SHMT1

protein-coding

serine hydroxymethyltransferase 1, the group of Serine hydroxymethyltransferase family|MicroRNA protein coding host genes

Gene summary

This gene encodes the cytosolic form of serine hydroxymethyltransferase, a pyridoxal phosphate-containing enzyme that catalyzes the reversible conversion of serine and tetrahydrofolate to glycine and 5,10-methylene tetrahydrofolate. This reaction provides one-carbon units for synthesis of methionine, thymidylate, and purines in the cytoplasm. This gene is located within the Smith-Magenis syndrome region on chromosome 17. A pseudogene of this gene is located on the short arm of chromosome 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

MANE transcript

NM_004169.5

Inheritance

—

ClinVar variants

U:62B:12

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.95

Max pathogenic AF

—

Genomic locus

chr17:18,327,873-18,363,550

External References & Databases

Ensembl (ENSG00000176974)

Transcript & Mutation Effects

hg38 • Region Span ~35.7 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 SHMT1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 60

not providedTotal: 14

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_004169.5. 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	3 clinvar	4
missense			58 clinvar	4 clinvar	2 clinvar	64
nonsense						0
start loss				1 clinvar	1 clinvar	2
frameshift						0
splice donor/acceptor (+/-2bp)			4 clinvar			4
Total	0	0	62	6	6	74

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 159 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_004169.5	RefSeq	NP_004160.3	11	MANE Select
ENST00000316694.8	Ensembl	ENSP00000318868.3	11	MANE Select
NM_001281786.2	RefSeq	NP_001268715.1	8	Standard
NM_148918.3	RefSeq	NP_683718.1	10	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Antimetabolite Pathway - Folate Cycle, Pharmacodynamics
One carbon pool by folate - Homo sapiens (human)
Glycine, serine and threonine metabolism - Homo sapiens (human)
Glyoxylate and dicarboxylate metabolism - Homo sapiens (human)
Methotrexate Pathway (Cancer Cell), Pharmacodynamics

Biological Process

dTMP biosynthetic process
glycine metabolic process
L-serine metabolic process
L-serine catabolic process
one-carbon metabolic process

Molecular Function

translation repressor activity, mRNA regulatory element binding
glycine hydroxymethyltransferase activity
protein binding
zinc ion binding
L-allo-threonine aldolase activity

Cellular Component

nucleus
cytosol
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000316694
Coding exons: 11
Length: 35670
Individuals with no LoFs: 125656
Homozygous LoFs: 0
Heterozygous LoFs: 92
Defined: 125748
p: 0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.352	259	275	0.940	0.0000168	3127
Missense (PolyPhen)		113	135.39	0.83462		1439
Synonymous	-0.661	125	116	1.08	0.00000744	983
Loss of Function	0.205	22	23.1	0.954	0.00000146	263

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00062	0.00062	rare
Latino/Admixed American	0.00061	0.00061	rare
Ashkenazi Jewish	0.00080	0.00079	rare
East Asian	0.00054	0.00049	rare
Finnish	0.00023	0.00023	rare
European (Non-Finnish)	0.00022	0.00022	rare
South Asian	0.00036	0.00036	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interconversion of serine and glycine (PubMed:8505317, PubMed:24698160). {ECO:0000269|PubMed:24698160, ECO:0000269|PubMed:8505317}.;

Recessive Scores

pRec: 0.388

Intolerance Scores

LoFtool: 0.940
RVIS EVS: 0.22
RVIS percentile EVS: 68.38

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.821

Gene Damage Prediction

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