METTL23

methyltransferase like 23

Basic information

Region (hg38): 17:76726829-76733936

Previous symbols: [ "C17orf95" ]

Links

ENSG00000181038 ∙ NCBI:124512 ∙ OMIM:615262 ∙ HGNC:26988 ∙ Uniprot:Q86XA0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability, autosomal recessive 44 (Moderate), mode of inheritance: AR
• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• intellectual disability, autosomal recessive 44 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, autosomal recessive 44	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; Musculoskeletal; Neurologic	24501276; 24626631

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the METTL23 gene.

• not provided (21 variants)
• Intellectual disability, autosomal recessive 44 (16 variants)
• Inborn genetic diseases (12 variants)
• not specified (6 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the METTL23 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			15	3		18
nonsense	1		1			2
start loss			1			1
frameshift	3	8	3			14
inframe indel						0
splice donor/acceptor (+/-2bp)	1	1				2
splice region	1		2	1		4
non coding			1			1
Total	5	9	21	4	0

Highest pathogenic variant AF is 0.0000263

Variants in METTL23

This is a list of pathogenic ClinVar variants found in the METTL23 region.

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

Position	Type	Phenotype	Significance	ClinVar
17-76729714-T-C		Inborn genetic diseases	Uncertain significance (Jan 16, 2024)
17-76729730-C-T		Inborn genetic diseases • Intellectual disability, autosomal recessive 44	Uncertain significance (Jun 01, 2022)
17-76732969-ACTT-A		Inborn genetic diseases	Uncertain significance (Jul 08, 2021)
17-76732976-AGATTG-A			Likely pathogenic (Jun 17, 2021)
17-76733016-CA-C		Intellectual disability, autosomal recessive 44	Likely pathogenic (Oct 01, 2019)
17-76733020-T-C			Uncertain significance (Sep 01, 2022)
17-76733029-G-C		METTL23-related disorder	Benign/Likely benign (Dec 31, 2019)
17-76733029-GAAGT-G			Uncertain significance (Apr 29, 2020)
17-76733041-T-TCA			Pathogenic (Oct 27, 2017)
17-76733042-C-CA		Inborn genetic diseases	Pathogenic (Oct 25, 2015)
17-76733059-CCTCA-C		Intellectual disability, autosomal recessive 44 • Inborn genetic diseases	Pathogenic/Likely pathogenic (Apr 21, 2023)
17-76733063-ACTGT-A		Inborn genetic diseases • Intellectual disability, autosomal recessive 44	Pathogenic/Likely pathogenic (Dec 17, 2023)
17-76733069-TG-T		Inborn genetic diseases	Pathogenic (Mar 09, 2015)
17-76733069-T-TG		Intellectual disability, autosomal recessive 44	Pathogenic (Jul 21, 2022)
17-76733081-G-A		Inborn genetic diseases	Uncertain significance (Jul 12, 2022)
17-76733093-AAATG-A		Intellectual disability, autosomal recessive 44	Likely pathogenic (-)
17-76733129-TA-T			Likely pathogenic (-)
17-76733143-A-G		Intellectual disability, autosomal recessive 44	Uncertain significance (Aug 30, 2018)
17-76733148-T-G		not specified	Benign/Likely benign (Dec 31, 2019)
17-76733159-T-A		Intellectual disability, autosomal recessive 44	Uncertain significance (Mar 23, 2022)
17-76733164-C-G		not specified	Uncertain significance (Sep 23, 2015)
17-76733165-TACC-T		Inborn genetic diseases • Intellectual disability, autosomal recessive 44	Conflicting classifications of pathogenicity (Jun 06, 2023)
17-76733171-C-T		Inborn genetic diseases	Uncertain significance (Aug 22, 2023)
17-76733173-CAAGAT-C		Intellectual disability, autosomal recessive 44	Pathogenic (Aug 01, 2014)
17-76733174-A-T		Inborn genetic diseases	Uncertain significance (Oct 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
METTL23	protein_coding	protein_coding	ENST00000341249	4	7107

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.31e-7	0.116	124553	0	85	124638	0.000341

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.973	123	96.1	1.28	0.00000423	1227
Missense in Polyphen		37	34.202	1.0818		442
Synonymous	-0.964	40	33.0	1.21	0.00000141	368
Loss of Function	-0.299	10	9.03	1.11	3.83e-7	108

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000602	0.000584
Ashkenazi Jewish	0.000298	0.000298
East Asian	0.000518	0.000501
Finnish	0.0000928	0.0000928
European (Non-Finnish)	0.000441	0.000425
Middle Eastern	0.000518	0.000501
South Asian	0.000272	0.000261
Other	0.000170	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable methyltransferase. {ECO:0000250}.
• Disease: DISEASE: Mental retardation, autosomal recessive 44 (MRT44) [MIM:615942]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT44 manifestations include mild to severe cognitive impairment, delayed psychomotor development, seizures in some patients, and dysmorphic features. {ECO:0000269|PubMed:24501276, ECO:0000269|PubMed:24626631}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.0822

Intolerance Scores

• rvis_EVS: 0.35
• rvis_percentile_EVS: 74.18

Haploinsufficiency Scores

• hipred: N
• hipred_score: 0.131
• ghis: 0.469

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.114

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Mettl23

Gene ontology

• Biological process: methylation;positive regulation of transcription by RNA polymerase II;cognition
• Cellular component: nucleus;cytoplasm;integral component of membrane;protein-containing complex
• Molecular function: protein binding;transcription factor binding;methyltransferase activity;heat shock protein binding