SARDH

protein-coding

sarcosine dehydrogenase

Gene summary

This gene encodes an enzyme localized to the mitochondrial matrix which catalyzes the oxidative demethylation of sarcosine. This enzyme is distinct from another mitochondrial matrix enzyme, dimethylglycine dehydrogenase, which catalyzes a reaction resulting in the formation of sarcosine. Mutations in this gene are associated with sarcosinemia. Alternatively spliced transcript variants have been described. [provided by RefSeq, Oct 2008]

Previous symbols:

DMGDHL1

MANE transcript

NM_001134707.2

Inheritance

ClinVar variants

P:2U:186B:39

Top phenotype

sarcosinemia

gnomAD constraint

pLI —, LoF o/e 0.66

Max pathogenic AF

—

Genomic locus

chr9:133,663,560-133,739,955

External References & Databases

Ensembl (ENSG00000123453)

Transcript & Mutation Effects

hg38 • Region Span ~76.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

sarcosinemiaSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0010008

Submitter: Orphanet

sarcosinemiaLIMITED

Inheritance Pattern: Unknown

Disease ID:MONDO:0010008

Submitter: Labcorp Genetics (formerly Invitae)

sarcosinemiaLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0010008

Submitter: ClinGen

The relationship between *SARDH* and autosomal recessive sarcosinemia was evaluated using the ClinGen Clinical Validity Framework as of 04/18/19. Sarcosinemia is caused by a defect in the conversion of sarcosine to glycine, which is catalyzed by SARDH. The clinical phenotypes of sarcosinemia vary considerably and it has been suggested that it is a benign condition (Bar-joseph et al., 2010). All known variants in *SARDH* were reported in humans with this disease in 2012 (Bar-joseph et al., 22825317). Evidence supporting this gene-disease relationship includes only one paper with case-level data. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence, both genetic and experimental, is needed to support a causal role, no convincing evidence that contradicts the gene-disease relationship has been found. This classification was approved by the ClinGen Aminoacidopathy Working Group on 06/28/19 (SOP Version 6). It was reevaluated on 10/14/2022 and 11/18/2025 with no new evidence found. As a result of this reevaluation, the classification remained Limited.

sarcosinemiaMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0010008

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SARDH variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 172

not providedTotal: 31

SARDH-related disorderTotal: 16

Sarcosine dehydrogenase deficiencyTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001134707.2. 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			4 clinvar	14 clinvar	8 clinvar	26
missense			179 clinvar	12 clinvar	5 clinvar	196
nonsense			2 clinvar			2
start loss						0
frameshift	1 clinvar	1 clinvar				2
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	1	1	186	26	13	227

Highest pathogenic variant AF is 0.000024794947

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 54 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001134707.2	RefSeq	NP_001128179.1	20	MANE Select
ENST00000439388.6	Ensembl	ENSP00000403084.1	20	MANE Select
NM_007101.4	RefSeq	NP_009032.2	20	Standard
ENST00000298628.6	Ensembl	ENSP00000298628.5	6	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Glycine, serine and threonine metabolism - Homo sapiens (human)
3-Phosphoglycerate dehydrogenase deficiency
Non Ketotic Hyperglycinemia
Glycine and Serine Metabolism
sarcosine oncometabolite pathway

Biological Process

choline catabolic process
oxidation-reduction process
sarcosine catabolic process

Molecular Function

sarcosine dehydrogenase activity
oxidoreductase activity

Cellular Component

cytoplasm
mitochondrion
mitochondrial matrix

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000371872
Coding exons: 20
Length: 76396
Individuals with no LoFs: 125455
Homozygous LoFs: 0
Heterozygous LoFs: 293
Defined: 125748
p: 0.00117

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.679	561	608	0.923	0.0000407	5870
Missense (PolyPhen)		194	245.77	0.78936		2404
Synonymous	0.102	262	264	0.992	0.0000192	1872
Loss of Function	2.23	32	48.8	0.655	0.00000285	471

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0011	0.0010	notable
Latino/Admixed American	0.00091	0.00090	rare
Ashkenazi Jewish	0.0019	0.0019	notable
East Asian	0.00050	0.00049	rare
Finnish	0.0033	0.0033	notable
European (Non-Finnish)	0.0011	0.0011	notable
South Asian	0.00046	0.00046	rare
Other	0.00098	0.00098	rare

dbNSFP Gene Annotations

Source: dbNSFP

Disease: DISEASE: Sarcosinemia (SARCOS) [MIM:268900]: A metabolic disorder characterized by an increased concentration of sarcosine in plasma and an increased excretion of sarcosine in urine. Sarcosinemia is most probably a benign condition without significant clinical problems. Some reports have associated sarcosinemia with mental retardation and neurologic problems. {ECO:0000269|PubMed:10444331, ECO:0000269|PubMed:22825317}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.317

Intolerance Scores

LoFtool: 0.115
RVIS EVS: 1.41
RVIS percentile EVS: 94.81

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.887

Gene Damage Prediction

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