SMIM43

Summary

SMIM43 (small integral membrane protein 43, HGNC:55077) is a protein-coding gene on chromosome 4q27, encoding Small integral membrane protein 43 (Q4W5P6). Required for mesendoderm differentiation.

Enables transmembrane transporter binding activity. Predicted to be involved in mesendoderm development. Predicted to be located in plasma membrane.

Source: NCBI Gene 132332 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 13 total
• MANE Select transcript: NM_001384332

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:55077
Approved symbol	SMIM43
Name	small integral membrane protein 43
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	NEMEP
Ensembl gene	ENSG00000164112
Ensembl biotype	protein_coding
Entrez	132332

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 4 retained_intron, 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000394394, ENST00000394396, ENST00000461198, ENST00000505198, ENST00000506551, ENST00000513254, ENST00000514885, ENST00000643663, ENST00000643802

RefSeq mRNA: 3 — MANE Select: NM_001384332 NM_001384332, NM_001384333, NM_001384334

CCDS: CCDS93616

Canonical transcript exons

ENST00000643802 — 6 exons

Exon	Start	End
ENSE00003820493	121758930	121760474
ENSE00003821109	121761538	121761695
ENSE00003836497	121763764	121763872
ENSE00003839097	121762727	121762798
ENSE00003911610	121761830	121761892
ENSE00003915814	121764817	121765164

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 94.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.7705 / max 49.3040, expressed in 182 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
53838	0.7705	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 46	UBERON:0006483	94.36	gold quality
endothelial cell	CL:0000115	94.14	gold quality
prefrontal cortex	UBERON:0000451	92.50	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.12	gold quality
Brodmann (1909) area 23	UBERON:0013554	90.08	gold quality
frontal cortex	UBERON:0001870	89.85	gold quality
middle temporal gyrus	UBERON:0002771	88.67	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.49	gold quality
superior frontal gyrus	UBERON:0002661	88.06	gold quality
neocortex	UBERON:0001950	87.94	gold quality
primary visual cortex	UBERON:0002436	87.65	gold quality
right frontal lobe	UBERON:0002810	87.63	gold quality
anterior cingulate cortex	UBERON:0009835	87.02	gold quality
postcentral gyrus	UBERON:0002581	85.65	gold quality
occipital lobe	UBERON:0002021	85.18	gold quality
parietal lobe	UBERON:0001872	84.88	gold quality
cerebral cortex	UBERON:0000956	84.61	gold quality
placenta	UBERON:0001987	76.38	gold quality
entorhinal cortex	UBERON:0002728	74.98	gold quality
pancreatic ductal cell	CL:0002079	74.97	silver quality
pigmented layer of retina	UBERON:0001782	73.35	gold quality
Ammon’s horn	UBERON:0001954	72.91	gold quality
temporal lobe	UBERON:0001871	72.20	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.99	gold quality
tibial nerve	UBERON:0001323	71.77	gold quality
adult organism	UBERON:0007023	69.95	gold quality
amygdala	UBERON:0001876	69.59	gold quality
lymph node	UBERON:0000029	67.02	gold quality
forebrain	UBERON:0001890	66.97	gold quality
stromal cell of endometrium	CL:0002255	65.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.11

Regulation

Is transcription factor: no

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Smim43	ENSMUSG00000085007
rattus_norvegicus	Smim43	ENSRNOG00000080346

Protein

Protein identifiers

Small integral membrane protein 43 — Q4W5P6 (reviewed: Q4W5P6)

Alternative names: Nodal enhanced mesendoderm micropeptide

All UniProt accessions (2): A0A7E1QX52, Q4W5P6

UniProt curated annotations — full annotation on UniProt →

Function. Required for mesendoderm differentiation. Interacts with glucose transporters and promotes glucose uptake. Probably augments the glucose uptake capacity of glucose transporter proteins to meet the energy needs of mesendoderm differentiation.

Subunit / interactions. Interacts with glucose transporters SLC2A1/GLUT1 and SLC2A3/GLUT3; the interactions may promote SLC2A1- and SLC2A3-mediated glucose transport to meet the energy needs of mesendoderm differentiation.

Subcellular location. Cell membrane.

RefSeq proteins (3): NP_001371261, NP_001371262, NP_001371263 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR054149	SMIM43	Family

Pfam: PF21976

UniProt features (5 total): region of interest 2, chain 1, transmembrane region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4W5P6-F1	77.44	0.48

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 26 (showing top): CAGCTG_AP4_Q5, BILD_E2F3_ONCOGENIC_SIGNATURE, TCF11_01, TGGAAA_NFAT_Q4_01, PEDRIOLI_MIR31_TARGETS_UP, MIR520D_5P, MIR524_5P, MIR1252_5P, MIR4680_3P, MIR4778_3P, MIR3123, MIR4704_3P, MIR3925_5P, MIR6758_5P, MIR6856_5P

GO Biological Process (1): mesendoderm development (GO:0048382)

GO Molecular Function (1): transmembrane transporter binding (GO:0044325)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endoderm development	1
mesoderm development	1
anatomical structure development	1
protein binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

164 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM43	EXOSC9	Q06265	531
SMIM43	BLTP1	Q2LD37	432
SMIM43	TRPC3	Q13507	413
SMIM43	TTC27	Q6P3X3	399
SMIM43	BBS7	Q8IWZ6	374
SMIM43	PAQR4	Q8N4S7	374
SMIM43	FAM131B	Q86XD5	369
SMIM43	SFXN3	Q9BWM7	364
SMIM43	ST8SIA5	O15466	350
SMIM43	JAKMIP1	Q96N16	348
SMIM43	AP1S1	P61966	292
SMIM43	RCAN2	Q14206	292
SMIM43	CPVL	Q9H3G5	285
SMIM43	GIMAP4	Q9NUV9	271
SMIM43	CLEC2D	Q9UHP7	220

IntAct

4 interactions, top by confidence:

A	B	Type	Score
SMIM43	LMBR1	psi-mi:“MI:0915”(physical association)	0.400
SMIM43	SLC2A3	psi-mi:“MI:0915”(physical association)	0.400
SMIM43	SLC2A1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (4): TMEM259 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), LMBR1 (Affinity Capture-MS), TMEM155 (Protein-peptide)

ESM2 similar proteins: A0A023PZB8, A0A1B0GWH6, A0A1W2P7I0, A0A1W2PQU2, A0A286YD83, A0T0S8, B1XMN4, C0HJK4, C1P614, O35982, O71196, O78514, O96812, P06426, P0C5P3, P0C5R8, P0CK45, P0CK46, P0CU59, P0CU60, P0DO60, P0DTG1, P0DV63, P0DW56, P11330, P11339, P13268, P14237, P19191, P20729, P21403, P31280, P34033, P56348, P56782, P80055, P80056, P80718, P87273, P9WEJ6

Diamond homologs: A0A286YD83, Q4W5P6, Q5R4Y3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	9
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

909 predictions. Top by Δscore:

Variant	Effect	Δscore
4:121761828:A:AC	donor_gain	1.0000
4:121761829:C:CC	donor_gain	1.0000
4:121763760:TTAC:T	donor_loss	1.0000
4:121763761:TA:T	donor_loss	1.0000
4:121763762:A:AC	donor_gain	1.0000
4:121763762:A:AT	donor_loss	1.0000
4:121763762:AC:A	donor_gain	1.0000
4:121763763:C:CA	donor_gain	1.0000
4:121763763:CC:C	donor_gain	1.0000
4:121763763:CCA:C	donor_gain	1.0000
4:121763763:CCAT:C	donor_gain	1.0000
4:121763763:CCATT:C	donor_gain	1.0000
4:121763868:CGGCT:C	acceptor_gain	1.0000
4:121763871:CT:C	acceptor_gain	1.0000
4:121761534:TCA:T	donor_loss	0.9900
4:121761535:CAC:C	donor_loss	0.9900
4:121761694:CC:C	acceptor_gain	0.9900
4:121761695:CC:C	acceptor_gain	0.9900
4:121761695:CCTAA:C	acceptor_loss	0.9900
4:121761696:CT:C	acceptor_loss	0.9900
4:121761697:T:G	acceptor_loss	0.9900
4:121761798:G:A	donor_gain	0.9900
4:121761829:CAA:C	donor_gain	0.9900
4:121761829:CAAG:C	donor_gain	0.9900
4:121761829:CAAGT:C	donor_gain	0.9900
4:121762796:CTG:C	acceptor_gain	0.9900
4:121762799:C:CC	acceptor_gain	0.9900
4:121763869:GGCT:G	acceptor_gain	0.9900
4:121763870:GCT:G	acceptor_gain	0.9900
4:121763871:CTC:C	acceptor_gain	0.9900

AlphaMissense

397 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:121765011:A:G	L32P	0.982
4:121765044:A:C	L21R	0.957
4:121765032:A:C	L25R	0.955
4:121765071:G:T	A12E	0.954
4:121765032:A:T	L25H	0.953
4:121765056:A:C	L17R	0.951
4:121765035:A:C	L24R	0.947
4:121765097:C:A	W3C	0.946
4:121765097:C:G	W3C	0.946
4:121765023:A:T	V28D	0.945
4:121765053:A:C	L18R	0.944
4:121765044:A:T	L21H	0.941
4:121765007:C:A	K33N	0.940
4:121765007:C:G	K33N	0.940
4:121765053:A:T	L18H	0.932
4:121765068:A:T	L13H	0.930
4:121765038:A:C	L23R	0.921
4:121765038:A:T	L23H	0.914
4:121765016:C:A	K30N	0.911
4:121765016:C:G	K30N	0.911
4:121765068:A:C	L13R	0.906
4:121765028:G:C	F26L	0.895
4:121765028:G:T	F26L	0.895
4:121765030:A:G	F26L	0.895
4:121765032:A:G	L25P	0.894
4:121765008:T:A	K33M	0.893
4:121765038:A:G	L23P	0.877
4:121765056:A:G	L17P	0.874
4:121765035:A:G	L24P	0.863
4:121765099:A:G	W3R	0.859

dbSNP variants (sampled 300 via entrez): RS1000120367 (4:121765057 G>A), RS1000471416 (4:121765195 A>G), RS1001077142 (4:121766634 A>G), RS1001393452 (4:121759507 G>A,T), RS1001466926 (4:121759957 T>C), RS1001543118 (4:121763753 T>C), RS1001693612 (4:121766313 G>A), RS1001920961 (4:121759764 T>C), RS1002462217 (4:121763642 G>A,C), RS10025131 (4:121765435 T>A,C,G), RS1003595166 (4:121761184 C>T), RS1003637576 (4:121765142 G>A,C,T), RS1004012658 (4:121764755 G>A,T), RS1004133477 (4:121764869 G>A), RS1005523411 (4:121764277 G>T)

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

14 total (human), top 14 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases methylation, increases expression	3
entinostat	increases expression, affects cotreatment	2
Particulate Matter	increases abundance, decreases expression	2
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
trichostatin A	increases expression	1
exemestane	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
dorsomorphin	increases expression, affects cotreatment	1
MT19c compound	decreases expression	1
Dasatinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Estradiol	affects expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	affects expression	1

Clinical trials (associated diseases)

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