MOSMO

Summary

MOSMO (modulator of smoothened, HGNC:27087) is a protein-coding gene on chromosome 16p12.2, encoding Modulator of smoothened protein (Q8NHV5). Acts as a negative regulator of hedgehog signaling probably by promoting internalization and subsequent degradation of smoothened protein (SMO) present in the ciliary membrane.

Predicted to be involved in negative regulation of smoothened signaling pathway; regulation of neuron differentiation; and regulation of protein stability. Predicted to act upstream of or within several processes, including chordate embryonic development; embryonic limb morphogenesis; and smoothened signaling pathway. Predicted to be located in plasma membrane. Predicted to be active in Golgi apparatus and ciliary membrane.

Source: NCBI Gene 730094 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 8 total — 3 likely-pathogenic
• MANE Select transcript: NM_001164579

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27087
Approved symbol	MOSMO
Name	modulator of smoothened
Location	16p12.2
Locus type	gene with protein product
Status	Approved
Aliases	ATTHOG, BC030336
Ensembl gene	ENSG00000185716
Ensembl biotype	protein_coding
Entrez	730094

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000331057, ENST00000542527, ENST00000562186, ENST00000562695, ENST00000567004, ENST00000568049, ENST00000569656, ENST00000874460

RefSeq mRNA: 1 — MANE Select: NM_001164579 NM_001164579

CCDS: CCDS58431

Canonical transcript exons

ENST00000542527 — 3 exons

Exon	Start	End
ENSE00002306410	22080696	22084654
ENSE00003530235	22075487	22075699
ENSE00003848544	22008111	22008407

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.2118 / max 162.8225, expressed in 1760 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153121	7.8950	1757
153122	0.3168	118

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	98.33	gold quality
Brodmann (1909) area 23	UBERON:0013554	98.27	gold quality
buccal mucosa cell	CL:0002336	97.57	gold quality
middle temporal gyrus	UBERON:0002771	97.37	gold quality
parietal lobe	UBERON:0001872	97.20	gold quality
postcentral gyrus	UBERON:0002581	97.15	gold quality
entorhinal cortex	UBERON:0002728	96.50	gold quality
superior frontal gyrus	UBERON:0002661	95.65	gold quality
Brodmann (1909) area 46	UBERON:0006483	95.31	gold quality
occipital lobe	UBERON:0002021	95.11	gold quality
lateral nuclear group of thalamus	UBERON:0002736	95.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.00	gold quality
lower lobe of lung	UBERON:0008949	95.00	gold quality
ventral tegmental area	UBERON:0002691	94.53	gold quality
primary visual cortex	UBERON:0002436	94.35	gold quality
nipple	UBERON:0002030	94.15	gold quality
substantia nigra pars compacta	UBERON:0001965	94.12	gold quality
superior vestibular nucleus	UBERON:0007227	94.10	gold quality
kidney epithelium	UBERON:0004819	93.92	gold quality
medulla oblongata	UBERON:0001896	93.58	gold quality
dorsal plus ventral thalamus	UBERON:0001897	93.41	gold quality
skin of hip	UBERON:0001554	93.40	gold quality
inferior vagus X ganglion	UBERON:0005363	93.27	gold quality
tibialis anterior	UBERON:0001385	93.25	gold quality
pons	UBERON:0000988	93.13	gold quality
pylorus	UBERON:0001166	93.00	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.94	gold quality
caput epididymis	UBERON:0004358	92.64	gold quality
cauda epididymis	UBERON:0004360	92.58	gold quality
dorsal root ganglion	UBERON:0000044	92.55	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.95

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

277 targeting MOSMO, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-5692A	100.00	74.40	6850
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-513A-5P	100.00	69.77	2465
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-548AW	99.99	72.57	3559
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mosmob	ENSDARG00000035837
mus_musculus	Mosmo	ENSMUSG00000046096
rattus_norvegicus	Mosmo	ENSRNOG00000062406
drosophila_melanogaster	CG14182	FBGN0036922

Protein

Protein identifiers

Modulator of smoothened protein — Q8NHV5 (reviewed: Q8NHV5)

Alternative names: Attenuator of hedgehog

All UniProt accessions (5): A0A075B731, Q8NHV5, H3BP60, H3BQB3, H3BS23

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of hedgehog signaling probably by promoting internalization and subsequent degradation of smoothened protein (SMO) present in the ciliary membrane. Plays a role in sonic hedgehog (SHH)-induced spinal neural progenitor cells differentiation.

Subcellular location. Cell projection. Cilium membrane. Cell membrane.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NHV5-1	1	yes
Q8NHV5-3	2

RefSeq proteins (1): NP_001158051* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR037663	Mosmo	Family

Pfam: PF18800

UniProt features (8 total): transmembrane region 4, splice variant 2, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
9QQS	ELECTRON MICROSCOPY	2.65
9QTY	ELECTRON MICROSCOPY	2.98
9QRU	ELECTRON MICROSCOPY	3.03
9QS6	ELECTRON MICROSCOPY	3.3
9QSH	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHV5-F1	88.93	0.60

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 135

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 203 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, NKX25_02, GOBP_EMBRYONIC_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_NEUROGENESIS, HNF1_Q6, LHX3_01, CAGCTG_AP4_Q5, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, TCF4_Q5, IRF7_01, YGACNNYACAR_UNKNOWN, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, GOBP_REGULATION_OF_NEURON_DIFFERENTIATION, GATA1_01

GO Biological Process (13): in utero embryonic development (GO:0001701), smoothened signaling pathway (GO:0007224), heart development (GO:0007507), intracellular protein localization (GO:0008104), gene expression (GO:0010467), cell differentiation (GO:0030154), lung development (GO:0030324), embryonic limb morphogenesis (GO:0030326), regulation of protein stability (GO:0031647), regulation of neuron differentiation (GO:0045664), negative regulation of smoothened signaling pathway (GO:0045879), embryonic skeletal system development (GO:0048706), left/right pattern formation (GO:0060972)

GO Molecular Function (0):

GO Cellular Component (5): Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), ciliary membrane (GO:0060170), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chordate embryonic development	2
animal organ development	2
cellular anatomical structure	2
cell surface receptor signaling pathway	1
circulatory system development	1
macromolecule localization	1
macromolecule biosynthetic process	1
cellular developmental process	1
respiratory tube development	1
respiratory system development	1
limb morphogenesis	1
embryonic appendage morphogenesis	1
regulation of biological quality	1
neuron differentiation	1
regulation of cell differentiation	1
smoothened signaling pathway	1
regulation of smoothened signaling pathway	1
negative regulation of signal transduction	1
skeletal system development	1
regionalization	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cilium	1
cell projection membrane	1
bounding membrane of organelle	1

Protein interactions and networks

STRING

344 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MOSMO	MEGF8	Q7Z7M0	662
MOSMO	RNF157	Q96PX1	616
MOSMO	VWA3A	A6NCI4	584
MOSMO	MGRN1	O60291	512
MOSMO	LHFPL5	Q8TAF8	511
MOSMO	FAM20B	O75063	475
MOSMO	SETD5	Q9C0A6	454
MOSMO	TDG	Q13569	452
MOSMO	POLR3E	Q9NVU0	450
MOSMO	PDZD9	Q8IXQ8	435
MOSMO	TUBD1	Q9UJT1	431
MOSMO	KRABD5	Q7Z2F6	420
MOSMO	FAM86C1P	Q9NVL1	400
MOSMO	FLYWCH2	Q96CP2	394
MOSMO	IFT80	Q9P2H3	388

IntAct

0 interactions, top by confidence:

BioGRID (1): C16orf52 (Affinity Capture-RNA)

ESM2 similar proteins: A0A8M2B5N2, A0A8V0ZLT4, A1L157, F7BWT7, O35566, O60636, O60637, O75841, O95858, P11049, P20274, P21926, P30413, P30932, P31053, P38573, P40239, P40240, P40241, P48509, P54825, P55344, P56563, P61170, P61171, Q1JQA4, Q2KHY8, Q3SZR9, Q3ZBH3, Q566D0, Q58CY8, Q5RE11, Q61470, Q6GQF5, Q6GR34, Q6IP19, Q6PBE5, Q6PFT6, Q7SZ07, Q80WR1

Diamond homologs: Q0D289, Q6GR34, Q7SZ07, Q8C784, Q8NHV5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	3
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1172567	GRCh37/hg19 16p12.2(chr16:21936726-22461225)x1	Likely pathogenic
1879353	GRCh37/hg19 16p12.2(chr16:21846039-22385630)x1	Likely pathogenic
2498684	GRCh37/hg19 16p12.2(chr16:21964745-22385630)x1	Likely pathogenic

SpliceAI

1125 predictions. Top by Δscore:

Variant	Effect	Δscore
16:22008397:G:GT	donor_gain	1.0000
16:22008397:G:T	donor_gain	1.0000
16:22008404:GCGG:G	donor_gain	1.0000
16:22008405:CGGGT:C	donor_loss	1.0000
16:22008406:GG:G	donor_gain	1.0000
16:22008407:GG:G	donor_gain	1.0000
16:22008407:GGT:G	donor_loss	1.0000
16:22008408:GTG:G	donor_loss	1.0000
16:22035801:G:GT	donor_gain	1.0000
16:22080789:T:TA	donor_gain	1.0000
16:22080790:A:AA	donor_gain	1.0000
16:22008408:G:GG	donor_gain	0.9900
16:22008409:T:A	donor_loss	0.9900
16:22010353:TTAC:T	donor_gain	0.9900
16:22065494:G:T	donor_gain	0.9900
16:22073105:G:GT	donor_gain	0.9900
16:22073108:GT:G	donor_gain	0.9900
16:22073109:TT:T	donor_gain	0.9900
16:22075481:CCCCA:C	acceptor_loss	0.9900
16:22075482:CCCA:C	acceptor_loss	0.9900
16:22075483:CCA:C	acceptor_loss	0.9900
16:22075484:CAG:C	acceptor_loss	0.9900
16:22075485:A:AG	acceptor_gain	0.9900
16:22075485:AGG:A	acceptor_loss	0.9900
16:22075486:G:GG	acceptor_gain	0.9900
16:22075486:G:T	acceptor_loss	0.9900
16:22075486:GGA:G	acceptor_gain	0.9900
16:22080792:T:G	donor_gain	0.9900
16:22072089:G:GG	donor_gain	0.9800
16:22075477:A:AG	acceptor_gain	0.9800

AlphaMissense

1056 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:22008383:T:A	W28R	1.000
16:22008383:T:C	W28R	1.000
16:22075603:G:A	G75R	1.000
16:22075603:G:C	G75R	1.000
16:22080737:T:C	F121L	1.000
16:22080739:T:A	F121L	1.000
16:22080739:T:G	F121L	1.000
16:22080794:G:A	G140R	1.000
16:22080794:G:C	G140R	1.000
16:22080794:G:T	G140W	1.000
16:22080795:G:A	G140E	1.000
16:22080842:G:A	G156R	1.000
16:22080842:G:C	G156R	1.000
16:22008365:A:C	S22R	0.999
16:22008367:C:A	S22R	0.999
16:22008367:C:G	S22R	0.999
16:22008385:G:C	W28C	0.999
16:22008385:G:T	W28C	0.999
16:22075501:G:C	G41R	0.999
16:22075573:T:A	W65R	0.999
16:22075573:T:C	W65R	0.999
16:22075575:G:C	W65C	0.999
16:22075575:G:T	W65C	0.999
16:22075604:G:A	G75E	0.999
16:22075696:G:A	G106R	0.999
16:22075696:G:C	G106R	0.999
16:22075697:G:A	G106E	0.999
16:22080707:T:C	C111R	0.999
16:22080728:C:T	P118S	0.999
16:22080729:C:A	P118Q	0.999

dbSNP variants (sampled 300 via entrez): RS1000026454 (16:22010444 G>A,T), RS1000029079 (16:22025957 C>T), RS1000032265 (16:22065155 C>A), RS1000049504 (16:22025236 T>C), RS1000070750 (16:22018058 A>G), RS1000101534 (16:22025021 T>A), RS1000138227 (16:22071188 T>C), RS1000141657 (16:22075708 C>A,G,T), RS1000154987 (16:22008034 G>A,T), RS1000189972 (16:22092497 T>A,C,G), RS1000279694 (16:22069007 G>A), RS1000282719 (16:22033593 AGATCAC>A), RS1000292467 (16:22054699 G>A), RS1000294531 (16:22068636 T>C), RS1000303341 (16:22048184 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	7
trichostatin A	affects cotreatment, decreases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
Arsenic	affects methylation, increases abundance, increases expression	2
Calcitriol	increases expression, affects cotreatment	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	increases expression	2
Cadmium Chloride	increases abundance, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
bisphenol F	affects cotreatment, decreases expression	1
urushiol	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
sodium arsenate	increases expression, increases abundance	1
manganese chloride	increases abundance, increases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	increases expression	1
Acetaminophen	increases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

Clinical trials (associated diseases)

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