MSMO1

Summary

MSMO1 (methylsterol monooxygenase 1, HGNC:10545) is a protein-coding gene on chromosome 4q32.3, encoding Methylsterol monooxygenase 1 (Q15800). Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be subsequently metabolized to cholesterol.

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.

Source: NCBI Gene 6307 — RefSeq curated summary.

At a glance

• Gene–disease (curated): microcephaly-congenital cataract-psoriasiform dermatitis syndrome (Strong, GenCC)
• GWAS associations: 4
• Clinical variants (ClinVar): 92 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 20
• Druggable target: yes
• MANE Select transcript: NM_006745

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10545
Approved symbol	MSMO1
Name	methylsterol monooxygenase 1
Location	4q32.3
Locus type	gene with protein product
Status	Approved
Aliases	DESP4, ERG25
Ensembl gene	ENSG00000052802
Ensembl biotype	protein_coding
OMIM	607545
Entrez	6307

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000261507, ENST00000393766, ENST00000504317, ENST00000505270, ENST00000507013, ENST00000906531, ENST00000906532, ENST00000906533, ENST00000906534, ENST00000936200, ENST00000963503, ENST00000963504, ENST00000963505

RefSeq mRNA: 2 — MANE Select: NM_006745 NM_001017369, NM_006745

CCDS: CCDS3809, CCDS43280

Canonical transcript exons

ENST00000261507 — 6 exons

Exon	Start	End
ENSE00000740527	165340221	165340375
ENSE00000740530	165338652	165338778
ENSE00002034971	165327669	165327764
ENSE00002045259	165341751	165343164
ENSE00003570965	165337789	165337937
ENSE00003785190	165333340	165333625

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.75.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 100.1418 / max 1154.0075, expressed in 1810 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
50439	99.7921	1810
50440	0.3497	175

Top tissues by expression

300 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
adrenal tissue	UBERON:0018303	99.75	gold quality
upper leg skin	UBERON:0004262	99.32	gold quality
mammalian vulva	UBERON:0000997	99.00	gold quality
pigmented layer of retina	UBERON:0001782	98.98	gold quality
ganglionic eminence	UBERON:0004023	98.78	gold quality
ventricular zone	UBERON:0003053	98.65	gold quality
bronchial epithelial cell	CL:0002328	98.61	gold quality
esophagus squamous epithelium	UBERON:0006920	98.54	gold quality
embryo	UBERON:0000922	98.46	gold quality
jejunal mucosa	UBERON:0000399	98.34	gold quality
cranial nerve II	UBERON:0000941	98.21	gold quality
cortical plate	UBERON:0005343	98.21	gold quality
liver	UBERON:0002107	98.12	gold quality
right lobe of liver	UBERON:0001114	98.11	gold quality
corpus epididymis	UBERON:0004359	98.07	gold quality
amniotic fluid	UBERON:0000173	98.03	gold quality
upper arm skin	UBERON:0004263	98.00	gold quality
oral cavity	UBERON:0000167	97.94	gold quality
cartilage tissue	UBERON:0002418	97.89	gold quality
epithelium of esophagus	UBERON:0001976	97.83	gold quality
endothelial cell	CL:0000115	97.77	gold quality
lower esophagus mucosa	UBERON:0035834	97.70	gold quality
squamous epithelium	UBERON:0006914	97.65	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.64	gold quality
superior vestibular nucleus	UBERON:0007227	97.51	gold quality
epithelium of bronchus	UBERON:0002031	97.50	gold quality
gingiva	UBERON:0001828	97.47	gold quality
esophagus mucosa	UBERON:0002469	97.41	gold quality
lower lobe of lung	UBERON:0008949	97.41	gold quality
gingival epithelium	UBERON:0001949	97.36	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	1061.40
E-MTAB-8495	yes	591.89
E-HCAD-1	yes	75.25
E-GEOD-84465	yes	22.97
E-GEOD-135922	yes	15.30
E-MTAB-6819	no	1818.56
E-CURD-10	no	1237.28
E-MTAB-3929	no	620.81
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

96 targeting MSMO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-106A-5P	99.90	73.94	2683

Literature-anchored findings (GeneRIF, showing 4)

• human SC4MOL encodes a methyl sterol oxidase that may have a role in psoriasiform dermatitis, microcephaly, and developmental delay (PMID:21285510)
• variants in/near SC4MOL, were associated with FI and IR in this cohort of African Amer (PMID:22791750)
• SC4MOL is situated within the psoriasis susceptibility locus PSORS9, and may be a genetic risk factor for common skin conditions. [review] (PMID:24144731)
• New Homozygous Missense MSMO1 Mutation in Two Siblings with SC4MOL Deficiency Presenting with Psoriasiform Dermatitis. (PMID:33161406)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	msmo1	ENSDARG00000055876
mus_musculus	Msmo1	ENSMUSG00000031604
rattus_norvegicus	Msmo1	ENSRNOG00000032297

Paralogs (3): SC5D (ENSG00000109929), CH25H (ENSG00000138135), FAXDC2 (ENSG00000170271)

Protein

Protein identifiers

Methylsterol monooxygenase 1 — Q15800 (reviewed: Q15800)

Alternative names: C-4 methylsterol oxidase, Sterol-C4-methyl oxidase

All UniProt accessions (4): Q15800, D6R952, D6RDP9, D6REA2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the three-step monooxygenation required for the demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be subsequently metabolized to cholesterol. Also involved in drug metabolism, as it can metabolize eldecalcitol (ED-71 or 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)-cholecalciferol), a second-generation vitamin D analog, into 1alpha,2beta,25-trihydroxy vitamin D3; this reaction occurs via enzymatic hydroxylation and spontaneous O-dehydroxypropylation.

Subcellular location. Endoplasmic reticulum membrane.

Post-translational modifications. Ubiquitinated by MARCHF6, leading to proteasomal degradation.

Disease relevance. 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. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The histidine box domains may contain the active site and/or be involved in metal ion binding.

Pathway. Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 3/6. Steroid biosynthesis; cholesterol biosynthesis.

Similarity. Belongs to the sterol desaturase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15800-1	1	yes
Q15800-2	2

RefSeq proteins (2): NP_001017369, NP_006736* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006694	Fatty_acid_hydroxylase	Domain
IPR050307	Sterol_desaturase-rel	Family

Pfam: PF04116

Enzyme classification (BRENDA):

• EC 1.14.18.9 — 4alpha-methylsterol monooxygenase (BRENDA: 6 organisms, 18 substrates, 19 inhibitors, 2 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
4ALPHA-METHYL-5ALPHA-CHOLESTAN-3BETA-OL	0.125	1

Catalyzed reactions (Rhea), 7 shown:

• 4alpha-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4alpha-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:47056)
• 4,4-dimethyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4alpha-carboxy-4beta-methyl-5alpha-cholest-7-ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:55220)
• 4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4beta-methylzymosterol-4alpha-carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:55244)
• 4alpha-methyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4alpha-carboxy-5alpha-cholest-7-en-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:62768)
• 4,4-dimethyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4alpha-carboxy-4beta-methyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:62776)
• 4alpha-methyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-[cytochrome b5] + 3 O2 + 5 H(+) = 4alpha-carboxy-5alpha-cholest-8-ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O (RHEA:62780)
• 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)-cholecalciferol + 2 Fe(II)-[cytochrome b5] + O2 + 2 H(+) = 1alpha,25-dihydroxy-2beta-(1,3-dihydroxypropoxy)-cholecalciferol + 2 Fe(III)-[cytochrome b5] + H2O (RHEA:62820)

UniProt features (13 total): sequence variant 4, transmembrane region 3, short sequence motif 3, chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15800-F1	94.13	0.87

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6807047	Cholesterol biosynthesis via desmosterol (Bloch pathway)
R-HSA-6807062	Zymostenol biosynthesis via lathosterol (Kandutsch-Russell pathway)
R-HSA-191273	Cholesterol biosynthesis
R-HSA-1430728	Metabolism
R-HSA-556833	Metabolism of lipids
R-HSA-8957322	Metabolism of steroids

MSigDB gene sets: 321 (showing top): GSE45365_CTRL_VS_MCMV_INFECTION_NK_CELL_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, MODULE_93, MODULE_52, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, chr4q32, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS

GO Biological Process (9): fatty acid metabolic process (GO:0006631), cholesterol biosynthetic process (GO:0006695), steroid metabolic process (GO:0008202), sterol biosynthetic process (GO:0016126), obsolete cholesterol biosynthetic process via lathosterol (GO:0033490), lipid metabolic process (GO:0006629), steroid biosynthetic process (GO:0006694), cholesterol metabolic process (GO:0008203), lipid biosynthetic process (GO:0008610)

GO Molecular Function (4): C-4 methylsterol oxidase activity (GO:0000254), iron ion binding (GO:0005506), protein binding (GO:0005515), oxidoreductase activity (GO:0016491)

GO Cellular Component (4): endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cholesterol biosynthesis	2
Metabolism of steroids	1
Metabolism	1
Metabolism of lipids	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	3
sterol metabolic process	2
monocarboxylic acid metabolic process	1
cholesterol metabolic process	1
sterol biosynthetic process	1
secondary alcohol biosynthetic process	1
steroid biosynthetic process	1
primary metabolic process	1
steroid metabolic process	1
lipid biosynthetic process	1
secondary alcohol metabolic process	1
biosynthetic process	1
oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, another compound as one donor, and incorporation of one atom of oxygen	1
transition metal ion binding	1
binding	1
catalytic activity	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1412 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MSMO1	ERG28	Q9UKR5	966
MSMO1	FDFT1	P37268	917
MSMO1	HSD17B7	P56937	905
MSMO1	NSDHL	Q15738	886
MSMO1	SQLE	Q14534	837
MSMO1	CYP51A1	Q16850	832
MSMO1	HMGCS1	Q01581	770
MSMO1	IDI1	Q13907	767
MSMO1	DHCR24	Q15392	764
MSMO1	DHCR7	Q9UBM7	763
MSMO1	SREBF2	Q12772	720
MSMO1	TM7SF2	O76062	719
MSMO1	LSS	P48449	713
MSMO1	HMGCR	P04035	704
MSMO1	SC5D	O75845	699

IntAct

129 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
ERG28	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
TMEM242	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
STRIT1	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
GOLT1A	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
TMEM86B	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
YIF1A	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	GOLT1A	psi-mi:“MI:0915”(physical association)	0.560
MMP14	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
HMOX1	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	CYP4F22	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	ERG28	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	TMEM86B	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	TMEM65	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	DNAJC30	psi-mi:“MI:0915”(physical association)	0.560
TMEM11	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	TMEM140	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	TMEM242	psi-mi:“MI:0915”(physical association)	0.560
STX3	MSMO1	psi-mi:“MI:0915”(physical association)	0.560
MSMO1	GPR35	psi-mi:“MI:0915”(physical association)	0.550
C3AR1	TMEM120B	psi-mi:“MI:0914”(association)	0.530

BioGRID (108): MSMO1 (Affinity Capture-MS), MSMO1 (Affinity Capture-MS), MSMO1 (Affinity Capture-MS), MSMO1 (Affinity Capture-MS), MSMO1 (Affinity Capture-MS), MSMO1 (Affinity Capture-MS), HMOX1 (Two-hybrid), C14orf1 (Two-hybrid), TMEM140 (Two-hybrid), MMP14 (Two-hybrid), TMEM65 (Two-hybrid), STX3 (Two-hybrid), CYP4F22 (Two-hybrid), GOLT1A (Two-hybrid), YIF1A (Two-hybrid)

ESM2 similar proteins: A0A0E0SNE8, A8WGT1, B4YQU1, C4R613, I1RFM2, O00767, O13666, O35532, O59715, O59933, O62849, O75845, O88822, O93875, O94298, O94457, O94523, P32353, P38992, P48618, P50860, P53045, Q15800, Q1LX59, Q20027, Q4R4Q4, Q4WB51, Q4WBI8, Q4WDL3, Q4WIX5, Q55D52, Q55D54, Q567X1, Q59VG6, Q5AJX2, Q5R574, Q5ZLL6, Q618G2, Q6CMK7, Q6UGB2

Diamond homologs: A0A0D1DT68, B8B6I2, I1RFM2, I1S1Q3, O35532, O75845, P50860, P53045, Q15800, Q4R4Q4, Q4W9I3, Q4WDL3, Q4WIX5, Q55D54, Q5R574, Q5ZLL6, Q69L93, Q6UGB2, Q754B9, Q7SBB6, Q7ZW77, Q8J207, Q96IV6, Q9CRA4, Q9GKT2, A0A0E0SNE8, O13666, O88822, O93875, O94457, P32353, Q39208, Q4WB51, Q59VG6, Q8NJ57, Q9AST3, Q9EQS5, Q9M883, Q9UUH4, Q9ZT29

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 131 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Class A/1 (Rhodopsin-like receptors)	11	10.9×	1e-06
GPCR ligand binding	10	8.6×	4e-05
GPCR downstream signalling	10	5.8×	5e-04
G alpha (i) signalling events	11	5.7×	3e-04
Signaling by GPCR	10	5.3×	9e-04

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway	9	17.1×	2e-06
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger	5	13.6×	4e-03
positive regulation of cytosolic calcium ion concentration	10	10.2×	1e-05
phospholipase C-activating G protein-coupled receptor signaling pathway	7	8.0×	4e-03
adenylate cyclase-activating G protein-coupled receptor signaling pathway	8	7.9×	1e-03
G protein-coupled receptor signaling pathway	17	5.4×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

92 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	45
Likely benign	17
Benign	23

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
222974	NM_006745.5(MSMO1):c.519T>A (p.His173Gln)	Pathogenic
222976	NM_006745.5(MSMO1):c.736G>C (p.Gly246Arg)	Pathogenic
222975	NM_006745.5(MSMO1):c.731A>G (p.Tyr244Cys)	Likely pathogenic

SpliceAI

838 predictions. Top by Δscore:

Variant	Effect	Δscore
4:165337818:G:GT	donor_gain	1.0000
4:165337934:GATG:G	donor_gain	1.0000
4:165338668:A:G	acceptor_gain	1.0000
4:165338774:TTCAG:T	donor_loss	1.0000
4:165338775:TCAG:T	donor_loss	1.0000
4:165338776:CAG:C	donor_loss	1.0000
4:165338777:AGG:A	donor_loss	1.0000
4:165338778:GG:G	donor_loss	1.0000
4:165338779:GT:G	donor_loss	1.0000
4:165338780:T:G	donor_loss	1.0000
4:165340213:T:TA	acceptor_gain	1.0000
4:165340217:TTAG:T	acceptor_loss	1.0000
4:165340218:TAG:T	acceptor_loss	1.0000
4:165340219:A:AG	acceptor_gain	1.0000
4:165340219:A:AT	acceptor_loss	1.0000
4:165340219:AG:A	acceptor_gain	1.0000
4:165340220:G:A	acceptor_gain	1.0000
4:165340220:G:GT	acceptor_gain	1.0000
4:165340220:GGCTC:G	acceptor_gain	1.0000
4:165340312:ATCAT:A	donor_gain	1.0000
4:165340373:TAGG:T	donor_loss	1.0000
4:165340375:GGTG:G	donor_loss	1.0000
4:165340376:G:GG	donor_gain	1.0000
4:165340377:T:A	donor_loss	1.0000
4:165340378:GAGTA:G	donor_loss	1.0000
4:165341749:A:AG	acceptor_gain	1.0000
4:165341749:AGT:A	acceptor_gain	1.0000
4:165341749:AGTG:A	acceptor_gain	1.0000
4:165341750:G:GT	acceptor_gain	1.0000
4:165341750:GT:G	acceptor_gain	1.0000

AlphaMissense

1961 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:165338695:G:C	D150H	0.999
4:165338696:A:C	D150A	0.999
4:165338696:A:T	D150V	0.999
4:165338716:C:G	H157D	0.999
4:165338755:C:G	H170D	0.999
4:165338764:C:G	H173D	0.999
4:165338767:C:G	H174D	0.999
4:165338769:T:A	H174Q	0.999
4:165338769:T:G	H174Q	0.999
4:165340261:A:T	E191V	0.999
4:165340282:G:A	G198E	0.999
4:165340329:T:A	W214R	0.999
4:165340329:T:C	W214R	0.999
4:165340335:T:A	W216R	0.999
4:165340335:T:C	W216R	0.999
4:165341821:C:G	H253D	0.999
4:165341869:G:C	D269H	0.999
4:165341870:A:C	D269A	0.999
4:165338695:G:T	D150Y	0.998
4:165338701:T:A	W152R	0.998
4:165338701:T:C	W152R	0.998
4:165338716:C:A	H157N	0.998
4:165338718:T:A	H157Q	0.998
4:165338718:T:G	H157Q	0.998
4:165338728:C:G	H161D	0.998
4:165338755:C:A	H170N	0.998
4:165338764:C:A	H173N	0.998
4:165338767:C:A	H174N	0.998
4:165340281:G:A	G198R	0.998
4:165340281:G:C	G198R	0.998

dbSNP variants (sampled 300 via entrez): RS1000117378 (4:165342732 A>C,G), RS10001184 (4:165327871 G>T), RS1000145612 (4:165337394 G>A), RS1000175797 (4:165337620 G>A), RS1000462234 (4:165331320 A>G), RS1000513308 (4:165334476 A>C,G), RS1000925057 (4:165327578 CG>C), RS1000937705 (4:165327015 T>A,C), RS1000963621 (4:165327315 C>G,T), RS10009994 (4:165327050 T>C), RS1001110049 (4:165333067 GA>G), RS1001147287 (4:165339009 T>G), RS1001416234 (4:165332617 C>T), RS1001454646 (4:165338049 A>G), RS1001562788 (4:165333287 T>A)

Disease associations

OMIM: gene MIM:607545 | disease phenotypes: MIM:616834

GenCC curated gene-disease

Disease	Classification	Inheritance
microcephaly-congenital cataract-psoriasiform dermatitis syndrome	Strong	Autosomal recessive

Mondo (1): microcephaly-congenital cataract-psoriasiform dermatitis syndrome (MONDO:0014793)

Orphanet (1): Microcephaly-congenital cataract-psoriasiform dermatitis syndrome (Orphanet:488168)

HPO phenotypes

20 total (20 of 20 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000252	Microcephaly
HP:0000498	Blepharitis
HP:0000519	Developmental cataract
HP:0000823	Delayed puberty
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001508	Failure to thrive
HP:0002750	Delayed skeletal maturation
HP:0002829	Arthralgia
HP:0003146	Hypocholesterolemia
HP:0003233	Decreased HDL cholesterol concentration
HP:0003563	Decreased LDL cholesterol concentration
HP:0003765	Psoriasiform dermatitis
HP:0004322	Short stature
HP:0008064	Ichthyosis
HP:0011463	Childhood onset
HP:6000753	Elevated circulating monomethyl sterol concentration
HP:6000754	Elevated circulating dimethyl sterol concentration
HP:6001113	Elevated circulating methysterol concentration

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001604_2	Insulin-related traits	2.000000e-08
GCST001604_5	Insulin-related traits	3.000000e-08
GCST003447_4	Neuroticism	4.000000e-08
GCST006979_760	Heel bone mineral density	4.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007660	neuroticism measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067069 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.42	Kd	384.4	nM	CHEMBL5653589
6.30	ED50	498.3	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148786: Binding affinity to human MSMO1 incubated for 45 mins by Kinobead based pull down assay	kd	0.3844	uM

CTD chemical–gene interactions

133 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, affects methylation, affects cotreatment, decreases expression, increases abundance (+1 more)	5
Benzo(a)pyrene	decreases expression, increases methylation	5
perfluorooctane sulfonic acid	decreases expression	4
Cyclosporine	affects cotreatment, affects expression, decreases expression, increases expression	4
bisphenol A	affects expression, increases expression	3
Cisplatin	affects expression, decreases expression	3
Valproic Acid	affects expression, decreases expression	3
methylmercuric chloride	decreases expression	2
potassium chromate(VI)	affects cotreatment, decreases expression	2
monomethylarsonous acid	decreases expression	2
bisphenol S	decreases methylation, increases expression	2
Dasatinib	affects cotreatment, decreases expression, decreases response to substance	2
Decitabine	decreases expression, affects expression	2
Arsenic Trioxide	decreases expression, affects cotreatment	2
Acetaminophen	decreases expression	2
Calcitriol	increases expression, affects cotreatment	2
Testosterone	decreases expression, affects cotreatment, increases expression	2
Tretinoin	affects cotreatment, decreases expression, increases expression	2
Tunicamycin	decreases expression	2
Aflatoxin B1	decreases expression, decreases methylation	2
Cadmium Chloride	increases expression	2
Copper Sulfate	decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
afuresertib	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
bisphenol F	increases expression	1
dicrotophos	decreases expression	1
lathosterol	increases abundance	1
22-hydroxycholesterol	decreases expression	1
tremortin	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651828	Binding	Binding affinity to human MSMO1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

1 cell lines: 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_E4Q9	KOLF2.1J MSMO1 15.9kbdel DEL/WT	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.