MSMO1
protein-codingmethylsterol monooxygenase 1, the group of Fatty acid hydroxylase domain containing
Gene summary
Sterol-C4-mehtyl oxidase-like protein was isolated based on its similarity to the yeast ERG25 protein. It contains a set of putative metal binding motifs with similarity to that seen in a family of membrane desaturases-hydroxylases. The protein is localized to the endoplasmic reticulum membrane and is believed to function in cholesterol biosynthesis. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
- SC4MOL
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0014793
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0014793
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0014793
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Allergy/Immunology/Infectious; Biochemical; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic
Intervention: Allergy/Immunology/Infectious; Biochemical; Dermatologic
Rationale: Medical management (with oral and topical cholesterol and statin supplements,) has been described as beneficial in terms of laboratory (eg, immunocyte profiles) and clinical parameters (eg, growth, arthralgias, skin disease)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to MSMO1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006745.5. 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 | 9 | 9 | ||||
| missense | 2 | 1 | 43 | 4 | 2 | 52 |
| nonsense | 2 | 2 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 2 | 1 | 45 | 13 | 2 | 63 |
Highest pathogenic variant AF is 0.000028741846
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006736.1 | 5 | MANE Select | |
| Ensembl | ENSP00000261507.6 | 5 | MANE Select | |
| RefSeq | NP_001017369.1 | 4 | Standard | |
| RefSeq | NP_001427463.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Steroid biosynthesis - Homo sapiens (human)
- Simvastatin Action Pathway
- Pravastatin Action Pathway
- Atorvastatin Action Pathway
- Hyper-IgD syndrome
Biological Process
- fatty acid metabolic process
- cholesterol biosynthetic process
- steroid metabolic process
- sterol biosynthetic process
- oxidation-reduction process
Molecular Function
- C-4 methylsterol oxidase activity
- iron ion binding
Cellular Component
- endoplasmic reticulum
- endoplasmic reticulum membrane
- plasma membrane
- integral component of membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000261507
- Coding exons
- 5
- Length
- 15538
- Individuals with no LoFs
- 125705
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125713
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.590 | 129 | 149 | 0.864 | 0.00000664 | 1954 |
| Missense (PolyPhen) | 37 | 47.953 | 0.77159 | 606 | ||
| Synonymous | 1.42 | 36 | 48.6 | 0.740 | 0.00000216 | 502 |
| Loss of Function | 2.32 | 4 | 13.0 | 0.307 | 5.48e-7 | 180 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Catalyzes the first step in the removal of the two C-4 methyl groups of 4,4-dimethylzymosterol. {ECO:0000250|UniProtKB:P53045}.;
- Disease
- DISEASE: Microcephaly, congenital cataract, and psoriasiform dermatitis (MCCPD) [MIM:616834]: An autosomal recessive inborn error of cholesterol metabolism characterized by accumulation of a large amount of methylsterols, particularly dimethylsterols, in affected individuals. Patients manifest psoriasiform dermatitis, arthralgias, congenital cataracts, microcephaly, and developmental delay. {ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:24144731}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Recessive Scores
- pRec
- 0.187
Intolerance Scores
- RVIS EVS
- 0.7
- RVIS percentile EVS
- 85.42
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.830
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |