SEL1L3

Summary

SEL1L3 (SEL1L family member 3, HGNC:29108) is a protein-coding gene on chromosome 4p15.2, encoding Protein sel-1 homolog 3 (Q68CR1).

Predicted to be located in membrane.

Source: NCBI Gene 23231 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 205 total
• MANE Select transcript: NM_015187

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29108
Approved symbol	SEL1L3
Name	SEL1L family member 3
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0746
Ensembl gene	ENSG00000091490
Ensembl biotype	protein_coding
OMIM	619914
Entrez	23231

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 20 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000264868, ENST00000399878, ENST00000502949, ENST00000507618, ENST00000509290, ENST00000510448, ENST00000510880, ENST00000512286, ENST00000513364, ENST00000513416, ENST00000513691, ENST00000514321, ENST00000514872, ENST00000889110, ENST00000889111, ENST00000889112, ENST00000929301, ENST00000929302, ENST00000929303, ENST00000929304, ENST00000929305, ENST00000960870, ENST00000960871, ENST00000960872

RefSeq mRNA: 3 — MANE Select: NM_015187 NM_001297592, NM_001297594, NM_015187

CCDS: CCDS47037, CCDS75113, CCDS77907

Canonical transcript exons

ENST00000399878 — 24 exons

Exon	Start	End
ENSE00000583125	25818138	25818278
ENSE00000583128	25832995	25833110
ENSE00000708680	25819808	25819940
ENSE00000708681	25821996	25822128
ENSE00000708683	25830098	25830156
ENSE00000969430	25782242	25782418
ENSE00001034832	25788224	25788364
ENSE00001034834	25767525	25767609
ENSE00001034836	25802283	25802462
ENSE00001034840	25779076	25779203
ENSE00001034842	25804541	25804752
ENSE00001034850	25776277	25776360
ENSE00001034855	25765326	25765435
ENSE00001034858	25758941	25759068
ENSE00001034864	25784228	25784290
ENSE00001074018	25790455	25790574
ENSE00002033154	25747433	25748564
ENSE00002058700	25862675	25862988
ENSE00003465231	25757688	25757790
ENSE00003509117	25767740	25767830
ENSE00003602421	25847294	25847864
ENSE00003614012	25835197	25835323
ENSE00003648137	25757534	25757606
ENSE00003667740	25833448	25833569

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 98.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.6818 / max 231.5812, expressed in 1602 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
51692	5.5017	1386
51691	5.3664	1305
51693	0.5109	292
51694	0.2758	127
51695	0.0270	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pylorus	UBERON:0001166	98.83	gold quality
ventricular zone	UBERON:0003053	98.73	gold quality
epithelium of nasopharynx	UBERON:0001951	98.46	gold quality
nasopharynx	UBERON:0001728	98.44	gold quality
ganglionic eminence	UBERON:0004023	97.95	gold quality
jejunal mucosa	UBERON:0000399	97.69	gold quality
duodenum	UBERON:0002114	97.57	gold quality
mucosa of sigmoid colon	UBERON:0004993	97.47	gold quality
bronchial epithelial cell	CL:0002328	97.36	gold quality
lymph node	UBERON:0000029	97.28	gold quality
colonic mucosa	UBERON:0000317	97.22	gold quality
germinal epithelium of ovary	UBERON:0001304	97.19	gold quality
cardia of stomach	UBERON:0001162	97.16	gold quality
epithelium of bronchus	UBERON:0002031	97.12	gold quality
bronchus	UBERON:0002185	97.09	gold quality
palpebral conjunctiva	UBERON:0001812	96.84	gold quality
rectum	UBERON:0001052	96.68	gold quality
cerebellar hemisphere	UBERON:0002245	96.51	gold quality
corpus epididymis	UBERON:0004359	96.50	gold quality
gall bladder	UBERON:0002110	96.48	gold quality
spleen	UBERON:0002106	96.41	gold quality
cerebellar cortex	UBERON:0002129	96.41	gold quality
visceral pleura	UBERON:0002401	96.41	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.18	gold quality
cerebellum	UBERON:0002037	96.01	gold quality
vermiform appendix	UBERON:0001154	96.00	gold quality
cortical plate	UBERON:0005343	95.88	gold quality
pleura	UBERON:0000977	95.81	gold quality
parietal pleura	UBERON:0002400	95.63	gold quality
caecum	UBERON:0001153	95.60	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	382.77
E-MTAB-9467	yes	54.06
E-CURD-122	yes	48.36
E-HCAD-1	yes	37.68
E-ANND-3	yes	32.65
E-MTAB-5061	yes	25.98
E-MTAB-8142	yes	19.36
E-MTAB-9221	yes	18.42
E-CURD-112	yes	15.08
E-MTAB-8498	yes	12.32
E-MTAB-10553	yes	10.12
E-MTAB-9801	yes	7.98
E-HCAD-10	yes	7.71
E-ENAD-27	yes	6.50
E-MTAB-6678	yes	5.34

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

70 targeting SEL1L3, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-7110-3P	100.00	73.18	2486
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-548AW	99.99	72.57	3559
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-15A-5P	99.90	72.80	2787

Literature-anchored findings (GeneRIF, showing 2)

• Tissue Proteogenomic Landscape Reveals the Role of Uncharacterized SEL1L3 in Progression and Immunotherapy Response in Lung Adenocarcinoma. (PMID:36349894)
• SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification. (PMID:37993256)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Sel1l3	ENSMUSG00000029189
rattus_norvegicus	Sel1l3	ENSRNOG00000004932
caenorhabditis_elegans		WBGENE00004759

Paralogs (4): SEL1L (ENSG00000071537), DELE1 (ENSG00000081791), SEL1L2 (ENSG00000101251), LRP2BP (ENSG00000109771)

Protein

Protein identifiers

Protein sel-1 homolog 3 — Q68CR1 (reviewed: Q68CR1)

Alternative names: Suppressor of lin-12-like protein 3

All UniProt accessions (7): Q68CR1, D6RCE1, D6RDH1, D6RF11, H0Y8P8, H0Y9M6, H0YA36

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Isoforms (3)

UniProt ID	Names	Canonical?
Q68CR1-1	1	yes
Q68CR1-2	2
Q68CR1-3	3

RefSeq proteins (3): NP_001284521, NP_001284523, NP_056002* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006597	Sel1-like	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR013320	ConA-like_dom_sf	Homologous_superfamily
IPR042756	Sel-1L3	Family

Pfam: PF08238

UniProt features (28 total): repeat 8, sequence variant 5, glycosylation site 4, region of interest 2, compositionally biased region 2, splice variant 2, sequence conflict 2, chain 1, transmembrane region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q68CR1-F1	81.99	0.53

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): 608

Glycosylation sites (4): 201, 382, 527, 937

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 258 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_DN, MULLIGHAN_NPM1_SIGNATURE_3_UP, MCLACHLAN_DENTAL_CARIES_UP, LU_IL4_SIGNALING, YANG_BREAST_CANCER_ESR1_LASER_DN, TAL1ALPHAE47_01, TRAYNOR_RETT_SYNDROM_DN, ONKEN_UVEAL_MELANOMA_UP, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, FREAC3_01, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM2, RHEIN_ALL_GLUCOCORTICOID_THERAPY_UP, TGANTCA_AP1_C, SCHLOSSER_SERUM_RESPONSE_DN

GO Biological Process (0):

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

GO Cellular Component (1): membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SEL1L3	FHAD1	B1AJZ9	490
SEL1L3	ZNF407	Q9C0G0	460
SEL1L3	SUSD4	Q5VX71	457
SEL1L3	CCDC13	Q8IYE1	453
SEL1L3	KRABD3	A5PL33	440
SEL1L3	KRTAP13-4	Q3LI77	419
SEL1L3	SLC37A1	P57057	415
SEL1L3	BCAS3	Q9H6U6	415
SEL1L3	SPRYD7	Q5W111	411
SEL1L3	ZNF385C	Q66K41	411
SEL1L3	IGSF22	Q8N9C0	401
SEL1L3	WDR33	Q9C0J8	382
SEL1L3	BMS1	Q14692	373
SEL1L3	IWS1	Q96ST2	371
SEL1L3	DIPK1A	Q5T7M9	370

IntAct

72 interactions, top by confidence:

A	B	Type	Score
EMC7	EMC8	psi-mi:“MI:0914”(association)	0.790
SCGB1D1	MANBA	psi-mi:“MI:0914”(association)	0.640
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LAMP3	METTL15	psi-mi:“MI:0914”(association)	0.530
CLGN	NPC1	psi-mi:“MI:0914”(association)	0.530
ERF	TBL1X	psi-mi:“MI:0914”(association)	0.530
FBXL19	MED19	psi-mi:“MI:0914”(association)	0.530
NPDC1	TCAF2	psi-mi:“MI:0914”(association)	0.530
C1orf54	EXTL3	psi-mi:“MI:0914”(association)	0.530
GPIHBP1	ADAM10	psi-mi:“MI:0914”(association)	0.530
PLTP	SEL1L3	psi-mi:“MI:0914”(association)	0.530
SYVN1	PSMA7	psi-mi:“MI:0914”(association)	0.350
KLK15	SPINT1	psi-mi:“MI:0914”(association)	0.350
LLCFC1	POTEF	psi-mi:“MI:0914”(association)	0.350
ST14	LIPT2	psi-mi:“MI:0914”(association)	0.350
RLN1	RTL8C	psi-mi:“MI:0914”(association)	0.350
GPIHBP1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
PLTP	CLGN	psi-mi:“MI:0914”(association)	0.350
DEFB109B	CHST10	psi-mi:“MI:0914”(association)	0.350
DIPK1A	SGPL1	psi-mi:“MI:0914”(association)	0.350
TM2D3	SEMG1	psi-mi:“MI:0914”(association)	0.350
SEL1L3	CANX	psi-mi:“MI:0914”(association)	0.350
GPR182	SLC12A8	psi-mi:“MI:0914”(association)	0.350
TMEM106A	TMEM131L	psi-mi:“MI:0914”(association)	0.350
HLA-G	TMEM131L	psi-mi:“MI:0914”(association)	0.350
BTNL2	TMEM131L	psi-mi:“MI:0914”(association)	0.350

BioGRID (64): SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), FAM63A (Affinity Capture-MS), SEL1L3 (Affinity Capture-RNA), SEL1L3 (Affinity Capture-RNA), SEL1L3 (Two-hybrid), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), NPLOC4 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS), SEL1L3 (Affinity Capture-MS)

ESM2 similar proteins: A0JPE1, A4D0V7, D3Z2R5, O43916, P97259, Q08834, Q09328, Q1RLQ5, Q3TUA9, Q4V8A9, Q58CX7, Q5F349, Q5FVL3, Q5HZP7, Q5NDE4, Q5NDE5, Q5NDE7, Q5NDE8, Q5R634, Q5R9Q9, Q5RJQ0, Q5T7M9, Q5U3W1, Q5VUD6, Q640M6, Q68CR1, Q6DBY9, Q6DCL6, Q6Q2W4, Q80TS8, Q8C1F4, Q8C3I9, Q8N6G5, Q8NBP0, Q8NHY0, Q8R4G6, Q8R553, Q8WTR4, Q92179, Q95JJ0

Diamond homologs: Q68CR1, Q80TS8, O59732

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 100 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.

GO biological processes:

GO term	Partners	Fold	FDR
ERAD pathway	7	13.9×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	144
Likely benign	14
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

4561 predictions. Top by Δscore:

Variant	Effect	Δscore
4:25757603:AGATC:A	acceptor_loss	1.0000
4:25757605:ATCTG:A	acceptor_loss	1.0000
4:25757606:TCTG:T	acceptor_loss	1.0000
4:25757607:C:CC	acceptor_gain	1.0000
4:25757607:CTGCA:C	acceptor_loss	1.0000
4:25757608:T:G	acceptor_loss	1.0000
4:25765320:GTTTA:G	donor_loss	1.0000
4:25765321:TTTAC:T	donor_loss	1.0000
4:25765322:TTAC:T	donor_loss	1.0000
4:25765323:TA:T	donor_loss	1.0000
4:25765325:CC:C	donor_loss	1.0000
4:25765431:ATATG:A	acceptor_gain	1.0000
4:25765432:TATG:T	acceptor_gain	1.0000
4:25765433:ATG:A	acceptor_gain	1.0000
4:25765434:TG:T	acceptor_gain	1.0000
4:25765436:C:CC	acceptor_gain	1.0000
4:25765436:C:CG	acceptor_loss	1.0000
4:25767738:A:AC	donor_gain	1.0000
4:25767738:ACTGG:A	donor_gain	1.0000
4:25767739:C:CC	donor_gain	1.0000
4:25767739:CTGGC:C	donor_gain	1.0000
4:25779074:A:AC	donor_gain	1.0000
4:25779075:C:CC	donor_gain	1.0000
4:25779075:CA:C	donor_gain	1.0000
4:25779075:CACAA:C	donor_gain	1.0000
4:25782237:CTCA:C	donor_gain	1.0000
4:25782238:T:TC	donor_loss	1.0000
4:25782239:CACTT:C	donor_loss	1.0000
4:25782240:A:AC	donor_gain	1.0000
4:25782240:A:AT	donor_loss	1.0000

AlphaMissense

7411 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:25759055:A:G	L990P	0.999
4:25779152:C:A	G837W	0.999
4:25765420:C:T	G954E	0.998
4:25765421:C:G	G954R	0.998
4:25765421:C:T	G954R	0.998
4:25782291:C:T	G803E	0.998
4:25782390:C:T	G770E	0.998
4:25790481:C:G	A684P	0.998
4:25759068:C:G	G986R	0.997
4:25759068:C:T	G986R	0.997
4:25765345:G:T	A979D	0.997
4:25765346:C:G	A979P	0.997
4:25765349:C:G	A978P	0.997
4:25776344:C:G	A868P	0.997
4:25779152:C:G	G837R	0.997
4:25779152:C:T	G837R	0.997
4:25782292:C:G	G803R	0.997
4:25782292:C:T	G803R	0.997
4:25782306:G:T	A798E	0.997
4:25782331:C:G	A790P	0.997
4:25782340:A:G	W787R	0.997
4:25782340:A:T	W787R	0.997
4:25782391:C:G	G770R	0.997
4:25782391:C:T	G770R	0.997
4:25757787:G:C	C1029W	0.996
4:25758950:A:G	L1025P	0.996
4:25765420:C:A	G954V	0.996
4:25779173:C:G	A830P	0.996
4:25779176:C:G	A829P	0.996
4:25782294:A:G	L802P	0.996

dbSNP variants (sampled 300 via entrez): RS1000017682 (4:25809058 G>A), RS1000018967 (4:25739936 A>G,T), RS1000041555 (4:25819374 C>T), RS1000042003 (4:25720315 TG>T), RS10000609 (4:25814426 A>G,T), RS10000681 (4:25752335 T>A,C,G), RS1000112843 (4:25842305 A>G), RS1000130256 (4:25841452 C>T), RS1000131634 (4:25758656 TTTTTCTTTC>T), RS1000136497 (4:25720538 TATA>T), RS1000175619 (4:25824472 A>G), RS1000176023 (4:25802550 T>C), RS1000194531 (4:25842786 C>T), RS1000207787 (4:25742250 A>C), RS1000248194 (4:25818798 C>G,T)

Disease associations

OMIM: gene MIM:619914 | 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
GCST007829_3	Systolic blood pressure	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006944	systolic blood pressure change measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	9
Cyclosporine	increases expression	4
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Tretinoin	increases expression, decreases expression	3
bisphenol A	increases expression	2
entinostat	increases expression, affects cotreatment	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Cisplatin	affects cotreatment, increases expression	2
Copper	affects binding, increases expression	2
Doxorubicin	decreases expression, increases expression	2
Nickel	increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Thiram	increases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Aflatoxin B1	affects expression, decreases methylation	2
Cadmium Chloride	increases expression	2
aristolochic acid I	decreases expression	1
testosterone enanthate	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
captax	increases expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
lead acetate	increases expression	1
cinnamaldehyde	increases expression	1
arsenite	affects binding, decreases reaction	1
1,6-hexamethylene diisocyanate	increases expression	1
sulforaphane	increases expression	1
ammonium hexachloroplatinate	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
potassium chromate(VI)	decreases expression	1

Clinical trials (associated diseases)

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