SMIM3

Summary

SMIM3 (small integral membrane protein 3, HGNC:30248) is a protein-coding gene on chromosome 5q33.1, encoding Small integral membrane protein 3 (Q9BZL3).

Enables identical protein binding activity. Predicted to be located in membrane.

Source: NCBI Gene 85027 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 16 total
• MANE Select transcript: NM_032947

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30248
Approved symbol	SMIM3
Name	small integral membrane protein 3
Location	5q33.1
Locus type	gene with protein product
Status	Approved
Aliases	MSTP150, NID67
Ensembl gene	ENSG00000256235
Ensembl biotype	protein_coding
OMIM	608324
Entrez	85027

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000526627, ENST00000648745, ENST00000915028, ENST00000915029, ENST00000941849, ENST00000941850

RefSeq mRNA: 1 — MANE Select: NM_032947 NM_032947

CCDS: CCDS47312

Canonical transcript exons

ENST00000526627 — 2 exons

Exon	Start	End
ENSE00002278372	150778757	150778972
ENSE00002283328	150795430	150796734

Expression profiles

Bgee: expression breadth ubiquitous, 217 present calls, max score 96.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.2640 / max 692.8045, expressed in 1768 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59522	28.0683	1728
59523	12.3154	1540
59521	0.3815	131
59520	0.1486	69
59519	0.1146	60
59517	0.1124	62
59518	0.0691	30
59524	0.0542	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
adipose tissue of abdominal region	UBERON:0007808	96.76	gold quality
omental fat pad	UBERON:0010414	96.72	gold quality
peritoneum	UBERON:0002358	96.63	gold quality
adipose tissue	UBERON:0001013	96.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.19	gold quality
metanephros cortex	UBERON:0010533	95.07	gold quality
right lung	UBERON:0002167	94.52	gold quality
mucosa of stomach	UBERON:0001199	94.09	gold quality
monocyte	CL:0000576	93.20	gold quality
stromal cell of endometrium	CL:0002255	93.20	gold quality
left uterine tube	UBERON:0001303	92.82	gold quality
descending thoracic aorta	UBERON:0002345	92.71	gold quality
leukocyte	CL:0000738	92.64	gold quality
ascending aorta	UBERON:0001496	92.44	gold quality
thoracic aorta	UBERON:0001515	92.30	gold quality
tibial artery	UBERON:0007610	92.24	gold quality
popliteal artery	UBERON:0002250	92.22	gold quality
aorta	UBERON:0000947	92.17	gold quality
body of pancreas	UBERON:0001150	91.74	gold quality
left coronary artery	UBERON:0001626	91.73	gold quality
tibialis anterior	UBERON:0001385	91.41	gold quality
right atrium auricular region	UBERON:0006631	91.11	gold quality
metanephros	UBERON:0000081	90.97	gold quality
apex of heart	UBERON:0002098	90.85	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.75	gold quality
coronary artery	UBERON:0001621	90.71	gold quality
upper lobe of left lung	UBERON:0008952	90.68	gold quality
cardiac atrium	UBERON:0002081	90.59	gold quality
heart left ventricle	UBERON:0002084	90.40	gold quality
upper lobe of lung	UBERON:0008948	90.32	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-MTAB-10018	yes	110.82
E-HCAD-4	yes	45.15
E-HCAD-6	yes	36.95
E-MTAB-5061	yes	10.93
E-ANND-3	yes	10.79
E-GEOD-81547	yes	8.65
E-CURD-122	yes	6.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting SMIM3, 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-4500	99.99	72.72	2367
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-LET-7D-5P	99.96	71.76	1632
HSA-MIR-4458	99.96	71.64	1650
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4658	99.77	64.94	514
HSA-MIR-6790-5P	99.77	65.24	505
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4756-3P	99.62	66.30	1319
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4672	99.50	71.58	2893

Literature-anchored findings (GeneRIF, showing 2)

• Reports cloning of rat NID67 and discussion of mouse and human orthologs. (PMID:11288140)
• Downregulation of SMIM3 inhibits growth of leukemia via PI3K-AKT signaling pathway and correlates with prognosis of adult acute myeloid leukemia with normal karyotype. (PMID:36550462)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smim3	ENSMUSG00000038059
rattus_norvegicus	Smim3	ENSRNOG00000019536

Protein

Protein identifiers

Small integral membrane protein 3 — Q9BZL3 (reviewed: Q9BZL3)

Alternative names: NGF-induced differentiation clone 67 protein, Small membrane protein NID67

All UniProt accessions (1): Q9BZL3

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Induction. By NGF.

RefSeq proteins (1): NP_116565* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR035275	Smim3	Family

Pfam: PF17307

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

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BZL3-F1	76.75	0.27

Functional residue map

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

Catalytic / active sites (1): 19–20 (cleavage)

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 149 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, MODULE_418, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, TGACCTY_ERR1_Q2, ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, TGCTGAY_UNKNOWN, ZHOU_INFLAMMATORY_RESPONSE_LIVE_DN, BENPORATH_NOS_TARGETS, BENPORATH_OCT4_TARGETS, BOCHKIS_FOXA2_TARGETS, NAKAMURA_ADIPOGENESIS_EARLY_UP, NAKAMURA_ADIPOGENESIS_LATE_UP, MARTENS_BOUND_BY_PML_RARA_FUSION, JOHNSTONE_PARVB_TARGETS_3_DN, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_A

GO Biological Process (0):

GO Molecular Function (2): identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

394 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM3	RPS14	P06366	556
SMIM3	DCTN4	Q9UJW0	547
SMIM3	SMIM1	B2RUZ4	530
SMIM3	KCTD14	Q9BQ13	514
SMIM3	KCNE1	P15382	496
SMIM3	TLCD4	Q96MV1	493
SMIM3	SPRED3	Q2MJR0	490
SMIM3	TMEM40	Q8WWA1	480
SMIM3	RTL8B	Q17RB0	479
SMIM3	SMLR1	H3BR10	477
SMIM3	ACTMAP	Q5BKX5	464
SMIM3	RBM22	Q9NW64	458
SMIM3	MYOZ3	Q8TDC0	449
SMIM3	NOCT	Q9UK39	438
SMIM3	FGF16	O43320	430

IntAct

200 interactions, top by confidence:

A	B	Type	Score
PMP22	SMIM3	psi-mi:“MI:0915”(physical association)	0.810
MAL	SMIM3	psi-mi:“MI:0915”(physical association)	0.720
SMIM3	ATP6V0C	psi-mi:“MI:0915”(physical association)	0.720
SMIM3	EMP1	psi-mi:“MI:0915”(physical association)	0.720
EMP1	SMIM3	psi-mi:“MI:0915”(physical association)	0.720
SMIM3	MAL	psi-mi:“MI:0915”(physical association)	0.720
ATP6V0C	SMIM3	psi-mi:“MI:0915”(physical association)	0.720
SMIM3	BSCL2	psi-mi:“MI:0915”(physical association)	0.670
BSCL2	SMIM3	psi-mi:“MI:0915”(physical association)	0.670
SFTPC	SMIM3	psi-mi:“MI:0915”(physical association)	0.600
BSCL2	SMIM3	psi-mi:“MI:0915”(physical association)	0.600
CNIH1	SMIM3	psi-mi:“MI:0915”(physical association)	0.600
PLP1	SMIM3	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (61): SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid), SMIM3 (Two-hybrid)

ESM2 similar proteins: A0A0B4K753, A4GCI7, A4K144, A8AFM8, O55653, O55654, P05139, P06591, P07613, P09048, P0C2Q1, P0C2Q2, P0C2Q3, P0C2Q4, P0C2Q5, P0C2Q6, P0C2Q7, P0C2Q8, P0C2Q9, P0C2R0, P0DOM9, P0DON0, P0DTI2, P15775, P15779, P17590, P20843, P22655, P29076, P30248, P36696, P41661, P69610, P69611, Q03561, Q04854, Q0ZME5, Q14EA8, Q52PA5, Q5MQC8

Diamond homologs: Q99PE5, Q99PE6, Q9BZL3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

292 predictions. Top by Δscore:

Variant	Effect	Δscore
5:150795424:TTGCA:T	acceptor_loss	1.0000
5:150795425:TGCA:T	acceptor_loss	1.0000
5:150795426:GCAG:G	acceptor_loss	1.0000
5:150795427:CA:C	acceptor_loss	1.0000
5:150795427:CAG:C	acceptor_gain	1.0000
5:150795428:A:AG	acceptor_gain	1.0000
5:150795428:AGA:A	acceptor_gain	1.0000
5:150795428:AGAGT:A	acceptor_gain	1.0000
5:150795429:G:A	acceptor_loss	1.0000
5:150795429:G:GA	acceptor_gain	1.0000
5:150795429:GA:G	acceptor_gain	1.0000
5:150795429:GAG:G	acceptor_gain	1.0000
5:150795429:GAGT:G	acceptor_gain	1.0000
5:150795429:GAGTG:G	acceptor_gain	1.0000
5:150778969:TGGGG:T	donor_loss	0.9900
5:150778970:GGG:G	donor_gain	0.9900
5:150778970:GGGGT:G	donor_loss	0.9900
5:150778971:GG:G	donor_gain	0.9900
5:150778971:GGG:G	donor_gain	0.9900
5:150778971:GGGT:G	donor_loss	0.9900
5:150778972:GG:G	donor_gain	0.9900
5:150778972:GGTG:G	donor_loss	0.9900
5:150778974:T:A	donor_loss	0.9900
5:150795422:T:TA	acceptor_gain	0.9900
5:150795423:GTTGC:G	acceptor_loss	0.9900
5:150778943:G:GT	donor_gain	0.9800
5:150778973:G:GG	donor_gain	0.9800
5:150778974:T:G	donor_loss	0.9800
5:150778975:GA:G	donor_loss	0.9800
5:150795418:T:TA	acceptor_gain	0.9700

AlphaMissense

385 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:150795501:T:A	W21R	0.967
5:150795501:T:C	W21R	0.967
5:150795514:T:A	L25H	0.963
5:150795558:T:C	C40R	0.961
5:150795535:T:A	V32D	0.947
5:150795511:T:A	V24D	0.945
5:150795565:C:A	A42D	0.933
5:150795514:T:G	L25R	0.931
5:150795523:T:G	L28R	0.931
5:150795526:C:A	A29D	0.930
5:150795542:G:A	M34I	0.921
5:150795542:G:C	M34I	0.921
5:150795542:G:T	M34I	0.921
5:150795538:T:A	I33N	0.913
5:150795514:T:C	L25P	0.904
5:150795586:G:C	R49P	0.896
5:150795556:T:G	L39R	0.891
5:150795562:C:A	P41Q	0.891
5:150795503:G:C	W21C	0.890
5:150795503:G:T	W21C	0.890
5:150795520:T:A	I27N	0.882
5:150795574:T:A	V45E	0.881
5:150795577:T:A	I46N	0.879
5:150795523:T:A	L28Q	0.878
5:150795541:T:A	M34K	0.875
5:150795508:T:A	I23N	0.872
5:150795541:T:G	M34R	0.863
5:150795523:T:C	L28P	0.860
5:150795525:G:C	A29P	0.857
5:150795556:T:A	L39Q	0.847

dbSNP variants (sampled 300 via entrez): RS1000260503 (5:150796403 G>A,C,T), RS1000282995 (5:150778323 G>C), RS1000406452 (5:150782461 C>T), RS1000448542 (5:150788173 C>G), RS1000467326 (5:150784372 C>A,T), RS1000564128 (5:150789613 G>A,C), RS1000625864 (5:150791477 A>G), RS1000750366 (5:150788544 G>T), RS1000901616 (5:150784191 A>G), RS1001013868 (5:150794718 A>G), RS1001966058 (5:150776816 T>C), RS1002125134 (5:150786429 A>T), RS1002175697 (5:150782644 G>A,C), RS1002274127 (5:150790488 C>T), RS1002318043 (5:150793620 T>C,G)

Disease associations

OMIM: gene MIM:608324 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST004131_47	Inflammatory bowel disease	3.000000e-15
GCST004132_24	Crohn’s disease	2.000000e-19
GCST005758_8	Dimensional psychopathology (Arousal)	5.000000e-07
GCST005855_1	Cholangiocarcinoma in primary sclerosing cholangitis	1.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009099	arousal domain measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	decreases expression	3
methylmercuric chloride	decreases expression	2
bisphenol A	decreases methylation, affects expression	2
entinostat	increases expression, affects cotreatment	2
Cisplatin	increases expression	2
Estradiol	decreases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
Valproic Acid	increases expression, affects expression	2
Aflatoxin B1	increases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases expression	1
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	decreases expression, increases response to substance	1
gardiquimod	increases expression, decreases reaction	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	increases expression	1
Temozolomide	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Calcitriol	increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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