Sarcosinemia

Summary

Sarcosinemia (MONDO:0010008) is a disease with 1 cohort gene.

At a glance

• Prevalence: 1-9 / 100 000 (Worldwide) [Orphanet-validated]
• Cohort genes: 1
• ClinVar variants: 11
• Phenotypes (HPO): 22

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Point prevalence	1-9 / 100 000		Worldwide	Validated
Prevalence at birth	1-9 / 100 000	2	Worldwide	Validated
Prevalence at birth	1-9 / 1 000 000	0.28	United States	Validated
Prevalence at birth	1-9 / 100 000	2.3	Specific population	Validated

Signs & symptoms

Clinical features (HPO)

22 HPO clinical features (Orphanet curated; top 22 by frequency):

HPO ID	Term	Frequency
HP:0010896	Hypersarcosinemia	Obligate (100%)
HP:0010897	Hypersarcosinuria	Very frequent (80-99%)
HP:0000486	Strabismus	Occasional (5-29%)
HP:0000648	Optic atrophy	Occasional (5-29%)
HP:0000712	Emotional lability	Occasional (5-29%)
HP:0001251	Ataxia	Occasional (5-29%)
HP:0001256	Intellectual disability, mild	Occasional (5-29%)
HP:0001263	Global developmental delay	Occasional (5-29%)
HP:0001270	Motor delay	Occasional (5-29%)
HP:0001639	Hypertrophic cardiomyopathy	Occasional (5-29%)
HP:0001642	Pulmonic stenosis	Occasional (5-29%)
HP:0002069	Bilateral tonic-clonic seizure	Occasional (5-29%)
HP:0002273	Tetraparesis	Occasional (5-29%)
HP:0002360	Sleep abnormality	Occasional (5-29%)
HP:0002371	Loss of speech	Occasional (5-29%)
HP:0002465	Poor speech	Occasional (5-29%)
HP:0007875	Congenital blindness	Occasional (5-29%)
HP:0008610	Infantile sensorineural hearing impairment	Occasional (5-29%)
HP:0008947	Floppy infant	Occasional (5-29%)
HP:0010522	Dyslexia	Occasional (5-29%)
HP:0011727	Peroneal muscle weakness	Occasional (5-29%)
HP:0100022	Abnormality of movement	Occasional (5-29%)

Identifiers

Disease identifiers

Field	Value
Canonical name	sarcosinemia
Mondo ID	MONDO:0010008
MeSH	C537236
OMIM	268900
Orphanet	3129
DOID	DOID:0112307
ICD-11	1901733714
SNOMED CT	64852002
UMLS	C0268563
MedGen	120651
GARD	0000158
MedDRA	10059299
Is cancer (heuristic)	no

Also known as: SARCOS · sarcosinemia

Data availability: 11 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by etiologic mechanism › disease of genetic or genomic mechanism › hereditary disease › inborn errors of metabolism › disorder of peptide and amine metabolism › disorder of methylamine metabolism › sarcosinemia

Related subtypes (1): dimethylglycine dehydrogenase deficiency

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

11 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 4 affects, 1 likely pathogenic, 1 benign/likely benign, 1 benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
2433137	NM_001134707.2(SARDH):c.1306del (p.Asp436fs)	SARDH	Likely pathogenic	criteria provided, single submitter
2462102	NM_001134707.2(SARDH):c.434C>T (p.Thr145Met)	SARDH	Uncertain significance	criteria provided, multiple submitters, no conflicts
2664774	NM_001134707.2(SARDH):c.1442G>A (p.Arg481His)	SARDH	Uncertain significance	criteria provided, single submitter
3596753	NM_001134707.2(SARDH):c.1577G>C (p.Gly526Ala)	SARDH	Uncertain significance	criteria provided, multiple submitters, no conflicts
39448	NM_001134707.2(SARDH):c.211G>T (p.Val71Phe)	SARDH	Affects	no assertion criteria provided
39449	NM_001134707.2(SARDH):c.860C>T (p.Pro287Leu)	SARDH	Affects	no assertion criteria provided
39450	NM_001134707.2(SARDH):c.2167C>T (p.Arg723Ter)	SARDH	Affects	no assertion criteria provided
39451	NM_001134707.2(SARDH):c.1540C>T (p.Arg514Ter)	SARDH	Affects	no assertion criteria provided
4292891	NM_001134707.2(SARDH):c.2378C>T (p.Ala793Val)	SARDH	Uncertain significance	criteria provided, single submitter
711531	NM_001134707.2(SARDH):c.1299G>A (p.Pro433=)	SARDH	Benign/Likely benign	criteria provided, multiple submitters, no conflicts
786146	NM_001134707.2(SARDH):c.473A>G (p.Asn158Ser)	SARDH	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
SARDH	Moderate	Autosomal recessive	sarcosinemia	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SARDH	Orphanet:3129	Sarcosinemia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SARDH	HGNC:10536	ENSG00000123453	Q9UL12	Sarcosine dehydrogenase, mitochondrial	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SARDH	Sarcosine dehydrogenase, mitochondrial	Catalyzes the last step of the oxidative degradation of choline to glycine.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SARDH	Other/Unknown	no		FAD-dep_OxRdtase, GCVT_N, GcvT_C

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
buccal mucosa cell	1
liver	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SARDH	173	broad	marker	right lobe of liver, buccal mucosa cell, liver

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SARDH	1,836

Structural data

PDB: 0 · AlphaFold-only: 1 · No structure: 0

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SARDH	Q9UL12	93.03

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 3. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Choline catabolism	1	1427.5×	0.002	SARDH
Metabolism of amino acids and derivatives	1	67.6×	0.022	SARDH
Metabolism	1	11.6×	0.086	SARDH

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete sarcosine catabolic process	1	16852.0×	6e-05	SARDH

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
SARDH	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	SARDH

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
SARDH	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.