YTHDC1

protein-coding

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

Gene summary

Enables N6-methyladenosine-containing RNA reader activity and RNA binding activity. Involved in gene expression and regulation of gene expression. Located in nuclear speck. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001031732.4

Inheritance

ClinVar variants

U:73B:1

Top phenotype

YTHDC1-related disorder

gnomAD constraint

pLI —, LoF o/e 0.02

Max pathogenic AF

—

Genomic locus

chr4:68,310,387-68,350,090

External References & Databases

Ensembl (ENSG00000083896)

Transcript & Mutation Effects

hg38 • Region Span ~39.7 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

autism spectrum disorderLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0005258

Submitter: Ambry Genetics

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to YTHDC1 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 61

not providedTotal: 1

YTHDC1-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001031732.4. 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			2 clinvar			2
missense			64 clinvar	1 clinvar		65
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	0	73	1	0	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001031732.4	RefSeq	NP_001026902.1	17	MANE Select
ENST00000344157.9	Ensembl	ENSP00000339245.4	17	MANE Select
NM_001330698.2	RefSeq	NP_001317627.1	17	Standard
NM_133370.4	RefSeq	NP_588611.2	16	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

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

Molecular Function

RNA binding
protein binding
N6-methyladenosine-containing RNA binding

Cellular Component

nucleus
nucleoplasm
plasma membrane
nuclear speck

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000344157
Coding exons: 17
Length: 39703
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 2
Defined: 125736
p: 0.00000795

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.48	269	410	0.656	0.0000230	4750
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000018	0.000018	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): E
Essential (CRISPR2): E
Essential (gene trap): E
Indispensability pred.: E
Indispensability score: 0.967

Gene Damage Prediction

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