SMIM22

Summary

SMIM22 (small integral membrane protein 22, HGNC:48329) is a protein-coding gene on chromosome 16p13.3, encoding Small integral membrane protein 22 (K7EJ46). May modulate lipid droplet formation throught interaction with SQLE.

Involved in several processes, including lipid droplet formation; positive regulation of cell migration; and regulation of actin cytoskeleton organization. Predicted to be located in late endosome and membrane.

Source: NCBI Gene 440335 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 1 total
• MANE Select transcript: NM_001253794

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:48329
Approved symbol	SMIM22
Name	small integral membrane protein 22
Location	16p13.3
Locus type	gene with protein product
Status	Approved
Aliases	CASIMO1
Ensembl gene	ENSG00000267795
Ensembl biotype	protein_coding
Entrez	440335

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 12 protein_coding, 3 retained_intron

ENST00000586005, ENST00000586440, ENST00000588500, ENST00000588606, ENST00000588894, ENST00000589327, ENST00000589721, ENST00000591004, ENST00000591870, ENST00000615471, ENST00000615889, ENST00000904659, ENST00000904660, ENST00000904661, ENST00000937276

RefSeq mRNA: 4 — MANE Select: NM_001253794 NM_001253790, NM_001253791, NM_001253793, NM_001253794

CCDS: CCDS59258, CCDS59259

Canonical transcript exons

ENST00000586005 — 4 exons

Exon	Start	End
ENSE00002761834	4795715	4795858
ENSE00002883420	4795369	4795449
ENSE00002889987	4795948	4796048
ENSE00002945716	4796190	4796491

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 99.38.

FANTOM5 (CAGE): breadth broad, TPM avg 3.3786 / max 101.1040, expressed in 257 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
152499	2.7529	247
152498	0.5814	168
152495	0.0203	3
152496	0.0152	3
152497	0.0088	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	99.38	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.39	gold quality
right uterine tube	UBERON:0001302	97.98	gold quality
rectum	UBERON:0001052	97.93	gold quality
body of pancreas	UBERON:0001150	97.01	gold quality
pancreas	UBERON:0001264	93.43	gold quality
islet of Langerhans	UBERON:0000006	92.02	gold quality
transverse colon	UBERON:0001157	91.67	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.31	gold quality
minor salivary gland	UBERON:0001830	91.09	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.96	silver quality
ileal mucosa	UBERON:0000331	90.83	gold quality
gall bladder	UBERON:0002110	90.68	gold quality
colonic mucosa	UBERON:0000317	90.30	gold quality
saliva-secreting gland	UBERON:0001044	90.06	gold quality
left testis	UBERON:0004533	90.01	gold quality
right testis	UBERON:0004534	89.82	gold quality
small intestine	UBERON:0002108	89.36	gold quality
adenohypophysis	UBERON:0002196	89.16	gold quality
body of stomach	UBERON:0001161	89.05	gold quality
duodenum	UBERON:0002114	87.20	gold quality
pituitary gland	UBERON:0000007	86.93	gold quality
pancreatic ductal cell	CL:0002079	86.63	gold quality
stomach	UBERON:0000945	86.59	gold quality
testis	UBERON:0000473	86.40	gold quality
metanephros cortex	UBERON:0010533	86.08	gold quality
mouth mucosa	UBERON:0003729	84.76	gold quality
lower esophagus mucosa	UBERON:0035834	84.65	gold quality
upper lobe of left lung	UBERON:0008952	83.28	gold quality
mucosa of stomach	UBERON:0001199	83.12	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-8410	yes	1452.77
E-MTAB-6308	yes	932.72
E-HCAD-1	yes	81.06
E-CURD-114	yes	64.28
E-MTAB-10287	yes	52.45
E-MTAB-6701	yes	22.69
E-HCAD-10	yes	21.61
E-ANND-3	yes	18.39
E-GEOD-130148	yes	11.85
E-GEOD-125970	no	28.56
E-HCAD-31	no	2.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting SMIM22, 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-7-5P	99.67	70.53	1809
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-4439	98.53	67.53	793
HSA-MIR-6816-5P	98.46	64.35	364
HSA-MIR-5089-5P	98.45	66.06	1388
HSA-MIR-484	98.16	66.92	1074
HSA-MIR-6857-3P	96.70	65.43	915

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch1073-443f11.2	ENSDARG00000105068
mus_musculus	Smim22	ENSMUSG00000096215
rattus_norvegicus	Smim22	ENSRNOG00000080339

Protein

Protein identifiers

Small integral membrane protein 22 — K7EJ46 (reviewed: K7EJ46)

Alternative names: Cancer-associated small integral membrane open reading frame 1

All UniProt accessions (2): A0A4V7I672, K7EJ46

UniProt curated annotations — full annotation on UniProt →

Function. May modulate lipid droplet formation throught interaction with SQLE.

Subunit / interactions. Interacts with CANX and DDOST. Interacts with SQLE; this interaction modulates lipid droplet formation.

Subcellular location. Membrane. Late endosome.

Induction. Up-regulated in breast cancer.

Isoforms (2)

UniProt ID	Names	Canonical?
K7EJ46-3	3	yes
K7EJ46-2	2

RefSeq proteins (4): NP_001240719, NP_001240720, NP_001240722, NP_001240723* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR031671	SMIM5/18/22	Family
IPR053081	SIM_Modulators	Family

Pfam: PF15831

UniProt features (5 total): chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-K7EJ46-F1	76.07	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOZGIT_ESR1_TARGETS_DN, GOBP_REGULATION_OF_ACTIN_FILAMENT_BASED_PROCESS, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_ORGANELLE_ASSEMBLY, GOBP_REGULATION_OF_CYTOSKELETON_ORGANIZATION, DODD_NASOPHARYNGEAL_CARCINOMA_DN, PANGAS_TUMOR_SUPPRESSION_BY_SMAD1_AND_SMAD5_UP, GOBP_LIPID_DROPLET_ORGANIZATION, YANG_BCL3_TARGETS_UP, NFE2L2.V2, GOBP_LIPID_DROPLET_FORMATION, DURANTE_ADULT_OLFACTORY_NEUROEPITHELIUM_RESPIRATORY_CILIATED_CELLS, BUSSLINGER_GASTRIC_MATURE_PIT_CELLS

GO Biological Process (5): positive regulation of cell migration (GO:0030335), regulation of actin cytoskeleton organization (GO:0032956), regulation of cell population proliferation (GO:0042127), regulation of cell cycle (GO:0051726), lipid droplet formation (GO:0140042)

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

GO Cellular Component (3): late endosome (GO:0005770), membrane (GO:0016020), endosome (GO:0005768)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
cell population proliferation	1
cell cycle	1
lipid storage	1
lipid droplet organization	1
membraneless organelle assembly	1
binding	1
endosome	1
cellular anatomical structure	1
endomembrane system	1
cytoplasmic vesicle	1

Protein interactions and networks

STRING

174 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM22	SQLE	Q14534	816
SMIM22	NBDY	A0A0U1RRE5	600
SMIM22	SMIM30	A4D0T7	540
SMIM22	MRLN	P0DMT0	476
SMIM22	REPS2	Q8NFH8	376
SMIM22	C8orf89	P0DMQ9	366
SMIM22	STRIT1	P0DN84	353
SMIM22	TMEM233	B4DJY2	349
SMIM22	SNN	O75324	348
SMIM22	HRCT1	Q6UXD1	348
SMIM22	ROGDI	Q9GZN7	339
SMIM22	NINL	Q9Y2I6	324
SMIM22	UBAP1	Q9NZ09	322
SMIM22	SPAAR	A0A1B0GVQ0	310
SMIM22	MTLN	Q8NCU8	308

IntAct

1 interactions, top by confidence:

ESM2 similar proteins: A0A1B0GST9, A0A1B0GTU2, A0A1B0GV90, A0A590UK83, A2RRL7, A7S641, A8WG88, A9JTJ0, B9X187, K7EJ46, O00168, O08589, O13001, P0C2S0, P15383, P41237, P56513, P60606, P63160, P63161, Q04645, Q04646, Q04679, Q04680, Q0P467, Q28EH9, Q3SZX0, Q3UJ81, Q3URE8, Q3ZBP2, Q4LDR2, Q4R6L9, Q502I1, Q592E4, Q5XF36, Q6AXF6, Q6NWH5, Q6PBK8, Q6Q3F5, Q71RC9

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

974 predictions. Top by Δscore:

Variant	Effect	Δscore
16:4794951:GGGA:G	acceptor_gain	1.0000
16:4794976:T:TA	acceptor_gain	1.0000
16:4794985:C:CA	acceptor_gain	1.0000
16:4794986:G:A	acceptor_gain	1.0000
16:4795854:CATGG:C	donor_gain	1.0000
16:4795855:ATGG:A	donor_gain	1.0000
16:4795855:ATGGG:A	donor_loss	1.0000
16:4795856:TGG:T	donor_gain	1.0000
16:4795856:TGGGT:T	donor_loss	1.0000
16:4795857:GG:G	donor_gain	1.0000
16:4795857:GGG:G	donor_gain	1.0000
16:4795858:GG:G	donor_gain	1.0000
16:4795858:GGT:G	donor_loss	1.0000
16:4795859:G:GG	donor_gain	1.0000
16:4795860:T:A	donor_loss	1.0000
16:4795942:CCCCA:C	acceptor_loss	1.0000
16:4795943:CCCAG:C	acceptor_loss	1.0000
16:4795944:CCA:C	acceptor_loss	1.0000
16:4795945:CAGGC:C	acceptor_loss	1.0000
16:4795946:A:AC	acceptor_loss	1.0000
16:4795946:A:AG	acceptor_gain	1.0000
16:4795947:G:GA	acceptor_gain	1.0000
16:4795947:GGC:G	acceptor_gain	1.0000
16:4794947:ATCAG:A	acceptor_gain	0.9900
16:4795139:A:AG	acceptor_gain	0.9900
16:4795140:T:G	acceptor_gain	0.9900
16:4795749:A:AG	acceptor_gain	0.9900
16:4795750:G:GG	acceptor_gain	0.9900
16:4795946:AG:A	acceptor_gain	0.9900
16:4795947:GG:G	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000266886 (16:4789191 T>C), RS1000340856 (16:4789395 G>A,T), RS1000631884 (16:4790247 G>C), RS1000663083 (16:4790407 T>A), RS1000905336 (16:4795500 G>A), RS1000930505 (16:4791147 G>A), RS1001090054 (16:4787243 C>A), RS1001532183 (16:4796812 C>T), RS1001570432 (16:4792858 C>A,G,T), RS1001979465 (16:4793988 T>G), RS1002030212 (16:4789727 G>A,C), RS1002061568 (16:4789929 T>C), RS1002191675 (16:4791494 A>G), RS1002245413 (16:4791646 C>A,G), RS1002404184 (16:4787728 T>C,G)

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

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	affects expression, decreases expression	2
arsenite	affects binding, increases reaction	1
jinfukang	affects cotreatment, decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cisplatin	decreases expression, affects cotreatment	1
Silicon Dioxide	affects expression	1
Smoke	increases abundance, increases expression	1
Tretinoin	decreases expression	1
Permethrin	increases expression	1

Clinical trials (associated diseases)

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