SMIM21

Summary

SMIM21 (small integral membrane protein 21, HGNC:27598) is a protein-coding gene on chromosome 18q23, encoding Small integral membrane protein 21 (Q3B7S5).

Predicted to be located in membrane.

Source: NCBI Gene 284274 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 20 total
• MANE Select transcript: NM_001037331

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27598
Approved symbol	SMIM21
Name	small integral membrane protein 21
Location	18q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000206026
Ensembl biotype	protein_coding
Entrez	284274

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000382638, ENST00000579022, ENST00000584508

RefSeq mRNA: 2 — MANE Select: NM_001037331 NM_001037331, NM_001303482

CCDS: CCDS32845, CCDS77200

Canonical transcript exons

ENST00000579022 — 3 exons

Exon	Start	End
ENSE00001492843	75418786	75418916
ENSE00002717222	75409476	75410909
ENSE00002722474	75427435	75427703

Expression profiles

Bgee: expression breadth broad, 11 present calls, max score 90.52.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	90.52	gold quality
buccal mucosa cell	CL:0002336	85.41	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.81	gold quality
right testis	UBERON:0004534	59.86	gold quality
left testis	UBERON:0004533	59.56	gold quality
testis	UBERON:0000473	58.92	gold quality
lower lobe of lung	UBERON:0008949	49.07	silver quality
skin of hip	UBERON:0001554	46.98	silver quality
lateral globus pallidus	UBERON:0002476	44.95	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
secondary oocyte	CL:0000655	42.57	gold quality
upper leg skin	UBERON:0004262	42.39	silver quality
substantia nigra pars reticulata	UBERON:0001966	42.18	gold quality
vastus lateralis	UBERON:0001379	41.41	gold quality
middle temporal gyrus	UBERON:0002771	41.40	gold quality
quadriceps femoris	UBERON:0001377	41.37	gold quality
superficial temporal artery	UBERON:0001614	41.33	gold quality
palpebral conjunctiva	UBERON:0001812	41.10	gold quality
mucosa of paranasal sinus	UBERON:0005030	40.98	gold quality
amniotic fluid	UBERON:0000173	40.69	gold quality
trabecular bone tissue	UBERON:0002483	40.60	gold quality
jejunal mucosa	UBERON:0000399	40.59	gold quality
biceps brachii	UBERON:0001507	40.57	gold quality
epithelium of nasopharynx	UBERON:0001951	40.45	gold quality
myocardium	UBERON:0002349	40.45	gold quality
gingival epithelium	UBERON:0001949	40.43	gold quality
germinal epithelium of ovary	UBERON:0001304	40.33	gold quality
esophagus squamous epithelium	UBERON:0006920	40.29	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	40.27	gold quality
jejunum	UBERON:0002115	40.18	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

54 targeting SMIM21, 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-6867-5P	100.00	82.21	3464
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3059-5P	99.70	69.93	2491
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-5009-3P	99.45	69.43	1341
HSA-MIR-3692-5P	99.29	67.04	1421
HSA-MIR-7158-5P	99.25	67.95	796
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-6830-5P	99.01	68.73	1884

Cross-species orthologs

0 orthologs

Protein

Protein identifiers

Small integral membrane protein 21 — Q3B7S5 (reviewed: Q3B7S5)

All UniProt accessions (3): Q3B7S5, J3KSN8, J9JIF2

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

RefSeq proteins (2): NP_001032408, NP_001290411 (=MANE)

Domains & families (InterPro)

UniProt features (2 total): chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q3B7S5-F1	70.07	0.15

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 27 (showing top): MIR6867_5P, MIR4668_5P, MIR33A_3P, MIR6833_3P, MIR548AZ_5P, MIR548T_5P, MIR6875_3P, MIR6873_3P, MIR4768_5P, MIR1290, MIR3123, MIR6878_5P, MIR5682, MIR876_5P, MIR3692_5P

GO Biological Process (0):

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

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

260 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM21	PTGR3	Q8N4Q0	621
SMIM21	C3orf22	Q8N5N4	572
SMIM21	C12orf56	Q8IXR9	507
SMIM21	RNASE12	Q5GAN4	507
SMIM21	SMIM17	P0DL12	506
SMIM21	ZNF407	Q9C0G0	480
SMIM21	SH2D7	A6NKC9	479
SMIM21	C22orf42	Q6IC83	476
SMIM21	CC2D2B	Q6DHV5	476
SMIM21	C1orf167	Q5SNV9	476
SMIM21	SMIM10L2A	P0DMW4	476
SMIM21	ANKRD62	A6NC57	474
SMIM21	TSHZ1	Q6ZSZ6	473
SMIM21	SPDYE4	A6NLX3	447
SMIM21	CLPSL1	A2RUU4	447
SMIM21	MROH7	Q68CQ1	447
SMIM21	C16orf95	Q9H693	447

IntAct

7 interactions, top by confidence:

A	B	Type	Score
DESI1	SMIM21	psi-mi:“MI:0915”(physical association)	0.560
SMIM21	DESI1	psi-mi:“MI:0915”(physical association)	0.560
SMIM21	RMND1	psi-mi:“MI:0915”(physical association)	0.400
CFTR	SMIM21	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (3): SMIM21 (Two-hybrid), RMND1 (Affinity Capture-MS), SMIM21 (PCA)

ESM2 similar proteins: A0A023PZF2, C0H421, C7U330, G2TRK6, G2TRL8, G2TRM4, G2TRR5, O13532, O29949, O86239, P0CAI8, P0CAI9, P0CAJ0, P0CE99, P0CL25, P0CL26, P0CY14, P0CY15, P0DTB5, P27554, P30653, P34830, P35006, P38311, P40211, P40448, P43576, P46986, P53216, P53225, P53229, P53340, Q04897, Q05503, Q08259, Q08321, Q08915, Q12225, Q13166, Q3B7S5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	17
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

724 predictions. Top by Δscore:

Variant	Effect	Δscore
18:75410789:T:TA	donor_gain	1.0000
18:75410905:GAAAG:G	acceptor_gain	1.0000
18:75410907:AAG:A	acceptor_gain	1.0000
18:75410908:AG:A	acceptor_gain	1.0000
18:75410909:GC:G	acceptor_loss	1.0000
18:75410910:C:CA	acceptor_loss	1.0000
18:75410910:C:CC	acceptor_gain	1.0000
18:75418784:A:AC	donor_gain	1.0000
18:75418785:C:CC	donor_gain	1.0000
18:75410906:AAAG:A	acceptor_gain	0.9900
18:75410911:T:A	acceptor_loss	0.9900
18:75416788:A:C	donor_gain	0.9900
18:75418781:CCTA:C	donor_gain	0.9900
18:75418785:CTTT:C	donor_gain	0.9900
18:75418917:C:CC	acceptor_gain	0.9900
18:75427433:A:AC	donor_gain	0.9800
18:75427434:C:CC	donor_gain	0.9800
18:75417316:A:T	acceptor_gain	0.9700
18:75419824:AT:A	donor_gain	0.9600
18:75427554:A:AC	donor_gain	0.9600
18:75427555:C:CC	donor_gain	0.9600
18:75410913:C:CT	acceptor_gain	0.9500
18:75410920:C:CT	acceptor_gain	0.9500
18:75416787:A:AC	donor_gain	0.9500
18:75418866:A:C	acceptor_gain	0.9500
18:75427434:CT:C	donor_gain	0.9500
18:75410921:A:T	acceptor_gain	0.9400
18:75418913:CAAA:C	acceptor_gain	0.9400
18:75410914:A:T	acceptor_gain	0.9300
18:75417312:TCCCA:T	acceptor_gain	0.9300

AlphaMissense

666 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:75418812:C:A	W78C	0.878
18:75418812:C:G	W78C	0.878
18:75410906:A:C	F88L	0.863
18:75410906:A:T	F88L	0.863
18:75410908:A:G	F88L	0.863
18:75427528:G:C	F12L	0.819
18:75427528:G:T	F12L	0.819
18:75427530:A:G	F12L	0.819
18:75418814:A:G	W78R	0.816
18:75418814:A:T	W78R	0.816
18:75418876:A:T	V57D	0.800
18:75418805:C:G	A81P	0.793
18:75418791:A:C	F85L	0.789
18:75418791:A:T	F85L	0.789
18:75418793:A:G	F85L	0.789
18:75418887:G:C	F53L	0.787
18:75418887:G:T	F53L	0.787
18:75418889:A:G	F53L	0.787
18:75418869:G:C	F59L	0.724
18:75418869:G:T	F59L	0.724
18:75418871:A:G	F59L	0.724
18:75418817:C:G	D77H	0.716
18:75418804:G:T	A81D	0.706
18:75418813:C:G	W78S	0.702
18:75418868:G:C	H60D	0.680
18:75418873:A:G	L58P	0.677
18:75418795:A:T	I84K	0.667
18:75418816:T:A	D77V	0.660
18:75427504:A:C	F20L	0.657
18:75427504:A:T	F20L	0.657

dbSNP variants (sampled 300 via entrez): RS1000039958 (18:75414077 A>G,T), RS1000057000 (18:75413986 A>G), RS1000187475 (18:75424641 T>C,G), RS1000236788 (18:75412406 A>G), RS1000238831 (18:75426071 G>A), RS1000244546 (18:75420047 A>C,T), RS1000418351 (18:75413820 C>T), RS1000433682 (18:75418508 C>T), RS1000469628 (18:75420395 C>G,T), RS1000614635 (18:75416933 T>C), RS1000644866 (18:75423419 G>C), RS1000665410 (18:75424848 C>T), RS1000771412 (18:75417206 G>A,T), RS1000826119 (18:75425698 A>G), RS1001000595 (18:75418542 A>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

7 associations (top):

Study	Trait	p-value
GCST001113_10	Age at smoking initiation in chronic obstructive pulmonary disease	5.000000e-06
GCST001428_17	Intelligence	5.000000e-06
GCST001961_3	Anorexia nervosa	3.000000e-07
GCST002357_6	Rheumatoid arthritis (ACPA-negative)	2.000000e-08
GCST004751_20	Serum uric acid levels in response to allopurinol in gout	4.000000e-07
GCST006073_52	Tenofovir clearance in HIV infection	4.000000e-06
GCST007576_120	Chronotype	3.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation
EFO:0004337	intelligence
EFO:0004761	uric acid measurement
EFO:0008328	chronotype measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation, affects cotreatment	1
Fulvestrant	affects cotreatment, increases methylation	1
Benzo(a)pyrene	increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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