MISO1

Summary

MISO1 (mitochondrial inner membrane subdomain organizer 1, HGNC:26434) is a protein-coding gene on chromosome 3q25.31, encoding Protein C3orf33 (Q6P1S2). Secreted protein may play a role in transcription regulation via the MAPK3/MAPK1 pathway through an unidentified receptor on the plasma membrane.

Involved in negative regulation of ERK1 and ERK2 cascade and regulation of DNA-binding transcription factor activity. Located in extracellular space.

Source: NCBI Gene 285315 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 15 total
• MANE Select transcript: NM_001308229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26434
Approved symbol	MISO1
Name	mitochondrial inner membrane subdomain organizer 1
Location	3q25.31
Locus type	gene with protein product
Status	Approved
Aliases	MISO, FLJ31139, AC3-33
Ensembl gene	ENSG00000174928
Ensembl biotype	protein_coding
OMIM	619654
Entrez	285315

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 7 protein_coding, 3 nonsense_mediated_decay

ENST00000340171, ENST00000465810, ENST00000482061, ENST00000486435, ENST00000534941, ENST00000861419, ENST00000861420, ENST00000929582, ENST00000965045, ENST00000965046

RefSeq mRNA: 2 — MANE Select: NM_001308229 NM_001308229, NM_173657

CCDS: CCDS54659, CCDS77843

Canonical transcript exons

ENST00000340171 — 5 exons

Exon	Start	End
ENSE00001919406	155806139	155806278
ENSE00003500516	155802532	155802591
ENSE00003580081	155767509	155767669
ENSE00003624692	155775701	155775848
ENSE00003627103	155762617	155763918

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 83.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.3098 / max 41.6971, expressed in 1263 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
45241	2.3098	1263

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	83.59	gold quality
right adrenal gland cortex	UBERON:0035827	83.49	gold quality
left adrenal gland	UBERON:0001234	82.79	gold quality
left adrenal gland cortex	UBERON:0035825	82.47	gold quality
adrenal gland	UBERON:0002369	81.77	gold quality
adrenal tissue	UBERON:0018303	80.32	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.31	gold quality
body of pancreas	UBERON:0001150	79.22	gold quality
right lobe of thyroid gland	UBERON:0001119	78.62	gold quality
islet of Langerhans	UBERON:0000006	78.33	gold quality
pancreas	UBERON:0001264	78.26	gold quality
thyroid gland	UBERON:0002046	78.10	gold quality
left lobe of thyroid gland	UBERON:0001120	78.08	gold quality
muscle of leg	UBERON:0001383	77.91	gold quality
gastrocnemius	UBERON:0001388	77.86	gold quality
ventricular zone	UBERON:0003053	77.78	gold quality
calcaneal tendon	UBERON:0003701	77.56	gold quality
heart left ventricle	UBERON:0002084	77.47	gold quality
hindlimb stylopod muscle	UBERON:0004252	77.41	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.23	gold quality
prefrontal cortex	UBERON:0000451	77.19	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	77.12	gold quality
right atrium auricular region	UBERON:0006631	77.11	gold quality
anterior cingulate cortex	UBERON:0009835	76.78	gold quality
cerebral cortex	UBERON:0000956	76.69	gold quality
cortical plate	UBERON:0005343	76.66	gold quality
heart	UBERON:0000948	76.64	gold quality
frontal cortex	UBERON:0001870	76.61	gold quality
Ammon’s horn	UBERON:0001954	76.23	gold quality
hypothalamus	UBERON:0001898	76.22	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

39 targeting MISO1, 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-6748-5P	100.00	65.81	1057
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-6719-3P	99.29	67.78	1387
HSA-MIR-661	99.09	65.94	2062

Literature-anchored findings (GeneRIF, showing 2)

• The preliminary results showed that AC3-33 is an important novel gene related to supress AP-1 activity. (PMID:18487146)
• AC3-33 is a novel member of the secretory family and inhibits Elk1 transcriptional activity via ERK1/2 MAP (PMID:20680465)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	C18H3orf33	ENSDARG00000040582
mus_musculus	E130311K13Rik	ENSMUSG00000048581
rattus_norvegicus	C2h3orf33	ENSRNOG00000021324
caenorhabditis_elegans		WBGENE00009307

Protein

Protein identifiers

Protein C3orf33 — Q6P1S2 (reviewed: Q6P1S2)

Alternative names: Protein AC3-33

All UniProt accessions (4): Q6P1S2, F8WCI5, F8WDI1, H7C4I0

UniProt curated annotations — full annotation on UniProt →

Function. Secreted protein may play a role in transcription regulation via the MAPK3/MAPK1 pathway through an unidentified receptor on the plasma membrane.

Subcellular location. Membrane Secreted.

Tissue specificity. Highly expressed in ileocecal tissue and endometrium.

Isoforms (2)

UniProt ID	Names	Canonical?
Q6P1S2-1	1	yes
Q6P1S2-2	2

RefSeq proteins (2): NP_001295158, NP_775928 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR035437	SNase_OB-fold_sf	Homologous_superfamily
IPR042421	C3orf33-like	Family

UniProt features (8 total): sequence variant 2, initiator methionine 1, chain 1, transmembrane region 1, modified residue 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6P1S2-F1	67.88	0.09

Functional residue map

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

Post-translational modifications (1): 2

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 60 (showing top): GOBP_NEGATIVE_REGULATION_OF_ERK1_AND_ERK2_CASCADE, GOBP_NEGATIVE_REGULATION_OF_MAPK_CASCADE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_ERK1_AND_ERK2_CASCADE, GOBP_REGULATION_OF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, chr3q25, DURAND_STROMA_S_UP, SFMBT1_TARGET_GENES, SKIL_TARGET_GENES, MIR5688, MIR495_3P, MIR627_3P, MIR4422, GSE11057_EFF_MEM_VS_CENT_MEM_CD4_TCELL_UP, MIR3667_3P

GO Biological Process (2): obsolete regulation of DNA-binding transcription factor activity (GO:0051090), negative regulation of ERK1 and ERK2 cascade (GO:0070373)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): obsolete extracellular space (GO:0005615), mitochondrion (GO:0005739), membrane (GO:0016020), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
negative regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MISO1	C15orf61	A6NNL5	687
MISO1	C15orf62	A8K5M9	626
MISO1	MRPS18A	Q9NVS2	449
MISO1	DNAJC4	Q9NNZ3	441
MISO1	GFM2	Q969S9	439
MISO1	MRPL53	Q96EL3	428
MISO1	MTERF4	Q7Z6M4	421
MISO1	DNAJC11	Q9NVH1	398
MISO1	NDUFAF1	Q9Y375	364
MISO1	MTHFD2L	Q9H903	359
MISO1	GLYAT	Q6IB77	357
MISO1	MVB12B	Q9H7P6	354
MISO1	TSPOAP1	O95153	353
MISO1	RPL36AL	Q969Q0	328
MISO1	SLC10A7	Q0GE19	324

IntAct

42 interactions, top by confidence:

A	B	Type	Score
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
TEX44	C3orf33	psi-mi:“MI:0915”(physical association)	0.560
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
PEX19	FAM20B	psi-mi:“MI:0914”(association)	0.530
SLC39A4	TMEM120B	psi-mi:“MI:0914”(association)	0.530
PDCD1	RTL8C	psi-mi:“MI:0914”(association)	0.530
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
PEX19	MYO1D	psi-mi:“MI:0914”(association)	0.530
BSG	METTL15	psi-mi:“MI:0914”(association)	0.350
PCDHGB1	FAM171A2	psi-mi:“MI:0914”(association)	0.350
EDEM2	HACD1	psi-mi:“MI:0914”(association)	0.350
KCNA2	TMEM129	psi-mi:“MI:0914”(association)	0.350
TTYH1	TMEM223	psi-mi:“MI:0914”(association)	0.350
HLA-DRA	TMEM223	psi-mi:“MI:0914”(association)	0.350
HTR3B	TMEM223	psi-mi:“MI:0914”(association)	0.350
RAMP2	GXYLT2	psi-mi:“MI:0914”(association)	0.350
LRRC55	TMEM120B	psi-mi:“MI:0914”(association)	0.350
ATP2A1	TMEM120B	psi-mi:“MI:0914”(association)	0.350
S100A2	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CLRN2	FAM234B	psi-mi:“MI:0914”(association)	0.350
SLC39A12		psi-mi:“MI:0914”(association)	0.350
MAMDC4		psi-mi:“MI:0914”(association)	0.350
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350
PNMA8A	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (44): C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C2orf57 (Two-hybrid), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS), C3orf33 (Affinity Capture-MS)

ESM2 similar proteins: A6QPR9, A7MBC7, B1WB06, F4HVW5, F4I933, F4IVI0, F4KFT7, O14524, O35099, O82387, Q0WPN7, Q149N8, Q14AW5, Q2TBQ7, Q3UFM5, Q498D5, Q4KM51, Q4R7Q1, Q5I047, Q5R7B0, Q5RDB4, Q5SSK3, Q6NTT6, Q6P1S2, Q6PBN5, Q7X6P3, Q8BN57, Q8BSE0, Q8L7N4, Q8LBV4, Q8NE18, Q8RWG3, Q8VYP9, Q8W032, Q90678, Q93VH2, Q94AS5, Q94BM7, Q95LL7, Q96LZ7

Diamond homologs: Q6P1S2, Q8BN57

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 50 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
R-HSA-425366	5	31.2×	1e-05
SLC-mediated transmembrane transport	5	10.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
intracellular monoatomic cation homeostasis	5	140.4×	2e-08
zinc ion transmembrane transport	5	87.8×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1032 predictions. Top by Δscore:

Variant	Effect	Δscore
3:155767503:GCTTA:G	donor_loss	1.0000
3:155767504:CTTA:C	donor_loss	1.0000
3:155767505:TTA:T	donor_loss	1.0000
3:155767506:TACCT:T	donor_loss	1.0000
3:155767507:A:T	donor_loss	1.0000
3:155767508:C:A	donor_loss	1.0000
3:155767508:CCTTA:C	donor_gain	1.0000
3:155767665:CTCTT:C	acceptor_gain	1.0000
3:155767667:CTT:C	acceptor_gain	1.0000
3:155767670:C:CC	acceptor_gain	1.0000
3:155775699:A:AC	donor_gain	1.0000
3:155775700:C:CC	donor_gain	1.0000
3:155775700:CTT:C	donor_gain	1.0000
3:155775857:T:C	acceptor_gain	1.0000
3:155775857:T:TC	acceptor_gain	1.0000
3:155806168:A:AC	donor_gain	1.0000
3:155806169:C:CC	donor_gain	1.0000
3:155767668:TT:T	acceptor_gain	0.9900
3:155767669:TCTA:T	acceptor_loss	0.9900
3:155767670:CTAAA:C	acceptor_loss	0.9900
3:155767679:T:TC	acceptor_gain	0.9900
3:155775696:CTTA:C	donor_gain	0.9900
3:155775700:CTTCT:C	donor_gain	0.9900
3:155775748:TCTAA:T	donor_gain	0.9900
3:155775849:C:CC	acceptor_gain	0.9900
3:155775860:C:CT	acceptor_gain	0.9900
3:155802592:C:CC	acceptor_gain	0.9900
3:155806136:TA:T	donor_loss	0.9900
3:155806137:A:AC	donor_gain	0.9900
3:155806137:A:AT	donor_loss	0.9900

AlphaMissense

1902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:155802583:G:C	S41R	0.994
3:155802583:G:T	S41R	0.994
3:155802585:T:G	S41R	0.994
3:155775837:A:C	F62L	0.993
3:155775837:A:T	F62L	0.993
3:155775839:A:G	F62L	0.993
3:155775807:A:C	F72L	0.991
3:155775807:A:T	F72L	0.991
3:155775809:A:G	F72L	0.991
3:155775838:A:G	F62S	0.991
3:155767527:G:C	C155W	0.989
3:155767564:A:G	F143S	0.988
3:155763792:C:G	A204P	0.986
3:155767645:A:T	V116D	0.985
3:155763779:G:T	A208D	0.982
3:155775738:A:C	H95Q	0.982
3:155775738:A:T	H95Q	0.982
3:155775808:A:G	F72S	0.980
3:155775838:A:C	F62C	0.979
3:155775781:C:T	G81E	0.978
3:155802575:A:T	M44K	0.978
3:155767529:A:G	C155R	0.977
3:155775787:A:G	L79P	0.977
3:155763892:A:C	N170K	0.976
3:155763892:A:T	N170K	0.976
3:155775820:A:C	I68S	0.976
3:155802572:G:T	A45D	0.976
3:155763866:C:T	G179D	0.974
3:155767528:C:T	C155Y	0.974
3:155775739:T:C	H95R	0.974

dbSNP variants (sampled 300 via entrez): RS1000007567 (3:155797462 T>A,C), RS1000237901 (3:155792486 A>T), RS1000288973 (3:155791139 G>C), RS1000394122 (3:155804520 A>T), RS1000459641 (3:155793699 A>G), RS1000563774 (3:155785562 C>G), RS1000575177 (3:155794191 G>A), RS1000676702 (3:155786008 C>A), RS1000755693 (3:155779481 G>A,C), RS1000819889 (3:155778160 A>C), RS1000842856 (3:155798817 A>G), RS1000860928 (3:155780569 A>G), RS1001023809 (3:155787120 T>C), RS1001083110 (3:155800147 G>A,C), RS1001168810 (3:155805171 A>G)

Disease associations

OMIM: gene MIM:619654 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST007350_1	Focal epilepsy (with hippocampal sclerosis)	1.000000e-11

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	3
Panobinostat	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	affects expression	1
potassium chromate(VI)	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
(+)-JQ1 compound	decreases expression	1
Sunitinib	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Amiodarone	increases expression	1
Arsenic	affects methylation	1
Hydrogen Peroxide	affects expression	1
Quercetin	decreases expression	1
Smoke	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	increases expression	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	decreases expression	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SG30	HAP1 C3orf33 (-) 1	Cancer cell line	Male
CVCL_XM35	HAP1 C3orf33 (-) 2	Cancer cell line	Male
CVCL_XM36	HAP1 C3orf33 (-) 3	Cancer cell line	Male
CVCL_XM37	HAP1 C3orf33 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

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