SMIM8

Summary

SMIM8 (small integral membrane protein 8, HGNC:21401) is a protein-coding gene on chromosome 6q15, encoding Small integral membrane protein 8 (Q96KF7).

Located in mitochondrion.

Source: NCBI Gene 57150 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 22 total
• MANE Select transcript: NM_001042493

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:21401
Approved symbol	SMIM8
Name	small integral membrane protein 8
Location	6q15
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586E1923, dJ102H19.2
Ensembl gene	ENSG00000111850
Ensembl biotype	protein_coding
Entrez	57150

Gene structure

Transcript identifiers

Ensembl transcripts: 23 — 19 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000229570, ENST00000369570, ENST00000369572, ENST00000392863, ENST00000448282, ENST00000608353, ENST00000608525, ENST00000608535, ENST00000608868, ENST00000893999, ENST00000894000, ENST00000894001, ENST00000894002, ENST00000894003, ENST00000894004, ENST00000894005, ENST00000936131, ENST00000936132, ENST00000936133, ENST00000968377, ENST00000968378, ENST00000968379, ENST00000968380

RefSeq mRNA: 3 — MANE Select: NM_001042493 NM_001042493, NM_001287445, NM_020425

CCDS: CCDS34496, CCDS75493

Canonical transcript exons

ENST00000392863 — 4 exons

Exon	Start	End
ENSE00001209204	87340116	87342329
ENSE00001419199	87322588	87322632
ENSE00001513394	87330692	87330712
ENSE00003893262	87337009	87337166

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 92.58.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.5778 / max 71.5713, expressed in 1582 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
68837	4.5778	1582

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	92.58	gold quality
cortical plate	UBERON:0005343	88.98	gold quality
tendon of biceps brachii	UBERON:0008188	88.98	silver quality
ganglionic eminence	UBERON:0004023	87.16	gold quality
oocyte	CL:0000023	87.02	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.89	gold quality
endothelial cell	CL:0000115	84.48	gold quality
calcaneal tendon	UBERON:0003701	83.68	gold quality
tendon	UBERON:0000043	83.34	gold quality
right uterine tube	UBERON:0001302	83.13	gold quality
corpus epididymis	UBERON:0004359	83.02	gold quality
ventricular zone	UBERON:0003053	82.97	gold quality
secondary oocyte	CL:0000655	82.43	gold quality
prefrontal cortex	UBERON:0000451	82.39	gold quality
caput epididymis	UBERON:0004358	82.31	gold quality
right atrium auricular region	UBERON:0006631	82.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.05	gold quality
apex of heart	UBERON:0002098	81.41	gold quality
hindlimb stylopod muscle	UBERON:0004252	81.27	gold quality
muscle of leg	UBERON:0001383	80.51	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.42	gold quality
gastrocnemius	UBERON:0001388	80.40	gold quality
islet of Langerhans	UBERON:0000006	80.24	gold quality
adrenal tissue	UBERON:0018303	79.99	gold quality
cardiac atrium	UBERON:0002081	79.93	gold quality
trabecular bone tissue	UBERON:0002483	79.86	gold quality
heart left ventricle	UBERON:0002084	79.72	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.51	gold quality
cardiac ventricle	UBERON:0002082	79.35	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.73
E-MTAB-6379	no	894.85

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting SMIM8, 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-4283	100.00	66.42	2097
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
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-4803	99.98	71.99	3117
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-8063	99.91	69.76	3146

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	smim8	ENSDARG00000071040
mus_musculus	Smim8	ENSMUSG00000028295
rattus_norvegicus	Smim8	ENSRNOG00000023035
drosophila_melanogaster	CG32448	FBGN0052448

Protein

Protein identifiers

Small integral membrane protein 8 — Q96KF7 (reviewed: Q96KF7)

All UniProt accessions (3): Q96KF7, V9GYF9, V9GYL2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the SMIM8 family.

RefSeq proteins (3): NP_001035958, NP_001274374, NP_065158 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR026686	UPF0708	Family

Pfam: PF14937

UniProt features (4 total): chain 1, transmembrane region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96KF7-F1	66.14	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 108 (showing top): chr6q15, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_UP, DARWICHE_SQUAMOUS_CELL_CARCINOMA_UP, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, MULLIGHAN_MLL_SIGNATURE_2_DN, NUYTTEN_EZH2_TARGETS_DN, MEF2_03, THUM_SYSTOLIC_HEART_FAILURE_DN, STEIN_ESRRA_TARGETS_UP, WIERENGA_STAT5A_TARGETS_DN, JOHNSTONE_PARVB_TARGETS_3_DN, BRUINS_UVC_RESPONSE_LATE, GSE14699_NAIVE_VS_ACT_CD8_TCELL_UP

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (2): mitochondrion (GO:0005739), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

326 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM8	TMEM210	A6NLX4	656
SMIM8	SMIM9	A6NGZ8	626
SMIM8	C6orf163	Q5TEZ5	506
SMIM8	SLC25A41	Q8N5S1	451
SMIM8	ZNF736	B4DX44	431
SMIM8	RWDD2A	Q9UIY3	414
SMIM8	TOMM20L	Q6UXN7	407
SMIM8	UBE3D	Q7Z6J8	373
SMIM8	CFAP206	Q8IYR0	372
SMIM8	CBY2	Q8NA61	370
SMIM8	GKAP1	Q5VSY0	370
SMIM8	TMEM125	Q96AQ2	370
SMIM8	ZNF76	P36508	359
SMIM8	GJB7	Q6PEY0	350
SMIM8	RIPPLY2	Q5TAB7	323

IntAct

7 interactions, top by confidence:

A	B	Type	Score
RANBP6	SLC27A2	psi-mi:“MI:0914”(association)	0.640
AQP3	RTL8C	psi-mi:“MI:0914”(association)	0.350
SMIM8	HP	psi-mi:“MI:0914”(association)	0.350
SMIM8	MAGEA6	psi-mi:“MI:0914”(association)	0.350
SLC2A5	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): SMIM8 (Affinity Capture-MS), SMIM8 (Affinity Capture-RNA), SMIM8 (Affinity Capture-MS), SMIM8 (Affinity Capture-MS), IGHG2 (Affinity Capture-MS), LTF (Affinity Capture-MS), IGLC2 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), CTSG (Affinity Capture-MS), TF (Affinity Capture-MS), HP (Affinity Capture-MS), MNDA (Affinity Capture-MS), VIM (Affinity Capture-MS), ORM1 (Affinity Capture-MS), IGHG1 (Affinity Capture-MS)

ESM2 similar proteins: A1XQS2, D3Z9R8, E2R4X3, E9PQ53, O14548, O60397, O82067, P14790, P34660, P46269, P46270, P56378, P56379, Q02827, Q1RMH3, Q29259, Q2KI08, Q3SZ13, Q3T061, Q3ZBI7, Q4V8S3, Q56JY4, Q5R987, Q5RDZ8, Q5XFV8, Q5ZML6, Q61387, Q63ZZ0, Q69YU5, Q78IK2, Q7SXI1, Q8BH51, Q8BTC1, Q8C1Q6, Q8N0X7, Q96B49, Q96I36, Q96IX5, Q96KF7, Q99KD6

Diamond homologs: A2VDV9, Q28GF4, Q502E5, Q5REX0, Q96KF7, Q9CQQ0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	20
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1328 predictions. Top by Δscore:

Variant	Effect	Δscore
6:87337167:G:GG	donor_gain	1.0000
6:87356481:G:GT	donor_gain	1.0000
6:87364959:A:AG	acceptor_gain	1.0000
6:87364960:G:GG	acceptor_gain	1.0000
6:87337163:ACCT:A	donor_gain	0.9900
6:87337164:CCT:C	donor_gain	0.9900
6:87337184:GA:G	donor_gain	0.9900
6:87345246:AGGTA:A	donor_loss	0.9900
6:87345247:GGTA:G	donor_loss	0.9900
6:87345248:GT:G	donor_loss	0.9900
6:87350135:G:GG	donor_gain	0.9900
6:87356300:GGAA:G	acceptor_gain	0.9900
6:87364956:TGTA:T	acceptor_loss	0.9900
6:87364957:GTA:G	acceptor_loss	0.9900
6:87364958:TA:T	acceptor_loss	0.9900
6:87364959:A:AC	acceptor_loss	0.9900
6:87364960:G:GA	acceptor_loss	0.9900
6:87364960:GC:G	acceptor_gain	0.9900
6:87364960:GCA:G	acceptor_gain	0.9900
6:87364960:GCAAA:G	acceptor_gain	0.9900
6:87322633:G:GG	donor_gain	0.9800
6:87322634:T:A	donor_loss	0.9800
6:87329134:TTA:T	donor_loss	0.9800
6:87329136:ACC:A	donor_loss	0.9800
6:87329137:C:CG	donor_loss	0.9800
6:87329159:C:CA	donor_gain	0.9800
6:87330678:C:G	acceptor_gain	0.9800
6:87340114:A:AG	acceptor_gain	0.9800
6:87340115:G:GG	acceptor_gain	0.9800
6:87345244:CTAG:C	donor_gain	0.9800

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000015505 (6:87333862 A>G), RS1000060726 (6:87340389 A>G,T), RS1000130638 (6:87339017 G>A), RS1000227413 (6:87323408 A>G), RS1000744043 (6:87329296 A>G), RS1000805102 (6:87324130 T>C), RS1001022543 (6:87332366 A>G), RS1001074424 (6:87332086 A>C,G), RS1001250095 (6:87339261 C>T), RS1001260568 (6:87328900 C>G,T), RS1001429569 (6:87334679 T>C), RS1001573625 (6:87342000 G>A), RS1001649560 (6:87328785 T>C), RS1001685181 (6:87323667 T>G), RS1001737772 (6:87323836 T>C)

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

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression	5
trichostatin A	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases expression, decreases methylation	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
kojic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
MT19c compound	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	increases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Doxorubicin	decreases expression	1
Nickel	decreases expression	1
Plant Extracts	increases expression, affects cotreatment	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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