Microcephaly-congenital cataract-psoriasiform dermatitis syndrome

Summary

Microcephaly-congenital cataract-psoriasiform dermatitis syndrome (MONDO:0014793) is a disease caused by MSMO1 (GenCC Strong), with 1 cohort gene.

At a glance

• Prevalence: <1 / 1 000 000 (Worldwide) [Orphanet-validated]
• Causal gene: MSMO1 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 7

Clinical features

Epidemiology

Prevalence records

2 prevalence record(s), Orphanet:

Type	Class	Value	Geography	Validation
Cases/families		5	Worldwide	Validated
Point prevalence	<1 / 1 000 000		Worldwide	Validated

Identifiers

Disease identifiers

Field	Value
Canonical name	microcephaly-congenital cataract-psoriasiform dermatitis syndrome
Mondo ID	MONDO:0014793
OMIM	616834
Orphanet	488168
UMLS	C5567510
MedGen	1798933
GARD	0017886
Is cancer (heuristic)	no

Also known as: MCCPD · microcephaly, congenital cataract, and psoriasiform dermatitis · smo deficiency · sterol-C4-methyl oxidase deficiency

Data availability: 7 ClinVar variants · 3 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 › microcephaly-congenital cataract-psoriasiform dermatitis syndrome

Related subtypes (6): Greenberg dysplasia, MEND syndrome, X-linked chondrodysplasia punctata, CHILD syndrome, mevalonate kinase deficiency, cholesterol biosynthetic process disease

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

7 retrieved; paginated sample, class counts are floors:

4 uncertain significance, 2 pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
222974	NM_006745.5(MSMO1):c.519T>A (p.His173Gln)	MSMO1	Pathogenic	no assertion criteria provided
222976	NM_006745.5(MSMO1):c.736G>C (p.Gly246Arg)	MSMO1	Pathogenic	no assertion criteria provided
222975	NM_006745.5(MSMO1):c.731A>G (p.Tyr244Cys)	MSMO1	Likely pathogenic	criteria provided, single submitter
4056627	NM_006745.5(MSMO1):c.754T>G (p.Phe252Val)	MSMO1	Uncertain significance	criteria provided, single submitter
4079289	NM_006745.5(MSMO1):c.801_804delinsATGA (p.Trp267_Trp268delinsTer)	MSMO1	Uncertain significance	criteria provided, single submitter
4079290	NM_006745.5(MSMO1):c.405G>T (p.Trp135Cys)	MSMO1	Uncertain significance	criteria provided, multiple submitters, no conflicts
4759463	NM_006745.5(MSMO1):c.801G>A (p.Trp267Ter)	MSMO1	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
MSMO1	Strong	Autosomal recessive	microcephaly-congenital cataract-psoriasiform dermatitis syndrome	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MSMO1	Orphanet:488168	Microcephaly-congenital cataract-psoriasiform dermatitis syndrome

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
MSMO1	HGNC:10545	ENSG00000052802	Q15800	Methylsterol monooxygenase 1	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MSMO1	Methylsterol monooxygenase 1	Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be subsequently metabolized to cholesterol.

Protein-family classification

Druggable: 1 · 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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
MSMO1	Enzyme (other)	yes	1.14.18.9	Fatty_acid_hydroxylase, Sterol_desaturase-rel

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
adrenal tissue	1
mammalian vulva	1
upper leg skin	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MSMO1	297	ubiquitous	marker	adrenal tissue, upper leg skin, mammalian vulva

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MSMO1	1,649

Structural data

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

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
MSMO1	Q15800	94.13

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 6. 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
Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)	1	1268.9×	0.002	MSMO1
Cholesterol biosynthesis	1	1142.0×	0.002	MSMO1
Cholesterol biosynthesis via desmosterol (Bloch pathway)	1	1142.0×	0.002	MSMO1
Metabolism of steroids	1	137.6×	0.011	MSMO1
Metabolism of lipids	1	31.6×	0.038	MSMO1
Metabolism	1	11.6×	0.086	MSMO1

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 cholesterol biosynthetic process via lathosterol	1	2106.5×	0.001	MSMO1
sterol biosynthetic process	1	1685.2×	0.001	MSMO1
cholesterol biosynthetic process	1	421.3×	0.004	MSMO1
steroid metabolic process	1	337.0×	0.004	MSMO1
fatty acid metabolic process	1	193.7×	0.005	MSMO1

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
MSMO1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
MSMO1	1	Binding:1

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MSMO1	1.14.18.9	4alpha-methylsterol monooxygenase

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	1	MSMO1
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)
MSMO1	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.