METTL5

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

Basic information

Region (hg38): 2:169810081-169824931

Links

ENSG00000138382 ∙ NCBI:29081 ∙ OMIM:618628 ∙ HGNC:25006 ∙ Uniprot:Q9NRN9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual developmental disorder, autosomal recessive 72 (Moderate), mode of inheritance: AR
• intellectual developmental disorder, autosomal recessive 72 (Strong), mode of inheritance: AR
• autosomal recessive primary microcephaly (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 72	AR	General	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	Craniofacial; Neurologic	29302074; 31564433

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the METTL5 gene.

• Intellectual developmental disorder, autosomal recessive 72 (3 variants)
• Intellectual disability, severe (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the METTL5 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					1	1
missense			9			9
nonsense			3			3
start loss						0
frameshift	1	1	1			3
inframe indel						0
splice donor/acceptor (+/-2bp)	2	3				5
splice region			2			2
non coding			6			6
Total	3	4	19	0	1

Variants in METTL5

This is a list of pathogenic ClinVar variants found in the METTL5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-169810297-A-C		not specified	Uncertain significance (Jul 12, 2023)
2-169810323-C-T		not specified	Uncertain significance (Nov 15, 2021)
2-169810406-G-A		not specified	Uncertain significance (Nov 29, 2023)
2-169810912-G-A		not specified	Uncertain significance (Nov 07, 2022)
2-169811185-C-G		not specified	Uncertain significance (Mar 01, 2023)
2-169811185-C-T		not specified	Uncertain significance (Nov 10, 2024)
2-169811186-G-T		not specified	Uncertain significance (Oct 12, 2024)
2-169811270-C-T		not specified	Uncertain significance (May 03, 2023)
2-169811284-GATGATGAAC-G			Likely benign (Sep 01, 2024)
2-169811288-A-G		not specified	Uncertain significance (Sep 09, 2024)
2-169811293-C-A		not specified	Uncertain significance (Mar 18, 2024)
2-169811299-G-C		not specified	Uncertain significance (Mar 30, 2024)
2-169812455-A-C		Intellectual developmental disorder, autosomal recessive 72	Pathogenic (May 04, 2022)
2-169812461-T-G		Inborn genetic diseases	Uncertain significance (Mar 31, 2024)
2-169812475-CTT-C		Intellectual developmental disorder, autosomal recessive 72 • Intellectual disability, severe	Pathogenic/Likely pathogenic (Nov 16, 2020)
2-169812478-G-C		Inborn genetic diseases	Uncertain significance (Oct 13, 2023)
2-169812480-A-G		Inborn genetic diseases	Uncertain significance (Aug 04, 2024)
2-169812501-G-A			Uncertain significance (Sep 12, 2022)
2-169812507-C-A		Intellectual developmental disorder, autosomal recessive 72	Pathogenic (Dec 18, 2024)
2-169815476-C-G		Intellectual developmental disorder, autosomal recessive 72	Likely pathogenic (Jan 03, 2020)
2-169815527-T-G		Inborn genetic diseases	Uncertain significance (Jan 11, 2023)
2-169819604-G-C		Inborn genetic diseases	Uncertain significance (Feb 27, 2023)
2-169819634-A-G		Inborn genetic diseases	Uncertain significance (Jun 24, 2022)
2-169819636-A-C		Inborn genetic diseases	Uncertain significance (Mar 06, 2023)
2-169821087-C-T		Intellectual developmental disorder, autosomal recessive 72	Uncertain significance (-)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
METTL5	protein_coding	protein_coding	ENST00000260953	7	14851

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000517	0.690	125723	0	25	125748	0.0000994

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.559	94	111	0.850	0.00000523	1380
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000542	0.000521
Ashkenazi Jewish	0.00	0.00
East Asian	0.000273	0.000272
Finnish	0.00	0.00
European (Non-Finnish)	0.0000267	0.0000264
Middle Eastern	0.000273	0.000272
South Asian	0.000325	0.000261
Other	0.00	0.00

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.352
• hipred: N
• hipred_score: 0.344
• ghis: 0.608

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.466

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mettl5

Gene ontology

• Biological process: methylation
• Molecular function: nucleic acid binding;methyltransferase activity