ETFRF1

Summary

ETFRF1 (electron transfer flavoprotein regulatory factor 1, HGNC:27052) is a protein-coding gene on chromosome 12p12.1, encoding Electron transfer flavoprotein regulatory factor 1 (Q6IPR1). Acts as a regulator of the electron transfer flavoprotein by promoting the removal of flavin from the ETF holoenzyme (composed of ETFA and ETFB).

Enables enzyme inhibitor activity. Involved in respiratory electron transport chain. Located in mitochondrion.

Source: NCBI Gene 144363 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001001660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27052
Approved symbol	ETFRF1
Name	electron transfer flavoprotein regulatory factor 1
Location	12p12.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000205707
Ensembl biotype	protein_coding
Entrez	144363

Gene structure

Transcript identifiers

Ensembl transcripts: 26 — 25 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000381356, ENST00000553788, ENST00000554266, ENST00000555151, ENST00000555711, ENST00000556198, ENST00000556351, ENST00000556402, ENST00000556927, ENST00000557540, ENST00000878628, ENST00000878629, ENST00000878630, ENST00000878631, ENST00000878632, ENST00000878633, ENST00000878634, ENST00000878635, ENST00000878636, ENST00000878637, ENST00000878638, ENST00000878639, ENST00000938211, ENST00000972121, ENST00000972122, ENST00000972123

RefSeq mRNA: 1 — MANE Select: NM_001001660 NM_001001660

CCDS: CCDS53764

Canonical transcript exons

ENST00000381356 — 3 exons

Exon	Start	End
ENSE00001488394	25204091	25205143
ENSE00001488396	25203920	25204007
ENSE00001488397	25195237	25195337

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 98.53.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.3799 / max 2551.7781, expressed in 1808 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
124783	25.7747	1791
124782	8.9972	1669
124781	4.6080	1409

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left ventricle myocardium	UBERON:0006566	98.53	gold quality
vastus lateralis	UBERON:0001379	98.22	gold quality
quadriceps femoris	UBERON:0001377	98.09	gold quality
sperm	CL:0000019	98.03	gold quality
biceps brachii	UBERON:0001507	97.87	gold quality
deltoid	UBERON:0001476	97.78	gold quality
upper arm skin	UBERON:0004263	97.72	gold quality
tibialis anterior	UBERON:0001385	97.54	gold quality
myocardium	UBERON:0002349	97.52	gold quality
adrenal tissue	UBERON:0018303	97.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	97.39	gold quality
spinal cord	UBERON:0002240	97.11	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.10	gold quality
epithelial cell of pancreas	CL:0000083	96.98	gold quality
upper leg skin	UBERON:0004262	96.96	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	96.68	gold quality
oocyte	CL:0000023	96.62	gold quality
heart right ventricle	UBERON:0002080	96.61	gold quality
inferior vagus X ganglion	UBERON:0005363	96.61	gold quality
secondary oocyte	CL:0000655	96.31	gold quality
endothelial cell	CL:0000115	96.29	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.14	gold quality
subthalamic nucleus	UBERON:0001906	96.13	gold quality
pons	UBERON:0000988	96.12	gold quality
skeletal muscle tissue	UBERON:0001134	96.03	gold quality
lateral globus pallidus	UBERON:0002476	95.90	gold quality
corpus epididymis	UBERON:0004359	95.86	gold quality
substantia nigra	UBERON:0002038	95.84	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.73	gold quality
medulla oblongata	UBERON:0001896	95.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

46 targeting ETFRF1, 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-3924	100.00	72.09	2394
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-567	99.63	68.57	1219
HSA-MIR-141-5P	99.57	67.86	897
HSA-MIR-4801	98.96	69.42	2096
HSA-MIR-4731-3P	98.56	68.60	1860
HSA-MIR-548AO-5P	98.55	69.57	1362

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyrm5a	ENSDARG00000099560
mus_musculus	Etfrf1	ENSMUSG00000040370
rattus_norvegicus	Etfrf1	ENSRNOG00000063524
drosophila_melanogaster	osi	FBGN0040985
caenorhabditis_elegans		WBGENE00012780

Protein

Protein identifiers

Electron transfer flavoprotein regulatory factor 1 — Q6IPR1 (reviewed: Q6IPR1)

Alternative names: LYR motif-containing protein 5

All UniProt accessions (5): Q6IPR1, G3V332, G3V427, G3V4R2, G3V521

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a regulator of the electron transfer flavoprotein by promoting the removal of flavin from the ETF holoenzyme (composed of ETFA and ETFB).

Subunit / interactions. homotetramer. Interacts with NDUFAB1. Interacts with ETFA. Interacts with ETFB.

Subcellular location. Mitochondrion.

Similarity. Belongs to the complex I LYR family.

RefSeq proteins (1): NP_001001660* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008011	Complex1_LYR_dom	Domain
IPR045296	Complex1_LYR_ETFRF1_LYRM5	Domain
IPR052000	ETFRF1	Family

Pfam: PF05347

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6IPR1-F1	91.46	0.86

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 103 (showing top): TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, IVANOVA_HEMATOPOIESIS_MATURE_CELL, TGACCTY_ERR1_Q2, GOBP_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, GOBP_REGULATION_OF_OXIDATIVE_PHOSPHORYLATION, MARTINEZ_RB1_TARGETS_DN, GOBP_OXIDATIVE_PHOSPHORYLATION, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_REGULATION_OF_GENERATION_OF_PRECURSOR_METABOLITES_AND_ENERGY, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_REGULATION_OF_CELLULAR_RESPIRATION, GOBP_CELLULAR_RESPIRATION, MARTINEZ_RB1_AND_TP53_TARGETS_UP, chr12p12

GO Biological Process (2): negative regulation of oxidative phosphorylation (GO:0090324), negative regulation of cellular respiration (GO:1901856)

GO Molecular Function (2): enzyme inhibitor activity (GO:0004857), protein binding (GO:0005515)

GO Cellular Component (1): mitochondrion (GO:0005739)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of oxidative phosphorylation	1
oxidative phosphorylation	1
negative regulation of cellular respiration	1
negative regulation of metabolic process	1
regulation of cellular respiration	1
cellular respiration	1
catalytic activity	1
enzyme regulator activity	1
molecular function inhibitor activity	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ETFRF1	LYRM1	O43325	805
ETFRF1	LYRM2	Q9NU23	782
ETFRF1	NDUFAB1	O14561	734
ETFRF1	LYRM4	Q9HD34	705
ETFRF1	LYRM9	A8MSI8	703
ETFRF1	LYRM7	Q5U5X0	673
ETFRF1	SDHAF3	Q9NRP4	661
ETFRF1	ETFDH	Q16134	626
ETFRF1	ETFA	P13804	623
ETFRF1	FMC1	Q96HJ9	578
ETFRF1	SDHAF1	A6NFY7	564
ETFRF1	DNAI7	Q6TDU7	507
ETFRF1	NDUFAF8	A1L188	507
ETFRF1	NPIPA7	E9PJI5	507
ETFRF1	NFS1	Q9Y697	487

IntAct

22 interactions, top by confidence:

A	B	Type	Score
ETFA	ETFB	psi-mi:“MI:0915”(physical association)	0.810
ETFRF1	ETFA	psi-mi:“MI:0914”(association)	0.740
ETFB	ETFRF1	psi-mi:“MI:0915”(physical association)	0.660
ETFRF1	NDUFAB1	psi-mi:“MI:0914”(association)	0.640
ETFRF1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
ETFRF1	JPH3	psi-mi:“MI:0915”(physical association)	0.560
ETFRF1	ETFRF1	psi-mi:“MI:0407”(direct interaction)	0.440
EVL	RPL23	psi-mi:“MI:0914”(association)	0.350
FEM1A	RNF113A	psi-mi:“MI:0914”(association)	0.350
EVL	PFN2	psi-mi:“MI:0914”(association)	0.350
ETFRF1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (48): LYRM5 (Affinity Capture-MS), LYRM5 (Affinity Capture-MS), LYRM5 (Affinity Capture-MS), LYRM5 (Co-fractionation), ETFA (Affinity Capture-Western), ETFB (Affinity Capture-Western), ETFA (Reconstituted Complex), ETFB (Reconstituted Complex), LYRM5 (Affinity Capture-MS), NT5DC2 (Affinity Capture-MS), MRPL46 (Affinity Capture-MS), ETFA (Affinity Capture-MS), CYCS (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), ECH1 (Affinity Capture-MS)

ESM2 similar proteins: A3KNJ8, A3LNG8, A5D7J1, A5DH70, A5DY61, A7S1A4, A8MSI8, A9SNJ1, A9UMQ3, B2RYU8, B2RZD7, B3DFV0, B4F6X2, B5FXA0, B5FYC7, B5FZA8, B5X5U9, B5XCZ6, B6NK32, B8JLQ0, B9WD12, C4R7H7, C4Y4R9, C5DEI4, C5DR94, C9SBR9, D1Z4E1, L0R8F8, O43325, O60068, P42114, P82116, Q0UIG9, Q0VCG0, Q0VCR0, Q3UN90, Q503U1, Q5A7N3, Q6BQH4, Q6CTI7

Diamond homologs: A3KNJ8, B5FXA0, B5XCZ6, Q0VCR0, Q503U1, Q54PT6, Q6IPR1, Q91V16, Q9VJG4, B5FZA8, Q0VCG0, Q8K215, Q9HD34

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

668 predictions. Top by Δscore:

Variant	Effect	Δscore
12:25195335:A:T	donor_gain	1.0000
12:25195338:GTGC:G	donor_gain	1.0000
12:25195340:GC:G	donor_gain	1.0000
12:25195342:G:GG	donor_gain	1.0000
12:25195359:G:GT	donor_gain	1.0000
12:25195439:GGTTC:G	donor_gain	1.0000
12:25204086:T:TA	acceptor_gain	1.0000
12:25195333:GGAAA:G	donor_gain	0.9900
12:25195334:GAAA:G	donor_gain	0.9900
12:25195334:GAAAG:G	donor_gain	0.9900
12:25195339:TGC:T	donor_gain	0.9900
12:25195340:GCG:G	donor_gain	0.9900
12:25195359:G:T	donor_gain	0.9900
12:25203914:CTTTA:C	acceptor_loss	0.9900
12:25203915:TTTA:T	acceptor_loss	0.9900
12:25203916:TTAGG:T	acceptor_loss	0.9900
12:25203917:TAGGT:T	acceptor_loss	0.9900
12:25203918:AGGT:A	acceptor_loss	0.9900
12:25203919:G:GT	acceptor_loss	0.9900
12:25203919:GGTAT:G	acceptor_gain	0.9900
12:25204006:AT:A	donor_gain	0.9900
12:25204008:G:GG	donor_gain	0.9900
12:25204089:A:AG	acceptor_gain	0.9900
12:25204090:G:GG	acceptor_gain	0.9900
12:25204090:GCT:G	acceptor_gain	0.9900
12:25203919:GGT:G	acceptor_gain	0.9800
12:25204004:AAAT:A	donor_gain	0.9800
12:25204004:AAATG:A	donor_loss	0.9800
12:25204005:AAT:A	donor_gain	0.9800
12:25204005:AATGT:A	donor_loss	0.9800

AlphaMissense

589 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:25204092:T:C	L18P	0.972
12:25204220:T:C	F61L	0.971
12:25204222:T:A	F61L	0.971
12:25204222:T:G	F61L	0.971
12:25204157:T:C	F40L	0.968
12:25204159:C:A	F40L	0.968
12:25204159:C:G	F40L	0.968
12:25204267:A:C	R76S	0.963
12:25204267:A:T	R76S	0.963
12:25204281:G:C	R81P	0.959
12:25204004:A:C	K16N	0.944
12:25204004:A:T	K16N	0.944
12:25204261:A:C	K74N	0.943
12:25204261:A:T	K74N	0.943
12:25204107:G:C	R23P	0.939
12:25204133:T:C	F32L	0.939
12:25204135:T:A	F32L	0.939
12:25204135:T:G	F32L	0.939
12:25204268:G:C	A77P	0.939
12:25204146:T:G	L36W	0.935
12:25203997:T:C	L14P	0.931
12:25204260:A:T	K74I	0.924
12:25204003:A:T	K16I	0.920
12:25204215:G:A	G59D	0.916
12:25204203:T:C	L55P	0.915
12:25204241:G:C	A68P	0.915
12:25204103:G:A	G22R	0.914
12:25204103:G:C	G22R	0.914
12:25204104:G:A	G22E	0.914
12:25204236:T:C	L66P	0.914

dbSNP variants (sampled 300 via entrez): RS1000222340 (12:25204910 C>T), RS1000375518 (12:25198117 T>G), RS1000525797 (12:25202828 T>A), RS1000711307 (12:25195938 T>C), RS1000752442 (12:25197108 C>T), RS1000875885 (12:25202961 T>C,G), RS1000893338 (12:25198523 T>C), RS1000988141 (12:25203157 C>A,T), RS1001122254 (12:25196881 G>A), RS1001503715 (12:25197712 C>T), RS1001667381 (12:25200845 T>C), RS1001717478 (12:25203911 T>C), RS1001804795 (12:25196079 C>T), RS1001837381 (12:25196477 A>G), RS1002086497 (12:25203644 A>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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs61764370	ETFRF1, KRAS	3	2.75	1	cetuximab;panitumumab

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects cotreatment, decreases expression	2
Air Pollutants	decreases expression, increases abundance	2
Cyclosporine	decreases expression	2
aristolochic acid I	decreases expression	1
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
sodium arsenite	affects methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
beta-methylcholine	affects expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1
Estradiol	decreases expression	1
Folic Acid	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	decreases expression	1
Valproic Acid	decreases methylation	1
Aflatoxin B1	decreases expression, decreases methylation	1
Okadaic Acid	decreases expression	1
Lactic Acid	decreases expression	1

Clinical trials (associated diseases)

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