BHMT2

protein-coding

betaine--homocysteine S-methyltransferase 2, the group of Homocysteine methyltransferases

Gene summary

Homocysteine is a sulfur-containing amino acid that plays a crucial role in methylation reactions. Transfer of the methyl group from betaine to homocysteine creates methionine, which donates the methyl group to methylate DNA, proteins, lipids, and other intracellular metabolites. The protein encoded by this gene is one of two methyl transferases that can catalyze the transfer of the methyl group from betaine to homocysteine. Anomalies in homocysteine metabolism have been implicated in disorders ranging from vascular disease to neural tube birth defects such as spina bifida. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

MANE transcript

NM_017614.5

Inheritance

—

ClinVar variants

U:60B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.15

Max pathogenic AF

—

Genomic locus

chr5:79,069,767-79,090,069

External References & Databases

Ensembl (ENSG00000132840)

Transcript & Mutation Effects

hg38 • Region Span ~20.3 kb

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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 BHMT2 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 2

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_017614.5. 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			59 clinvar	1 clinvar	1 clinvar	61
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	60	2	1	63

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 47 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_017614.5	RefSeq	NP_060084.2	8	MANE Select
ENST00000255192.8	Ensembl	ENSP00000255192.3	8	MANE Select
NM_001178005.2	RefSeq	NP_001171476.1	7	Standard
ENST00000518666.5	Ensembl	ENSP00000428640.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cysteine and methionine metabolism - Homo sapiens (human)
Allograft Rejection
One carbon metabolism and related pathways
Metabolism of amino acids and derivatives
Metabolism

Biological Process

sulfur amino acid metabolic process
amino-acid betaine metabolic process
methylation
S-methylmethionine metabolic process
S-adenosylmethionine metabolic process

Molecular Function

zinc ion binding
betaine-homocysteine S-methyltransferase activity
S-methylmethionine-homocysteine S-methyltransferase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000255192
Coding exons: 8
Length: 19750
Individuals with no LoFs: 125318
Homozygous LoFs: 1
Heterozygous LoFs: 429
Defined: 125748
p: 0.00171

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.680	177	204	0.866	0.0000106	2365
Missense (PolyPhen)		57	63.16	0.90247		744
Synonymous	0.463	71	76.1	0.932	0.00000455	690
Loss of Function	-0.578	21	18.3	1.15	9.02e-7	220

Population LoF Frequency

Population	CAF	p-value	Status
African	0.011	0.011	notable
Latino/Admixed American	0.0010	0.0010	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00051	0.00049	rare
Finnish	0.0017	0.0017	notable
European (Non-Finnish)	0.00077	0.00076	rare
South Asian	0.0022	0.0022	notable
Other	0.0020	0.0020	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of homocysteine metabolism. Converts homocysteine to methionine using S-methylmethionine (SMM) as a methyl donor. {ECO:0000269|PubMed:18230605}.;

Intolerance Scores

LoFtool: 0.977
RVIS EVS: 0.17
RVIS percentile EVS: 65.96

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0515

Gene Damage Prediction

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