SMIM20

Summary

SMIM20 (small integral membrane protein 20, HGNC:37260) is a protein-coding gene on chromosome 4p15.2, encoding Small integral membrane protein 20 (Q8N5G0). Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.

Involved in mitochondrial cytochrome c oxidase assembly. Located in mitochondrial inner membrane.

Source: NCBI Gene 389203 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_001145432

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37260
Approved symbol	SMIM20
Name	small integral membrane protein 20
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	PNX, MITRAC7
Ensembl gene	ENSG00000250317
Ensembl biotype	protein_coding
OMIM	617465
Entrez	389203

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000506197, ENST00000514384, ENST00000515764, ENST00000522137, ENST00000940878

RefSeq mRNA: 2 — MANE Select: NM_001145432 NM_001145432, NM_001394130

CCDS: CCDS47038, CCDS93489

Canonical transcript exons

ENST00000506197 — 3 exons

Exon	Start	End
ENSE00002054697	25929154	25929812
ENSE00002241890	25914220	25914422
ENSE00003558423	25928313	25928369

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 95.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 31.0279 / max 237.4867, expressed in 1818 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47156	24.8580	1813
47155	5.2437	1669
47157	0.7616	502
47154	0.1646	83

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	95.83	gold quality
deltoid	UBERON:0001476	95.74	gold quality
muscle of leg	UBERON:0001383	95.01	gold quality
gastrocnemius	UBERON:0001388	94.87	gold quality
tibialis anterior	UBERON:0001385	94.82	gold quality
calcaneal tendon	UBERON:0003701	94.53	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.47	gold quality
quadriceps femoris	UBERON:0001377	94.46	gold quality
vastus lateralis	UBERON:0001379	94.30	gold quality
biceps brachii	UBERON:0001507	94.18	gold quality
skeletal muscle tissue	UBERON:0001134	93.78	gold quality
body of pancreas	UBERON:0001150	93.71	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.63	gold quality
mucosa of transverse colon	UBERON:0004991	93.46	gold quality
right adrenal gland cortex	UBERON:0035827	93.41	gold quality
right adrenal gland	UBERON:0001233	93.34	gold quality
muscle tissue	UBERON:0002385	93.02	gold quality
left ventricle myocardium	UBERON:0006566	93.01	gold quality
heart left ventricle	UBERON:0002084	92.78	gold quality
pancreas	UBERON:0001264	92.76	gold quality
adrenal tissue	UBERON:0018303	92.68	gold quality
cardiac ventricle	UBERON:0002082	92.56	gold quality
duodenum	UBERON:0002114	92.53	gold quality
islet of Langerhans	UBERON:0000006	92.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.42	gold quality
right atrium auricular region	UBERON:0006631	92.40	gold quality
body of stomach	UBERON:0001161	92.37	gold quality
left adrenal gland	UBERON:0001234	92.19	gold quality
cardiac atrium	UBERON:0002081	92.10	gold quality
parotid gland	UBERON:0001831	92.02	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting SMIM20, 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-3925-3P	100.00	69.95	1237
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-766-3P	99.47	65.24	1811
HSA-MIR-4797-5P	99.39	68.01	1354
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-10399-5P	99.17	69.87	2610
HSA-MIR-6504-3P	99.17	69.31	2891
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-302F	98.44	69.02	1776
HSA-MIR-6764-3P	98.44	67.64	1153
HSA-MIR-6824-3P	98.44	67.62	1154
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-4268	94.45	64.09	819

Literature-anchored findings (GeneRIF, showing 2)

• MITRAC7 affects the biogenesis pathway by stabilizing newly synthesized COX1 in assembly intermediates, concomitantly preventing turnover. (PMID:26321642)
• SMIM20 (MITRAC7) is a COX1 specific chaperone which is necessary for cytochrome c oxidase biogenesis. (PMID:26321642)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	smim20	ENSDARG00000112670
mus_musculus	Smim20	ENSMUSG00000061461
rattus_norvegicus	Smim20	ENSRNOG00000051190

Protein

Protein identifiers

Small integral membrane protein 20 — Q8N5G0 (reviewed: Q8N5G0)

Alternative names: Mitochondrial translation regulation assembly intermediate of cytochrome c oxidase protein of 7 kDa

All UniProt accessions (2): Q8N5G0, E5RH91

UniProt curated annotations — full annotation on UniProt →

Function. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. Promotes the progression of complex assembly after the association of MT-CO1/COX1 with COX4I1 and COX6C. Chaperone-like assembly factor required to stabilize newly synthesized MT-CO1/COX1 and to prevent its premature turnover. Peptide involved in a broad spectrum of regulatory functions. Is a ligand for GPR173. As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone. Plays a protective role in memory retention through activation of GNRHR. Regulates the secretion of AVP by hypothalamic neurons. Plays a role in the transduction of the itch sensation. Induces anxiolytic effects, reducing behavior associated with anxiety. Regulates food intake as well as satiation and satiety. In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR. It also increases the production of estradiol (E2). In the heart, it regulates contractility and relaxation. It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways. Stimulates the proliferation and differentiation of preadipocytes. In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS. Peptide involved in a broad spectrum of regulatory functions. Is a ligand for GPR173. As part of the reproductive cycle, it regulates gonadotropin-releasing hormone (GnRH) signaling in the hypothalamus and pituitary gland which augments the release of luteinizing hormone. Plays a protective role in memory retention through activation of GNRHR. Regulates the secretion of AVP by hypothalamic neurons. Plays a role in the transduction of the itch sensation. Induces anxiolytic effects, reducing behavior associated with anxiety. Regulates food intake as well as satiation and satiety. In the ovary, it regulates follicular growth by stimulating granulosa cell proliferation by increasing the expression of GPR173, CREB1, CYP19A1, KITLG, FSHR, and LHCGR. It also increases the production of estradiol (E2). In the heart, it regulates contractility and relaxation. It also plays a cardioprotective role during ischemia, where it activates the SAFE and RISK pathways. Stimulates the proliferation and differentiation of preadipocytes. In pancreatic islet cells, it induces proliferation of islet cells as well as the production of INS.

Subunit / interactions. Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14. Interacts with COA3/MITRAC12 and COX4I1. Directly interacts with newly synthesized MT-CO1/COX1.

Subcellular location. Mitochondrion inner membrane Secreted Secreted.

Tissue specificity. Expressed in the ovary, specifically in granulosa cells of follicles that have passed the primary stage and in oocytes (at protein level).

Miscellaneous. Gene prediction.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8N5G0-1	1	yes
Q8N5G0-2	2

RefSeq proteins (2): NP_001138904, NP_001381059 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR027917	MITRAC7/Phoenixin	Family

Pfam: PF15061

UniProt features (12 total): sequence variant 4, peptide 2, topological domain 2, chain 1, transmembrane region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N5G0-F1	90.48	0.62

Functional residue map

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

Post-translational modifications (1): 64

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-9864848	Complex IV assembly
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-611105	Respiratory electron transport

MSigDB gene sets: 73 (showing top): GOBP_RESPIRATORY_CHAIN_COMPLEX_IV_ASSEMBLY, GOBP_MITOCHONDRIAL_RESPIRATORY_CHAIN_COMPLEX_ASSEMBLY, GOBP_CYTOCHROME_COMPLEX_ASSEMBLY, GOCC_MITOCHONDRIAL_ENVELOPE, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, SENESE_HDAC3_TARGETS_DN, GOCC_ORGANELLE_INNER_MEMBRANE, chr4p15, GOCC_ORGANELLE_ENVELOPE, BRUINS_UVC_RESPONSE_VIA_TP53_GROUP_C, BRUINS_UVC_RESPONSE_LATE, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_QTL_TRANS, GCNP_SHH_UP_LATE.V1_UP, DACH1_TARGET_GENES, DIDO1_TARGET_GENES

GO Biological Process (1): mitochondrial respiratory chain complex IV assembly (GO:0033617)

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

GO Cellular Component (4): extracellular region (GO:0005576), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Respiratory electron transport	1
Metabolism	1
Aerobic respiration and respiratory electron transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
mitochondrion	1
respiratory chain complex IV assembly	1
mitochondrial respiratory chain complex assembly	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1

Protein interactions and networks

STRING

766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SMIM20	GPR173	Q9NS66	883
SMIM20	COA3	Q9Y2R0	703
SMIM20	COX14	Q96I36	675
SMIM20	COX4I1	P13073	537
SMIM20	COA1	Q9GZY4	527
SMIM20	COX6C	P09669	501
SMIM20	GNRHR	P30968	481
SMIM20	TMEM11	P17152	479
SMIM20	GPR85	P60893	457
SMIM20	TIMM21	Q9BVV7	443
SMIM20	NUCB2	P80303	420
SMIM20	KISS1R	Q969F8	419
SMIM20	SCN10A	Q9Y5Y9	419
SMIM20	GNRH1	P01148	412
SMIM20	CAGE1	Q8TC20	399

IntAct

24 interactions, top by confidence:

A	B	Type	Score
ERBB2	SMIM20	psi-mi:“MI:0915”(physical association)	0.550
ERBB3	SMIM20	psi-mi:“MI:0915”(physical association)	0.370
ERBB4	SMIM20	psi-mi:“MI:0915”(physical association)	0.370
	AP3B1	psi-mi:“MI:0914”(association)	0.350
	NDUFAF8	psi-mi:“MI:0914”(association)	0.350
RAMP3	MGST3	psi-mi:“MI:0914”(association)	0.350
ADCY9	TAPBP	psi-mi:“MI:0914”(association)	0.350
C1QA	VWA8	psi-mi:“MI:0914”(association)	0.350
GPR182	TMEM120B	psi-mi:“MI:0914”(association)	0.350
SAAL1	TMEM223	psi-mi:“MI:0914”(association)	0.350
COA3	TMEM223	psi-mi:“MI:0914”(association)	0.350
SLC25A5	TMEM223	psi-mi:“MI:0914”(association)	0.350
ATF3	ILVBL	psi-mi:“MI:0914”(association)	0.350
CASP3	TMEM223	psi-mi:“MI:0914”(association)	0.350
CTNNA1	ILVBL	psi-mi:“MI:0914”(association)	0.350
FOS	ILVBL	psi-mi:“MI:0914”(association)	0.350
GATA2	ILVBL	psi-mi:“MI:0914”(association)	0.350
ATF2	AGPS	psi-mi:“MI:0914”(association)	0.350
CEBPA	HAX1	psi-mi:“MI:0914”(association)	0.350
ERBB2	AP3B1	psi-mi:“MI:0914”(association)	0.350
MYB	C11orf98	psi-mi:“MI:0914”(association)	0.350
MYC	AP3B1	psi-mi:“MI:0914”(association)	0.350
STAT3	HAX1	psi-mi:“MI:0914”(association)	0.350

BioGRID (14): SMIM20 (Two-hybrid), SMIM20 (Two-hybrid), SMIM20 (Two-hybrid), SMIM20 (Proximity Label-MS), SMIM20 (Proximity Label-MS), SMIM20 (Affinity Capture-MS), SMIM20 (Affinity Capture-MS), SMIM20 (Affinity Capture-MS), SMIM20 (Cross-Linking-MS (XL-MS)), SMIM20 (Proximity Label-MS), SMIM20 (Co-fractionation), SMIM20 (Co-fractionation), SMIM20 (Co-fractionation), SMIM20 (Co-fractionation)

ESM2 similar proteins: A2VDV9, A5PJ82, C0HLM6, D2H617, D3Z7Q2, D3Z9R8, D4ACP2, E2R5I0, E7EXZ6, F1MDB2, F6USH3, G1QDE8, G1S9B8, O00483, P00130, P10818, P11951, P13182, P43024, P56378, P56379, Q01321, Q0MQ97, Q0MQ98, Q0MQ99, Q0Q4Z0, Q28851, Q2NKS2, Q3SZ44, Q3YAJ5, Q4FZG9, Q4R542, Q5RCY6, Q5RDZ8, Q5REX0, Q62425, Q69YU5, Q6PBH5, Q78RX3, Q7YRK7

Diamond homologs: C0HLM6, D3Z7Q2, F1MDB2, Q8N5G0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation of granulopoiesis	5	26.1×	4e-04
Estrogen-dependent gene expression	5	15.8×	8e-04

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	5	53.8×	2e-05
neuron differentiation	5	18.6×	7e-04
positive regulation of gene expression	8	11.5×	8e-05
negative regulation of apoptotic process	6	7.7×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

721 predictions. Top by Δscore:

Variant	Effect	Δscore
4:25914418:GTACA:G	donor_gain	1.0000
4:25914423:G:GG	donor_gain	1.0000
4:25925699:GGGCT:G	donor_gain	1.0000
4:25925700:GGCT:G	donor_gain	1.0000
4:25925701:GCT:G	donor_gain	1.0000
4:25925738:TTC:T	donor_gain	1.0000
4:25925794:GA:G	donor_gain	1.0000
4:25928302:AT:A	acceptor_gain	1.0000
4:25928303:T:G	acceptor_gain	1.0000
4:25928303:T:TA	acceptor_gain	1.0000
4:25928311:A:AG	acceptor_gain	1.0000
4:25928312:G:GA	acceptor_gain	1.0000
4:25928312:GA:G	acceptor_gain	1.0000
4:25928312:GAGA:G	acceptor_gain	1.0000
4:25928312:GAGAA:G	acceptor_gain	1.0000
4:25929150:ATAG:A	acceptor_gain	1.0000
4:25929152:AG:A	acceptor_gain	1.0000
4:25929153:GG:G	acceptor_gain	1.0000
4:25862669:GCTCA:G	donor_loss	0.9900
4:25862670:CTCA:C	donor_loss	0.9900
4:25862671:TCACC:T	donor_loss	0.9900
4:25862672:CA:C	donor_loss	0.9900
4:25862673:ACC:A	donor_loss	0.9900
4:25914415:G:GT	donor_gain	0.9900
4:25914415:GGA:G	donor_gain	0.9900
4:25914416:GAG:G	donor_gain	0.9900
4:25925692:G:GT	donor_gain	0.9900
4:25925703:T:G	donor_gain	0.9900
4:25925703:T:TG	donor_gain	0.9900
4:25928302:A:AG	acceptor_gain	0.9900

AlphaMissense

428 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:25929167:G:C	W60C	0.992
4:25929167:G:T	W60C	0.992
4:25929165:T:A	W60R	0.991
4:25929165:T:C	W60R	0.991
4:25929177:T:C	F64L	0.986
4:25929179:T:A	F64L	0.986
4:25929179:T:G	F64L	0.986
4:25928334:G:C	R44P	0.971
4:25929178:T:G	F64C	0.966
4:25929177:T:A	F64I	0.957
4:25914350:G:C	G13R	0.956
4:25929166:G:C	W60S	0.954
4:25914387:T:A	I25N	0.953
4:25929175:C:A	P63Q	0.952
4:25914369:G:A	G19D	0.949
4:25929157:T:C	L57S	0.948
4:25914368:G:C	G19R	0.944
4:25929166:G:T	W60L	0.944
4:25914389:T:G	Y26D	0.941
4:25914372:C:A	A20D	0.937
4:25928362:G:C	Q53H	0.937
4:25928362:G:T	Q53H	0.937
4:25929168:T:C	S61P	0.933
4:25914375:C:A	A21D	0.930
4:25914348:G:A	G12D	0.928
4:25929174:C:T	P63S	0.926
4:25914351:G:A	G13D	0.925
4:25929177:T:G	F64V	0.916
4:25929178:T:C	F64S	0.915
4:25928323:A:C	Q40H	0.914

dbSNP variants (sampled 300 via entrez): RS1000018823 (4:25927787 T>C), RS1000039231 (4:25916575 T>C), RS1000977907 (4:25929918 C>T), RS1001640498 (4:25927043 T>C), RS1001869390 (4:25921137 C>T), RS1002208905 (4:25920163 A>G), RS1002487822 (4:25921421 C>A,T), RS1002540804 (4:25925640 C>A), RS1002600178 (4:25927313 G>A), RS1002793687 (4:25915197 C>G), RS1002868920 (4:25914149 C>A), RS1003051609 (4:25925417 A>G), RS1003148463 (4:25918396 C>T), RS1003387677 (4:25913896 A>G), RS1003491362 (4:25919938 G>A,T)

Disease associations

OMIM: gene MIM:617465 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001762_857	Obesity-related traits	2.000000e-07
GCST002223_20	HDL cholesterol	5.000000e-08
GCST002318_15	Rheumatoid arthritis	1.000000e-16
GCST006048_49	Rheumatoid arthritis (ACPA-positive)	8.000000e-14
GCST006959_140	Rheumatoid arthritis	2.000000e-15
GCST006959_47	Rheumatoid arthritis	1.000000e-16
GCST010242_417	HDL cholesterol levels	2.000000e-23
GCST010244_71	Triglyceride levels	1.000000e-27
GCST90020025_302	Waist-to-hip ratio adjusted for BMI	3.000000e-08
GCST90020025_303	Waist-to-hip ratio adjusted for BMI	4.000000e-10
GCST90020027_1876	Waist-hip index	2.000000e-08
GCST90020027_1877	Waist-hip index	2.000000e-10
GCST90020029_689	Waist circumference adjusted for body mass index	4.000000e-08

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression	2
dicrotophos	decreases expression	1
bisphenol A	affects expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Acetaminophen	affects response to substance	1
Air Pollutants	decreases expression, increases abundance	1
Diethylstilbestrol	decreases expression	1
Lipopolysaccharides	decreases reaction, increases expression, increases reaction	1
Quercetin	decreases expression	1
Rotenone	decreases expression	1
Testosterone	decreases expression	1
Valproic Acid	affects expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	increases abundance, decreases expression	1

Clinical trials (associated diseases)

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