SEL1L2

Summary

SEL1L2 (SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase, HGNC:15897) is a protein-coding gene on chromosome 20p12.1, encoding Protein sel-1 homolog 2 (Q5TEA6).

Predicted to be involved in ERAD pathway. Located in cilium and nuclear speck.

Source: NCBI Gene 80343 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 14 total — 1 pathogenic
• MANE Select transcript: NM_025229

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15897
Approved symbol	SEL1L2
Name	SEL1L2 adaptor subunit of SYVN1 ubiquitin ligase
Location	20p12.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp434C1826
Ensembl gene	ENSG00000101251
Ensembl biotype	protein_coding
OMIM	614289
Entrez	80343

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 5 protein_coding_CDS_not_defined, 4 protein_coding, 3 nonsense_mediated_decay

ENST00000284951, ENST00000378072, ENST00000423870, ENST00000473203, ENST00000475649, ENST00000476952, ENST00000477435, ENST00000482196, ENST00000486903, ENST00000492548, ENST00000495437, ENST00000646153

RefSeq mRNA: 3 — MANE Select: NM_025229 NM_001271539, NM_001363752, NM_025229

CCDS: CCDS59443, CCDS86933

Canonical transcript exons

ENST00000284951 — 20 exons

Exon	Start	End
ENSE00001932979	13990477	13990614
ENSE00003460729	13859262	13859434
ENSE00003462972	13876038	13876115
ENSE00003475355	13913782	13913944
ENSE00003489719	13866702	13866850
ENSE00003517278	13870141	13870203
ENSE00003529382	13886288	13886442
ENSE00003545620	13888459	13888512
ENSE00003546432	13869503	13869590
ENSE00003547710	13877520	13877588
ENSE00003550543	13887942	13888001
ENSE00003551744	13865167	13865241
ENSE00003563765	13956076	13956131
ENSE00003572236	13865349	13865514
ENSE00003581354	13919021	13919123
ENSE00003583289	13887769	13887850
ENSE00003600785	13885347	13885403
ENSE00003646456	13850191	13850319
ENSE00003664542	13931603	13931771
ENSE00003899974	13849247	13849604

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 86.54.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.2966 / max 40.2723, expressed in 76 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
186474	0.2381	57
186473	0.0553	16
186475	0.0033	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.54	gold quality
sperm	CL:0000019	83.53	gold quality
germinal epithelium of ovary	UBERON:0001304	78.79	gold quality
left testis	UBERON:0004533	75.57	gold quality
right testis	UBERON:0004534	75.10	gold quality
smooth muscle tissue	UBERON:0001135	74.56	gold quality
testis	UBERON:0000473	74.25	gold quality
left uterine tube	UBERON:0001303	70.65	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.46	gold quality
popliteal artery	UBERON:0002250	69.81	gold quality
tibial artery	UBERON:0007610	69.78	gold quality
body of uterus	UBERON:0009853	69.34	gold quality
right coronary artery	UBERON:0001625	66.42	gold quality
myometrium	UBERON:0001296	66.01	gold quality
aorta	UBERON:0000947	63.82	gold quality
left coronary artery	UBERON:0001626	62.33	gold quality
coronary artery	UBERON:0001621	61.45	gold quality
ectocervix	UBERON:0012249	60.52	gold quality
apex of heart	UBERON:0002098	58.91	gold quality
hindlimb stylopod muscle	UBERON:0004252	58.53	gold quality
adipose tissue	UBERON:0001013	58.28	gold quality
fallopian tube	UBERON:0003889	57.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	57.06	gold quality
endocervix	UBERON:0000458	56.75	gold quality
right ovary	UBERON:0002118	56.43	gold quality
thoracic aorta	UBERON:0001515	56.16	gold quality
ascending aorta	UBERON:0001496	56.15	gold quality
left ovary	UBERON:0002119	55.25	gold quality
ovary	UBERON:0000992	55.16	gold quality
superficial temporal artery	UBERON:0001614	55.06	silver quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.88

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sel1l2	ENSMUSG00000074764
rattus_norvegicus	Sel1l2	ENSRNOG00000004852
caenorhabditis_elegans		WBGENE00004759

Paralogs (4): SEL1L (ENSG00000071537), DELE1 (ENSG00000081791), SEL1L3 (ENSG00000091490), LRP2BP (ENSG00000109771)

Protein

Protein identifiers

Protein sel-1 homolog 2 — Q5TEA6 (reviewed: Q5TEA6)

Alternative names: Suppressor of lin-12-like protein 2

All UniProt accessions (6): Q5TEA6, A0A2R8Y3T2, A0A2R8YF92, C9JNX3, F8WE69, H7C4S6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane. Cell projection. Cilium. Nucleus speckle.

Similarity. Belongs to the sel-1 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5TEA6-1	1	yes
Q5TEA6-2	2

RefSeq proteins (3): NP_001258468, NP_001350681, NP_079505* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006597	Sel1-like	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR050767	Sel1_AlgK	Family

Pfam: PF08238

UniProt features (20 total): repeat 11, sequence variant 2, topological domain 2, signal peptide 1, chain 1, glycosylation site 1, splice variant 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5TEA6-F1	84.89	0.61

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (1): 34

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 40 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_PROTEASOMAL_PROTEIN_CATABOLIC_PROCESS, GOBP_ERAD_PATHWAY, IVANOVA_HEMATOPOIESIS_INTERMEDIATE_PROGENITOR, GOBP_PROTEIN_CATABOLIC_PROCESS, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_NUCLEAR_OUTER_MEMBRANE_ENDOPLASMIC_RETICULUM_MEMBRANE_NETWORK, GOBP_PROTEOLYSIS, GOCC_CILIUM, GOCC_ORGANELLE_SUBCOMPARTMENT, RATTENBACHER_BOUND_BY_CELF1

GO Biological Process (1): ERAD pathway (GO:0036503)

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

GO Cellular Component (6): endoplasmic reticulum membrane (GO:0005789), cilium (GO:0005929), nuclear speck (GO:0016607), nucleus (GO:0005634), membrane (GO:0016020), cell projection (GO:0042995)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
proteasomal protein catabolic process	1
response to endoplasmic reticulum stress	1
response to chemical	1
binding	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
intraciliary transport particle	1
membrane-bounded organelle	1
plasma membrane bounded cell projection	1
nuclear ribonucleoprotein granule	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

610 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEL1L2	GAGE12H	A6NDE8	540
SEL1L2	C14orf119	Q9NWQ9	518
SEL1L2	GAGE12B	A1L429	474
SEL1L2	LRP2BP	Q9P2M1	446
SEL1L2	TMEM125	Q96AQ2	408
SEL1L2	FAM168B	A1KXE4	394
SEL1L2	SYVN1	Q86TM6	364
SEL1L2	FAM168A	Q92567	362
SEL1L2	OS9	Q13438	361
SEL1L2	CDC50B	Q3MIR4	350
SEL1L2	CDC50A	Q9NV96	347
SEL1L2	IQSEC2	Q5JU85	343
SEL1L2	CYB5R4	Q7L1T6	341
SEL1L2	PHF21A	Q96BD5	339
SEL1L2	EDEM1	Q92611	316

IntAct

6 interactions, top by confidence:

A	B	Type	Score
EZR	MACROD2	psi-mi:“MI:0914”(association)	0.350
FGFR1	NDUFA4	psi-mi:“MI:0914”(association)	0.350
TYRO3	HAX1	psi-mi:“MI:0914”(association)	0.350
TOMM20	NUDT19	psi-mi:“MI:2364”(proximity)	0.270
EPHB4	ABL2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (5): SEL1L2 (Affinity Capture-MS), SEL1L2 (Proximity Label-MS), SEL1L2 (Affinity Capture-MS), SEL1L2 (Proximity Label-MS), SEL1L2 (Affinity Capture-MS)

ESM2 similar proteins: A0AVF1, A1L1K3, A4III8, A5PLI4, A6H6E9, A8JA42, E9Q6P5, P09913, Q06AN9, Q14DN9, Q2KHY7, Q2TBM9, Q32NR4, Q3U213, Q3V172, Q4R3N2, Q4R6M4, Q4R7Z9, Q4V7F0, Q569C2, Q57ZL2, Q5PR66, Q5RE52, Q5TEA6, Q5U2N8, Q5W5X9, Q5XI05, Q5ZKK3, Q60462, Q64112, Q64282, Q66GN3, Q6AYP3, Q6IND7, Q80VM3, Q80YE7, Q86TV6, Q86TZ1, Q8BGB2, Q8BS45

Diamond homologs: O13875, Q3V172, Q5TEA6, Q5XI05, Q80Z70, Q9C6B6, Q9ESM7, Q9LM25, Q9UBV2, Q9Z2G6, Q05787, Q10NT7, Q6FNV5, Q9USV0, P44277, P77296, D3ZTE0, O18733, O60449, O97507, P00748, P02751, P04937, P07589, P08169, P08253, P11276, P11717, P11722, P14780, P22897, P33434, P33436, P41245, P41246, P49259, P49260, P50282, P50757, P52176

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	3
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2426810	NC_000020.10:g.(?13765715)(14308152_?)del	Pathogenic

SpliceAI

3551 predictions. Top by Δscore:

Variant	Effect	Δscore
20:13865237:CTTTT:C	acceptor_gain	1.0000
20:13886357:A:AC	donor_gain	1.0000
20:13886358:C:CC	donor_gain	1.0000
20:13887767:A:AC	donor_gain	1.0000
20:13887768:C:CC	donor_gain	1.0000
20:13887848:CCC:C	acceptor_gain	1.0000
20:13887849:CCC:C	acceptor_gain	1.0000
20:13931595:CTACT:C	donor_loss	1.0000
20:13931596:TACTT:T	donor_loss	1.0000
20:13931597:ACTT:A	donor_loss	1.0000
20:13931598:CT:C	donor_loss	1.0000
20:13931599:TTACA:T	donor_loss	1.0000
20:13931600:TACAA:T	donor_loss	1.0000
20:13931601:A:AC	donor_gain	1.0000
20:13931601:A:C	donor_loss	1.0000
20:13931602:C:A	donor_loss	1.0000
20:13931602:C:CA	donor_gain	1.0000
20:13931602:CA:C	donor_gain	1.0000
20:13931602:CAA:C	donor_gain	1.0000
20:13931602:CAAT:C	donor_gain	1.0000
20:13931602:CAATG:C	donor_gain	1.0000
20:13956071:TTTA:T	donor_loss	1.0000
20:13956072:TTACC:T	donor_loss	1.0000
20:13956073:TACC:T	donor_loss	1.0000
20:13956075:C:A	donor_loss	1.0000
20:13956129:TAG:T	acceptor_gain	1.0000
20:13956132:C:CC	acceptor_gain	1.0000
20:13850189:A:AC	donor_gain	0.9900
20:13850190:C:CC	donor_gain	0.9900
20:13850316:TGTC:T	acceptor_gain	0.9900

AlphaMissense

4546 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:13865381:G:T	A513D	0.998
20:13869517:C:T	G414D	0.998
20:13885393:C:T	G304E	0.998
20:13865403:C:G	A506P	0.997
20:13870175:C:T	G378D	0.997
20:13876049:C:G	A365P	0.997
20:13885394:C:G	G304R	0.997
20:13885394:C:T	G304R	0.997
20:13885396:A:G	L303P	0.997
20:13886314:C:G	A292P	0.997
20:13865366:G:T	A518E	0.996
20:13865462:G:T	A486D	0.996
20:13869518:C:G	G414R	0.996
20:13869554:C:G	A402P	0.996
20:13869557:C:G	A401P	0.996
20:13870190:C:T	G373D	0.996
20:13865423:A:G	L499P	0.995
20:13870176:C:G	G378R	0.995
20:13877524:C:T	G341E	0.995
20:13885381:A:G	L308P	0.995
20:13888505:C:T	G186E	0.995
20:13859299:A:G	L594P	0.994
20:13865176:C:G	A546P	0.994
20:13865179:C:G	A545P	0.994
20:13865181:C:G	R544P	0.994
20:13869578:C:G	A394P	0.994
20:13870191:C:G	G373R	0.994
20:13876069:G:T	A358D	0.994
20:13877564:C:G	A328P	0.994
20:13877585:C:G	A321P	0.994

dbSNP variants (sampled 300 via entrez): RS1000002052 (20:13887063 G>A), RS1000029244 (20:13981069 C>T), RS1000076129 (20:13925337 G>A), RS1000076952 (20:13907484 G>A,C), RS1000088708 (20:13952691 T>G), RS1000113814 (20:13880067 A>T), RS1000130454 (20:13930194 T>C), RS1000168416 (20:13878463 T>C), RS1000169624 (20:13882781 A>C,G), RS1000170028 (20:13895267 A>C), RS1000175177 (20:13873554 G>T), RS1000195298 (20:13962136 C>T), RS1000223410 (20:13969559 G>A,C), RS1000230426 (20:13981990 T>C), RS1000232324 (20:13925577 A>G)

Disease associations

OMIM: gene MIM:614289 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009391_7	Metabolite levels	2.000000e-06
GCST012490_470	Femur bone mineral density x serum urate levels interaction	7.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007813	cotinine measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
aflatoxin B2	affects methylation	1
bisphenol S	decreases methylation	1
Fulvestrant	increases methylation	1

Clinical trials (associated diseases)

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