MSMO1
methylsterol monooxygenase 1, the group of Fatty acid hydroxylase domain containing
Basic information
Region (hg38): 4:165327666-165343164
Previous symbols: [ "SC4MOL" ]
Links
Phenotypes
GenCC
Source:
- microcephaly-congenital cataract-psoriasiform dermatitis syndrome (Limited), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Microcephaly, congenital cataract, and psoriasiform dermatitis | AR | Allergy/Immunology/Infectious; Biochemical; Dermatologic | 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) | Allergy/Immunology/Infectious; Biochemical; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic | 21285510; 24144731 |
ClinVar
This is a list of variants' phenotypes submitted to
- not provided (47 variants)
- Inborn genetic diseases (4 variants)
- Microcephaly-congenital cataract-psoriasiform dermatitis syndrome (3 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSMO1 gene is commonly pathogenic or not.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 2 | 1 | 16 | 2 | 3 | 24 |
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice variant | 1 | 1 | ||||
| non coding | 3 | 18 | 21 | |||
| Total | 2 | 1 | 16 | 10 | 22 |
Variants in MSMO1
This is a list of pathogenic ClinVar variants found in the MSMO1 region.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 4-165333022-C-G | Benign (Jun 19, 2021) | |||
| 4-165333201-C-G | Benign (Nov 12, 2018) | |||
| 4-165333383-G-C | Likely benign (Jun 04, 2022) | |||
| 4-165333401-A-C | Inborn genetic diseases | Uncertain significance (Sep 27, 2021) | ||
| 4-165333514-G-T | Inborn genetic diseases | Uncertain significance (Apr 04, 2023) | ||
| 4-165333526-G-C | Uncertain significance (Jul 05, 2022) | |||
| 4-165333538-A-G | Uncertain significance (Jul 18, 2022) | |||
| 4-165333549-C-G | Uncertain significance (Jun 23, 2022) | |||
| 4-165333801-A-C | Benign (Nov 12, 2018) | |||
| 4-165333821-A-G | Benign (Nov 12, 2018) | |||
| 4-165337753-G-A | Benign (Jun 19, 2021) | |||
| 4-165337785-G-A | Likely benign (Sep 06, 2022) | |||
| 4-165337815-A-G | Likely benign (Oct 24, 2022) | |||
| 4-165337817-G-C | Inborn genetic diseases | Uncertain significance (Apr 04, 2023) | ||
| 4-165337829-A-G | Benign (Oct 31, 2022) | |||
| 4-165337836-T-C | Likely benign (Oct 25, 2017) | |||
| 4-165337839-C-T | Likely benign (Feb 14, 2022) | |||
| 4-165337848-C-A | Uncertain significance (Dec 25, 2021) | |||
| 4-165337885-T-C | Uncertain significance (Feb 04, 2022) | |||
| 4-165337904-A-G | Benign (Oct 27, 2022) | |||
| 4-165337905-T-C | Likely benign (Jun 24, 2022) | |||
| 4-165337909-C-G | Benign (Sep 06, 2022) | |||
| 4-165338009-C-T | Benign (Jun 19, 2021) | |||
| 4-165338329-T-C | Benign (Jun 19, 2021) | |||
| 4-165338355-T-C | Benign (Jun 19, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| MSMO1 | protein_coding | protein_coding | ENST00000261507 | 5 | 15538 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0900 | 0.902 | 125705 | 0 | 8 | 125713 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.590 | 129 | 149 | 0.864 | 0.00000664 | 1954 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000152 | 0.000152 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000165 | 0.000163 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000176 | 0.0000176 |
| Middle Eastern | 0.000165 | 0.000163 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
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.;
- Pathway
- Steroid biosynthesis - Homo sapiens (human);Simvastatin Action Pathway;Pravastatin Action Pathway;Atorvastatin Action Pathway;Hyper-IgD syndrome;Cholesteryl ester storage disease;Lysosomal Acid Lipase Deficiency (Wolman Disease);Alendronate Action Pathway;Rosuvastatin Action Pathway;Lovastatin Action Pathway;Mevalonic aciduria;Wolman disease;Risedronate Action Pathway;Cerivastatin Action Pathway;Pamidronate Action Pathway;Fluvastatin Action Pathway;Smith-Lemli-Opitz Syndrome (SLOS);Chondrodysplasia Punctata II, X Linked Dominant (CDPX2);CHILD Syndrome;Desmosterolosis;Hypercholesterolemia;Steroid Biosynthesis;Zoledronate Action Pathway;Ibandronate Action Pathway;Cholesterol Biosynthesis;Metabolism of lipids;zymosterol biosynthesis;Squalene and cholesterol biosynthesis;Metabolism;cholesterol biosynthesis III (via desmosterol);cholesterol biosynthesis II (via 24,25-dihydrolanosterol);superpathway of cholesterol biosynthesis;Metabolism of steroids;cholesterol biosynthesis I;Cholesterol biosynthesis
(Consensus)
Recessive Scores
- pRec
- 0.187
Intolerance Scores
- loftool
- rvis_EVS
- 0.7
- rvis_percentile_EVS
- 85.42
Haploinsufficiency Scores
- pHI
- 0.566
- hipred
- Y
- hipred_score
- 0.800
- ghis
- 0.481
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.830
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Msmo1
- Phenotype
Gene ontology
- Biological process
- fatty acid metabolic process;cholesterol biosynthetic process;steroid metabolic process;sterol biosynthetic process;oxidation-reduction process
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;plasma membrane;integral component of membrane
- Molecular function
- C-4 methylsterol oxidase activity;iron ion binding