ISLR

Summary

ISLR (immunoglobulin superfamily containing leucine rich repeat, HGNC:6133) is a protein-coding gene on chromosome 15q24.1, encoding Immunoglobulin superfamily containing leucine-rich repeat protein (O14498).

Predicted to be involved in cell adhesion. Located in extracellular exosome.

Source: NCBI Gene 3671 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 85 total
• MANE Select transcript: NM_005545

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6133
Approved symbol	ISLR
Name	immunoglobulin superfamily containing leucine rich repeat
Location	15q24.1
Locus type	gene with protein product
Status	Approved
Aliases	HsT17563
Ensembl gene	ENSG00000129009
Ensembl biotype	protein_coding
OMIM	602059
Entrez	3671

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000249842, ENST00000395118, ENST00000559510, ENST00000560862, ENST00000879093, ENST00000948783

RefSeq mRNA: 2 — MANE Select: NM_005545 NM_005545, NM_201526

CCDS: CCDS10260

Canonical transcript exons

ENST00000249842 — 2 exons

Exon	Start	End
ENSE00001045487	74173710	74174019
ENSE00003844422	74174851	74176871

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 98.69.

FANTOM5 (CAGE): breadth broad, TPM avg 41.0834 / max 1551.3238, expressed in 819 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
147660	17.5652	680
147654	10.4067	633
147655	6.6739	593
147656	4.2301	499
147657	0.9465	281
147664	0.3957	188
147661	0.3766	158
147663	0.2371	131
147662	0.1455	90
147658	0.0716	38

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	98.69	gold quality
body of uterus	UBERON:0009853	98.42	gold quality
endocervix	UBERON:0000458	98.38	gold quality
stromal cell of endometrium	CL:0002255	98.30	gold quality
myometrium	UBERON:0001296	97.95	gold quality
right coronary artery	UBERON:0001625	97.90	gold quality
left ovary	UBERON:0002119	97.82	gold quality
right ovary	UBERON:0002118	97.68	gold quality
ovary	UBERON:0000992	97.50	gold quality
left uterine tube	UBERON:0001303	96.90	gold quality
gall bladder	UBERON:0002110	96.86	gold quality
popliteal artery	UBERON:0002250	96.66	gold quality
tibial artery	UBERON:0007610	96.66	gold quality
ectocervix	UBERON:0012249	96.38	gold quality
descending thoracic aorta	UBERON:0002345	96.26	gold quality
vagina	UBERON:0000996	96.11	gold quality
ascending aorta	UBERON:0001496	96.08	gold quality
thoracic aorta	UBERON:0001515	96.02	gold quality
left coronary artery	UBERON:0001626	95.79	gold quality
uterine cervix	UBERON:0000002	95.77	gold quality
nerve	UBERON:0001021	95.28	gold quality
tibial nerve	UBERON:0001323	95.28	gold quality
fallopian tube	UBERON:0003889	94.74	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.53	gold quality
smooth muscle tissue	UBERON:0001135	94.43	gold quality
mammary gland	UBERON:0001911	94.19	gold quality
thoracic mammary gland	UBERON:0005200	94.19	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.93	gold quality
uterus	UBERON:0000995	93.90	gold quality
adipose tissue	UBERON:0001013	93.81	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-GEOD-84465	yes	961.84
E-ANND-5	yes	617.73
E-MTAB-10287	yes	602.68
E-ANND-3	yes	34.22
E-MTAB-6678	yes	29.52
E-GEOD-124858	no	180.98

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

58 targeting ISLR, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767

Literature-anchored findings (GeneRIF, showing 6)

• Meflin is expressed by pancreatic stellate cells that are a source of cancer-associated fibroblasts in pancreatic ductal adenocarcinoma. Delivery of a Meflin-expressing lentivirus into the tumor stroma or overexpression of Meflin in CAFs suppressed the growth of xenograft tumors. Meflin deficiency or low expression resulted in straightened stromal collagen fibers, a signature for aggressive tumors, in human PDAC tissues. (PMID:31439548)
• Secreted stromal protein ISLR promotes intestinal regeneration by suppressing epithelial Hippo signaling. (PMID:32128839)
• The Balance of Stromal BMP Signaling Mediated by GREM1 and ISLR Drives Colorectal Carcinogenesis. (PMID:33197448)
• Silencing of ISLR inhibits tumour progression and glycolysis by inactivating the IL6/JAK/STAT3 pathway in nonsmall cell lung cancer. (PMID:34713300)
• Meflin is a marker of pancreatic stellate cells involved in fibrosis and epithelial regeneration in the pancreas. (PMID:37796386)
• Immunoglobulin Superfamily Containing Leucine-Rich Repeat (ISLR) Serves as a Redox Sensor That Modulates Antioxidant Capacity by Suppressing Pyruvate Kinase Isozyme M2 Activity. (PMID:38786060)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	islr2	ENSDARG00000051875
mus_musculus	Islr	ENSMUSG00000037206
rattus_norvegicus	Islr	ENSRNOG00000048924

Paralogs (3): LRRN4 (ENSG00000125872), ISLR2 (ENSG00000167178), LRRN4CL (ENSG00000177363)

Protein

Protein identifiers

Immunoglobulin superfamily containing leucine-rich repeat protein — O14498 (reviewed: O14498)

All UniProt accessions (4): O14498, A0A146E5L3, H0YL90, H0YN67

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Secreted.

Tissue specificity. Expressed in various tissues including retina, heart, skeletal muscle, prostate, ovary, small intestine, thyroid, adrenal cortex, testis, stomach and spinal cord.

RefSeq proteins (2): NP_005536, NP_958934 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000483	Cys-rich_flank_reg_C	Domain
IPR001611	Leu-rich_rpt	Repeat
IPR003591	Leu-rich_rpt_typical-subtyp	Repeat
IPR003598	Ig_sub2	Domain
IPR007110	Ig-like_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR032675	LRR_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF13855

UniProt features (14 total): repeat 5, domain 3, glycosylation site 2, signal peptide 1, chain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14498-F1	80.88	0.63

Functional residue map

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

Disulfide bonds (1): 257–327

Glycosylation sites (2): 51, 309

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 143 (showing top): GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_E_UP, CEBALLOS_TARGETS_OF_TP53_AND_MYC_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, LUI_THYROID_CANCER_CLUSTER_5, GUO_HEX_TARGETS_UP, LINDVALL_IMMORTALIZED_BY_TERT_DN, CUI_TCF21_TARGETS_2_UP, MODULE_47, GOCC_PLATELET_ALPHA_GRANULE, GOCC_SECRETORY_VESICLE

GO Biological Process (1): cell adhesion (GO:0007155)

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

GO Cellular Component (3): extracellular region (GO:0005576), platelet alpha granule lumen (GO:0031093), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular process	1
binding	1
cellular anatomical structure	1
platelet alpha granule	1
secretory granule lumen	1
extracellular vesicle	1

Protein interactions and networks

STRING

1483 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ISLR	PCDH7	O60245	564
ISLR	MYO16	Q9Y6X6	512
ISLR	COL1A1	P02452	506
ISLR	COL3A1	P02461	503
ISLR	EGFR	P00533	489
ISLR	TUBB8	Q3ZCM7	473
ISLR	ITGA11	Q9UKX5	464
ISLR	COL1A2	P02464	463
ISLR	MFAP4	P55083	447
ISLR	EFEMP1	Q12805	408
ISLR	PI15	O43692	398
ISLR	ADAMTS16	Q8TE57	398
ISLR	TIE1	P35590	394
ISLR	GPC2	Q8N158	393
ISLR	SMOC2	Q9H3U7	393

IntAct

11 interactions, top by confidence:

A	B	Type	Score
ZNF562	ISLR	psi-mi:“MI:0914”(association)	0.530
ISLR	BCKDK	psi-mi:“MI:0914”(association)	0.530
ISLR	rep	psi-mi:“MI:0915”(physical association)	0.370
ISLR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
ISLR		psi-mi:“MI:0914”(association)	0.350
CHST9	ISLR	psi-mi:“MI:0914”(association)	0.350
ISLR	B4GALT5	psi-mi:“MI:0914”(association)	0.350
LTBR	ISLR	psi-mi:“MI:0914”(association)	0.350
S1PR1	ISLR	psi-mi:“MI:0914”(association)	0.350

BioGRID (209): TUBA4A (Affinity Capture-MS), TUBA1A (Affinity Capture-MS), TUBB4A (Affinity Capture-MS), TUBB3 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), SLC25A4 (Affinity Capture-MS), SLC25A6 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), MDN1 (Affinity Capture-MS), CACNA2D1 (Affinity Capture-MS), PGAP1 (Affinity Capture-MS), SGPL1 (Affinity Capture-MS), LPCAT4 (Affinity Capture-MS), CDC6 (Affinity Capture-MS), GALNS (Affinity Capture-MS)

ESM2 similar proteins: A0A140LHF2, A6H8M9, A7LCJ3, A8E0Y8, D3YX43, D3YZF7, O14498, O15197, O70394, O70540, P01877, P0C0K6, P0C788, P0DP72, P35590, P40223, P43121, P50895, P70289, Q00657, Q06418, Q06805, Q15109, Q28173, Q5BK54, Q5NVQ6, Q5TJE4, Q61790, Q61826, Q62151, Q62230, Q63495, Q64612, Q6UVK1, Q6UWB1, Q7Z442, Q86VR7, Q8IZF5, Q8R2Y2, Q8VHY0

Diamond homologs: A2AJ76, A4IFA6, A6NJW4, A8WHP9, O14498, P14770, P59034, P59035, Q13641, Q15109, Q28173, Q4R8Y9, Q5NVQ6, Q5RKR3, Q62151, Q63495, Q6GU68, Q6UXK2, Q6WRH9, Q96RW7, A3KNN3, A4IIW9, A6H789, A6H793, C3YZ59, E5DHB5, G5EFX6, O02678, O35367, O42235, O46542, O60938, O62702, O75093, O75094, O88186, O88279, O88280, O94813, P02750

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

194 predictions. Top by Δscore:

Variant	Effect	Δscore
15:74174849:A:AG	acceptor_gain	1.0000
15:74174850:G:GG	acceptor_gain	1.0000
15:74174850:GGA:G	acceptor_gain	1.0000
15:74173770:G:GT	donor_gain	0.9900
15:74174846:TGCA:T	acceptor_loss	0.9900
15:74174847:GCA:G	acceptor_loss	0.9900
15:74174848:CA:C	acceptor_loss	0.9900
15:74174849:AGG:A	acceptor_loss	0.9900
15:74174849:AGGAG:A	acceptor_gain	0.9900
15:74174850:GGAGG:G	acceptor_gain	0.9900
15:74174849:AG:A	acceptor_gain	0.9800
15:74174850:GG:G	acceptor_gain	0.9800
15:74173950:GGC:G	donor_gain	0.9700
15:74173830:C:T	donor_gain	0.9500
15:74174848:CAGGA:C	acceptor_gain	0.9500
15:74173763:G:GT	donor_gain	0.9400
15:74174848:CAGG:C	acceptor_gain	0.9400
15:74174849:AGGA:A	acceptor_gain	0.9400
15:74174850:GGAG:G	acceptor_gain	0.9400
15:74173823:TTCC:T	donor_gain	0.9200
15:74173848:G:T	donor_gain	0.9200
15:74174015:TGAAG:T	donor_loss	0.9200
15:74174016:GAAGG:G	donor_loss	0.9200
15:74174017:AAGGT:A	donor_loss	0.9200
15:74174018:AGGT:A	donor_loss	0.9200
15:74174019:GGT:G	donor_loss	0.9200
15:74174020:G:GA	donor_loss	0.9200
15:74174021:T:A	donor_loss	0.9200
15:74174846:T:TA	acceptor_gain	0.9200
15:74173847:G:GT	donor_gain	0.8900

AlphaMissense

2767 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:74175182:T:A	N108K	0.997
15:74175182:T:G	N108K	0.997
15:74175665:G:C	W269C	0.997
15:74175665:G:T	W269C	0.997
15:74175831:T:G	Y325D	0.996
15:74175098:G:C	W80C	0.995
15:74175098:G:T	W80C	0.995
15:74175109:A:T	N84I	0.995
15:74175181:A:T	N108I	0.995
15:74175229:T:A	L124H	0.995
15:74175238:T:C	L127P	0.995
15:74175310:T:C	L151P	0.995
15:74175382:T:C	L175P	0.995
15:74175793:T:C	L312P	0.995
15:74175837:T:A	C327S	0.995
15:74175838:G:C	C327S	0.995
15:74175175:G:T	S106I	0.994
15:74175180:A:T	N108Y	0.994
15:74175825:G:T	G323C	0.994
15:74175022:T:C	L55P	0.993
15:74175110:T:A	N84K	0.993
15:74175110:T:G	N84K	0.993
15:74175166:T:C	L103P	0.993
15:74175238:T:A	L127H	0.993
15:74175398:C:A	N180K	0.993
15:74175398:C:G	N180K	0.993
15:74175627:T:A	C257S	0.993
15:74175628:G:A	C257Y	0.993
15:74175628:G:C	C257S	0.993
15:74175629:T:G	C257W	0.993

dbSNP variants (sampled 300 via entrez): RS1000021784 (15:74176746 T>A), RS1000204094 (15:74174149 C>T), RS1000802828 (15:74172837 C>T), RS1001737312 (15:74175506 C>G), RS1001743704 (15:74177021 G>A), RS1001977650 (15:74174065 G>A), RS1002123685 (15:74172738 G>A,T), RS1002259522 (15:74172479 A>C), RS1002475747 (15:74174301 C>G), RS1004056846 (15:74172960 G>A), RS1004183609 (15:74172132 C>T), RS1004200952 (15:74173431 T>G), RS1004802230 (15:74173803 C>A,T), RS1004919806 (15:74173568 C>T), RS1005600988 (15:74173305 C>A)

Disease associations

OMIM: gene MIM:602059 | 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
GCST012227_513	Hip circumference adjusted for BMI	2.000000e-09
GCST012335_11	Hodgkin’s lymphoma	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	affects expression, affects methylation, increases abundance, increases expression	2
GSK-J4	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
Air Pollutants	affects expression, affects methylation, increases abundance	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Carmustine	decreases expression	1
Demecolcine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lead	increases expression	1
T-2 Toxin	decreases expression	1
Triclosan	increases expression	1
Vincristine	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Isotretinoin	increases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cyclosporine	decreases methylation	1

Clinical trials (associated diseases)

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