METTL23 (methyltransferase 23, arginine)

Gene

• Entrez ID: 124512
• Gene name: Methyltransferase 23, arginine
• Gene symbol: METTL23
• Synonyms (NCBI Gene): C17orf95, MRT44
• Chromosome: 17
• Chromosome location: 17q25.1
• Summary: The protein encoded by this gene functions as a transcription factor regulator in the transcriptional pathway for human cognition. It is a partner of the alpha subunit of the GA-binding protein transcription factor. Mutations in this gene cause mild autos

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587777644	CACT>-	Pathogenic	Coding sequence variant, frameshift variant, 5 prime UTR variant, intron variant
rs587777645	AGATA>-	Pathogenic	Coding sequence variant, frameshift variant, intron variant
rs587777646	C>T	Pathogenic	Coding sequence variant, stop gained, 3 prime UTR variant, non coding transcript variant
rs760933323	TT>-	Likely-pathogenic	Coding sequence variant, 3 prime UTR variant, frameshift variant, non coding transcript variant
rs1057521913	G>C	Likely-pathogenic	3 prime UTR variant, coding sequence variant, splice donor variant, missense variant
rs1382444181	G>-	Pathogenic	5 prime UTR variant, frameshift variant, coding sequence variant, intron variant
rs1462161137	->A	Pathogenic	5 prime UTR variant, frameshift variant, coding sequence variant, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT048607	hsa-miR-99a-5p	CLASH	23622248
MIRT039287	hsa-miR-671-5p	CLASH	23622248
MIRT1144524	hsa-miR-331-5p	CLIP-seq
MIRT1144525	hsa-miR-4678	CLIP-seq
MIRT1144526	hsa-miR-4773	CLIP-seq
MIRT1144527	hsa-miR-595	CLIP-seq
MIRT2270775	hsa-miR-3913-3p	CLIP-seq
MIRT2270776	hsa-miR-4775	CLIP-seq
MIRT2270777	hsa-miR-489	CLIP-seq
MIRT2270778	hsa-miR-590-3p	CLIP-seq
MIRT1144527	hsa-miR-595	CLIP-seq
MIRT1144524	hsa-miR-331-5p	CLIP-seq
MIRT1144525	hsa-miR-4678	CLIP-seq
MIRT1144526	hsa-miR-4773	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001939	Component	Female pronucleus	IEA
GO:0001939	Component	Female pronucleus	ISS
GO:0001940	Component	Male pronucleus	IEA
GO:0001940	Component	Male pronucleus	ISS
GO:0005515	Function	Protein binding	IPI	23349634
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IDA	24501276
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	23349634, 24501276
GO:0005737	Component	Cytoplasm	IEA
GO:0006325	Process	Chromatin organization	IEA
GO:0008168	Function	Methyltransferase activity	IEA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0031072	Function	Heat shock protein binding	IPI	23349634
GO:0032259	Process	Methylation	IEA
GO:0032991	Component	Protein-containing complex	IDA	23349634
GO:0032991	Component	Protein-containing complex	IEA
GO:0035242	Function	Protein-arginine omega-N asymmetric methyltransferase activity	IEA
GO:0035642	Function	Histone H3R17 methyltransferase activity	IBA
GO:0035642	Function	Histone H3R17 methyltransferase activity	IEA
GO:0035642	Function	Histone H3R17 methyltransferase activity	ISS
GO:0040029	Process	Epigenetic regulation of gene expression	IBA
GO:0044725	Process	Epigenetic programming in the zygotic pronuclei	IEA
GO:0044725	Process	Epigenetic programming in the zygotic pronuclei	ISS
GO:0044727	Process	Epigenetic programing of male pronucleus	IEA
GO:0044727	Process	Epigenetic programing of male pronucleus	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	24501276
GO:0050890	Process	Cognition	IMP	24501276
GO:0140297	Function	DNA-binding transcription factor binding	IPI	24501276

Other IDs

• MIM: 615262
• HGNC: 26988
• e!Ensembl: ENSG00000181038

Protein

• UniProt ID: Q86XA0
• Protein name: Histone-arginine methyltransferase METTL23 (EC 2.1.1.319) (Methyltransferase-like protein 23)
• Protein function: Histone methyltransferase that dimethylates histone H3 at 'Arg-17', forming asymmetric dimethylarginine (H3R17me2a), leading to activate transcription via chromatin remodeling (By similarity). Maternal factor involved in epigenetic chromatin rep
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF10294	Methyltransf_16	1 → 141	Lysine methyltransferase	Family

• Sequence:

  MYVWPCAVVLAQYLWFHRRSLPGKAILEIGAGVSLPGILAAKCGAEVILSDSSELPHCLE
  VCRQSCQMNNLPHLQVVGLTWGHISWDLLALPPQDIILASDVFFEPEDFEDILATIYFLM
  HKNPKVQLWSTYQVRSADWSLEALLYKWDMKCVHIPLESFDADKEDIAESTLPGRHTVEM
  LVISFAKDSL

• Sequence length: 190

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Intellectual disability	Likely pathogenic; Pathogenic	rs587777644, rs767883844	RCV004798784 RCV004798946	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual disability, autosomal recessive 44	Likely pathogenic; Pathogenic	rs2143866789, rs587777644, rs587777645, rs587777646, rs1278342620, rs2509733625, rs2509730596, rs2509729261, rs760933323, rs1382444181, rs746453662	RCV001782436 RCV000133532 RCV000133533 RCV000133534 RCV002471732 RCV002471837 RCV003333945 RCV003883303 RCV005252912 RCV001251447 RCV001375998	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
AUTOSOMAL RECESSIVE NON-SYNDROMIC INTELLECTUAL DISABILITY	—	Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL RECESSIVE 44	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
MENTAL RETARDATION	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METTL23-related disorder	Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Absence of septum pellucidum	Absence Of Septum Pellucidum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autistic behavior	Autism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Autosomal recessive non-syndromic intellectual disability	Non-Syndromic Intellectual Disability	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Central visual impairment	Central Visual Impairment	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clumsiness - motor delay	Motor delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cortical Dysplasia	Cortical Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Depressive disorder	Mental Depression	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyskinetic syndrome	Dyskinetic Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dysmorphic features	Dysmorphic Features	CLINVAR_DG	24501276, 24626631		★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Generalized seizures	Seizure	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoplasia of corpus callosum	Hypoplasia Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Impaired cognition	Impaired Cognition	HPO_DG			★☆☆☆☆ Found in Text Mining only
Intellectual Disability	Mental retardation	BEFREE	24626631		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	CTD_human_DG	24626631		★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Intellectual developmental disorder	Pubtator	24626631, 32878022	Associate	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Intellectual Disability	Mental retardation	HPO_DG			★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Mental deficiency	Mental retardation	CTD_human_DG	24626631		★☆☆☆☆ Found in Text Mining only
Mental Retardation Autosomal Recessive 1	Intellectual developmental disorder	Pubtator	24501276	Associate	★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 44	Mental retardation	GENOMICS_ENGLAND_DG	24501276, 24626631		★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 44	Mental retardation	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 44	Mental retardation	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Mild Mental Retardation	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Moderate intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Multiple congenital anomalies	Multiple Congenital Anomalies	CLINVAR_DG	24501276, 24626631		★☆☆☆☆ Found in Text Mining only
Polymicrogyria	Polymicrogyria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Profound Mental Retardation	Mental retardation	CTD_human_DG	24626631		★☆☆☆☆ Found in Text Mining only
Salaam Seizures	Salaam Seizures	HPO_DG			★☆☆☆☆ Found in Text Mining only
Severe intellectual disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Stereotyped Behavior	Stereotyped Behavior	HPO_DG			★☆☆☆☆ Found in Text Mining only