LYRM1

Summary

LYRM1 (LYR motif containing 1, HGNC:25074) is a protein-coding gene on chromosome 16p12.3, encoding LYR motif-containing protein 1 (O43325). May promote cell proliferation and inhibition of apoptosis of preadipocytes.

The protein encoded by this gene belongs to the mitochondrial leucine/tyrosine/arginine motif family of proteins. Proteins of this family are short polypeptides that contain a leucine/tyrosine/arginine motif near the N-terminus. This gene is widely expressed with high levels in omental adipose tissue of obese individuals. In adipose tissue, the protein is localized to the nucleus where it promotes preadipocyte proliferation and lowers the rate of apoptosis to regulate adipose tissue homeostasis. Overexpression of this gene in adipocytes causes abnormal mitochondrial morphology and mitochondrial dysfunction. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 57149 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 34 total
• MANE Select transcript: NM_001128302

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25074
Approved symbol	LYRM1
Name	LYR motif containing 1
Location	16p12.3
Locus type	gene with protein product
Status	Approved
Aliases	A211C6.1
Ensembl gene	ENSG00000102897
Ensembl biotype	protein_coding
OMIM	614709
Entrez	57149

Gene structure

Transcript identifiers

Ensembl transcripts: 48 — 45 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000219168, ENST00000396052, ENST00000412082, ENST00000439021, ENST00000562740, ENST00000564457, ENST00000567165, ENST00000567954, ENST00000568663, ENST00000568820, ENST00000569023, ENST00000901103, ENST00000901104, ENST00000901105, ENST00000901106, ENST00000901107, ENST00000901108, ENST00000901109, ENST00000901110, ENST00000901111, ENST00000901112, ENST00000901113, ENST00000901114, ENST00000901115, ENST00000901116, ENST00000901117, ENST00000901118, ENST00000901119, ENST00000901120, ENST00000901121, ENST00000901122, ENST00000901123, ENST00000901124, ENST00000901125, ENST00000924038, ENST00000924039, ENST00000958007, ENST00000958008, ENST00000958009, ENST00000958010, ENST00000958011, ENST00000958012, ENST00000958013, ENST00000958014, ENST00000958015, ENST00000958016, ENST00000958017, ENST00000958018

RefSeq mRNA: 18 — MANE Select: NM_001128302 NM_001128301, NM_001128302, NM_001302835, NM_001302836, NM_001369631, NM_001369632, NM_001369633, NM_001369634, NM_001369635, NM_001369636, NM_001369637, NM_001369638, NM_001369639, NM_001369641, NM_001369642, NM_001369644, NM_001369645, NM_020424

CCDS: CCDS10593

Canonical transcript exons

ENST00000567954 — 4 exons

Exon	Start	End
ENSE00002609770	20900771	20900889
ENSE00003463982	20920122	20920214
ENSE00003756123	20915556	20915714
ENSE00003933834	20924000	20925006

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 98.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.7279 / max 195.4459, expressed in 1808 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
153089	8.6153	1733
153090	6.0046	1688
153084	5.2450	1602
153083	1.8390	656
153087	1.3995	516
153085	0.5491	228
153092	0.4511	214
153091	0.4496	231
153086	0.4315	204
153094	0.3451	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.45	gold quality
male germ cell	CL:0000015	97.15	gold quality
nephron tubule	UBERON:0001231	96.57	gold quality
endothelial cell	CL:0000115	95.36	gold quality
choroid plexus epithelium	UBERON:0003911	95.35	gold quality
heart right ventricle	UBERON:0002080	94.99	gold quality
palpebral conjunctiva	UBERON:0001812	94.87	gold quality
kidney epithelium	UBERON:0004819	94.84	gold quality
liver	UBERON:0002107	94.51	gold quality
germinal epithelium of ovary	UBERON:0001304	94.50	gold quality
diaphragm	UBERON:0001103	94.49	gold quality
right lobe of liver	UBERON:0001114	94.36	gold quality
pericardium	UBERON:0002407	94.36	gold quality
eye	UBERON:0000970	94.25	gold quality
renal glomerulus	UBERON:0000074	94.07	gold quality
metanephric glomerulus	UBERON:0004736	93.67	gold quality
vena cava	UBERON:0004087	93.55	gold quality
cardiac ventricle	UBERON:0002082	93.47	gold quality
heart left ventricle	UBERON:0002084	93.44	gold quality
cauda epididymis	UBERON:0004360	93.39	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.27	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.22	gold quality
adult organism	UBERON:0007023	93.19	gold quality
left ventricle myocardium	UBERON:0006566	93.05	gold quality
adult mammalian kidney	UBERON:0000082	92.92	gold quality
pons	UBERON:0000988	92.65	gold quality
kidney	UBERON:0002113	92.59	gold quality
vastus lateralis	UBERON:0001379	92.57	gold quality
cranial nerve II	UBERON:0000941	92.55	gold quality
vein	UBERON:0001638	92.51	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.11
E-MTAB-6386	no	261.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

60 targeting LYRM1, 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-4262	100.00	73.26	3931
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-7154-5P	99.69	70.52	1900
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-6507-5P	99.36	70.46	2524

Literature-anchored findings (GeneRIF, showing 4)

• By increasing cell proliferation and lowering the rate of apoptosis, LYRM1 has the potential to modulate the size of the preadipocyte pool and influence adipose tissue homeostasis (PMID:19022914)
• overexpression of LYRM1 caused mitochondrial dysfunction in adipocytes, which might be responsible for the development of LYRM1-induced insulin resistance (PMID:20826099)
• Data suggest that LYRM1 might have the potential to modulate cell growth, apoptosis, and heart development. (PMID:20938407)
• alpha-LA protects 3T3-L1 adipocytes from LYRM1-induced insulin resistance partially via its capacity to restore mitochondrial function and/or increase phosphorylation of IRS-1 and Akt. (PMID:22820890)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyrm1	ENSDARG00000026281
mus_musculus	Lyrm1	ENSMUSG00000030922
rattus_norvegicus	Lyrm1	ENSRNOG00000024530

Protein

Protein identifiers

LYR motif-containing protein 1 — O43325 (reviewed: O43325)

All UniProt accessions (3): O43325, H3BNA8, H3BNK2

UniProt curated annotations — full annotation on UniProt →

Function. May promote cell proliferation and inhibition of apoptosis of preadipocytes.

Subcellular location. Nucleus.

Tissue specificity. High levels in adipose tissue.

Disease relevance. When overexpressed, may be involved in obesity-associated insulin resistance, possibly by causing mitochondrial dysfunction in adipocytes.

Similarity. Belongs to the complex I LYR family.

RefSeq proteins (18): NP_001121773, NP_001121774, NP_001289764, NP_001289765, NP_001356560, NP_001356561, NP_001356562, NP_001356563, NP_001356564, NP_001356565, NP_001356566, NP_001356567, NP_001356568, NP_001356570, NP_001356571, NP_001356573, NP_001356574, NP_065157 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008011	Complex1_LYR_dom	Domain
IPR040330	LYRM1	Family
IPR045294	Complex1_LYR_LYRM1	Domain

Pfam: PF05347

UniProt features (1 total): chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43325-F1	86.10	0.60

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 158 (showing top): VALK_AML_WITH_FLT3_ITD, SHEPARD_BMYB_MORPHOLINO_UP, FAELT_B_CLL_WITH_VH_REARRANGEMENTS_DN, SHEPARD_CRASH_AND_BURN_MUTANT_UP, GGGTGGRR_PAX4_03, SP1_Q2_01, SRF_C, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, OCT1_06, OCT1_07, LXR_Q3, NRF2_01, CETS1P54_01, MULLIGHAN_MLL_SIGNATURE_2_DN

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (4): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), midbody (GO:0030496), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
intracellular membrane-bounded organelle	2
nuclear lumen	1
cytoplasm	1

Protein interactions and networks

STRING

296 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYRM1	ETFRF1	Q6IPR1	805
LYRM1	LYRM2	Q9NU23	788
LYRM1	LYRM9	A8MSI8	741
LYRM1	SDHAF3	Q9NRP4	711
LYRM1	LYRM4	Q9HD34	686
LYRM1	LYRM7	Q5U5X0	683
LYRM1	KNTC1	P50748	585
LYRM1	FMC1	Q96HJ9	582
LYRM1	MTRF1L	Q9UGC7	564
LYRM1	SDHAF1	A6NFY7	529
LYRM1	NDUFB9	Q9Y6M9	492
LYRM1	NDUFAB1	O14561	468
LYRM1	NDUFA6	P56556	467
LYRM1	MIEF1	L0R8F8	432
LYRM1	SAYSD1	Q9NPB0	400

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LYRM1	MTAP	psi-mi:“MI:0915”(physical association)	0.370
LYRM1	NDUFAB1	psi-mi:“MI:0914”(association)	0.350

BioGRID (11): LYRM1 (Affinity Capture-MS), PMPCA (Affinity Capture-MS), PITRM1 (Affinity Capture-MS), IDE (Affinity Capture-MS), NDUFAB1 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), LYRM1 (Affinity Capture-MS), LYRM1 (Affinity Capture-MS), TNFAIP2 (Co-fractionation), DENND6A (Co-fractionation), MTAP (Two-hybrid)

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: A9UMQ3, B2RYU8, B5FYC7, B5X5L2, O43325, Q54T58, Q6DGP7, Q9CQB7, Q8K215

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1466 predictions. Top by Δscore:

Variant	Effect	Δscore
16:20900203:CAG:C	donor_gain	1.0000
16:20915538:ATTTT:A	acceptor_gain	1.0000
16:20915539:T:G	acceptor_gain	1.0000
16:20915542:T:A	acceptor_gain	1.0000
16:20915543:G:A	acceptor_gain	1.0000
16:20915545:T:TA	acceptor_gain	1.0000
16:20916057:A:T	donor_gain	1.0000
16:20920215:G:GG	donor_gain	1.0000
16:20900202:A:AC	donor_gain	0.9900
16:20900203:C:CC	donor_gain	0.9900
16:20900536:G:GG	donor_gain	0.9900
16:20915538:A:AG	acceptor_gain	0.9900
16:20915546:G:A	acceptor_gain	0.9900
16:20915710:AAAAT:A	donor_gain	0.9900
16:20915712:AAT:A	donor_gain	0.9900
16:20915712:AATG:A	donor_loss	0.9900
16:20915713:AT:A	donor_gain	0.9900
16:20915713:ATGT:A	donor_loss	0.9900
16:20915714:TGT:T	donor_loss	0.9900
16:20915715:G:GG	donor_gain	0.9900
16:20915715:G:T	donor_loss	0.9900
16:20915716:T:A	donor_loss	0.9900
16:20915717:A:AG	donor_loss	0.9900
16:20916045:G:GT	donor_gain	0.9900
16:20920211:GCCA:G	donor_gain	0.9900
16:20920231:TTAAC:T	donor_gain	0.9900
16:20900452:G:GT	donor_gain	0.9800
16:20902648:C:G	donor_gain	0.9800
16:20911265:G:GG	donor_gain	0.9800
16:20915551:T:TA	acceptor_gain	0.9800

AlphaMissense

785 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:20920211:G:C	R83S	0.974
16:20920211:G:T	R83S	0.974
16:20915622:T:A	W23R	0.969
16:20915622:T:C	W23R	0.969
16:20915685:G:C	A44P	0.969
16:20920183:G:A	G74E	0.966
16:20920210:G:C	R83T	0.966
16:20915697:T:C	F48L	0.964
16:20915699:C:A	F48L	0.964
16:20915699:C:G	F48L	0.964
16:20920167:G:C	A69P	0.964
16:20920172:G:C	R70S	0.964
16:20920172:G:T	R70S	0.964
16:20915674:T:A	I40K	0.963
16:20920161:T:C	C67R	0.960
16:20920182:G:A	G74R	0.952
16:20920182:G:C	G74R	0.952
16:20920201:C:A	P80H	0.952
16:20920171:G:C	R70T	0.944
16:20915624:G:C	W23C	0.943
16:20915624:G:T	W23C	0.943
16:20920188:C:G	H76D	0.943
16:20920209:A:G	R83G	0.940
16:20915686:C:A	A44D	0.939
16:20915698:T:C	F48S	0.936
16:20915674:T:G	I40R	0.933
16:20920190:T:A	H76Q	0.931
16:20920190:T:G	H76Q	0.931
16:20920210:G:T	R83M	0.931
16:20915674:T:C	I40T	0.924

dbSNP variants (sampled 300 via entrez): RS1000047927 (16:20921227 C>T), RS1000063387 (16:20915477 A>C), RS1000077534 (16:20921443 C>T), RS1000212356 (16:20899735 G>A,C), RS1000277236 (16:20902920 C>T), RS1000449460 (16:20914441 G>A), RS1000461372 (16:20915706 A>G), RS1000530740 (16:20921320 G>A,T), RS1000893225 (16:20902281 G>A), RS1000981217 (16:20914909 C>A,G), RS1001435306 (16:20914512 G>A), RS1001473989 (16:20902258 A>G), RS1001796909 (16:20920489 T>C), RS1001807852 (16:20900901 G>A,T), RS1001874808 (16:20900703 C>G)

Disease associations

OMIM: gene MIM:614709 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST008310_13	Cardiac Troponin-T levels	1.000000e-07
GCST90002382_433	Eosinophil percentage of white cells	2.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005043	cardiac troponin T measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, increases expression, affects binding	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
abrine	increases expression	1
bisphenol S	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Carbamazepine	affects expression	1
Ethyl Methanesulfonate	increases expression	1
Methyl Methanesulfonate	increases expression	1
Fenofibrate	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	decreases expression, decreases methylation	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
Lactic Acid	decreases expression	1
Acrylamide	increases expression	1
Particulate Matter	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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