic

Intervention: General

Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing

Refs: 29302074; 31564433

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to METTL5 variants in ClinVar

6 Conditions Cataloged

Inborn genetic diseasesTotal: 27

Intellectual developmental disorder, autosomal recessive 72Total: 15

not providedTotal: 11

not specifiedTotal: 6

Severe intellectual disabilityTotal: 2

METTL5-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014168.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	2 clinvar	1 clinvar	4
missense		1 clinvar	31 clinvar			32
nonsense			4 clinvar			4
start loss						0
frameshift	1 clinvar	3 clinvar	1 clinvar			5
splice donor/acceptor (+/-2bp)	3 clinvar	3 clinvar	6 clinvar			12
Total	4	7	43	2	1	57

Highest pathogenic variant AF is 0.000065726344

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 36 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014168.4	RefSeq	NP_054887.2	7	MANE Select
ENST00000260953.10	Ensembl	ENSP00000260953.5	7	MANE Select
NM_001293186.2	RefSeq	NP_001280115.1	7	Standard
NM_001293187.2	RefSeq	NP_001280116.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

methylation

Molecular Function

nucleic acid binding
methyltransferase activity

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000260953
Coding exons: 7
Length: 14851
Individuals with no LoFs: 125723
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 125748
p: 0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.559	94	111	0.850	0.00000523	1380
Missense (PolyPhen)		21	25.501	0.82349		313
Synonymous	0.611	33	37.8	0.874	0.00000184	367
Loss of Function	0.939	8	11.4	0.700	5.42e-7	158

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00051	0.00049	rare
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00027	0.00027	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000027	0.000026	rare
South Asian	0.00033	0.00026	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable methyltransferase. {ECO:0000250}.;

Recessive Scores

pRec: 0.116

Intolerance Scores

LoFtool: 0.497
RVIS EVS: -0.07
RVIS percentile EVS: 48.12

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.466

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium