RELL2

Summary

RELL2 (RELT like 2, HGNC:26902) is a protein-coding gene on chromosome 5q31.3, encoding RELT-like protein 2 (Q8NC24). Induces activation of MAPK14/p38 cascade, when overexpressed.

Predicted to enable collagen binding activity. Involved in positive regulation of p38MAPK cascade. Predicted to be located in basement membrane and plasma membrane.

Source: NCBI Gene 285613 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 8 total
• MANE Select transcript: NM_173828

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26902
Approved symbol	RELL2
Name	RELT like 2
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ90583
Ensembl gene	ENSG00000164620
Ensembl biotype	protein_coding
OMIM	611213
Entrez	285613

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 5 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000297164, ENST00000444782, ENST00000517794, ENST00000518025, ENST00000518856, ENST00000520674, ENST00000521367, ENST00000896721

RefSeq mRNA: 2 — MANE Select: NM_173828 NM_001130029, NM_173828

CCDS: CCDS4265

Canonical transcript exons

ENST00000297164 — 7 exons

Exon	Start	End
ENSE00001160506	141636997	141638409
ENSE00002104435	141640671	141641064
ENSE00003460119	141638955	141639021
ENSE00003514338	141640412	141640445
ENSE00003544561	141638795	141638860
ENSE00003676392	141639920	141640295
ENSE00003681668	141639464	141639649

Expression profiles

Bgee: expression breadth ubiquitous, 183 present calls, max score 92.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.8266 / max 162.4997, expressed in 1643 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
59050	5.3571	1563
59051	2.3565	859
59049	0.1129	40

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right frontal lobe	UBERON:0002810	92.00	gold quality
lateral nuclear group of thalamus	UBERON:0002736	91.69	gold quality
prefrontal cortex	UBERON:0000451	90.35	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.27	gold quality
Brodmann (1909) area 9	UBERON:0013540	89.67	gold quality
anterior cingulate cortex	UBERON:0009835	88.46	gold quality
cerebellar cortex	UBERON:0002129	88.43	gold quality
cerebellar hemisphere	UBERON:0002245	88.43	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	88.17	gold quality
frontal cortex	UBERON:0001870	88.15	gold quality
hypothalamus	UBERON:0001898	88.12	gold quality
neocortex	UBERON:0001950	87.39	gold quality
cerebellum	UBERON:0002037	87.22	gold quality
adenohypophysis	UBERON:0002196	86.64	gold quality
pituitary gland	UBERON:0000007	86.47	gold quality
granulocyte	CL:0000094	85.68	gold quality
nucleus accumbens	UBERON:0001882	85.59	gold quality
cerebral cortex	UBERON:0000956	84.72	gold quality
primary visual cortex	UBERON:0002436	84.65	gold quality
substantia nigra	UBERON:0002038	84.32	gold quality
putamen	UBERON:0001874	84.01	gold quality
forebrain	UBERON:0001890	83.92	gold quality
brain	UBERON:0000955	83.85	gold quality
caudate nucleus	UBERON:0001873	83.74	gold quality
midbrain	UBERON:0001891	82.70	gold quality
pons	UBERON:0000988	82.06	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.79	silver quality
occipital lobe	UBERON:0002021	81.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.36	gold quality
cortical plate	UBERON:0005343	80.99	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	423.53
E-ANND-3	no	1.20

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting RELL2, 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-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1909-3P	99.03	66.56	1662
HSA-MIR-423-5P	98.69	67.48	1522
HSA-MIR-3184-5P	98.56	67.13	1491
HSA-MIR-581	98.39	67.42	835
HSA-MIR-6511B-5P	97.98	65.64	823
HSA-MIR-6811-5P	97.98	64.96	848
HSA-MIR-10526-3P	97.86	64.97	1342
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-1250-5P	94.32	64.74	78
HSA-MIR-6789-5P	94.05	66.19	285

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)
• Comprehensive Analysis of RELL2 as a Potential Biomarker Associated with Tumor Immune Infiltrating Cells in a Pan-Cancer Analysis. (PMID:35634441)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rell2	ENSDARG00000071876
mus_musculus	Rell2	ENSMUSG00000044024
rattus_norvegicus	Rell2	ENSRNOG00000019575

Protein

Protein identifiers

RELT-like protein 2 — Q8NC24 (reviewed: Q8NC24)

All UniProt accessions (3): E5RFS6, E5RHA7, Q8NC24

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, RELL1 and OXSR1. Interacts with PLSCR1. Interacts with TRAF2.

Subcellular location. Cell membrane.

Tissue specificity. Primarily expressed in spleen, thymus, testis, peripheral blood leukocytes, brain and placenta. Not detected in prostate, ovary, small intestine, colon, heart, lung, liver, skeletal muscle, kidney and pancreas.

Post-translational modifications. Phosphorylated in vitro by OXSR1.

Similarity. Belongs to the RELT family.

RefSeq proteins (2): NP_001123501, NP_776189* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022248	TNF_rcpt_RELT	Family
IPR042313	RELL2	Family

Pfam: PF12606

UniProt features (13 total): sequence variant 4, compositionally biased region 4, region of interest 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NC24-F1	60.01	0.08

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 (1): 52

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 79 (showing top): RNGTGGGC_UNKNOWN, AP1_01, AAGCAAT_MIR137, SP3_Q3, AREB6_03, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, TGACCTY_ERR1_Q2, GOBP_POSITIVE_REGULATION_OF_CELL_ADHESION, AP1_Q4_01, BACH2_01, GOBP_POSITIVE_REGULATION_OF_P38MAPK_CASCADE, TGANTCA_AP1_C, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_REGULATION_OF_CELL_SUBSTRATE_ADHESION, GATA2_01

GO Biological Process (2): positive regulation of cell-substrate adhesion (GO:0010811), positive regulation of p38MAPK cascade (GO:1900745)

GO Molecular Function (2): collagen binding (GO:0005518), protein binding (GO:0005515)

GO Cellular Component (4): basement membrane (GO:0005604), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular matrix (GO:0031012)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cell-substrate adhesion	1
cell-substrate adhesion	1
positive regulation of cell adhesion	1
p38MAPK cascade	1
positive regulation of MAPK cascade	1
regulation of p38MAPK cascade	1
protein-containing complex binding	1
binding	1
extracellular matrix	1
membrane	1
cell periphery	1
cellular anatomical structure	1
external encapsulating structure	1

Protein interactions and networks

STRING

248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RELL2	OXSR1	O95747	856
RELL2	CCDC15	Q0P6D6	528
RELL2	TRAF1	Q13077	506
RELL2	FCHSD1	Q86WN1	447
RELL2	M1AP	Q8TC57	392
RELL2	XKR6	Q5GH73	370
RELL2	ZDHHC16	Q969W1	365
RELL2	RELT	Q969Z4	362
RELL2	CCHCR1	Q8TD31	351
RELL2	PCDHGA6	Q9Y5G7	314
RELL2	AKAP11	Q9UKA4	311
RELL2	STK39	Q9UEW8	301
RELL2	RELL1	Q8IUW5	298
RELL2	PCDHGB6	Q9Y5F9	284
RELL2	SRSF4	Q08170	250
RELL2	SPZ1	Q9BXG8	250

IntAct

69 interactions, top by confidence:

A	B	Type	Score
OXSR1	RELL2	psi-mi:“MI:0915”(physical association)	0.830
RELL2	OXSR1	psi-mi:“MI:0915”(physical association)	0.830
RELL2	OXSR1	psi-mi:“MI:0914”(association)	0.830
ZNF32	RELL2	psi-mi:“MI:0915”(physical association)	0.590
PLP1	RELL2	psi-mi:“MI:0915”(physical association)	0.560
ANKRD46	RELL2	psi-mi:“MI:0915”(physical association)	0.560
SLC35A1	RELL2	psi-mi:“MI:0915”(physical association)	0.560
SEC22B	RELL2	psi-mi:“MI:0915”(physical association)	0.560
SLC30A8	RELL2	psi-mi:“MI:0915”(physical association)	0.560
COL4A5	RELL2	psi-mi:“MI:0915”(physical association)	0.560
ASPH	RELL2	psi-mi:“MI:0915”(physical association)	0.560
TSPO2	RELL2	psi-mi:“MI:0915”(physical association)	0.560
NSG1	RELL2	psi-mi:“MI:0915”(physical association)	0.560
RELL2	LPAR3	psi-mi:“MI:0915”(physical association)	0.560
RTP2	RELL2	psi-mi:“MI:0915”(physical association)	0.560
TSPAN33	RELL2	psi-mi:“MI:0915”(physical association)	0.560
RELL2	CLDND2	psi-mi:“MI:0915”(physical association)	0.560
CDIPT	RELL2	psi-mi:“MI:0915”(physical association)	0.560
ZFPL1	RELL2	psi-mi:“MI:0915”(physical association)	0.560
MIP	RELL2	psi-mi:“MI:0915”(physical association)	0.560
TFRC	RELL2	psi-mi:“MI:0915”(physical association)	0.560
RELL2	FAM3C	psi-mi:“MI:0915”(physical association)	0.560
SMIM1	RELL2	psi-mi:“MI:0915”(physical association)	0.560
RELL2	ATP9A	psi-mi:“MI:0914”(association)	0.350

BioGRID (68): RELL2 (Two-hybrid), TRIM9 (Affinity Capture-MS), OXSR1 (Affinity Capture-MS), LRR1 (Affinity Capture-MS), STK39 (Affinity Capture-MS), RELT (Affinity Capture-MS), AGBL5 (Affinity Capture-MS), MCM10 (Affinity Capture-MS), MGST2 (Affinity Capture-MS), HSPA14 (Affinity Capture-MS), DNAH14 (Affinity Capture-MS), SLC9A6 (Affinity Capture-MS), HADHB (Affinity Capture-MS), KIF2C (Affinity Capture-MS), C6orf120 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GW64, A0A5F4BST2, A0PJX4, A8MVS5, A8MWV9, B0FP48, E5RIL1, E9PGG2, O14836, O60320, O95998, P09564, Q01113, Q01114, Q13477, Q2KI80, Q2T9R2, Q3TS39, Q3UPR0, Q3URD2, Q4V9L6, Q5FVJ4, Q5M869, Q6A044, Q6UWJ8, Q75VT8, Q864V4, Q8BRJ3, Q8BX43, Q8C503, Q8IVY1, Q8K5A9, Q8N112, Q8NC24, Q8NDY8, Q8QZT4, Q8R138, Q969Z4, Q9BUF7, Q9CQM1

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

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of small molecules	5	9.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1314 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141638776:A:AG	acceptor_gain	1.0000
5:141638786:A:AG	acceptor_gain	1.0000
5:141638787:T:G	acceptor_gain	1.0000
5:141638793:A:AG	acceptor_gain	1.0000
5:141638794:G:GA	acceptor_gain	1.0000
5:141638794:GCT:G	acceptor_gain	1.0000
5:141638857:GAAG:G	donor_gain	1.0000
5:141638861:G:C	donor_loss	1.0000
5:141638861:G:GG	donor_gain	1.0000
5:141638953:A:AG	acceptor_gain	1.0000
5:141638954:G:GA	acceptor_gain	1.0000
5:141638954:GC:G	acceptor_gain	1.0000
5:141638954:GCC:G	acceptor_gain	1.0000
5:141638954:GCCA:G	acceptor_gain	1.0000
5:141638954:GCCAA:G	acceptor_gain	1.0000
5:141639017:TCCAG:T	donor_loss	1.0000
5:141639018:CCAG:C	donor_loss	1.0000
5:141639019:CAGGT:C	donor_loss	1.0000
5:141639020:AGGTG:A	donor_loss	1.0000
5:141639022:GTGAG:G	donor_loss	1.0000
5:141639023:T:A	donor_loss	1.0000
5:141639623:G:T	donor_gain	1.0000
5:141638405:GCCCC:G	donor_gain	0.9900
5:141638410:G:GG	donor_gain	0.9900
5:141638414:G:GG	donor_gain	0.9900
5:141638777:A:G	acceptor_gain	0.9900
5:141638790:TTCA:T	acceptor_loss	0.9900
5:141638791:TCAG:T	acceptor_loss	0.9900
5:141638792:CAG:C	acceptor_loss	0.9900
5:141638793:A:C	acceptor_loss	0.9900

AlphaMissense

1978 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141638846:T:A	I79N	1.000
5:141638846:T:C	I79T	1.000
5:141638846:T:G	I79S	1.000
5:141639921:T:C	F169L	1.000
5:141639922:T:C	F169S	1.000
5:141639922:T:G	F169C	1.000
5:141639923:C:A	F169L	1.000
5:141639923:C:G	F169L	1.000
5:141638298:T:C	F25L	0.999
5:141638300:C:A	F25L	0.999
5:141638300:C:G	F25L	0.999
5:141638310:G:C	G29R	0.999
5:141638319:G:C	G32R	0.999
5:141638320:G:A	G32D	0.999
5:141638331:T:C	C36R	0.999
5:141638332:G:A	C36Y	0.999
5:141638341:T:A	L39H	0.999
5:141638834:T:C	I75T	0.999
5:141638834:T:G	I75S	0.999
5:141638837:T:A	V76D	0.999
5:141638855:A:T	N82I	0.999
5:141638959:T:A	N85K	0.999
5:141638959:T:G	N85K	0.999
5:141638970:T:C	L89S	0.999
5:141638979:T:C	M92T	0.999
5:141639637:T:C	F164S	0.999
5:141639646:G:T	G167V	0.999
5:141639649:G:T	R168M	0.999
5:141639921:T:A	F169I	0.999
5:141639921:T:G	F169V	0.999

dbSNP variants (sampled 300 via entrez): RS1000405355 (5:141635653 TCAACTCAGG>T), RS1000738666 (5:141635114 G>A,C,T), RS1001189800 (5:141635758 C>T), RS1001569293 (5:141636124 C>T), RS1001725897 (5:141640771 G>A), RS1002461059 (5:141639398 C>A,T), RS1003058177 (5:141637411 C>T), RS1003125029 (5:141638426 G>A), RS1003727280 (5:141637685 T>G), RS1003949336 (5:141640457 T>C,G), RS1004085355 (5:141640764 A>C,G), RS1004905288 (5:141637331 C>A,T), RS1005119858 (5:141636209 A>G), RS1005501041 (5:141635703 C>G), RS1006540758 (5:141637344 G>A)

Disease associations

OMIM: gene MIM:611213 | 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
GCST010002_39	Refractive error	2.000000e-14

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases abundance, increases expression	2
tris(2-butoxyethyl) phosphate	affects expression	1
beta-lapachone	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1
Valproic Acid	increases expression	1
Cadmium Chloride	increases expression	1
Okadaic Acid	increases expression	1
Acrylamide	decreases expression	1

Clinical trials (associated diseases)

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