YTHDC1

YTH N6-methyladenosine RNA binding protein C1, the group of YTH domain containing N6-methyladenosine readers

Basic information

Region (hg38): 4:68310387-68350090

Links

ENSG00000083896 ∙ NCBI:91746 ∙ OMIM:617283 ∙ HGNC:30626 ∙ Uniprot:Q96MU7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autism spectrum disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the YTHDC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the YTHDC1 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						0
missense			24	1		25
nonsense						0
start loss						0
frameshift						0
inframe indel				1		1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	24	2	0

Variants in YTHDC1

This is a list of pathogenic ClinVar variants found in the YTHDC1 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-68314109-T-A		not specified	Uncertain significance (Oct 26, 2021)
4-68314127-C-T		not specified	Uncertain significance (Jul 20, 2022)
4-68314134-T-C		not specified	Uncertain significance (Sep 17, 2021)
4-68314187-C-T		not specified	Uncertain significance (Oct 03, 2022)
4-68314262-C-T		not specified	Uncertain significance (Mar 01, 2023)
4-68318532-G-A		not specified	Uncertain significance (May 10, 2024)
4-68318841-T-C		not specified	Uncertain significance (Mar 07, 2024)
4-68318860-A-G		not specified	Uncertain significance (Jul 15, 2021)
4-68320129-T-C		not specified	Uncertain significance (Jun 29, 2023)
4-68322785-C-T		not specified	Uncertain significance (Jan 24, 2024)
4-68332188-C-T		not specified	Uncertain significance (Mar 19, 2024)
4-68332838-T-C		not specified	Uncertain significance (Aug 08, 2022)
4-68337089-C-T		not specified	Likely benign (Jun 28, 2022)
4-68337153-C-T		not specified	Uncertain significance (Sep 27, 2022)
4-68337208-TTCC-T		YTHDC1-related disorder	Likely benign (Apr 25, 2023)
4-68337242-T-C		not specified	Uncertain significance (Jan 04, 2022)
4-68337328-T-A		not specified	Uncertain significance (Nov 12, 2021)
4-68337344-C-T		not specified	Uncertain significance (Mar 18, 2024)
4-68337614-A-T		not specified	Uncertain significance (Sep 12, 2023)
4-68337624-C-T		not specified	Uncertain significance (May 26, 2023)
4-68337642-G-A		not specified	Uncertain significance (Nov 08, 2022)
4-68337654-T-C		not specified	Uncertain significance (Jul 12, 2022)
4-68337693-C-T		not specified	Uncertain significance (Sep 22, 2022)
4-68337774-C-T		not specified	Uncertain significance (May 09, 2022)
4-68337825-A-G		not specified	Uncertain significance (Oct 27, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
YTHDC1	protein_coding	protein_coding	ENST00000344157	17	39703

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	5.76e-8	125734	0	2	125736	0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.48	269	410	0.656	0.0000230	4750
Missense in Polyphen		23	75.937	0.30288		879
Synonymous	-0.355	135	130	1.04	0.00000626	1326
Loss of Function	6.46	1	50.5	0.0198	0.00000353	543

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000178	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Regulator of alternative splicing that specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs (PubMed:26318451, PubMed:26876937, PubMed:25242552, PubMed:28984244). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability (PubMed:26318451, PubMed:25242552). Acts as a key regulator of exon-inclusion or exon-skipping during alternative splicing via interaction with mRNA splicing factors SRSF3 and SRSF10 (PubMed:26876937). Specifically binds m6A-containing mRNAs and promotes recruitment of SRSF3 to its mRNA-binding elements adjacent to m6A sites, leading to exon-inclusion during alternative splicing (PubMed:26876937). In contrast, interaction with SRSF3 prevents interaction with SRSF10, a splicing factor that promotes exon skipping: this prevents SRSF10 from binding to its mRNA-binding sites close to m6A-containing regions, leading to inhibit exon skipping during alternative splicing (PubMed:26876937). May also regulate alternative splice site selection (PubMed:20167602). Also involved in nuclear export of m6A-containing mRNAs via interaction with SRSF3: interaction with SRSF3 facilitates m6A-containing mRNA-binding to both SRSF3 and NXF1, promoting mRNA nuclear export (PubMed:28984244). Also recognizes and binds m6A on other RNA molecules (PubMed:27602518). Involved in random X inactivation mediated by Xist RNA: recognizes and binds m6A-containing Xist and promotes transcription repression activity of Xist (PubMed:27602518). Involved in S- adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts, probably by binding m6A-containing MAT2A mRNAs (By similarity). {ECO:0000250|UniProtKB:E9Q5K9, ECO:0000269|PubMed:20167602, ECO:0000269|PubMed:25242552, ECO:0000269|PubMed:26318451, ECO:0000269|PubMed:26876937, ECO:0000269|PubMed:27602518, ECO:0000269|PubMed:28984244}.

Recessive Scores

• pRec: 0.126

Intolerance Scores

• rvis_EVS: -0.58
• rvis_percentile_EVS: 18.59

Haploinsufficiency Scores

• pHI: 0.252
• hipred: Y
• hipred_score: 0.729
• ghis: 0.686

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.967

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ythdc1
• Phenotype: endocrine/exocrine gland phenotype; cellular phenotype; reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: mRNA splice site selection;mRNA export from nucleus;dosage compensation by inactivation of X chromosome;posttranscriptional regulation of gene expression;regulation of mRNA splicing, via spliceosome
• Cellular component: nucleus;nucleoplasm;plasma membrane;nuclear speck
• Molecular function: RNA binding;protein binding;N6-methyladenosine-containing RNA binding