BHMT

protein-coding

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

Gene summary

This gene encodes a cytosolic enzyme that catalyzes the conversion of betaine and homocysteine to dimethylglycine and methionine, respectively. Defects in this gene could lead to hyperhomocyst(e)inemia, but such a defect has not yet been observed. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001713.3

Inheritance

—

ClinVar variants

U:53B:5

Top phenotype

BHMT-related disorder

gnomAD constraint

pLI —, LoF o/e 0.97

Max pathogenic AF

—

Genomic locus

chr5:79,111,809-79,132,288

External References & Databases

Ensembl (ENSG00000145692)

Transcript & Mutation Effects

hg38 • Region Span ~20.5 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 BHMT variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 49

not providedTotal: 4

BHMT-related disorderTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001713.3. 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			2 clinvar		1 clinvar	3
missense			49 clinvar	3 clinvar	1 clinvar	53
nonsense						0
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	53	3	2	58

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 25 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001713.3	RefSeq	NP_001704.2	8	MANE Select
ENST00000274353.10	Ensembl	ENSP00000274353.5	8	MANE Select
ENST00000524080.1	Ensembl	ENSP00000428240.1	5	Standard
ENST00000524080.2	Ensembl	ENSP00000428240.1	5	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
bhmt	Danio rerio	Structure: pancreatic B cell Quality: increased amount abnormal

Gene / Model

Organism

Observed Phenotype

bhmt

Danio rerio

Structure: pancreatic B cell

Quality: increased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Cysteine and methionine metabolism - Homo sapiens (human)
Glycine, serine and threonine metabolism - Homo sapiens (human)
S-Adenosylhomocysteine (SAH) Hydrolase Deficiency
Methionine Metabolism
3-Phosphoglycerate dehydrogenase deficiency

Biological Process

sulfur amino acid metabolic process
protein methylation
amino-acid betaine metabolic process
amino-acid betaine catabolic process
choline catabolic process

Molecular Function

zinc ion binding
betaine-homocysteine S-methyltransferase activity

Cellular Component

cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000274353
Coding exons: 8
Length: 20507
Individuals with no LoFs: 125700
Homozygous LoFs: 0
Heterozygous LoFs: 48
Defined: 125748
p: 0.000191

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.147	218	224	0.972	0.0000116	2634
Missense (PolyPhen)		49	54.959	0.89158		648
Synonymous	1.28	69	84.0	0.822	0.00000479	770
Loss of Function	0.117	21	21.6	0.973	0.00000111	255

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00044	0.00043	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00049	0.00049	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00017	0.00017	rare
South Asian	0.00027	0.00023	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline.;

Recessive Scores

pRec: 0.225

Intolerance Scores

LoFtool: 0.850
RVIS EVS: -0.05
RVIS percentile EVS: 50.22

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.813

Gene Damage Prediction

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