BCDIN3D

protein-coding

BCDIN3 domain containing RNA methyltransferase, the group of 7BS DNA/RNA methyltransferases

Gene summary

This gene encodes an RNA methyltransferase which belongs to the rossmann fold methyltransferase family, and serves as a 5'-methylphosphate capping enzyme that is specific for cytoplasmic histidyl tRNA. The encoded protein contains an S-adenosylmethionine binding domain and uses the methyl group donor, S-adenosylmethionine. This gene is overexpressed in breast cancer cells, and is related to the tumorigenic phenotype and poor prognosis of breast cancer. The encoded protein is thought to promote the cellular invasion of breast cancer cells, by downregulating the expression of tumor suppressor miRNAs through the dimethylation of the 5-monophosphate of the corresponding precursor miRNAs. [provided by RefSeq, Apr 2017]

MANE transcript

NM_181708.3

Inheritance

—

ClinVar variants

U:42B:4

Top phenotype

Oromandibular-limb hypogenesis spectrum

gnomAD constraint

pLI —, LoF o/e 0.73

Max pathogenic AF

—

Genomic locus

chr12:49,836,043-49,843,106

External References & Databases

Ensembl (ENSG00000186666)

Transcript & Mutation Effects

hg38 • Region Span ~7.1 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to BCDIN3D variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 42

not providedTotal: 1

Oromandibular-limb hypogenesis spectrumTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_181708.3. 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			1 clinvar			1
missense			41 clinvar	3 clinvar	1 clinvar	45
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	42	3	1	46

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 3 of 3 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_181708.3	RefSeq	NP_859059.1	2	MANE Select
ENST00000333924.6	Ensembl	ENSP00000335201.4	2	MANE Select
ENST00001135314.1	Ensembl	ENSP00000807548.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Gene expression (Transcription)
MicroRNA (miRNA) biogenesis
Gene Silencing by RNA

Biological Process

RNA methylation
miRNA metabolic process
negative regulation of pre-miRNA processing

Molecular Function

protein binding
O-methyltransferase activity
RNA methyltransferase activity

Cellular Component

nucleus
cytoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000333924
Coding exons: 2
Length: 5340
Individuals with no LoFs: 125710
Homozygous LoFs: 0
Heterozygous LoFs: 38
Defined: 125748
p: 0.000151

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.226	159	167	0.951	0.00000841	1906
Missense (PolyPhen)		33	31.638	1.0431		326
Synonymous	0.404	62	66.2	0.937	0.00000321	594
Loss of Function	0.815	8	10.9	0.734	7.22e-7	97

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00012	0.00012	rare
Latino/Admixed American	0.00023	0.00023	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00033	0.00033	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: O-methyltransferase that specifically dimethylates the 5' monophosphate of pre-miRNAs, acting as a negative regulator of miRNA processing. The 5' monophosphate of pre-miRNAs is recognized by DICER1 and is required for pre-miRNAs processing: methylation at this position reduces the processing of pre-miRNAs by DICER1. Able to mediate methylation of pre-miR-145, as well as other pre- miRNAs. {ECO:0000269|PubMed:23063121}.;

Intolerance Scores

LoFtool: 0.746
RVIS EVS: 0.13
RVIS percentile EVS: 63.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): S
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.273

Gene Damage Prediction

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