LEKR1

Summary

LEKR1 (leucine, glutamate and lysine rich 1, HGNC:33765) is a protein-coding gene on chromosome 3q25.31, encoding Protein LEKR1 (Q6ZMV7).

At a glance

• GWAS associations: 75
• Clinical variants (ClinVar): 95 total
• MANE Select transcript: NM_001004316

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33765
Approved symbol	LEKR1
Name	leucine, glutamate and lysine rich 1
Location	3q25.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ16641
Ensembl gene	ENSG00000197980
Ensembl biotype	protein_coding
OMIM	613536
Entrez	389170

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 5 protein_coding, 3 protein_coding_CDS_not_defined, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000356539, ENST00000465728, ENST00000467376, ENST00000470811, ENST00000477399, ENST00000483177, ENST00000485017, ENST00000489350, ENST00000491763, ENST00000495252, ENST00000498839

RefSeq mRNA: 2 — MANE Select: NM_001004316 NM_001004316, NM_001193283

CCDS: CCDS54660

Canonical transcript exons

ENST00000356539 — 13 exons

Exon	Start	End
ENSE00001414648	157028103	157028402
ENSE00001415809	157045340	157046129
ENSE00001425675	157024760	157024924
ENSE00001433569	157011413	157011506
ENSE00001741575	156979194	156979275
ENSE00003499328	156993074	156993277
ENSE00003540426	156920575	156920694
ENSE00003561548	156992653	156992730
ENSE00003626620	156852768	156852982
ENSE00003634949	156829286	156829377
ENSE00003661857	156942529	156942714
ENSE00003680874	156927429	156927604
ENSE00003927389	156826353	156826376

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 87.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 2.6359 / max 64.5052, expressed in 1076 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
39444	2.6359	1076

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	87.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.21	gold quality
right uterine tube	UBERON:0001302	82.69	gold quality
left testis	UBERON:0004533	80.77	gold quality
right testis	UBERON:0004534	80.30	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.97	gold quality
testis	UBERON:0000473	78.88	gold quality
oviduct epithelium	UBERON:0004804	78.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.04	gold quality
mucosa of paranasal sinus	UBERON:0005030	74.41	gold quality
calcaneal tendon	UBERON:0003701	71.25	gold quality
fallopian tube	UBERON:0003889	71.18	gold quality
bronchial epithelial cell	CL:0002328	70.72	gold quality
bronchus	UBERON:0002185	69.59	gold quality
islet of Langerhans	UBERON:0000006	69.42	gold quality
adrenal tissue	UBERON:0018303	69.09	gold quality
left adrenal gland cortex	UBERON:0035825	68.60	gold quality
thyroid gland	UBERON:0002046	68.59	gold quality
left ovary	UBERON:0002119	68.57	gold quality
left lobe of thyroid gland	UBERON:0001120	68.40	gold quality
body of pancreas	UBERON:0001150	68.39	gold quality
adenohypophysis	UBERON:0002196	68.17	gold quality
right lobe of thyroid gland	UBERON:0001119	68.15	gold quality
pancreas	UBERON:0001264	67.72	gold quality
left adrenal gland	UBERON:0001234	66.82	gold quality
right ovary	UBERON:0002118	66.54	gold quality
ovary	UBERON:0000992	66.38	gold quality
pituitary gland	UBERON:0000007	66.28	gold quality
adrenal cortex	UBERON:0001235	65.64	gold quality
adrenal gland	UBERON:0002369	65.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

26 targeting LEKR1, 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-590-3P	99.96	74.34	6478
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4679	99.76	69.19	1229
HSA-MIR-2681-5P	99.75	67.64	1655
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-2113	99.58	71.22	1521
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-582-5P	99.47	70.79	2635
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-146A-3P	99.13	68.99	1881
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-371A-5P	99.08	66.51	1914
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-6074	98.89	69.64	2187
HSA-MIR-935	98.82	69.36	1072
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-4686	98.77	66.87	964
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-5581-5P	97.91	66.50	965

Literature-anchored findings (GeneRIF, showing 3)

• birth weight lowering effect of the C-allele of rs900400 located near LEKR1 and CCNL1 was replicated in the Danish population. Furthermore the C-allele was associated with increased insulin response following oral glucose stimulation (PMID:22073261)
• SNPs in LEKR1 and GALNT10 modulate sex-difference in carotid intima-media thickness. (PMID:25898001)
• Results suggest that LEKR1-CCNL1 and IGSF21-KLHDC7A gene polymorphisms influence the development of diabetic retinopathy (DR). (PMID:27607899)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lekr1	ENSMUSG00000074579
rattus_norvegicus	Lekr1	ENSRNOG00000031247

Protein

Protein identifiers

Protein LEKR1 — Q6ZMV7 (reviewed: Q6ZMV7)

All UniProt accessions (5): Q6ZMV7, A0A8I5FW65, D6RAK6, D6RJ01, J3KP02

RefSeq proteins (2): NP_001004316, NP_001180212 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR038799	LEKR1	Family

UniProt features (2 total): chain 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6ZMV7-F1	92.75	0.72

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 52 (showing top): BENPORATH_ES_WITH_H3K27ME3, DODD_NASOPHARYNGEAL_CARCINOMA_DN, MEISSNER_NPC_HCP_WITH_H3_UNMETHYLATED, chr3q25, ZWANG_CLASS_1_TRANSIENTLY_INDUCED_BY_EGF, SRC_UP.V1_UP, ATF5_TARGET_GENES, ATF6_TARGET_GENES, BARX1_TARGET_GENES, DLX2_TARGET_GENES, H1_6_TARGET_GENES, ID2_TARGET_GENES, LHX9_TARGET_GENES, MEF2D_TARGET_GENES, MSX1_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (0):

GO Cellular Component (0):

Protein interactions and networks

STRING

602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEKR1	SLC66A1LP	A1A4F0	434
LEKR1	GPATCH1	Q9BRR8	419
LEKR1	PLEKHG4	Q58EX7	413
LEKR1	WBP1L	Q9NX94	400
LEKR1	ZNF829	Q3KNS6	400
LEKR1	GALNT10	Q86SR1	398
LEKR1	SSR3	Q9UNL2	397
LEKR1	SLX4IP	Q5VYV7	388
LEKR1	ADCY5	O95622	383
LEKR1	ZBTB40	Q9NUA8	370
LEKR1	EFCAB9	A8MZ26	368
LEKR1	AADACL2	Q6P093	364
LEKR1	PALMD	Q9NP74	354
LEKR1	KIAA0825	Q8IV33	354
LEKR1	CCNL1	Q9UK58	349

IntAct

4 interactions, top by confidence:

A	B	Type	Score
LEKR1	TRIP11	psi-mi:“MI:0915”(physical association)	0.400
LEKR1	RALY	psi-mi:“MI:0915”(physical association)	0.400
	LEKR1	psi-mi:“MI:0915”(physical association)	0.000

ESM2 similar proteins: A0PJP4, B7ZAP0, F1RCP1, O18737, O88597, Q0IHE5, Q0VCP9, Q13137, Q14457, Q14BN4, Q15650, Q28623, Q2HJ93, Q3SYW5, Q3URD3, Q4A1L3, Q4A1L4, Q4A1L5, Q4R3X1, Q4R914, Q5EA89, Q5R467, Q5R7H1, Q5R878, Q5RD40, Q5RFL7, Q5ZJ65, Q5ZKS6, Q68CZ1, Q68FX7, Q6GP52, Q6ZMV7, Q7Z3E2, Q8BG18, Q8BHN1, Q8C9S4, Q8CG73, Q8IWR0, Q8N987, Q8TAV0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	80
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

3825 predictions. Top by Δscore:

Variant	Effect	Δscore
3:156852767:GAT:G	acceptor_gain	1.0000
3:156852978:GAAAG:G	donor_gain	1.0000
3:156852981:AGGT:A	donor_loss	1.0000
3:156852982:GGT:G	donor_gain	1.0000
3:156852982:GGTT:G	donor_loss	1.0000
3:156852984:T:TG	donor_gain	1.0000
3:156852988:G:GG	donor_gain	1.0000
3:156942666:G:GT	donor_gain	1.0000
3:156942705:G:GT	donor_gain	1.0000
3:156979276:G:GG	donor_gain	1.0000
3:156992731:G:GG	donor_gain	1.0000
3:156993249:G:T	donor_gain	1.0000
3:157008671:A:G	donor_gain	1.0000
3:157008714:GCAT:G	donor_gain	1.0000
3:157024755:TCTA:T	acceptor_loss	1.0000
3:157024757:TAGAT:T	acceptor_loss	1.0000
3:157024758:A:AG	acceptor_gain	1.0000
3:157024758:A:AT	acceptor_loss	1.0000
3:157024759:G:GG	acceptor_gain	1.0000
3:157024759:GATT:G	acceptor_gain	1.0000
3:157024922:AAG:A	donor_loss	1.0000
3:157024924:GG:G	donor_loss	1.0000
3:157024925:G:A	donor_loss	1.0000
3:157024925:GTCT:G	donor_gain	1.0000
3:157045335:TTCA:T	acceptor_loss	1.0000
3:157045337:CAG:C	acceptor_loss	1.0000
3:157045338:A:AG	acceptor_gain	1.0000
3:157045339:G:GG	acceptor_gain	1.0000
3:157045339:GA:G	acceptor_gain	1.0000
3:157045339:GAA:G	acceptor_gain	1.0000

AlphaMissense

4600 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002950 (3:156899257 T>C), RS1000012526 (3:157023563 A>G), RS1000030012 (3:156891226 C>T), RS1000084214 (3:156852809 C>T), RS1000096473 (3:156985182 A>G,T), RS1000122697 (3:156908731 A>G), RS1000140236 (3:156842783 A>G), RS1000163083 (3:156866546 C>T), RS1000178126 (3:156933122 A>G), RS1000219028 (3:157029317 G>A), RS1000223406 (3:156884683 T>C), RS1000232670 (3:156859674 A>C,G), RS1000254357 (3:156915419 A>T), RS1000264064 (3:156859946 G>A,T), RS1000272476 (3:156980597 C>G,T)

Disease associations

OMIM: gene MIM:613536 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

75 associations (top):

Study	Trait	p-value
GCST000266_8	Multiple sclerosis (severity)	2.000000e-06
GCST000648_1	Birth weight	2.000000e-35
GCST001017_10	Diabetic retinopathy	7.000000e-07
GCST001482_2	Lumbar spine bone mineral density	4.000000e-12
GCST001644_2	Eating disorders	3.000000e-06
GCST001964_1	Anthropometric traits in newborns	3.000000e-19
GCST001964_2	Anthropometric traits in newborns	2.000000e-13
GCST001964_3	Anthropometric traits in newborns	4.000000e-09
GCST001964_4	Anthropometric traits in newborns	6.000000e-07
GCST001964_5	Anthropometric traits in newborns	9.000000e-06
GCST002541_5	Menarche (age at onset)	2.000000e-11
GCST002777_2	Clozapine-induced cytotoxicity	3.000000e-06
GCST002782_240	Waist-to-hip ratio adjusted for body mass index	1.000000e-06
GCST002782_241	Waist-to-hip ratio adjusted for body mass index	1.000000e-08
GCST002782_242	Waist-to-hip ratio adjusted for body mass index	1.000000e-12
GCST002782_243	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST002782_244	Waist-to-hip ratio adjusted for body mass index	6.000000e-06
GCST002782_245	Waist-to-hip ratio adjusted for body mass index	4.000000e-11
GCST002856_1	Carotid artery intima media thickness (sex interaction)	4.000000e-06
GCST002856_3	Carotid artery intima media thickness (sex interaction)	1.000000e-06
GCST003999_18	Nose size	2.000000e-07
GCST004063_25	Waist circumference adjusted for body mass index	4.000000e-12
GCST004063_52	Waist circumference adjusted for body mass index	1.000000e-13
GCST004064_31	Waist-hip ratio	3.000000e-06
GCST004064_38	Waist-hip ratio	3.000000e-11
GCST004064_45	Waist-hip ratio	3.000000e-07
GCST004068_16	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	9.000000e-06
GCST004289_3	Adiponectin levels in pregnancy	1.000000e-07
GCST004500_103	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	6.000000e-13
GCST004500_65	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	3.000000e-12

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0006266	sum of skinfolds
EFO:0004703	age at menarche
EFO:0006952	cytotoxicity measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008343	sex interaction measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0004343	waist-hip ratio
EFO:0004502	adiponectin measurement
EFO:0004318	smoking behavior
EFO:0008002	physical activity measurement
EFO:0009270	heel bone mineral density
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004329	alcohol drinking
EFO:0004530	triglyceride measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004736	aspartate aminotransferase measurement

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
Valproic Acid	decreases methylation, increases expression	2
aristolochic acid I	increases expression	1
propionaldehyde	increases expression	1
bisphenol A	increases methylation	1
tri-o-cresyl phosphate	increases expression	1
2-palmitoylglycerol	increases expression	1
abrine	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Phthalic Acids	increases methylation	1
Tobacco Smoke Pollution	affects expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	decreases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Permethrin	decreases expression	1

Clinical trials (associated diseases)

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