CREBRF

Summary

CREBRF (CREB3 regulatory factor, HGNC:24050) is a protein-coding gene on chromosome 5q35.1, encoding CREB3 regulatory factor (Q8IUR6). Acts as a negative regulator of the endoplasmic reticulum stress response or unfolded protein response (UPR).

Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific DNA binding activity. Involved in several processes, including negative regulation of endoplasmic reticulum unfolded protein response; positive regulation of protein catabolic process; and regulation of transcription by RNA polymerase II. Located in cytoplasm and nuclear body.

Source: NCBI Gene 153222 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inherited obesity (Limited, GenCC)
• GWAS associations: 5
• Clinical variants (ClinVar): 74 total
• Druggable target: yes
• MANE Select transcript: NM_153607

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24050
Approved symbol	CREBRF
Name	CREB3 regulatory factor
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	LRF
Ensembl gene	ENSG00000164463
Ensembl biotype	protein_coding
OMIM	617109
Entrez	153222

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 16 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000296953, ENST00000517882, ENST00000520420, ENST00000520464, ENST00000522692, ENST00000523161, ENST00000863346, ENST00000863347, ENST00000934785, ENST00000934786, ENST00000965315, ENST00000965316, ENST00000965317, ENST00000965318, ENST00000965319, ENST00000965320, ENST00000965321, ENST00000965322

RefSeq mRNA: 3 — MANE Select: NM_153607 NM_001168393, NM_001168394, NM_153607

CCDS: CCDS34293, CCDS54948

Canonical transcript exons

ENST00000296953 — 9 exons

Exon	Start	End
ENSE00001084573	173108624	173108818
ENSE00001084574	173110522	173110711
ENSE00001084580	173123080	173123202
ENSE00001369971	173080585	173080784
ENSE00002103392	173133630	173139284
ENSE00002120049	173056352	173056479
ENSE00003462232	173112306	173112379
ENSE00003614195	173090315	173091401
ENSE00003648134	173086501	173086626

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 96.32.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.8120 / max 310.3080, expressed in 1652 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60283	12.1040	1571
60285	1.0356	659
60284	0.4405	152
60286	0.2319	76

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.32	gold quality
kidney epithelium	UBERON:0004819	96.18	gold quality
superficial temporal artery	UBERON:0001614	94.73	gold quality
layer of synovial tissue	UBERON:0007616	94.50	gold quality
medial globus pallidus	UBERON:0002477	94.10	gold quality
globus pallidus	UBERON:0001875	93.78	gold quality
lower lobe of lung	UBERON:0008949	93.65	gold quality
urethra	UBERON:0000057	93.56	gold quality
bone marrow cell	CL:0002092	93.48	gold quality
cardiac muscle of right atrium	UBERON:0003379	93.30	gold quality
caput epididymis	UBERON:0004358	93.23	gold quality
cauda epididymis	UBERON:0004360	92.86	gold quality
bone marrow	UBERON:0002371	92.70	gold quality
corpus epididymis	UBERON:0004359	92.54	gold quality
myocardium	UBERON:0002349	92.47	gold quality
mammary duct	UBERON:0001765	92.42	gold quality
epithelium of mammary gland	UBERON:0003244	92.37	gold quality
mucosa of paranasal sinus	UBERON:0005030	92.28	gold quality
nipple	UBERON:0002030	92.20	gold quality
lateral globus pallidus	UBERON:0002476	92.16	gold quality
tendon	UBERON:0000043	92.10	gold quality
substantia nigra pars compacta	UBERON:0001965	91.99	gold quality
jejunal mucosa	UBERON:0000399	91.86	gold quality
blood	UBERON:0000178	91.80	gold quality
cartilage tissue	UBERON:0002418	91.79	gold quality
pericardium	UBERON:0002407	91.77	gold quality
inferior vagus X ganglion	UBERON:0005363	91.67	gold quality
penis	UBERON:0000989	91.65	gold quality
renal medulla	UBERON:0000362	91.60	gold quality
trabecular bone tissue	UBERON:0002483	91.53	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.05

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
COMP	Unknown
HERPUD1	Activation

miRNA regulators (miRDB)

565 targeting CREBRF, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-656-3P	100.00	72.15	2788
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4476	100.00	68.18	2030

Literature-anchored findings (GeneRIF, showing 21)

• Findings provide new insight into the molecular mechanisms underlying hypoxia-induced glioblastoma cell autophagy and indicate that the hypoxia/CREBRF/CREB3/ATG5 pathway plays a central role in malignant glioma progression. (PMID:27278737)
• Missense Mutation in CREBRF gene is associated with obesity. (PMID:27455349)
• The rs373863828-A allele was not found in both AN-speaking and non-AN-speaking Melanesians living in Papua New Guinea. Our results suggest that rs373863828-A of CREBRF, a promising thrifty variant, arose in recent ancestors of AN-speaking Polynesians. (PMID:28405013)
• Studied CREBRF genetic variants in association to height and weight in young children; found that the rs373863828 variant was significantly associated with growth at 4 years of age; also found the variants to be prevalent in other Pacific populations, including Maori. (PMID:28928463)
• The presence of each additional CREBRF rs373863828 A allele is associated with increased BMI yet reduced odds of type 2 diabetes in adults of Maori and Pacific (Polynesian) ancestry living in Aotearoa/New Zealand. (PMID:29721634)
• CREBRF promotes the proliferation of human gastric cancer cells via the AKT signaling pathway. (PMID:29729692)
• The rs373863828-A allele (a missense variant of the CREBRF gene) may not directly affect the level of serum HDL-cholesterol independent of BMI. (PMID:29877158)
• We found that CREBRF and TRIM2 mRNA were significantly upregulated by rHDL, particularly in response to its phospholipid component 1-palmitoyl-2-linoleoyl-phosphatidylcholine, however, protein expression was not significantly altered. (PMID:29958463)
• CREBRF G allele (rs12513649) and A allele (rs373863828)are associated with higher BMI and lower risk of diabetes in Pacific Islander (Guam and Saipan) populations. (PMID:31280340)
• The Maori and Pacific specific CREBRF variant and adult height. (PMID:31543511)
• A missense variant in CREBRF is associated with taller stature in Samoans. (PMID:32190945)
• Population-specific reference panels are crucial for genetic analyses: an example of the CREBRF locus in Native Hawaiians. (PMID:32491157)
• The Pacific-specific CREBRF rs373863828 allele protects against gestational diabetes mellitus in Maori and Pacific women with obesity. (PMID:32654027)
• A missense variant in CREBRF, rs373863828, is associated with fat-free mass, not fat mass in Samoan infants. (PMID:32884101)
• CREBRF missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesian peoples living in Samoa and Aotearoa New Zealand. (PMID:35144939)
• The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition. (PMID:35218947)
• The missense variant, rs373863828, in CREBRF plays a role in longitudinal changes in body mass index in Samoans. (PMID:35606300)
• The protective effect of rs373863828 on type 2 diabetes does not operate through a body composition pathway in adult Samoans. (PMID:36284436)
• Multivariate analysis of a missense variant in CREBRF reveals associations with measures of adiposity in people of Polynesian ancestries. (PMID:36352773)
• miR-181d-5p, which is upregulated in fetal growth restriction placentas, inhibits trophoblast fusion via CREBRF. (PMID:37610607)
• The impact of CREBRF rs373863828 Pacific-variant on infant body composition. (PMID:38627436)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	crebrf	ENSDARG00000105114
mus_musculus	Crebrf	ENSMUSG00000048249
rattus_norvegicus	Crebrf	ENSRNOG00000020769
drosophila_melanogaster	REPTOR	FBGN0039209

Protein

Protein identifiers

CREB3 regulatory factor — Q8IUR6 (reviewed: Q8IUR6)

Alternative names: Luman recruitment factor

All UniProt accessions (2): E5RI19, Q8IUR6

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a negative regulator of the endoplasmic reticulum stress response or unfolded protein response (UPR). Represses the transcriptional activity of CREB3 during the UPR. Recruits CREB3 into nuclear foci.

Subunit / interactions. Interacts (via leucine-zipper domain) with CREB3 (via leucine-zipper domain); the interaction promotes CREB3 degradation.

Subcellular location. Nucleus.

Post-translational modifications. Probably degraded by the proteasome.

Induction. Up-regulated by endoplasmic reticulum stress.

Similarity. Belongs to the bZIP family. CREBRF subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8IUR6-1	1	yes
Q8IUR6-2	2
Q8IUR6-3	3

RefSeq proteins (3): NP_001161865, NP_001161866, NP_705835* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004827	bZIP	Domain
IPR039165	CREBRF	Family
IPR046347	bZIP_sf	Homologous_superfamily

UniProt features (17 total): compositionally biased region 5, splice variant 3, sequence conflict 3, region of interest 3, chain 1, domain 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUR6-F1	57.02	0.15

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-8874211	CREB3 factors activate genes

MSigDB gene sets: 519 (showing top): GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, RNGTGGGC_UNKNOWN, AGGAAGC_MIR5163P, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, FREAC2_01, GOBP_BEHAVIOR, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_RESPONSE_TO_PEPTIDE, GOBP_CELLULAR_RESPONSE_TO_LIPID, AAGTCCA_MIR422B_MIR422A, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GCM_ZNF198, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (11): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), response to unfolded protein (GO:0006986), response to endoplasmic reticulum stress (GO:0034976), maternal behavior (GO:0042711), positive regulation of protein catabolic process (GO:0045732), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of endoplasmic reticulum unfolded protein response (GO:1900102), positive regulation of prolactin signaling pathway (GO:1902213), negative regulation of nuclear receptor-mediated glucocorticoid signaling pathway (GO:2000323), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear body (GO:0016604)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Unfolded Protein Response (UPR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
regulation of DNA-templated transcription	2
transcription cis-regulatory region binding	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
response to topologically incorrect protein	1
cellular response to stress	1
parental behavior	1
positive regulation of catabolic process	1
protein catabolic process	1
regulation of protein catabolic process	1
positive regulation of protein metabolic process	1
positive regulation of DNA-templated transcription	1
endoplasmic reticulum unfolded protein response	1
regulation of endoplasmic reticulum unfolded protein response	1
negative regulation of intracellular signal transduction	1
negative regulation of response to endoplasmic reticulum stress	1
positive regulation of cytokine-mediated signaling pathway	1
prolactin signaling pathway	1
regulation of prolactin signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
nuclear receptor-mediated glucocorticoid signaling pathway	1
regulation of nuclear receptor-mediated glucocorticoid signaling pathway	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
transcription regulator activity	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nucleoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1486 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CREBRF	CREB3	O43889	756
CREBRF	CREB3L4	Q8TEY5	752
CREBRF	CREBL2	O60519	580
CREBRF	KLHL24	Q6TFL4	518
CREBRF	DNAJC16	Q9Y2G8	440
CREBRF	RNF14	Q9UBS8	435
CREBRF	KSR2	Q6VAB6	429
CREBRF	PJA2	O43164	426
CREBRF	SKI	P12755	359
CREBRF	PAH	P00439	353
CREBRF	FLT1	P16057	348
CREBRF	UBXN4	Q92575	347
CREBRF	TSC22D2	O75157	346
CREBRF	TRIB2	Q92519	345
CREBRF	SDR39U1	Q9NRG7	331

IntAct

27 interactions, top by confidence:

A	B	Type	Score
NAA10	CREBRF	psi-mi:“MI:0915”(physical association)	0.670
CREBRF	CREB3	psi-mi:“MI:0915”(physical association)	0.580
CREB3	CREBRF	psi-mi:“MI:0915”(physical association)	0.580
CREBRF	NAA11	psi-mi:“MI:0915”(physical association)	0.560
CREBRF	MID2	psi-mi:“MI:0915”(physical association)	0.560
CREBL2	CREBRF	psi-mi:“MI:0915”(physical association)	0.560
GRB7	CREBRF	psi-mi:“MI:0915”(physical association)	0.560
CREBRF	ATF1	psi-mi:“MI:0915”(physical association)	0.400
CREBRF	CREBRF	psi-mi:“MI:0915”(physical association)	0.400
NAA10	SUPT5H	psi-mi:“MI:0914”(association)	0.350
CREBRF	CREB3	psi-mi:“MI:0403”(colocalization)	0.270
CD2BP2	CREBRF	psi-mi:“MI:0915”(physical association)	0.000
NAA11	CREBRF	psi-mi:“MI:0915”(physical association)	0.000
CREBL2	CREBRF	psi-mi:“MI:0915”(physical association)	0.000
MID2	CREBRF	psi-mi:“MI:0915”(physical association)	0.000
NAA10	CREBRF	psi-mi:“MI:0915”(physical association)	0.000
GRB7	CREBRF	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): CREBRF (Proximity Label-MS), ATF1 (Affinity Capture-MS), CREBRF (Affinity Capture-MS), CREBRF (Affinity Capture-RNA), CREBRF (Two-hybrid), CREBRF (Two-hybrid), CREBRF (Two-hybrid), CREBRF (Two-hybrid), CREBRF (Two-hybrid), CREBRF (Proximity Label-MS), ATF1 (Affinity Capture-MS), CREBRF (Cross-Linking-MS (XL-MS)), TFRC (Cross-Linking-MS (XL-MS)), CREBRF (Affinity Capture-RNA)

ESM2 similar proteins: A0A087WRU1, A0JNH1, A2RUB1, A6QNQ6, B0S6S9, B1WC58, D3Z987, D3ZJ47, E1BC15, O60673, P28358, P28359, P56716, P70347, Q0P5X5, Q0VAV2, Q0VBV7, Q15468, Q2M2Z5, Q3UXL4, Q3V089, Q49A88, Q569L8, Q5BQN8, Q5CZC0, Q5QGS0, Q5T1N1, Q5VWN6, Q60988, Q61493, Q62924, Q6ZP01, Q6ZU52, Q6ZVD7, Q80U59, Q80WQ8, Q86WS4, Q86YC2, Q8CB14, Q8IUR6

Diamond homologs: Q8CDG5, Q8IUR6, Q9VC61

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CREBRF	“up-regulates quantity by expression”	HERPUD1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1856 predictions. Top by Δscore:

Variant	Effect	Δscore
5:173056476:ACAGG:A	donor_loss	1.0000
5:173056479:GGTG:G	donor_loss	1.0000
5:173080583:A:AG	acceptor_gain	1.0000
5:173080584:G:GG	acceptor_gain	1.0000
5:173080584:GACA:G	acceptor_gain	1.0000
5:173080797:GA:G	donor_gain	1.0000
5:173083696:G:T	donor_gain	1.0000
5:173086496:TGTA:T	acceptor_loss	1.0000
5:173086497:GTA:G	acceptor_loss	1.0000
5:173086498:TAG:T	acceptor_loss	1.0000
5:173086499:A:AG	acceptor_gain	1.0000
5:173086500:G:GA	acceptor_gain	1.0000
5:173086500:GCCT:G	acceptor_gain	1.0000
5:173086500:GCCTA:G	acceptor_gain	1.0000
5:173086623:ACTG:A	donor_gain	1.0000
5:173086624:CTG:C	donor_gain	1.0000
5:173086627:G:GA	donor_loss	1.0000
5:173086627:G:GG	donor_gain	1.0000
5:173086628:T:A	donor_loss	1.0000
5:173091368:G:GT	donor_gain	1.0000
5:173091384:A:AG	donor_gain	1.0000
5:173108622:A:G	acceptor_gain	1.0000
5:173110509:AAACT:A	acceptor_gain	1.0000
5:173110510:A:G	acceptor_gain	1.0000
5:173110511:A:AG	acceptor_gain	1.0000
5:173110513:T:A	acceptor_gain	1.0000
5:173110518:A:AG	acceptor_gain	1.0000
5:173110518:ATAG:A	acceptor_gain	1.0000
5:173110519:T:G	acceptor_gain	1.0000
5:173110520:A:AG	acceptor_gain	1.0000

AlphaMissense

4232 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:173090595:T:C	L139S	1.000
5:173090604:T:C	L142P	1.000
5:173108704:T:A	W435R	1.000
5:173108704:T:C	W435R	1.000
5:173108706:G:C	W435C	1.000
5:173108706:G:T	W435C	1.000
5:173110573:C:A	P490Q	1.000
5:173110579:C:A	P492H	1.000
5:173110588:T:A	L495H	1.000
5:173110588:T:C	L495P	1.000
5:173110609:T:A	L502H	1.000
5:173110609:T:C	L502P	1.000
5:173110618:T:C	L505P	1.000
5:173110630:T:A	I509N	1.000
5:173110639:T:C	L512P	1.000
5:173110657:T:C	L518P	1.000
5:173110684:G:C	R527T	1.000
5:173110684:G:T	R527M	1.000
5:173110685:G:C	R527S	1.000
5:173110685:G:T	R527S	1.000
5:173110686:A:G	K528E	1.000
5:173110688:G:C	K528N	1.000
5:173110688:G:T	K528N	1.000
5:173110692:A:G	K530E	1.000
5:173110693:A:T	K530I	1.000
5:173110694:A:C	K530N	1.000
5:173110694:A:T	K530N	1.000
5:173110695:A:G	N531D	1.000
5:173110697:T:A	N531K	1.000
5:173110697:T:G	N531K	1.000

dbSNP variants (sampled 300 via entrez): RS1000146760 (5:173130369 T>C,G), RS1000168626 (5:173097755 T>C), RS1000169934 (5:173101844 C>T), RS1000174262 (5:173115670 C>T), RS1000286214 (5:173089336 T>C), RS1000341386 (5:173075019 A>G), RS1000387882 (5:173082549 G>T), RS1000417595 (5:173134722 TACTGTATGA>T), RS1000505354 (5:173096199 A>G), RS1000510943 (5:173070186 A>G), RS1000557054 (5:173096333 T>C), RS1000643454 (5:173123994 T>C), RS1000670150 (5:173084317 A>G,T), RS1000691908 (5:173075445 G>A), RS1000700867 (5:173057871 A>G)

Disease associations

OMIM: gene MIM:617109 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inherited obesity	Limited	Autosomal dominant

Mondo (1): inherited obesity (MONDO:0019182)

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST000562_7	PR interval	9.000000e-13
GCST004146_28	Chronic lymphocytic leukemia	5.000000e-08
GCST005181_1	Body mass index	5.000000e-14
GCST010321_139	PR interval	5.000000e-55
GCST90000025_505	Appendicular lean mass	7.000000e-10

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004340	body mass index
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291607 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	8
sodium arsenite	decreases expression, increases expression	3
Tobacco Smoke Pollution	increases expression	3
bisphenol A	affects cotreatment, increases expression	2
didecyldimethylammonium	increases expression	2
entinostat	decreases expression, affects cotreatment	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation	2
GSK-J4	increases expression	1
afuresertib	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	increases abundance, increases expression	1
2-butenal	increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
dodecyldimethylamine oxide	increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
nickel chloride	increases expression	1
potassium chromate(VI)	affects cotreatment, increases expression	1
ferrous chloride	increases expression	1
diallyl trisulfide	increases expression	1
epigallocatechin gallate	affects cotreatment, increases expression	1
avobenzone	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
pentabromodiphenyl ether	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5226237	Binding	Binding affinity to LRF (unknown origin) assessed as fold change	Discovery of OICR12694: A Novel, Potent, Selective, and Orally Bioavailable BCL6 BTB Inhibitor. — ACS Med Chem Lett

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05093634	PHASE3	ACTIVE_NOT_RECRUITING	EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
NCT07220772	PHASE3	RECRUITING	A Study Evaluating Mibavademab Treatment of Obesity Due to Leptin (LEP) Gene Mutations in Children, Adolescents and Adults
NCT03013543	PHASE2	COMPLETED	Setmelanotide Phase 2 Treatment Trial in Participants With Rare Genetic Disorders of Obesity
NCT04963231	PHASE2	COMPLETED	DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
NCT04710056	Not specified	AVAILABLE	Expanded Access to REGN4461 for Patients With Diseases Associated With Deficient Leptin Signaling
NCT05362565	Not specified	UNKNOWN	Genetic Research of Monogenic Obesity in a Pediatric Cohort With Severe and Early Onset Obesity
NCT06113523	Not specified	UNKNOWN	Genetic Research of Monogenic Obesity in a Pediatric Cohort With Severe and Early Onset Obesity (GENOBE)
NCT06380426	Not specified	RECRUITING	Real-life Evaluation of WEGOVY (Semaglutide) Treatment in Adults With Monogenic Obesity (ObGeSema)
NCT07296900	Not specified	RECRUITING	International Genetic Obesity Registry
NCT07302802	Not specified	RECRUITING	Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice