LCORL

Summary

LCORL (ligand dependent nuclear receptor corepressor like, HGNC:30776) is a protein-coding gene on chromosome 4p15.31, encoding Ligand-dependent nuclear receptor corepressor-like protein (Q8N3X6). May act as transcription activator that binds DNA elements with the sequence 5’-CCCTATCGATCGATCTCTACCT-3'.

This gene encodes a transcription factor that appears to function in spermatogenesis. Polymorphisms in this gene are associated with measures of skeletal frame size and adult height. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 254251 — RefSeq curated summary.

At a glance

• GWAS associations: 99
• Clinical variants (ClinVar): 98 total
• MANE Select transcript: NM_001394446

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30776
Approved symbol	LCORL
Name	ligand dependent nuclear receptor corepressor like
Location	4p15.31
Locus type	gene with protein product
Status	Approved
Aliases	MLR1, FLJ30696
Ensembl gene	ENSG00000178177
Ensembl biotype	protein_coding
OMIM	611799
Entrez	254251

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 11 protein_coding, 4 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000326877, ENST00000382224, ENST00000382226, ENST00000510121, ENST00000510451, ENST00000512376, ENST00000635767, ENST00000637787, ENST00000674942, ENST00000675131, ENST00000675143, ENST00000675605, ENST00000675927, ENST00000676061, ENST00000676180, ENST00000883817, ENST00000883818

RefSeq mRNA: 10 — MANE Select: NM_001394446 NM_001166139, NM_001365658, NM_001365659, NM_001365660, NM_001365661, NM_001365662, NM_001365663, NM_001365665, NM_001394446, NM_153686

CCDS: CCDS3425, CCDS54749, CCDS93484, CCDS93485, CCDS93486

Canonical transcript exons

ENST00000635767 — 8 exons

Exon	Start	End
ENSE00003488224	17909094	17909345
ENSE00003490261	17962970	17963049
ENSE00003492308	17961903	17962032
ENSE00003502870	17972820	17972885
ENSE00003511525	17886068	17886161
ENSE00003791854	17873388	17878213
ENSE00003796473	17841187	17845901
ENSE00003903643	18021598	18021755

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 96.89.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.6966 / max 183.3407, expressed in 1692 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51545	8.4809	1682
51544	0.2157	86

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	96.89	gold quality
endothelial cell	CL:0000115	95.18	gold quality
sperm	CL:0000019	95.06	gold quality
jejunal mucosa	UBERON:0000399	94.45	gold quality
visceral pleura	UBERON:0002401	93.35	gold quality
ileal mucosa	UBERON:0000331	93.27	gold quality
tibia	UBERON:0000979	91.33	gold quality
parietal pleura	UBERON:0002400	90.89	gold quality
pancreatic ductal cell	CL:0002079	90.78	gold quality
ventricular zone	UBERON:0003053	90.30	gold quality
cortical plate	UBERON:0005343	90.11	gold quality
epithelial cell of pancreas	CL:0000083	90.04	silver quality
ganglionic eminence	UBERON:0004023	90.00	gold quality
adrenal tissue	UBERON:0018303	89.47	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.25	gold quality
germinal epithelium of ovary	UBERON:0001304	88.89	gold quality
pigmented layer of retina	UBERON:0001782	88.08	gold quality
oviduct epithelium	UBERON:0004804	87.70	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.68	gold quality
colonic mucosa	UBERON:0000317	87.61	gold quality
jejunum	UBERON:0002115	87.28	gold quality
palpebral conjunctiva	UBERON:0001812	86.59	gold quality
duodenum	UBERON:0002114	86.09	gold quality
corpus callosum	UBERON:0002336	86.07	gold quality
deltoid	UBERON:0001476	86.05	gold quality
tibialis anterior	UBERON:0001385	85.62	silver quality
bone marrow cell	CL:0002092	85.44	gold quality
upper leg skin	UBERON:0004262	84.30	gold quality
esophagus squamous epithelium	UBERON:0006920	83.68	gold quality
calcaneal tendon	UBERON:0003701	83.59	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	8.89
E-ANND-3	yes	5.54

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

251 targeting LCORL, 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-340-5P	100.00	72.50	4437
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784
HSA-LET-7I-5P	99.98	72.37	1788
HSA-MIR-98-5P	99.98	72.33	1787
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883

Literature-anchored findings (GeneRIF, showing 1)

• Identification and characterization of an homologous gene in mouse. (PMID:12560079)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Lcorl	ENSMUSG00000015882
rattus_norvegicus		ENSRNOG00000080164

Paralogs (1): LCOR (ENSG00000196233)

Protein

Protein identifiers

Ligand-dependent nuclear receptor corepressor-like protein — Q8N3X6 (reviewed: Q8N3X6)

All UniProt accessions (12): Q8N3X6, A0A1B0GVP4, A0A1B0GWC6, A0A6Q8PFA3, A0A6Q8PFB4, A0A6Q8PFT7, A0A6Q8PFX9, A0A6Q8PG24, A0A6Q8PHE0, A0A6Q8PHT2, C9JI46, D6RA10

UniProt curated annotations — full annotation on UniProt →

Function. May act as transcription activator that binds DNA elements with the sequence 5’-CCCTATCGATCGATCTCTACCT-3’. May play a role in spermatogenesis.

Subcellular location. Nucleus.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8N3X6-1	1	yes
Q8N3X6-2	2
Q8N3X6-3	3

RefSeq proteins (10): NP_001159611, NP_001352587, NP_001352588, NP_001352589, NP_001352590, NP_001352591, NP_001352592, NP_001352594, NP_001381375, NP_710153 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR007889	HTH_Psq	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily

Pfam: PF05225

UniProt features (16 total): cross-link 4, splice variant 3, region of interest 3, compositionally biased region 2, chain 1, domain 1, sequence conflict 1, DNA-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N3X6-F1	58.40	0.10

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 (4): 340, 397, 242, 319

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 156 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACTACCT_MIR196A_MIR196B, MENSE_HYPOXIA_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP, COATES_MACROPHAGE_M1_VS_M2_UP, FISCHER_DREAM_TARGETS, ZHANG_BREAST_CANCER_PROGENITORS_UP, IVANOVA_HEMATOPOIESIS_EARLY_PROGENITOR, AGCATTA_MIR155, MARSON_BOUND_BY_FOXP3_STIMULATED, LEE_RECENT_THYMIC_EMIGRANT, AAGCACA_MIR218, chr4p15, GABRIELY_MIR21_TARGETS

GO Biological Process (1): regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (3): DNA binding (GO:0003677), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
nucleic acid binding	1
enzyme binding	1
binding	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

984 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LCORL	NCAPG	Q9BPX3	860
LCORL	FAM184B	Q9ULE4	776
LCORL	DCAF16	Q9NXF7	714
LCORL	PLAG1	Q6DJT9	706
LCORL	ZFAT	Q9P243	634
LCORL	LAP3	P28838	613
LCORL	F5H6H0	F5H6H0	586
LCORL	CLCN2	P51788	570
LCORL	CHCHD7	Q9BUK0	549
LCORL	NR6A1	Q15406	493
LCORL	MED28	Q9H204	481
LCORL	KIT	P10721	474
LCORL	FAM110B	Q8TC76	468
LCORL	LASP1	Q14847	460
LCORL	LCOR	Q96JN0	460

IntAct

12 interactions, top by confidence:

A	B	Type	Score
CTBP1	LCORL	psi-mi:“MI:0915”(physical association)	0.840
CTBP1	CBX4	psi-mi:“MI:0914”(association)	0.700
LCORL	MAGEA6	psi-mi:“MI:0915”(physical association)	0.560
MAGEA6	LCORL	psi-mi:“MI:0915”(physical association)	0.560
LCORL	CKMT1A	psi-mi:“MI:0914”(association)	0.350
CTBP1	GSN	psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
NOL4	ZNF195	psi-mi:“MI:0914”(association)	0.350
CTBP1	SEC16A	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (25): LCORL (Two-hybrid), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Two-hybrid), MAGEA6 (Two-hybrid), LCORL (Protein-RNA), CHD4 (Affinity Capture-MS), CTBP1 (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-MS), LCORL (Affinity Capture-RNA), LCORL (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTS1, A0A1B0GWH4, A1A4L6, A1YGI6, A6NDR6, B8QB46, F1MJR8, F1QDF8, O35892, O35893, P09015, P15036, P15037, P23497, P52729, P59598, Q32NH9, Q3KRF1, Q3UM89, Q4G112, Q4V7E1, Q5M7N6, Q5ND04, Q5XIV2, Q5ZHX5, Q66IG8, Q6P1R3, Q6PCX9, Q6PJQ5, Q708W2, Q76I76, Q76I79, Q76N89, Q7M6U3, Q8AXQ4, Q8BVK9, Q8IUE0, Q8IUE1, Q8IWB6, Q8IXJ9

Diamond homologs: G5EGQ5, Q3U285, Q5ZJK5, Q6ZPI3, Q8N3X6, Q95YM8, Q96JN0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	86
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2035 predictions. Top by Δscore:

Variant	Effect	Δscore
4:17843300:A:AG	acceptor_gain	1.0000
4:17843300:AGT:A	acceptor_gain	1.0000
4:17843301:G:GA	acceptor_gain	1.0000
4:17843301:GT:G	acceptor_gain	1.0000
4:17843301:GTG:G	acceptor_gain	1.0000
4:17886159:CCC:C	acceptor_gain	1.0000
4:17886160:CCC:C	acceptor_gain	1.0000
4:17909088:TCTTA:T	donor_loss	1.0000
4:17909089:CTTA:C	donor_loss	1.0000
4:17909090:TTACC:T	donor_loss	1.0000
4:17909091:TA:T	donor_loss	1.0000
4:17909092:A:AC	donor_gain	1.0000
4:17909092:AC:A	donor_gain	1.0000
4:17909093:C:CC	donor_gain	1.0000
4:17909093:C:CT	donor_loss	1.0000
4:17909093:CC:C	donor_gain	1.0000
4:17909093:CCTTG:C	donor_gain	1.0000
4:17909341:AAGAT:A	acceptor_gain	1.0000
4:17909342:AGAT:A	acceptor_gain	1.0000
4:17909343:GAT:G	acceptor_gain	1.0000
4:17909344:AT:A	acceptor_gain	1.0000
4:17909346:C:CC	acceptor_gain	1.0000
4:17961901:A:AG	donor_loss	1.0000
4:17961902:CCT:C	donor_loss	1.0000
4:17961902:CCTTT:C	donor_gain	1.0000
4:17962028:CAATC:C	acceptor_gain	1.0000
4:17962031:TC:T	acceptor_gain	1.0000
4:17962032:CC:C	acceptor_gain	1.0000
4:17962033:C:CC	acceptor_gain	1.0000
4:17962033:C:CG	acceptor_loss	1.0000

AlphaMissense

12450 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:18021625:A:G	W43R	1.000
4:18021625:A:T	W43R	1.000
4:17909306:G:T	A157D	0.999
4:18021612:A:G	L47P	0.999
4:17886143:A:G	L234P	0.998
4:17909132:A:G	L215P	0.998
4:17909271:C:G	A169P	0.998
4:17909273:A:G	F168S	0.998
4:17961926:A:G	L136P	0.998
4:17963005:A:G	C89R	0.998
4:17963023:A:G	W83R	0.998
4:17963023:A:T	W83R	0.998
4:17972870:A:G	L57S	0.998
4:17972873:A:T	I56N	0.998
4:18021598:C:G	G52R	0.998
4:18021612:A:T	L47H	0.998
4:18021622:G:T	R44S	0.998
4:18021623:C:A	W43C	0.998
4:18021623:C:G	W43C	0.998
4:18021633:A:G	L40P	0.998
4:17886149:A:G	L232S	0.997
4:17909270:G:T	A169E	0.997
4:17909272:A:C	F168L	0.997
4:17909272:A:T	F168L	0.997
4:17909274:A:G	F168L	0.997
4:17909307:C:G	A157P	0.997
4:17962996:A:G	C92R	0.997
4:17972882:A:G	F53S	0.997
4:18021621:C:G	R44P	0.997
4:18021667:A:G	C29R	0.997

dbSNP variants (sampled 300 via entrez): RS1000009453 (4:17919561 C>T), RS1000013702 (4:18018826 A>C,G), RS1000019836 (4:17899016 G>C), RS1000035267 (4:17938708 C>T), RS1000044597 (4:17846096 C>A), RS1000045836 (4:18021824 C>G,T), RS1000063547 (4:17867649 T>C,G), RS1000097017 (4:17935291 T>C), RS1000103235 (4:17905434 G>A), RS1000123249 (4:17985422 G>A), RS1000133713 (4:17978222 G>GT,GTT), RS1000138673 (4:18000793 T>C), RS1000164945 (4:17953907 T>A), RS1000170390 (4:17935520 A>G), RS1000189119 (4:17895756 A>G)

Disease associations

OMIM: gene MIM:611799 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

99 associations (top):

Study	Trait	p-value
GCST000174_2	Height	2.000000e-13
GCST000175_39	Height	1.000000e-10
GCST000372_18	Height	5.000000e-09
GCST000611_25	Height	8.000000e-15
GCST000817_123	Height	7.000000e-46
GCST000817_24	Height	2.000000e-09
GCST001263_27	Height	1.000000e-15
GCST001290_1	Height	3.000000e-14
GCST001758_9	Birth weight	5.000000e-11
GCST001956_8	Height	3.000000e-22
GCST002178_3	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+doxorubicin+/-5FU)	2.000000e-06
GCST002415_13	Colorectal cancer (diet interaction)	1.000000e-06
GCST002644_4	Birth length	1.000000e-06
GCST002646_3	Infant length	3.000000e-14
GCST002647_22	Height	1.000000e-71
GCST002702_45	Height	1.000000e-53
GCST004063_115	Waist circumference adjusted for body mass index	4.000000e-08
GCST004063_139	Waist circumference adjusted for body mass index	3.000000e-07
GCST004067_101	Hip circumference adjusted for BMI	9.000000e-12
GCST004067_142	Hip circumference adjusted for BMI	1.000000e-10
GCST004212_14	Height	7.000000e-09
GCST004500_33	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	9.000000e-09
GCST004500_80	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	5.000000e-08
GCST004501_101	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	2.000000e-09
GCST004501_102	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	7.000000e-08
GCST004503_2	Waist circumference adjusted for BMI in smokers	9.000000e-06
GCST004504_73	Waist circumference adjusted for BMI in non-smokers	3.000000e-06
GCST004504_74	Waist circumference adjusted for BMI in non-smokers	6.000000e-06
GCST005146_11	Birth weight	1.000000e-15
GCST005830_83	Hand grip strength	9.000000e-09

EFO canonical traits (23, from GWAS)

EFO ID	Trait name
EFO:0004344	birth weight
EFO:0008111	diet measurement
EFO:0006784	body height at birth
EFO:0006785	infant body height
EFO:0007789	BMI-adjusted waist circumference
EFO:0008039	BMI-adjusted hip circumference
EFO:0004318	smoking behavior
EFO:0006941	grip strength measurement
EFO:0006953	family history of lung cancer
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0009959	diverticular disease
EFO:0006335	systolic blood pressure
EFO:0009270	heel bone mineral density
EFO:0004341	body fat distribution
EFO:0008579	risk-taking behaviour
EFO:0008328	chronotype measurement
EFO:0004338	body weight
EFO:0005939	parental genotype effect measurement
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004530	triglyceride measurement
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
Testosterone	affects cotreatment, decreases expression, increases expression	2
aristolochic acid I	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	increases methylation	1
ferrous chloride	increases expression	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
entinostat	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, decreases expression	1
Benzo(a)pyrene	affects methylation	1
Calcitriol	decreases expression, affects cotreatment	1
Cisplatin	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Drugs, Chinese Herbal	increases expression	1
Formaldehyde	decreases expression	1
Lead	affects splicing	1
Malathion	increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	increases expression	1
Naphthoquinones	increases expression	1
Niclosamide	increases expression	1

Clinical trials (associated diseases)

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