RELL1

Summary

RELL1 (RELT like 1, HGNC:27379) is a protein-coding gene on chromosome 4p14, encoding RELT-like protein 1 (Q8IUW5). Induces activation of MAPK14/p38 cascade, when overexpressed.

Involved in positive regulation of p38MAPK cascade. Located in microtubule cytoskeleton and plasma membrane.

Source: NCBI Gene 768211 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 46 total
• MANE Select transcript: NM_001085400

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27379
Approved symbol	RELL1
Name	RELT like 1
Location	4p14
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000181826
Ensembl biotype	protein_coding
OMIM	611212
Entrez	768211

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000314117, ENST00000454158, ENST00000512114, ENST00000858689, ENST00000858690, ENST00000942718, ENST00000942719

RefSeq mRNA: 2 — MANE Select: NM_001085400 NM_001085399, NM_001085400

CCDS: CCDS43221

Canonical transcript exons

ENST00000454158 — 7 exons

Exon	Start	End
ENSE00001252285	37638447	37638504
ENSE00001252296	37647368	37647439
ENSE00001252304	37649276	37649500
ENSE00001252313	37631385	37631523
ENSE00001329148	37686200	37686376
ENSE00001755381	37610634	37613342
ENSE00003788903	37634887	37635123

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 98.63.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.7952 / max 847.8642, expressed in 1752 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51784	17.7952	1752

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.63	gold quality
visceral pleura	UBERON:0002401	98.23	gold quality
skin of hip	UBERON:0001554	98.16	gold quality
ileal mucosa	UBERON:0000331	98.14	gold quality
upper arm skin	UBERON:0004263	98.11	gold quality
parietal pleura	UBERON:0002400	98.09	gold quality
endothelial cell	CL:0000115	97.91	gold quality
layer of synovial tissue	UBERON:0007616	97.41	gold quality
synovial joint	UBERON:0002217	97.37	gold quality
gingival epithelium	UBERON:0001949	97.18	gold quality
superficial temporal artery	UBERON:0001614	97.08	gold quality
pericardium	UBERON:0002407	97.04	gold quality
upper leg skin	UBERON:0004262	96.94	gold quality
palpebral conjunctiva	UBERON:0001812	96.86	gold quality
epithelial cell of pancreas	CL:0000083	96.75	gold quality
eye	UBERON:0000970	96.75	gold quality
vena cava	UBERON:0004087	96.68	gold quality
gingiva	UBERON:0001828	96.66	gold quality
epithelium of mammary gland	UBERON:0003244	96.59	gold quality
mammary duct	UBERON:0001765	96.56	gold quality
pigmented layer of retina	UBERON:0001782	96.45	gold quality
retina	UBERON:0000966	96.43	gold quality
esophagus squamous epithelium	UBERON:0006920	96.04	gold quality
tibia	UBERON:0000979	96.02	gold quality
colonic mucosa	UBERON:0000317	95.93	gold quality
mucosa of sigmoid colon	UBERON:0004993	95.83	gold quality
penis	UBERON:0000989	95.50	gold quality
saphenous vein	UBERON:0007318	95.47	gold quality
epithelium of nasopharynx	UBERON:0001951	95.44	gold quality
trigeminal ganglion	UBERON:0001675	95.41	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9543	yes	7.96
E-MTAB-5061	yes	6.50
E-MTAB-7249	no	422.78
E-MTAB-6911	no	364.44
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

173 targeting RELL1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408

Literature-anchored findings (GeneRIF, showing 3)

• Binds to the TNF receptor family member RELT; homologue of RELT. (PMID:16389068)
• report that overexpression of RELT or its homologues RELL1 and RELL2 in HEK 293 epithelial cells results in cell death with morphological characteristics consistent with the activation of an apoptotic pathway. (PMID:19969290)
• RELL1, a novel oncogene, accelerates tumor progression and regulates immune infiltrates in glioma. (PMID:32683297)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rell1	ENSDARG00000018312
mus_musculus	Rell1	ENSMUSG00000047881
rattus_norvegicus	Rell1	ENSRNOG00000002192

Protein

Protein identifiers

RELT-like protein 1 — Q8IUW5 (reviewed: Q8IUW5)

All UniProt accessions (2): Q8IUW5, D6RBN9

UniProt curated annotations — full annotation on UniProt →

Function. Induces activation of MAPK14/p38 cascade, when overexpressed. Induces apoptosis, when overexpressed.

Subunit / interactions. Interacts with RELT, RELL2 and OXSR1. Interacts with PLSCR1.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed. Expressed at highest levels in the placenta, skeletal muscle, spleen and testis.

Post-translational modifications. Phosphorylated in vitro by OXSR1.

Similarity. Belongs to the RELT family.

RefSeq proteins (2): NP_001078868, NP_001078869* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022248	TNF_rcpt_RELT	Family
IPR042315	RELL1	Family

Pfam: PF12606

UniProt features (19 total): modified residue 4, compositionally biased region 3, region of interest 3, glycosylation site 2, topological domain 2, signal peptide 1, chain 1, sequence conflict 1, transmembrane region 1, coiled-coil region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8IUW5-F1	60.86	0.09

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): 109, 114, 244, 247

Glycosylation sites (2): 31, 49

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 189 (showing top): GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOLDRATH_ANTIGEN_RESPONSE, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOBP_POSITIVE_REGULATION_OF_P38MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, ZHAN_MULTIPLE_MYELOMA_LB_UP, ZHANG_BREAST_CANCER_PROGENITORS_UP, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_DN, LINDGREN_BLADDER_CANCER_CLUSTER_1_DN, MATSUDA_NATURAL_KILLER_DIFFERENTIATION, JOHNSTONE_PARVB_TARGETS_1_DN, GOBP_P38MAPK_CASCADE, FORTSCHEGGER_PHF8_TARGETS_UP, RAO_BOUND_BY_SALL4_ISOFORM_A

GO Biological Process (1): positive regulation of p38MAPK cascade (GO:1900745)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
p38MAPK cascade	1
positive regulation of MAPK cascade	1
regulation of p38MAPK cascade	1
binding	1
membrane	1
cell periphery	1
cytoskeleton	1
cellular anatomical structure	1

Protein interactions and networks

STRING

442 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RELL1	OXSR1	O95747	847
RELL1	RELT	Q969Z4	540
RELL1	TRAF1	Q13077	475
RELL1	TMEM253	P0C7T8	434
RELL1	PLSCR1	O15162	400
RELL1	H0YIS7	H0YIS7	393
RELL1	ADGRG5	Q8IZF4	380
RELL1	CDH19	Q9H159	361
RELL1	NOXRED1	Q6NXP6	348
RELL1	DYTN	A2CJ06	348
RELL1	ZNF567	Q8N184	348
RELL1	MAN1A2	O60476	345
RELL1	SYCE1L	A8MT33	324
RELL1	SS18L2	Q9UHA2	324
RELL1	CIMIP2A	Q6J272	323

IntAct

43 interactions, top by confidence:

A	B	Type	Score
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
TRDN	TMEM223	psi-mi:“MI:0914”(association)	0.640
RELL1	TREX1	psi-mi:“MI:0915”(physical association)	0.560
RELL1	TCAF2	psi-mi:“MI:0914”(association)	0.530
ICMT	STXBP3	psi-mi:“MI:0914”(association)	0.530
NRAS	ESYT2	psi-mi:“MI:2364”(proximity)	0.480
RABL3	GPR89A	psi-mi:“MI:0914”(association)	0.350
CTNNA3	ARVCF	psi-mi:“MI:0914”(association)	0.350
TH	MAP3K7	psi-mi:“MI:0914”(association)	0.350
	SHTN1	psi-mi:“MI:0914”(association)	0.350
	TMEM223	psi-mi:“MI:0914”(association)	0.350
CHIA	SLC25A16	psi-mi:“MI:0914”(association)	0.350
LY86	MAP2K7	psi-mi:“MI:0914”(association)	0.350
PCDHGA5	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
VSIG4	TMEM223	psi-mi:“MI:0914”(association)	0.350
ZDHHC11	NRP1	psi-mi:“MI:0914”(association)	0.350
SLC30A10	GOLIM4	psi-mi:“MI:0914”(association)	0.350
SLC30A8	UPK3BL1	psi-mi:“MI:0914”(association)	0.350
SLC39A12	ESYT2	psi-mi:“MI:0914”(association)	0.350
SLC41A1	FADS2	psi-mi:“MI:0914”(association)	0.350
SLC7A9	CDC7	psi-mi:“MI:0914”(association)	0.350
SLC9A5	NBAS	psi-mi:“MI:0914”(association)	0.350
TMEM17	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
TMEM216	GPR89A	psi-mi:“MI:2364”(proximity)	0.270
BET1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	TRAPPC13	psi-mi:“MI:2364”(proximity)	0.270
LAMP1	PIPSL	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (103): RELL1 (Proximity Label-MS), RELL1 (Proximity Label-MS), RELL1 (Proximity Label-MS), RELL1 (Proximity Label-MS), OXSR1 (Affinity Capture-MS), STK39 (Affinity Capture-MS), RELL1 (Affinity Capture-MS), SNX18 (Affinity Capture-MS), FAM115C (Affinity Capture-MS), RELL1 (Affinity Capture-MS), RELL1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), MGAT1 (Affinity Capture-MS), KDSR (Affinity Capture-MS), CERS2 (Affinity Capture-MS)

ESM2 similar proteins: A0JPB5, A2A699, A5PLA0, A6QPA0, A8MVW0, B0BN44, B4DS77, D3ZZP4, O35451, P04921, P28906, Q06186, Q08DP3, Q08EA8, Q13113, Q1LVN1, Q28270, Q5F3A4, Q5FVQ7, Q5HZE8, Q5R5B8, Q60846, Q640B5, Q64314, Q7TNI2, Q810F0, Q86VZ4, Q8C4Q9, Q8CB67, Q8IUW5, Q8K064, Q8K201, Q8K2J7, Q8NC54, Q8NEA5, Q8R138, Q8TBP5, Q8WWG9, Q96L08, Q99941

Diamond homologs: Q08DP3, Q2KI80, Q5F3A4, Q5FVJ4, Q8BRJ3, Q8BX43, Q8IUW5, Q8K2J7, Q8NC24, Q969Z4, Q9N092, O95407, Q9HAV5, Q9NS68, Q9JLL3, Q8BX35

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1983 predictions. Top by Δscore:

Variant	Effect	Δscore
4:37613216:C:A	donor_gain	1.0000
4:37634881:TCTTA:T	donor_loss	1.0000
4:37634882:CTTA:C	donor_loss	1.0000
4:37634883:TTAC:T	donor_loss	1.0000
4:37634884:TA:T	donor_loss	1.0000
4:37635129:G:C	acceptor_gain	1.0000
4:37638501:TTCG:T	acceptor_gain	1.0000
4:37638502:TCG:T	acceptor_gain	1.0000
4:37638503:CG:C	acceptor_gain	1.0000
4:37638503:CGC:C	acceptor_gain	1.0000
4:37638505:C:CC	acceptor_gain	1.0000
4:37647435:CAATT:C	acceptor_gain	1.0000
4:37647438:TT:T	acceptor_gain	1.0000
4:37647438:TTCTG:T	acceptor_loss	1.0000
4:37647439:TCTGA:T	acceptor_loss	1.0000
4:37647440:C:CC	acceptor_gain	1.0000
4:37647440:CTGAA:C	acceptor_loss	1.0000
4:37647441:T:A	acceptor_loss	1.0000
4:37649273:TACCT:T	donor_loss	1.0000
4:37649274:A:T	donor_loss	1.0000
4:37649275:CCTAT:C	donor_gain	1.0000
4:37649278:AT:A	donor_gain	1.0000
4:37649279:T:C	donor_gain	1.0000
4:37649496:ATTGT:A	acceptor_gain	1.0000
4:37649497:TTGT:T	acceptor_gain	1.0000
4:37649498:TGT:T	acceptor_gain	1.0000
4:37649499:GT:G	acceptor_gain	1.0000
4:37649500:TCTA:T	acceptor_loss	1.0000
4:37649501:C:CC	acceptor_gain	1.0000
4:37649501:C:T	acceptor_loss	1.0000

AlphaMissense

1776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:37631520:A:C	F228L	1.000
4:37631520:A:T	F228L	1.000
4:37631521:A:G	F228S	1.000
4:37631522:A:G	F228L	1.000
4:37631515:A:T	V230D	0.999
4:37631521:A:C	F228C	0.999
4:37634893:A:T	V225D	0.999
4:37634984:A:G	C195R	0.999
4:37634993:A:G	C192R	0.999
4:37638489:A:G	L134S	0.999
4:37647382:A:T	I124N	0.999
4:37647391:A:T	V121D	0.999
4:37649368:C:T	G74D	0.999
4:37649378:C:G	G71R	0.999
4:37631522:A:C	F228V	0.998
4:37634890:C:A	G226V	0.998
4:37634890:C:T	G226D	0.998
4:37634891:C:G	G226R	0.998
4:37634899:A:G	L223P	0.998
4:37634902:A:T	V222D	0.998
4:37634983:C:G	C195S	0.998
4:37634984:A:T	C195S	0.998
4:37634991:A:C	C192W	0.998
4:37634992:C:G	C192S	0.998
4:37634992:C:T	C192Y	0.998
4:37634993:A:T	C192S	0.998
4:37647382:A:C	I124S	0.998
4:37647382:A:G	I124T	0.998
4:37647394:A:C	I120S	0.998
4:37647403:A:T	V117D	0.998

dbSNP variants (sampled 300 via entrez): RS1000029752 (4:37611878 G>A), RS1000063612 (4:37613450 A>G), RS1000066209 (4:37623114 T>C), RS1000073935 (4:37663880 C>T), RS1000090217 (4:37656077 T>C), RS1000118240 (4:37623465 C>A,T), RS1000200057 (4:37684064 A>G), RS1000209586 (4:37647617 T>C), RS1000223269 (4:37638304 C>A,G,T), RS1000254207 (4:37680392 C>T), RS1000266336 (4:37678614 G>A), RS1000280783 (4:37586621 T>C), RS1000298466 (4:37635497 C>A,T), RS1000306297 (4:37684531 C>A), RS10003342 (4:37656164 T>C)

Disease associations

OMIM: gene MIM:611212 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003181_4	Staphylococcus aureus nasal carriage (intermittent)	3.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007758	intermittent Staphylococcus aureus carrier status

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	6
trichostatin A	affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, decreases methylation, increases expression	2
sodium arsenite	affects expression, increases expression	2
Benzo(a)pyrene	increases methylation, increases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
cobaltous chloride	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
incobotulinumtoxinA	decreases expression	1
Fulvestrant	decreases methylation, affects cotreatment	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Formaldehyde	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Asbestos, Crocidolite	decreases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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