SARDH

sarcosine dehydrogenase

Basic information

Region (hg38): 9:133663559-133739955

Previous symbols: [ "DMGDHL1" ]

Links

ENSG00000123453

∙ NCBI:1757 ∙ OMIM:604455 ∙ HGNC:10536 ∙ Uniprot:Q9UL12 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed

Phenotypes

GenCC

Source: genCC

sarcosinemia (Supportive), mode of inheritance: AR
sarcosinemia (Limited), mode of inheritance: AR

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARDH gene.

Inborn genetic diseases (27 variants)
not provided (22 variants)
Sarcosine dehydrogenase deficiency (7 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARDH gene is commonly pathogenic or not.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				3	9	12
missense			24	6	5	35
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel						0
splice variant					1	1
non coding						0
Total	0	1	25	9	15

Variants in SARDH

This is a list of pathogenic ClinVar variants found in the SARDH region.

Position	Phenotype	Significance	ClinVar
9-133663914-T-C	Inborn genetic diseases	Uncertain significance (Dec 20, 2021)	link
9-133663932-G-A	Inborn genetic diseases	Uncertain significance (Sep 17, 2021)	link
9-133666739-C-T	Inborn genetic diseases	Uncertain significance (Aug 26, 2022)	link
9-133666754-T-C	Inborn genetic diseases	Likely benign (Dec 02, 2022)	link
9-133666770-C-T	Inborn genetic diseases	Uncertain significance (Mar 06, 2023)	link
9-133666782-C-T	Inborn genetic diseases	Likely benign (Jul 09, 2021)	link
9-133666783-G-C	Inborn genetic diseases	Uncertain significance (Jul 27, 2021)	link
9-133670611-C-T	Inborn genetic diseases	Uncertain significance (Jan 07, 2022)	link
9-133670612-G-A	Inborn genetic diseases	Uncertain significance (Jun 22, 2023)	link
9-133670615-G-A	Inborn genetic diseases	Uncertain significance (Jul 13, 2021)	link
9-133670624-C-T		Benign (Dec 31, 2019)	link
9-133670630-G-A	Inborn genetic diseases	Uncertain significance (Jul 20, 2021)	link
9-133670635-T-C	Inborn genetic diseases	Uncertain significance (Aug 23, 2021)	link
9-133670733-C-T		Benign (Dec 31, 2019)	link
9-133670734-G-A		Likely benign (Dec 31, 2019)	link
9-133671564-C-T	Inborn genetic diseases	Uncertain significance (Aug 08, 2022)	link
9-133671635-C-T		Likely benign (Nov 16, 2017)	link
9-133671636-G-A	Inborn genetic diseases	Uncertain significance (Feb 01, 2023)	link
9-133671694-G-A	Sarcosine dehydrogenase deficiency	Affects (Nov 01, 2012)	link
9-133685207-C-T	Inborn genetic diseases	Uncertain significance (Jun 28, 2022)	link
9-133690384-C-T	Inborn genetic diseases	Uncertain significance (May 28, 2023)	link
9-133694267-C-T	Inborn genetic diseases	Uncertain significance (Sep 14, 2022)	link
9-133696245-G-A		Benign (Mar 11, 2021)	link
9-133696245-G-C		Benign (Dec 31, 2019)	link
9-133696313-T-C	Inborn genetic diseases	Uncertain significance (Jan 26, 2022)	link

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SARDH	protein_coding	protein_coding	ENST00000371872	20	76396

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.27e-16	0.917	125455	0	293	125748	0.00117

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.679	561	608	0.923	0.0000407	5870
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00203	0.00195
Ashkenazi Jewish	0.00190	0.00189
East Asian	0.000502	0.000489
Finnish	0.00334	0.00329
European (Non-Finnish)	0.00112	0.00111
Middle Eastern	0.000502	0.000489
South Asian	0.000462	0.000457
Other	0.000981	0.000978

dbNSFP

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.;
Pathway: Glycine, serine and threonine metabolism - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;sarcosine oncometabolite pathway ;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);One carbon metabolism and related pathways;Metabolism of amino acids and derivatives;Metabolism;Choline catabolism;glycine betaine degradation;superpathway of choline degradation to L-serine;Glycine, serine, alanine and threonine metabolism (Consensus)

Recessive Scores

pRec: 0.317

Intolerance Scores

loftool: 0.115
rvis_EVS: 1.41
rvis_percentile_EVS: 94.81

Haploinsufficiency Scores

pHI: 0.365
hipred: Y
hipred_score: 0.755
ghis: 0.441

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.887

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Sardh
Phenotype

Gene ontology

Biological process: choline catabolic process;oxidation-reduction process;sarcosine catabolic process
Cellular component: cytoplasm;mitochondrion;mitochondrial matrix
Molecular function: sarcosine dehydrogenase activity;oxidoreductase activity