IGFBPL1

Summary

IGFBPL1 (insulin like growth factor binding protein like 1, HGNC:20081) is a protein-coding gene on chromosome 9p13.1, encoding Insulin-like growth factor-binding protein-like 1 (Q8WX77). IGF-binding proteins prolong the half-life of IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs in cell culture.

Predicted to enable insulin-like growth factor binding activity. Involved in cellular response to tumor cell. Located in extracellular space.

Source: NCBI Gene 347252 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 79 total
• MANE Select transcript: NM_001007563

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20081
Approved symbol	IGFBPL1
Name	insulin like growth factor binding protein like 1
Location	9p13.1
Locus type	gene with protein product
Status	Approved
Aliases	bA113O24.1
Ensembl gene	ENSG00000137142
Ensembl biotype	protein_coding
OMIM	610413
Entrez	347252

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000377694, ENST00000906221

RefSeq mRNA: 1 — MANE Select: NM_001007563 NM_001007563

CCDS: CCDS35017

Canonical transcript exons

ENST00000377694 — 5 exons

Exon	Start	End
ENSE00000982410	38414094	38414203
ENSE00000982411	38413237	38413353
ENSE00000982412	38411391	38411549
ENSE00001428226	38406528	38409217
ENSE00001474871	38423965	38424454

Expression profiles

Bgee: expression breadth ubiquitous, 140 present calls, max score 99.48.

FANTOM5 (CAGE): breadth broad, TPM avg 6.7630 / max 379.1402, expressed in 560 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
100774	5.1948	482
100772	1.1727	272
100766	0.2979	135
100773	0.0976	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.48	gold quality
cortical plate	UBERON:0005343	97.38	gold quality
ventricular zone	UBERON:0003053	90.15	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.13	gold quality
ascending aorta	UBERON:0001496	77.63	gold quality
thoracic aorta	UBERON:0001515	77.50	gold quality
islet of Langerhans	UBERON:0000006	77.17	gold quality
aorta	UBERON:0000947	76.37	gold quality
popliteal artery	UBERON:0002250	75.65	gold quality
tibial artery	UBERON:0007610	75.63	gold quality
thyroid gland	UBERON:0002046	74.81	gold quality
right coronary artery	UBERON:0001625	74.23	gold quality
left lobe of thyroid gland	UBERON:0001120	74.21	gold quality
secondary oocyte	CL:0000655	74.14	gold quality
descending thoracic aorta	UBERON:0002345	73.40	gold quality
nucleus accumbens	UBERON:0001882	72.34	gold quality
caudate nucleus	UBERON:0001873	71.81	gold quality
putamen	UBERON:0001874	71.53	gold quality
oocyte	CL:0000023	71.33	gold quality
right lobe of thyroid gland	UBERON:0001119	71.00	gold quality
cerebellar hemisphere	UBERON:0002245	69.18	gold quality
cerebellar cortex	UBERON:0002129	69.11	gold quality
cerebellum	UBERON:0002037	68.04	gold quality
right hemisphere of cerebellum	UBERON:0014890	67.95	gold quality
left coronary artery	UBERON:0001626	66.73	gold quality
decidua	UBERON:0002450	66.73	gold quality
prefrontal cortex	UBERON:0000451	66.65	gold quality
pituitary gland	UBERON:0000007	66.39	gold quality
coronary artery	UBERON:0001621	65.89	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-GEOD-75140	yes	11880.57
E-MTAB-9154	yes	2496.59
E-GEOD-93593	yes	1261.28
E-HCAD-5	yes	824.17
E-ENAD-27	yes	670.44
E-GEOD-81608	yes	542.60
E-MTAB-5061	yes	26.11
E-ANND-3	yes	5.44
E-MTAB-7008	no	964.25

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

88 targeting IGFBPL1, 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-4692	100.00	67.32	2066
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-4302	99.89	67.94	1187
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-548AC	99.84	70.77	4351

Literature-anchored findings (GeneRIF, showing 8)

• IGFBP-RP4 may be a novel putative tumor suppressor protein. (PMID:15845387)
• Expression of IGFBPL1 is regulated by aberrant hypermethylation in breast cancer, implying that inactivation of these genes is involved in the pathogenesis of this malignancy. (PMID:17634530)
• These results suggest that insulin-like growth factor-binding protein-related protein 1 may play a role in decidualization of human endometrial stromal cells. (PMID:17884839)
• Expression of IGFBPL1 correlates with RGC axon growth, and acute knockdown of IGFBPL1 with shRNA or IGFBPL1 knockout in vivo impaired RGC axon growth. IGFBPL1 binds IGF-1, induces calcium signaling mTOR phosphorylation. (PMID:29391597)
• Epigenetic silencing of IGFBPL1 promotes esophageal cancer growth by activating PI3K-AKT signaling. (PMID:32041673)
• Neural precursor cells tune striatal connectivity through the release of IGFBPL1. (PMID:36482070)
• IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy. (PMID:37527036)
• IGFBPL1 inhibits macrophage lipid accumulation by enhancing the activation of IGR1R/LXRalpha/ABCG1 pathway. (PMID:38157252)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Igfbpl1	ENSMUSG00000035551
rattus_norvegicus	Igfbpl1	ENSRNOG00000011320

Paralogs (2): KAZALD1 (ENSG00000107821), IGFBP7 (ENSG00000163453)

Protein

Protein identifiers

Insulin-like growth factor-binding protein-like 1 — Q8WX77 (reviewed: Q8WX77)

Alternative names: IGFBP-related protein 10, Insulin-like growth factor-binding-related protein 4

All UniProt accessions (1): Q8WX77

UniProt curated annotations — full annotation on UniProt →

Function. IGF-binding proteins prolong the half-life of IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs in cell culture. They alter the interaction of IGFs with their cell surface receptors. May be a putative tumor suppressor protein.

Subcellular location. Secreted.

Tissue specificity. Expressed at the highest level in both brain and testis, with lower levels in the prostate, bladder and lung.

Induction. Down-regulated in multiple tumors.

RefSeq proteins (1): NP_001007564* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000867	IGFBP-like	Domain
IPR002350	Kazal_dom	Domain
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011390	IGFBP_rP_mac25	Family
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036058	Kazal_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily

Pfam: PF00219, PF07648, PF07679

UniProt features (14 total): disulfide bond 8, domain 3, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
7MJ7	X-RAY DIFFRACTION	1.6
7MJ9	X-RAY DIFFRACTION	1.75
7MJ8	X-RAY DIFFRACTION	1.79
7MJ6	X-RAY DIFFRACTION	1.95

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WX77-F1	84.87	0.62

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 (8): 77–91, 85–106, 115–151, 176–243, 38–63, 41–65, 46–66, 52–69

Glycosylation sites (1): 166

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 77 (showing top): GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_GROWTH, MARTORIATI_MDM4_TARGETS_NEUROEPITHELIUM_DN, KINSEY_TARGETS_OF_EWSR1_FLII_FUSION_DN, chr9p13, GOMF_SIGNALING_RECEPTOR_BINDING, GRYDER_PAX3FOXO1_ENHANCERS_IN_TADS, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_CELL_GROWTH, GOBP_REGULATION_OF_GROWTH, GRYDER_PAX3FOXO1_TOP_ENHANCERS, GOMF_INSULIN_LIKE_GROWTH_FACTOR_BINDING, GOMF_SIGNALING_RECEPTOR_REGULATOR_ACTIVITY, MEISSNER_BRAIN_HCP_WITH_H3K27ME3, MEISSNER_NPC_HCP_WITH_H3K4ME2_AND_H3K27ME3

GO Biological Process (3): regulation of cell growth (GO:0001558), regulation of signal transduction (GO:0009966), cellular response to tumor cell (GO:0071228)

GO Molecular Function (2): insulin-like growth factor binding (GO:0005520), protein binding (GO:0005515)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), extracellular region (GO:0005576)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell growth	1
regulation of growth	1
regulation of cellular component organization	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
response to tumor cell	1
cellular response to biotic stimulus	1
growth factor binding	1
binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IGFBPL1	IGF1	P01343	513
IGFBPL1	MIPOL1	Q8TD10	442
IGFBPL1	DRAXIN	Q8NBI3	375
IGFBPL1	CIB4	A0PJX0	356
IGFBPL1	FREM3	P0C091	352
IGFBPL1	FREM1	Q5H8C1	352
IGFBPL1	MTRR	Q9UBK8	349
IGFBPL1	IGFL3	Q6UXB1	346
IGFBPL1	GCNT1	Q02742	330
IGFBPL1	IGFBP5	P24593	320
IGFBPL1	IGFL1	Q6UW32	320
IGFBPL1	GLTPD2	A6NH11	290
IGFBPL1	RFK	Q969G6	284
IGFBPL1	PROKR2	Q8NFJ6	281
IGFBPL1	PROKR1	Q8TCW9	281
IGFBPL1	MCF2	P10911	281

IntAct

11 interactions, top by confidence:

A	B	Type	Score
DCC	IGFBPL1	psi-mi:“MI:0915”(physical association)	0.540
IGFBPL1	DCC	psi-mi:“MI:0915”(physical association)	0.540
DCC	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.540
IGFBPL1	IGDCC3	psi-mi:“MI:0407”(direct interaction)	0.440
IGFBPL1	IGDCC4	psi-mi:“MI:0407”(direct interaction)	0.440
IL6R	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.440
ISLR2	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.440
NEO1	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.440
PRTG	IGFBPL1	psi-mi:“MI:0407”(direct interaction)	0.440
IGFBPL1	SNX2	psi-mi:“MI:0914”(association)	0.350

BioGRID (6): SNX6 (Affinity Capture-MS), SNX5 (Affinity Capture-MS), SNX2 (Affinity Capture-MS), SNX1 (Affinity Capture-MS), IGFBPL1 (Affinity Capture-MS), IGFBPL1 (Proximity Label-MS)

ESM2 similar proteins: A2A9Q0, A5A8Y8, A5PKD8, F1SAM7, O00468, O60500, O75325, P0C7J6, P12843, P13384, P18065, P24853, P49705, P50895, P60827, P60882, Q16270, Q24JP5, Q29400, Q2WF71, Q50LG9, Q5W7P8, Q61581, Q641Q3, Q6IQX7, Q6UKI2, Q6UWL6, Q75ZP3, Q7TSU7, Q7Z7M0, Q80W15, Q8BHA1, Q8BJ66, Q8IZ52, Q8N2S1, Q8NDA2, Q8WX77, Q91ZV8, Q96I82, Q96MS0

Diamond homologs: A0JNK3, A2RNT9, A2RT60, A4IHA1, A4XSC0, A5PKD8, A5W8F5, A6VUA4, A6YFB5, A9JRB3, B0KV30, B1J4D7, B3LVG7, B3P3J9, B4G316, B4HEM8, B4JTT7, B4K835, B4LY58, B4N937, B4PST0, B4QZU6, D0ZY51, D3ZA76, D3ZKF5, E1BJW1, E1V4H2, F1N152, F6AA62, O05942, O06291, O22609, O31754, O34358, O43464, O53896, O85291, P05676, P0A3Z5, P0AEE3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1019 predictions. Top by Δscore:

Variant	Effect	Δscore
9:38411390:CATTT:C	donor_gain	1.0000
9:38411445:A:AC	donor_gain	1.0000
9:38411446:C:CC	donor_gain	1.0000
9:38411450:G:C	donor_gain	1.0000
9:38413230:CACT:C	donor_loss	1.0000
9:38413231:ACTC:A	donor_loss	1.0000
9:38413232:CTCA:C	donor_loss	1.0000
9:38413233:TCAC:T	donor_loss	1.0000
9:38413234:CA:C	donor_loss	1.0000
9:38413235:A:AC	donor_gain	1.0000
9:38413235:ACCAA:A	donor_loss	1.0000
9:38413236:C:CA	donor_loss	1.0000
9:38413236:C:CC	donor_gain	1.0000
9:38423964:CCGAA:C	donor_gain	1.0000
9:38409216:CC:C	acceptor_gain	0.9900
9:38409217:CC:C	acceptor_gain	0.9900
9:38411379:TAGA:T	donor_gain	0.9900
9:38411380:AGAA:A	donor_gain	0.9900
9:38411381:G:C	donor_gain	0.9900
9:38411446:CT:C	donor_gain	0.9900
9:38411481:AG:A	donor_gain	0.9900
9:38413229:ACACT:A	donor_loss	0.9900
9:38413351:GACCT:G	acceptor_loss	0.9900
9:38413354:CTA:C	acceptor_loss	0.9900
9:38413355:T:C	acceptor_loss	0.9900
9:38414089:AATAC:A	donor_loss	0.9900
9:38414090:ATACC:A	donor_loss	0.9900
9:38414091:TA:T	donor_loss	0.9900
9:38414092:ACC:A	donor_loss	0.9900
9:38423961:TCAC:T	donor_loss	0.9900

AlphaMissense

1758 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:38414100:C:A	W188C	0.994
9:38414100:C:G	W188C	0.994
9:38411516:A:C	Y241D	0.987
9:38414102:A:G	W188R	0.987
9:38414102:A:T	W188R	0.987
9:38411509:C:G	C243S	0.986
9:38411510:A:T	C243S	0.986
9:38411496:G:C	N247K	0.977
9:38411496:G:T	N247K	0.977
9:38414137:C:G	C176S	0.974
9:38414138:A:T	C176S	0.974
9:38424048:C:G	C126S	0.974
9:38424049:A:T	C126S	0.974
9:38411510:A:G	C243R	0.973
9:38424081:C:G	C115S	0.972
9:38424082:A:T	C115S	0.972
9:38424108:C:G	C106S	0.972
9:38424109:A:T	C106S	0.972
9:38411515:T:C	Y241C	0.971
9:38414137:C:T	C176Y	0.970
9:38424102:C:G	C108S	0.970
9:38424103:A:T	C108S	0.970
9:38411516:A:T	Y241N	0.969
9:38424153:C:G	C91S	0.967
9:38424154:A:T	C91S	0.967
9:38423973:C:G	C151S	0.966
9:38423974:A:T	C151S	0.966
9:38423973:C:T	C151Y	0.965
9:38411497:T:A	N247I	0.964
9:38411515:T:G	Y241S	0.963

dbSNP variants (sampled 300 via entrez): RS1000127974 (9:38414000 T>A,C,G), RS1000444218 (9:38425662 C>T), RS1000451218 (9:38410591 T>G), RS1000512648 (9:38406567 C>T), RS1000632551 (9:38424322 GCCGGC>G), RS1000812413 (9:38417650 C>T), RS1001053486 (9:38412057 T>C), RS1001179372 (9:38425077 C>G,T), RS1001355445 (9:38423337 T>C), RS1001360586 (9:38419506 A>G), RS1001816181 (9:38419204 T>C), RS1001875406 (9:38419723 A>C), RS1001879546 (9:38418968 T>C), RS1002010562 (9:38413450 C>A,T), RS1002167542 (9:38407478 T>G)

Disease associations

OMIM: gene MIM:610413 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
entinostat	increases expression, affects cotreatment	2
Estradiol	decreases expression	2
trichostatin A	increases expression	1
sodium arsenite	decreases expression	1
butyraldehyde	increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
2,6-dichloro-(1,4)benzoquinone	increases expression	1
Resveratrol	decreases expression, affects cotreatment	1
Sunitinib	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Ethanol	increases expression	1
Benzo(a)pyrene	increases methylation	1
Catechin	affects cotreatment, increases expression	1
Lead	affects expression	1
Methylcholanthrene	affects binding, increases reaction	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases abundance, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Tretinoin	decreases expression	1
Okadaic Acid	increases expression	1

Clinical trials (associated diseases)

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