MSMO1

methylsterol monooxygenase 1, the group of Fatty acid hydroxylase domain containing

Basic information

Region (hg38): 4:165327666-165343164

Previous symbols: [ "SC4MOL" ]

Links

ENSG00000052802 ∙ NCBI:6307 ∙ OMIM:607545 ∙ HGNC:10545 ∙ Uniprot:Q15800 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• microcephaly-congenital cataract-psoriasiform dermatitis syndrome (Limited), mode of inheritance: AR
• microcephaly-congenital cataract-psoriasiform dermatitis syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

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 ClinVar and linked to the MSMO1 gene.

• not provided (49 variants)
• Inborn genetic diseases (7 variants)
• Microcephaly-congenital cataract-psoriasiform dermatitis syndrome (1 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.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				4	1	5
missense		1	20	3	2	26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding				4	20	24
Total	0	1	20	11	23

Variants in MSMO1

This is a list of pathogenic ClinVar variants found in the MSMO1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

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)
4-165333385-A-T		not specified	Uncertain significance (Feb 12, 2024)
4-165333401-A-C		not specified	Uncertain significance (Sep 27, 2021)
4-165333408-C-T		not specified	Uncertain significance (Sep 29, 2023)
4-165333514-G-T		not specified	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		not specified	Uncertain significance (Oct 13, 2023)
4-165333565-C-A			Uncertain significance (Dec 21, 2023)
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 05, 2023)
4-165337817-G-C		not specified	Uncertain significance (Apr 04, 2023)
4-165337829-A-G			Benign/Likely benign (Jan 02, 2024)
4-165337836-T-C			Likely benign (Oct 25, 2017)
4-165337839-C-T			Likely benign (Jun 14, 2023)
4-165337848-C-A		not specified	Uncertain significance (Dec 21, 2023)
4-165337885-T-C			Uncertain significance (Feb 04, 2022)
4-165337904-A-G			Benign (Jan 22, 2024)
4-165337905-T-C			Likely benign (Apr 29, 2023)
4-165337909-C-G		MSMO1-related disorder	Benign (Dec 07, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

• 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

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