Lathosterolosis

Summary

Lathosterolosis (MONDO:0011816) is a disease caused by SC5D (GenCC Definitive), with 2 cohort genes and 1 clinical trial.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: SC5D (GenCC Definitive)
• Cohort genes: 2
• ClinVar variants: 131
• Phenotypes (HPO): 45
• Clinical trials: 1

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		4	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Signs & symptoms

Clinical features (HPO)

45 HPO clinical features (Orphanet curated; top 45 by frequency):

HPO ID	Term	Frequency
HP:0000252	Microcephaly	Very frequent (80-99%)
HP:0000518	Cataract	Very frequent (80-99%)
HP:0001263	Global developmental delay	Very frequent (80-99%)
HP:0001328	Specific learning disability	Very frequent (80-99%)
HP:0001830	Postaxial foot polydactyly	Very frequent (80-99%)
HP:0008736	Hypoplasia of penis	Very frequent (80-99%)
HP:0000085	Horseshoe kidney	Frequent (30-79%)
HP:0000212	Gingival overgrowth	Frequent (30-79%)
HP:0000218	High palate	Frequent (30-79%)
HP:0000286	Epicanthus	Frequent (30-79%)
HP:0000293	Full cheeks	Frequent (30-79%)
HP:0000340	Sloping forehead	Frequent (30-79%)
HP:0000341	Narrow forehead	Frequent (30-79%)
HP:0000343	Long philtrum	Frequent (30-79%)
HP:0000347	Micrognathia	Frequent (30-79%)
HP:0000365	Hearing impairment	Frequent (30-79%)
HP:0000414	Bulbous nose	Frequent (30-79%)
HP:0000463	Anteverted nares	Frequent (30-79%)
HP:0000482	Microcornea	Frequent (30-79%)
HP:0000494	Downslanted palpebral fissures	Frequent (30-79%)
HP:0000508	Ptosis	Frequent (30-79%)
HP:0001162	Postaxial hand polydactyly	Frequent (30-79%)
HP:0001250	Seizure	Frequent (30-79%)
HP:0001252	Hypotonia	Frequent (30-79%)
HP:0001336	Myoclonus	Frequent (30-79%)
HP:0001399	Hepatic failure	Frequent (30-79%)
HP:0001406	Intrahepatic cholestasis	Frequent (30-79%)
HP:0001508	Failure to thrive	Frequent (30-79%)
HP:0001511	Intrauterine growth retardation	Frequent (30-79%)
HP:0001770	Toe syndactyly	Frequent (30-79%)
HP:0001873	Thrombocytopenia	Frequent (30-79%)
HP:0001883	Talipes	Frequent (30-79%)
HP:0002240	Hepatomegaly	Frequent (30-79%)
HP:0002308	Chiari malformation	Frequent (30-79%)
HP:0002435	Meningocele	Frequent (30-79%)
HP:0002514	Cerebral calcification	Frequent (30-79%)
HP:0002714	Downturned corners of mouth	Frequent (30-79%)
HP:0003196	Short nose	Frequent (30-79%)
HP:0004422	Biparietal narrowing	Frequent (30-79%)
HP:0004823	Anisopoikilocytosis	Frequent (30-79%)
HP:0005487	Prominent metopic ridge	Frequent (30-79%)
HP:0007759	Opacification of the corneal stroma	Frequent (30-79%)
HP:0008278	Cerebellar cortical atrophy	Frequent (30-79%)
HP:0011875	Abnormal platelet morphology	Frequent (30-79%)
HP:0100711	Abnormality of the thoracic spine	Frequent (30-79%)

Identifiers

Disease identifiers

Field	Value
Canonical name	lathosterolosis
Mondo ID	MONDO:0011816
MeSH	C537880
OMIM	607330
Orphanet	46059
ICD-11	1816858203
SNOMED CT	719257008
UMLS	C1846421
MedGen	375885
GARD	0009711
Is cancer (heuristic)	no

Also known as: lathosterolosis · sterol C5-desaturase deficiency

Data availability: 131 ClinVar variants · 4 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by developmental or physiological process › metabolic disease › developmental anomaly of metabolic origin › sterol biosynthesis disorder › cholesterol biosynthetic process disease › lathosterolosis

Related subtypes (2): Smith-Lemli-Opitz syndrome, desmosterolosis

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

131 retrieved; paginated sample, class counts are floors:

95 uncertain significance, 16 benign, 8 likely benign, 5 conflicting classifications of pathogenicity, 4 pathogenic, 2 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
17050	NM_001735.3(C5):c.55C>T (p.Gln19Ter)	C5	Pathogenic	criteria provided, multiple submitters, no conflicts
7356	NM_006918.5(SC5D):c.137A>C (p.Tyr46Ser)	SC5D	Pathogenic	no assertion criteria provided
916041	NM_006918.5(SC5D):c.630C>A (p.Asp210Glu)	SC5D	Pathogenic	no assertion criteria provided
916042	NM_006918.5(SC5D):c.479C>G (p.Pro160Arg)	SC5D	Pathogenic	no assertion criteria provided
7354	NM_006918.5(SC5D):c.86G>A (p.Arg29Gln)	SC5D	Likely pathogenic	criteria provided, single submitter
7355	NM_006918.5(SC5D):c.632G>A (p.Gly211Asp)	SC5D	Likely pathogenic	criteria provided, single submitter
1679342	NM_006918.5(SC5D):c.268_269del (p.Leu90fs)	SC5D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303054	NM_006918.5(SC5D):c.444+11T>C	SC5D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
303056	NM_006918.5(SC5D):c.753C>T (p.Gly251=)	SC5D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
638393	NM_006918.5(SC5D):c.223C>T (p.Arg75Ter)	SC5D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
877943	NM_006918.5(SC5D):c.344-15C>T	SC5D	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1333349	NM_006918.5(SC5D):c.656T>C (p.Leu219Ser)	SC5D	Uncertain significance	criteria provided, single submitter
1418599	NM_006918.5(SC5D):c.875A>G (p.Asn292Ser)	SC5D	Uncertain significance	criteria provided, multiple submitters, no conflicts
1679319	NM_006918.5(SC5D):c.535C>T (p.Pro179Ser)	SC5D	Uncertain significance	criteria provided, single submitter
1722313	NM_006918.5(SC5D):c.608T>C (p.Ile203Thr)	SC5D	Uncertain significance	criteria provided, single submitter
303051	NM_006918.5(SC5D):c.224G>A (p.Arg75Gln)	SC5D	Uncertain significance	criteria provided, single submitter
303053	NM_006918.5(SC5D):c.344-8T>C	SC5D	Uncertain significance	criteria provided, single submitter
303055	NM_006918.5(SC5D):c.447C>T (p.Arg149=)	SC5D	Uncertain significance	criteria provided, single submitter
303059	NM_006918.5(SC5D):c.*313A>T	SC5D	Uncertain significance	criteria provided, single submitter
303060	NM_006918.5(SC5D):c.*367A>T	SC5D	Uncertain significance	criteria provided, single submitter
303061	NM_006918.5(SC5D):c.*512G>A	SC5D	Uncertain significance	criteria provided, single submitter
303062	NM_006918.5(SC5D):c.*598T>C	SC5D	Uncertain significance	criteria provided, single submitter
303063	NM_006918.5(SC5D):c.*981C>T	SC5D	Uncertain significance	criteria provided, single submitter
303064	NM_006918.5(SC5D):c.*1012T>C	SC5D	Uncertain significance	criteria provided, single submitter
303067	NM_006918.5(SC5D):c.*1196T>A	SC5D	Uncertain significance	criteria provided, single submitter
303068	NM_006918.5(SC5D):c.*1223A>T	SC5D	Uncertain significance	criteria provided, single submitter
303071	NM_006918.5(SC5D):c.*1711T>C	SC5D	Uncertain significance	criteria provided, single submitter
303072	NM_006918.5(SC5D):c.*1818A>G	SC5D	Uncertain significance	criteria provided, single submitter
303074	NM_006918.5(SC5D):c.*1860A>G	SC5D	Uncertain significance	criteria provided, single submitter
303075	NM_006918.5(SC5D):c.*1876G>T	SC5D	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 4 · Orphanet: 2 · 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
SC5D	Definitive	Autosomal recessive	lathosterolosis	4

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
SC5D	Orphanet:46059	Lathosterolosis
C5	Orphanet:169150	Immunodeficiency due to a late component of complement deficiency

Cohort genes → proteins

2 cohort genes, 2 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	2

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
SC5D	HGNC:10547	ENSG00000109929	O75845	Lathosterol oxidase	gencc,clinvar
C5	HGNC:1331	ENSG00000106804	P01031	Complement C5	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
SC5D	Lathosterol oxidase	Catalyzes the penultimate step of the biosynthesis of cholesterol, the dehydrogenation of lathosterol into 7-dehydrocholesterol (7-DHC).
C5	Complement C5	Precursor of the C5a anaphylatoxin and complement C5b components of the complement pathways, which consist in a cascade of proteins that leads to phagocytosis and breakdown of pathogens and signaling that strengthens the adaptive immune sy…

Protein-family classification

Druggable: 2 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Complement	1	134.0×	0.015
Enzyme (other)	1	6.0×	0.160

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
SC5D	Enzyme (other)	yes	1.14.19.20	Fatty_acid_hydroxylase, Sterol_desaturase-rel
C5	Complement	yes	3.4.21.43	Anaphylatoxin/fibulin, Netrin_domain, Macroglobln_a2

Expression context

Cohort genes with no expression data: 0.

2 cohort genes 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)	2
unknown	0

Top tissues across cohort

Tissue	Cohort genes
adrenal tissue	1
pons	1
upper leg skin	1
liver	1
oocyte	1
right lobe of liver	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
SC5D	300	ubiquitous	marker	adrenal tissue, pons, upper leg skin
C5	231	ubiquitous	marker	right lobe of liver, liver, oocyte

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
SC5D	1,582
C5	1,337

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
C5	P01031	42

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
SC5D	O75845	92.05

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 14. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Cholesterol biosynthesis from zymosterol (modified Kandutsch-Russell pathway)	1	1427.5×	0.004	SC5D
Terminal pathway of complement	1	713.8×	0.004	C5
Activation of C3 and C5	1	634.4×	0.004	C5
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	634.4×	0.004	SC5D
Cholesterol biosynthesis	1	571.0×	0.004	SC5D
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	571.0×	0.004	SC5D
Regulation of cholesterol biosynthesis by SREBP (SREBF)	1	158.6×	0.013	SC5D
Activation of gene expression by SREBF (SREBP)	1	129.8×	0.013	SC5D
Regulation of Complement cascade	1	116.5×	0.013	C5
Metabolism of steroids	1	68.8×	0.020	SC5D
Peptide ligand-binding receptors	1	37.1×	0.034	C5
G alpha (i) signalling events	1	19.5×	0.059	C5
Metabolism of lipids	1	15.8×	0.067	SC5D
Metabolism	1	5.8×	0.165	SC5D

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
obsolete cholesterol biosynthetic process via desmosterol	1	2106.5×	0.005	SC5D
negative regulation of macrophage chemotaxis	1	1203.7×	0.005	C5
obsolete cholesterol biosynthetic process via lathosterol	1	1053.2×	0.005	SC5D
complement activation, GZMK pathway	1	648.1×	0.006	C5
complement activation, alternative pathway	1	495.6×	0.006	C5
negative regulation of ferroptosis	1	401.2×	0.006	SC5D
complement activation, classical pathway	1	271.8×	0.008	C5
positive regulation of vascular endothelial growth factor production	1	247.8×	0.008	C5
cholesterol biosynthetic process	1	210.7×	0.008	SC5D
positive regulation of chemokine production	1	187.2×	0.008	C5
killing of cells of another organism	1	135.9×	0.010	C5
chemotaxis	1	68.0×	0.018	C5
cell surface receptor signaling pathway	1	32.0×	0.036	C5
inflammatory response	1	18.9×	0.054	C5
G protein-coupled receptor signaling pathway	1	18.1×	0.054	C5

Therapeutics

Drug target analysis

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

Druggability breadth: 2 of 2 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
C5	OXAPROZIN

Top cohort targets by molecule count

Symbol	Molecules	Max phase
C5	4	4
SC5D	0	0

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
OXAPROZIN	4	C5
CARPROFEN	4	C5
SULINDAC	4	C5
RALOXIFENE	4	C5

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 2.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
C5	25	Binding:25
SC5D	2	Binding:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
SC5D	1.14.19.20	DELTA7-sterol 5(6)-desaturase
C5	3.4.21.43	classical-complement-pathway C3/C5 convertase

Pharmacogenomics

Cohort genes with a PharmGKB record: 2; with CPIC/DPWG dosing guidelines: 0.

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

Chemical tractability of cohort targets

4 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.

Compound	Max phase	Cohort target (bioactivity)
OXAPROZIN	4	C5
CARPROFEN	4	C5
SULINDAC	4	C5
RALOXIFENE	4	C5

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	C5
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	1	SC5D
E	Difficult family or no structure, no drug	0

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)
SC5D	2	—

Clinical trials & evidence

Clinical trials

Clinical trials: 1.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05047354	Not specified	RECRUITING	Biochemical and Phenotypical Aspects of Smith-Lemli-Opitz Syndrome and Related Disorders of Cholesterol Metabolism