SMIM26

Summary

SMIM26 (small integral membrane protein 26, HGNC:43430) is a protein-coding gene on chromosome 20p11.23, encoding Small integral membrane protein 26 (A0A096LP01). May play a role in cell viability.

Enables protein kinase binding activity and transmembrane transporter binding activity. Located in mitochondrial outer membrane.

Source: NCBI Gene 388789 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001348957

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:43430
Approved symbol	SMIM26
Name	small integral membrane protein 26
Location	20p11.23
Locus type	gene with protein product
Status	Approved
Aliases	LOC388789
Ensembl gene	ENSG00000232388
Ensembl biotype	protein_coding
Entrez	388789

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000411646, ENST00000435844, ENST00000608034

RefSeq mRNA: 2 — MANE Select: NM_001348957 NM_001348957, NM_001348958

CCDS: CCDS86936, CCDS86937

Canonical transcript exons

ENST00000411646 — 2 exons

Exon	Start	End
ENSE00001616030	18569236	18569560
ENSE00001700959	18567432	18567596

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 99.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 67.8289 / max 725.4731, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
183692	67.8289	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
quadriceps femoris	UBERON:0001377	99.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	98.33	gold quality
gastrocnemius	UBERON:0001388	98.20	gold quality
muscle of leg	UBERON:0001383	98.08	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	98.04	gold quality
islet of Langerhans	UBERON:0000006	97.67	gold quality
monocyte	CL:0000576	97.40	gold quality
heart left ventricle	UBERON:0002084	97.40	gold quality
right adrenal gland	UBERON:0001233	97.36	gold quality
mucosa of stomach	UBERON:0001199	97.33	gold quality
apex of heart	UBERON:0002098	97.31	gold quality
leukocyte	CL:0000738	97.30	gold quality
left adrenal gland	UBERON:0001234	97.29	gold quality
fundus of stomach	UBERON:0001160	97.28	gold quality
left ovary	UBERON:0002119	97.28	gold quality
left adrenal gland cortex	UBERON:0035825	97.28	gold quality
adenohypophysis	UBERON:0002196	97.26	gold quality
body of pancreas	UBERON:0001150	97.24	gold quality
right adrenal gland cortex	UBERON:0035827	97.24	gold quality
pituitary gland	UBERON:0000007	97.20	gold quality
ovary	UBERON:0000992	97.19	gold quality
heart	UBERON:0000948	97.17	gold quality
body of stomach	UBERON:0001161	97.14	gold quality
pancreas	UBERON:0001264	97.13	gold quality
skeletal muscle tissue	UBERON:0001134	97.12	gold quality
right atrium auricular region	UBERON:0006631	97.04	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.97	gold quality
gall bladder	UBERON:0002110	96.96	gold quality
muscle tissue	UBERON:0002385	96.90	gold quality
popliteal artery	UBERON:0002250	96.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.01

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

• Identification and analysis of short open reading frames (sORFs) in the initially annotated noncoding RNA LINC00493 from human cells. (PMID:33386847)
• Investigation of LINC00493/SMIM26 Gene Suggests Its Dual Functioning at mRNA and Protein Level. (PMID:34445188)
• LINC00493-encoded microprotein SMIM26 exerts anti-metastatic activity in renal cell carcinoma. (PMID:37009826)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smim26	ENSMUSG00000074754
rattus_norvegicus	Smim26	ENSRNOG00000036971

Protein

Protein identifiers

Small integral membrane protein 26 — A0A096LP01 (reviewed: A0A096LP01)

All UniProt accessions (2): A0A096LP01, A0A096LPB8

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in cell viability.

Subunit / interactions. Interacts with AGK and SLC25A11.

Subcellular location. Mitochondrion outer membrane.

Tissue specificity. Detected in kidney (at protein level).

Miscellaneous. Suppresses clear cell renal cell carcinoma growth and metastatis. In renal cancer cell lines, interaction with SLC25A11 maintains mitochondrial glutathione and enhances mitochondrial metabolism. In renal cancer cell lines, interaction with AGK promotes AGK mitochondrial localization and inactivates AGK-mediated AKT phosphorylation, leading to inhibition of AKT signaling and repression of metastasis.

Similarity. Belongs to the SMIM26 family.

Isoforms (2)

UniProt ID	Names	Canonical?
A0A096LP01-1	1	yes
A0A096LP01-2	2

RefSeq proteins (2): NP_001335886, NP_001335887 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038831	SMIM26	Family

UniProt features (3 total): chain 1, transmembrane region 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A096LP01-F1	72.61	0.16

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): STARK_PREFRONTAL_CORTEX_22Q11_DELETION_DN, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GOCC_MITOCHONDRIAL_ENVELOPE, chr20p11, GOMF_TRANSMEMBRANE_TRANSPORTER_BINDING, GOMF_KINASE_BINDING, GOCC_ORGANELLE_ENVELOPE, MIKKELSEN_ES_ICP_WITH_H3K4ME3, MIKKELSEN_NPC_ICP_WITH_H3K4ME3, KAT5_TARGET_GENES, SETD7_TARGET_GENES, UBN1_TARGET_GENES, ZNF2_TARGET_GENES, ZNF618_TARGET_GENES, ZNF711_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (3): protein kinase binding (GO:0019901), transmembrane transporter binding (GO:0044325), protein binding (GO:0005515)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial outer membrane (GO:0005741), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
kinase binding	1
protein binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrial membrane	1
organelle outer membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

480 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM26	OXLD1	Q5BKU9	451
SMIM26	ANTKMT	Q9BQD7	416
SMIM26	TMEM242	Q9NWH2	411
SMIM26	TEX261	Q6UWH6	401
SMIM26	PIGBOS1	A0A0B4J2F0	399
SMIM26	LYRM9	A8MSI8	383
SMIM26	SNAPC5	O75971	370
SMIM26	ZNF343	Q6P1L6	368
SMIM26	YARS1	P54577	351
SMIM26	FAM110A	Q9BQ89	348
SMIM26	LONRF3	Q496Y0	331
SMIM26	MIGA2	Q7L4E1	326
SMIM26	AP5S1	Q9NUS5	310
SMIM26	NRSN2	Q9GZP1	306
SMIM26	ZNF133	P52736	300

IntAct

26 interactions, top by confidence:

A	B	Type	Score
SMIM26	AGK	psi-mi:“MI:0915”(physical association)	0.650
SMIM26	AGK	psi-mi:“MI:0403”(colocalization)	0.650
AGK	SMIM26	psi-mi:“MI:0403”(colocalization)	0.650
AGK	SMIM26	psi-mi:“MI:0914”(association)	0.650
SMIM26	AGK	psi-mi:“MI:0914”(association)	0.650
SMIM26	SLC25A11	psi-mi:“MI:0915”(physical association)	0.630
SMIM26	SLC25A11	psi-mi:“MI:0403”(colocalization)	0.630
SLC25A11	SMIM26	psi-mi:“MI:0915”(physical association)	0.630
SMIM26	SLC25A11	psi-mi:“MI:0914”(association)	0.630
SMIM26	CNOT1	psi-mi:“MI:0914”(association)	0.350
SMIM26	ESYT2	psi-mi:“MI:0914”(association)	0.350
SMIM26	METTL15	psi-mi:“MI:0914”(association)	0.350

ESM2 similar proteins: A0A096LP01, A3LP48, A3LQD9, A5DLM7, A6SAY2, A6ZLK2, A7EJE5, A7TMN2, B3LMP9, B9WD58, C4YPM0, C5DRK2, C5E381, C7GMW8, D3UF10, G2TRJ9, O22912, O74383, O95167, P0DN34, P19173, P20609, P20610, P26310, P38341, P48306, Q02365, Q02371, Q0MQ94, Q0MQ95, Q0MQ96, Q2KP58, Q2V2Q3, Q42841, Q59LP6, Q59QC6, Q6BL60, Q6C5S0, Q6CHT7, Q752G2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 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

150 predictions. Top by Δscore:

Variant	Effect	Δscore
20:18567593:TCAG:T	donor_loss	1.0000
20:18567594:CAG:C	donor_loss	1.0000
20:18567595:AGG:A	donor_loss	1.0000
20:18567596:GGTAG:G	donor_loss	1.0000
20:18567597:GTA:G	donor_loss	1.0000
20:18567598:T:A	donor_loss	1.0000
20:18569223:A:AG	acceptor_gain	1.0000
20:18569223:AAT:A	acceptor_gain	1.0000
20:18569223:AATG:A	acceptor_gain	1.0000
20:18569224:A:G	acceptor_gain	1.0000
20:18569224:AT:A	acceptor_gain	1.0000
20:18569224:ATGGT:A	acceptor_gain	1.0000
20:18569225:T:A	acceptor_gain	1.0000
20:18569225:T:G	acceptor_gain	1.0000
20:18569235:GTA:G	acceptor_gain	1.0000
20:18569224:ATG:A	acceptor_gain	0.9900
20:18569226:G:A	acceptor_gain	0.9900
20:18569228:T:TA	acceptor_gain	0.9900
20:18569235:GT:G	acceptor_gain	0.9900
20:18569232:A:AG	acceptor_gain	0.9800
20:18569233:A:G	acceptor_gain	0.9800
20:18569234:A:AG	acceptor_gain	0.9800
20:18569235:G:GG	acceptor_gain	0.9800
20:18569237:A:AG	acceptor_gain	0.9800
20:18569238:G:GA	acceptor_gain	0.9800
20:18569235:GTAGA:G	acceptor_gain	0.9700
20:18567523:G:GA	donor_gain	0.9600
20:18567546:C:A	donor_gain	0.9500
20:18567597:G:GG	donor_gain	0.9500
20:18569231:TAAAG:T	acceptor_loss	0.9500

AlphaMissense

598 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:18567542:T:A	W22R	0.951
20:18567542:T:C	W22R	0.951
20:18567555:G:A	G26D	0.942
20:18567525:T:A	V16D	0.933
20:18567537:G:A	G20D	0.920
20:18567554:G:C	G26R	0.914
20:18567536:G:C	G20R	0.898
20:18567531:G:A	G18E	0.882
20:18567527:T:G	Y17D	0.881
20:18567530:G:A	G18R	0.867
20:18567530:G:C	G18R	0.867
20:18569298:T:C	F61L	0.856
20:18569300:T:A	F61L	0.856
20:18569300:T:G	F61L	0.856
20:18567534:T:A	I19N	0.851
20:18569334:T:C	F73L	0.851
20:18569336:T:A	F73L	0.851
20:18569336:T:G	F73L	0.851
20:18567549:T:A	V24E	0.840
20:18569356:T:C	I80T	0.839
20:18567494:T:C	F6L	0.808
20:18567496:C:A	F6L	0.808
20:18567496:C:G	F6L	0.808
20:18569376:T:A	W87R	0.800
20:18569376:T:C	W87R	0.800
20:18567522:T:A	V15E	0.795
20:18567545:T:C	S23P	0.793
20:18567503:T:A	W9R	0.791
20:18567503:T:C	W9R	0.791
20:18569378:G:C	W87C	0.790

dbSNP variants (sampled 300 via entrez): RS1000467834 (20:18567232 T>A), RS1001051530 (20:18568471 C>T), RS1001419066 (20:18568815 C>G,T), RS1001679556 (20:18565942 A>G), RS1001731867 (20:18565636 C>T), RS1003180458 (20:18566261 T>G), RS1003859963 (20:18567647 G>A), RS1004893706 (20:18568865 C>G), RS1005234333 (20:18566772 C>T), RS1005267976 (20:18569116 T>A), RS1005945284 (20:18566328 A>C,G,T), RS1006646254 (20:18565542 C>T), RS1006650677 (20:18569656 G>A,C), RS1007412627 (20:18565874 G>A), RS1008051770 (20:18568132 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

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
arsenite	affects binding, increases reaction	1
Temozolomide	increases expression	1
Testosterone	decreases expression	1
Zinc	decreases expression	1
Cadmium Chloride	increases expression	1
Lactic Acid	decreases expression	1
Particulate Matter	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E2KD	HAP1 SMIM26 (-) 1	Cancer cell line	Male
CVCL_E2KE	HAP1 SMIM26 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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