STAB1

Summary

STAB1 (stabilin 1, HGNC:18628) is a protein-coding gene on chromosome 3p21.1, encoding Stabilin-1 (Q9NY15). Acts as a scavenger receptor for acetylated low density lipoprotein.

This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The protein contains 7 fasciclin, 16 epidermal growth factor (EGF)-like, and 2 laminin-type EGF-like domains as well as a C-type lectin-like hyaluronan-binding Link module. The protein is primarily expressed on sinusoidal endothelial cells of liver, spleen, and lymph node. The receptor has been shown to endocytose ligands such as low density lipoprotein, Gram-positive and Gram-negative bacteria, and advanced glycosylation end products. Supporting its possible role as a scavenger receptor, the protein rapidly cycles between the plasma membrane and early endosomes.

Source: NCBI Gene 23166 — RefSeq curated summary.

At a glance

• Gene–disease (curated): isolated hyperferritinemia (Strong, GenCC)
• GWAS associations: 49
• Clinical variants (ClinVar): 565 total
• Phenotypes (HPO): 5
• MANE Select transcript: NM_015136

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18628
Approved symbol	STAB1
Name	stabilin 1
Location	3p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0246, STAB-1, FEEL-1, CLEVER-1, FELE-1, FEX1, SCARH2
Ensembl gene	ENSG00000010327
Ensembl biotype	protein_coding
OMIM	608560
Entrez	23166

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 7 retained_intron

ENST00000321725, ENST00000461325, ENST00000462681, ENST00000462741, ENST00000469989, ENST00000479355, ENST00000481607, ENST00000481626, ENST00000484850, ENST00000899926, ENST00000899927, ENST00000965141, ENST00000965142, ENST00000965143, ENST00000965144, ENST00000965145, ENST00000965146

RefSeq mRNA: 1 — MANE Select: NM_015136 NM_015136

CCDS: CCDS33768

Canonical transcript exons

ENST00000321725 — 69 exons

Exon	Start	End
ENSE00000770919	52512596	52512643
ENSE00000770921	52512828	52512958
ENSE00000770923	52513130	52513241
ENSE00000770929	52514115	52514213
ENSE00000860936	52510349	52510507
ENSE00000860937	52514365	52514496
ENSE00000860938	52514701	52514829
ENSE00000923293	52495338	52495491
ENSE00000923314	52509210	52509321
ENSE00000923315	52509870	52510056
ENSE00000923316	52510142	52510235
ENSE00000923318	52511650	52511745
ENSE00000923319	52512341	52512436
ENSE00000923323	52513717	52513794
ENSE00000923324	52513883	52513981
ENSE00000923328	52514989	52515045
ENSE00001126472	52523652	52523756
ENSE00001126522	52520804	52521005
ENSE00001126537	52520204	52520290
ENSE00001126552	52519505	52519564
ENSE00001126577	52518536	52518613
ENSE00001126583	52518312	52518359
ENSE00001126594	52517881	52518003
ENSE00001126614	52516984	52517109
ENSE00001126621	52516692	52516768
ENSE00001126631	52516356	52516451
ENSE00001242349	52523427	52523576
ENSE00001242396	52519944	52520120
ENSE00001242410	52516043	52516238
ENSE00001242597	52515423	52515506
ENSE00001242809	52520642	52520698
ENSE00001951570	52524300	52524495
ENSE00003460450	52517550	52517624
ENSE00003463008	52502159	52502228
ENSE00003467782	52520400	52520549
ENSE00003472162	52522037	52522230
ENSE00003475393	52523222	52523341
ENSE00003482387	52501638	52501753
ENSE00003487599	52522775	52522940
ENSE00003498218	52519264	52519404
ENSE00003505842	52505883	52505936
ENSE00003525128	52521844	52521951
ENSE00003526761	52522555	52522688
ENSE00003541117	52502632	52502727
ENSE00003542875	52504739	52504876
ENSE00003547956	52523025	52523134
ENSE00003555038	52521361	52521510
ENSE00003557930	52501166	52501302
ENSE00003563491	52518723	52518869
ENSE00003568783	52504028	52504155
ENSE00003570669	52503772	52503902
ENSE00003575321	52505319	52505381
ENSE00003579680	52504461	52504549
ENSE00003580507	52523871	52524017
ENSE00003584133	52508273	52508359
ENSE00003598304	52506170	52506250
ENSE00003607286	52502999	52503109
ENSE00003612080	52507931	52508026
ENSE00003612892	52522330	52522474
ENSE00003619907	52521596	52521700
ENSE00003622361	52505668	52505781
ENSE00003624738	52516542	52516587
ENSE00003636942	52503344	52503540
ENSE00003648553	52507613	52507675
ENSE00003661203	52517320	52517393
ENSE00003685020	52502006	52502091
ENSE00003685326	52524100	52524213
ENSE00003686314	52505003	52505143
ENSE00003687236	52506692	52506850

Expression profiles

Bgee: expression breadth ubiquitous, 233 present calls, max score 99.06.

FANTOM5 (CAGE): breadth broad, TPM avg 30.9537 / max 2376.1546, expressed in 600 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36868	26.5668	571
36869	2.9214	460
36870	1.4656	386

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	99.06	gold quality
right adrenal gland cortex	UBERON:0035827	98.88	gold quality
right adrenal gland	UBERON:0001233	98.77	gold quality
omental fat pad	UBERON:0010414	98.72	gold quality
right coronary artery	UBERON:0001625	98.68	gold quality
peritoneum	UBERON:0002358	98.67	gold quality
left adrenal gland cortex	UBERON:0035825	98.54	gold quality
left adrenal gland	UBERON:0001234	98.50	gold quality
mucosa of stomach	UBERON:0001199	98.43	gold quality
adrenal cortex	UBERON:0001235	98.32	gold quality
adipose tissue of abdominal region	UBERON:0007808	98.13	gold quality
apex of heart	UBERON:0002098	97.76	gold quality
left coronary artery	UBERON:0001626	97.71	gold quality
coronary artery	UBERON:0001621	97.64	gold quality
left uterine tube	UBERON:0001303	97.59	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.52	gold quality
tibial nerve	UBERON:0001323	97.44	gold quality
adrenal gland	UBERON:0002369	97.33	gold quality
upper lobe of left lung	UBERON:0008952	97.23	gold quality
right lung	UBERON:0002167	97.12	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.92	gold quality
ascending aorta	UBERON:0001496	96.91	gold quality
thoracic aorta	UBERON:0001515	96.90	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.90	gold quality
lower esophagus	UBERON:0013473	96.85	gold quality
upper lobe of lung	UBERON:0008948	96.84	gold quality
transverse colon	UBERON:0001157	96.82	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.80	gold quality
mucosa of transverse colon	UBERON:0004991	96.79	gold quality
granulocyte	CL:0000094	96.76	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-MTAB-8495	yes	5181.99
E-GEOD-84465	yes	2748.99
E-MTAB-6678	yes	1899.43
E-HCAD-36	yes	1865.87
E-MTAB-9906	yes	1381.77
E-MTAB-8498	yes	1375.79
E-GEOD-130473	yes	807.21
E-GEOD-135922	yes	743.57
E-ANND-5	yes	532.37
E-HCAD-10	yes	47.03
E-MTAB-10553	yes	46.38
E-ANND-3	yes	35.85
E-HCAD-9	yes	25.09
E-MTAB-9067	yes	7.32
E-MTAB-5061	no	3.55

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXC1, FOXO1, FOXO3, MYOD1, MYRF

miRNA regulators (miRDB)

8 targeting STAB1, 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-95-5P	99.89	72.17	3973
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-4703-5P	98.53	70.13	1645
HSA-MIR-3942-5P	98.52	69.51	1517
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-1226-5P	96.50	65.28	643

Literature-anchored findings (GeneRIF, showing 30)

• code for homologous transmembrane proteins featuring seven fasciclin-like adhesion domains, 18-20 epidermal-growth-factor domains, one X-link domain and three to six B-(X(7))-B hyaluronan-binding motifs (PMID:11829752)
• FEEL-1, a novel scavenger receptor with in vitro bacteria-binding and angiogenesis-modulating activities. (PMID:12077138)
• This and FEEL-2 are endocytic receptors for advanced glycation end products. (PMID:12473645)
• CLEVER-1 also known as stabilin-1 or FEEL-1) is a large multifunctional glycoprotein implicated in scavenging, angiogenesis, cell adhesion and angiogenesis (PMID:15297319)
• role for stabilin-1 as a rapidly recycling scavenger receptor (PMID:15345716)
• stabilin-1 may function in endocytic and secretory processes of human macrophages. (PMID:15345724)
• Stabilin-1 internalizes and targets secreted protein acidic and rich in cysteine (SPARC) to an endosomal pathway in stably transfected Chinese hamster ovary cells. (PMID:16670288)
• Expression of VAP-1, Stabilin-1, L-SIGN can be used to identify sinusoidal endothelium and to permit discrimination from vascular and lymphatic endothelial cells. (PMID:17006978)
• Stabilin-1 mediates internalization and endosomal sorting of placental lactogen. (PMID:18292525)
• role in endocytic clearance and secretion in macrophages; review (PMID:19457577)
• Stabilin-1, found on alternatively activated macrophages, is a phagocytic receptor mediating the clearance of apoptotic cells in a phosphatidylserine-dependent manner. (PMID:19726632)
• The novel GGA-binding site EDDADDD is essential for stabilin-1-mediated intracellular sorting but is not required for endocytosis. (PMID:19752197)
• these results indicate that GULP functions as an adaptor protein for stabilin-1-mediated phagocytosis. (PMID:20599701)
• Studies shoe that understanding stabilin-1 behavior in complex biological systems and would open perspectives for therapeutic targeting of stabilin-1 pathways in chronic inflammation. (PMID:20953554)
• Studies identified a binding site on SPARC for stabilin-1 by a solid-state peptide array coupled with a modified enzyme-linked immunosorbent assay. (PMID:21308731)
• CLEVER-1/stabilin-1 can support lymphocyte transendothelial migration; it also may provide an organ-specific signal for regulatory T cell recruitment to the inflamed liver and to hepatocellular carcinoma. (PMID:21368224)
• macrophage stabilin-1/CLEVER-1 can potentially regulate leukocyte migration and scavenging during the development of the placenta and fetus (PMID:21480214)
• The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. (PMID:21483103)
• Genes within recently identified loci associated with waist-hip ratio (WHR) exhibit fat depot-specific mRNA expression, which correlates with obesity-related traits. Adipose tissue (AT) mRNA expression of 6 genes (TBX15/WARS2, STAB1, PIGC, ZNRF3, GRB14 (PMID:23670221)
• The present findings suggest that STAB1 is a new and highly promising candidate gene in this region. The combining of gene expression and GWAS data may provide valuable insights into the biological mechanisms of BD. (PMID:25136889)
• These data define stabilin-1 as a new immunosuppressive molecule and suggest that stabilin-1(high) monocytes may dampen proinflammatory reactions in vivo. (PMID:26608916)
• Results suggest stabilin-1 mediated silent clearance of extracellular tumor growth-inhibiting factors as a mechanism of stabilin-1 induced tumor growth. (PMID:27105498)
• Systemic rAAV-DCN in neuroblastoma-grafted nude mice inhibited stabilin-1. (PMID:28631095)
• Not CD68 but stabilin-1 expression is associated with the risk of recurrence in patients with oral cavity squamous cell carcinoma. (PMID:30652402)
• This study identifies Clever-1 as an important molecule controlling lymphocyte entry into the spleen, along with a critical role for the splenic red pulp in this regulated trafficking. (PMID:30926591)
• New tools to prevent cancer growth and spread: a ‘Clever’ approach. (PMID:32595212)
• Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment. (PMID:34374322)
• Stabilin-1 mediates beneficial monocyte recruitment and tolerogenic macrophage programming during CVB3-induced viral myocarditis. (PMID:34968453)
• A form of inherited hyperferritinemia associated with bi-allelic pathogenic variants of STAB1. (PMID:37490907)
• Highly oxidized albumin is cleared by liver sinusoidal endothelial cells via the receptors stabilin-1 and -2. (PMID:37926735)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	stab1	ENSDARG00000076484
mus_musculus	Stab1	ENSMUSG00000042286
rattus_norvegicus	Stab1	ENSRNOG00000018434

Paralogs (2): TNFAIP6 (ENSG00000123610), STAB2 (ENSG00000136011)

Protein

Protein identifiers

Stabilin-1 — Q9NY15 (reviewed: Q9NY15)

Alternative names: Fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor 1, MS-1 antigen

All UniProt accessions (2): Q9NY15, H7C4W7

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a scavenger receptor for acetylated low density lipoprotein. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. When inhibited in endothelial tube formation assays, there is a marked decrease in cell-cell interactions, suggesting a role in angiogenesis. Involved in the delivery of newly synthesized CHID1/SI-CLP from the biosynthetic compartment to the endosomal/lysosomal system.

Subunit / interactions. Interacts with CHID1.

Subcellular location. Membrane.

Tissue specificity. High levels found in spleen, lymph node, liver and placenta. Also expressed in endothelial cells.

Disease relevance. Hyperferritinemia (HRFT) [MIM:620729] An autosomal recessive condition characterized by increased serum ferritin levels in the absence of iron overload or other clinical symptoms. The disease may be caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NY15-1	1	yes
Q9NY15-2	2

RefSeq proteins (1): NP_055951* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000538	Link_dom	Domain
IPR000742	EGF	Domain
IPR000782	FAS1_domain	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002049	LE_dom	Domain
IPR016186	C-type_lectin-like/link_sf	Homologous_superfamily
IPR016187	CTDL_fold	Homologous_superfamily
IPR024731	NELL2-like_EGF	Domain
IPR036378	FAS1_dom_sf	Homologous_superfamily
IPR056806	EGF_STAB1-2	Domain

Pfam: PF00193, PF02469, PF12947, PF24887

UniProt features (135 total): disulfide bond 59, glycosylation site 29, domain 26, sequence variant 12, splice variant 2, sequence conflict 2, topological domain 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NY15-F1	68.00	0.02

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 (59): 1551–1567, 1569–1581, 1971–1985, 1979–1995, 1997–2006, 2018–2029, 2023–2039, 2041–2050, 2060–2070, 2064–2076, 2078–2089, 2095–2108, 2102–2117, 2119–2130, 2136–2150, 2144–2160, 2162–2173, 2230–2299, 2254–2275, 112–126 …

Glycosylation sites (29): 133, 286, 312, 413, 606, 673, 712, 745, 816, 1087, 1096, 1170, 1178, 1222, 1274, 1378, 1471, 1626, 1727, 2107 …

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3000497	Scavenging by Class H Receptors
R-HSA-2173782	Binding and Uptake of Ligands by Scavenger Receptors
R-HSA-5653656	Vesicle-mediated transport

MSigDB gene sets: 275 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, MODULE_52, MCLACHLAN_DENTAL_CARIES_UP, GOBP_INFLAMMATORY_RESPONSE, MODULE_45, GOBP_VESICLE_MEDIATED_TRANSPORT, AP2_Q3, GOBP_CELL_CELL_SIGNALING, TERAMOTO_OPN_TARGETS_CLUSTER_5, VART_KSHV_INFECTION_ANGIOGENIC_MARKERS_UP, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS, TGCTGAY_UNKNOWN, ACEVEDO_LIVER_TUMOR_VS_NORMAL_ADJACENT_TISSUE_DN, GROSS_HYPOXIA_VIA_ELK3_UP, GOBP_BLOOD_VESSEL_MORPHOGENESIS

GO Biological Process (7): receptor-mediated endocytosis (GO:0006898), inflammatory response (GO:0006954), cell adhesion (GO:0007155), cell-cell signaling (GO:0007267), negative regulation of angiogenesis (GO:0016525), defense response to bacterium (GO:0042742), endocytosis (GO:0006897)

GO Molecular Function (7): low-density lipoprotein particle receptor activity (GO:0005041), scavenger receptor activity (GO:0005044), calcium ion binding (GO:0005509), hyaluronic acid binding (GO:0005540), protein-disulfide reductase activity (GO:0015035), low-density lipoprotein particle binding (GO:0030169), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), endocytic vesicle membrane (GO:0030666), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Binding and Uptake of Ligands by Scavenger Receptors	1
Vesicle-mediated transport	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
defense response	2
endocytosis	1
cellular process	1
cell communication	1
signaling	1
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
response to bacterium	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
cargo receptor activity	1
metal ion binding	1
carboxylic acid binding	1
disulfide oxidoreductase activity	1
catalytic activity, acting on a protein	1
lipoprotein particle binding	1
binding	1
membrane	1
cell periphery	1
endocytic vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STAB1	SCARF1	Q14162	861
STAB1	CHID1	Q9BWS9	840
STAB1	SNX17	Q15036	744
STAB1	HSPA4	P34932	671
STAB1	SPARC	P09486	656
STAB1	OLR1	P78380	646
STAB1	TIMD4	Q96H15	608
STAB1	ALB	P02768	592
STAB1	CHIT1	Q13231	576
STAB1	MRC1	P22897	561
STAB1	CX3CR1	P49238	550
STAB1	CSH1	P01243	543
STAB1	APOB	P04114	541
STAB1	CSH1	P01243	539
STAB1	CD163	Q86VB7	532

IntAct

78 interactions, top by confidence:

A	B	Type	Score
STAB1	FN1	psi-mi:“MI:0915”(physical association)	0.510
STAB1	RPN1	psi-mi:“MI:0915”(physical association)	0.400
rep	STAB1	psi-mi:“MI:0915”(physical association)	0.370
STAB1	NUFIP2	psi-mi:“MI:0915”(physical association)	0.370
STAB1	ORC5	psi-mi:“MI:0915”(physical association)	0.370
PIK3R2	STAB1	psi-mi:“MI:0915”(physical association)	0.370
STAB1		psi-mi:“MI:0915”(physical association)	0.370
CDC5L		psi-mi:“MI:0914”(association)	0.350
	STAB1	psi-mi:“MI:0915”(physical association)	0.000
STAB1	tsf	psi-mi:“MI:0915”(physical association)	0.000
lon	STAB1	psi-mi:“MI:0915”(physical association)	0.000
spo0J	STAB1	psi-mi:“MI:0915”(physical association)	0.000
metE	STAB1	psi-mi:“MI:0915”(physical association)	0.000
STAB1		psi-mi:“MI:0915”(physical association)	0.000
STAB1	ppsA	psi-mi:“MI:0915”(physical association)	0.000
STAB1	spmA	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): STAB1 (Affinity Capture-MS), STAB1 (Proximity Label-MS), STAB1 (Affinity Capture-MS), STAB1 (Two-hybrid), STAB1 (Positive Genetic), STAB1 (Two-hybrid), STAB1 (Two-hybrid), STAB1 (Cross-Linking-MS (XL-MS)), GGA1 (Reconstituted Complex), GGA2 (Reconstituted Complex), GGA3 (Reconstituted Complex), STAB1 (Two-hybrid), STAB1 (Two-hybrid)

ESM2 similar proteins: A0JM12, A1A5Y0, A2VCU8, A6BM72, A6QR11, E9QJQ6, O42182, O70534, O88281, P23142, P35555, P35953, P80370, P97607, P98133, P98155, P98156, P98165, P98166, Q08879, Q09163, Q28832, Q2VWQ2, Q5R3Z7, Q5VY43, Q61220, Q61554, Q61555, Q62918, Q62919, Q6DIB5, Q7ZXL5, Q80T14, Q80T91, Q80V70, Q86XX4, Q8C088, Q8R4Y4, Q8VIK5, Q90827

Diamond homologs: A0A182C2Z2, C6KFA3, F1RWC3, O08628, O08859, O14594, O14786, O35276, O35375, O43897, O57382, O57460, O60462, O60494, O70244, P03994, P07354, P07897, P07898, P10859, P10915, P13497, P13608, P13611, P14745, P16112, P25723, P28824, P42674, P55066, P55067, P55252, P79795, P97333, P98063, P98065, P98066, P98068, P98069, P98070

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	441
Likely benign	48
Benign	11

Top pathogenic / likely-pathogenic (0)

SpliceAI

10421 predictions. Top by Δscore:

Variant	Effect	Δscore
3:52495490:AGG:A	donor_loss	1.0000
3:52495492:GT:G	donor_loss	1.0000
3:52501295:G:GT	donor_gain	1.0000
3:52502156:CAG:C	acceptor_loss	1.0000
3:52502157:A:AG	acceptor_gain	1.0000
3:52502157:AGGA:A	acceptor_loss	1.0000
3:52502158:G:GG	acceptor_gain	1.0000
3:52502630:A:AG	acceptor_gain	1.0000
3:52502631:G:GG	acceptor_gain	1.0000
3:52502996:CAGAG:C	acceptor_loss	1.0000
3:52502997:A:AG	acceptor_gain	1.0000
3:52502998:G:GG	acceptor_gain	1.0000
3:52502998:GAGCT:G	acceptor_gain	1.0000
3:52503095:G:T	donor_gain	1.0000
3:52503762:C:A	acceptor_gain	1.0000
3:52503900:CAGG:C	donor_loss	1.0000
3:52503902:GG:G	donor_loss	1.0000
3:52503903:G:GC	donor_loss	1.0000
3:52504550:G:GG	donor_gain	1.0000
3:52504734:TGCA:T	acceptor_loss	1.0000
3:52504736:CA:C	acceptor_loss	1.0000
3:52504738:GGC:G	acceptor_gain	1.0000
3:52504873:CACG:C	donor_loss	1.0000
3:52504875:CGGTG:C	donor_loss	1.0000
3:52504876:GGTG:G	donor_loss	1.0000
3:52504877:GT:G	donor_loss	1.0000
3:52504878:T:G	donor_loss	1.0000
3:52504997:CACCA:C	acceptor_loss	1.0000
3:52504999:CCA:C	acceptor_loss	1.0000
3:52505000:CAGAA:C	acceptor_loss	1.0000

AlphaMissense

16834 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:52511695:T:A	C945S	0.996
3:52511696:G:C	C945S	0.996
3:52509893:T:A	C791S	0.995
3:52509894:G:C	C791S	0.995
3:52511662:T:A	C934S	0.994
3:52511663:G:C	C934S	0.994
3:52509923:T:A	C801S	0.993
3:52509924:G:C	C801S	0.993
3:52510405:G:C	W895C	0.993
3:52510405:G:T	W895C	0.993
3:52511663:G:A	C934Y	0.993
3:52511695:T:C	C945R	0.993
3:52511697:C:G	C945W	0.993
3:52511734:T:A	C958S	0.993
3:52511735:G:C	C958S	0.993
3:52510484:T:A	C922S	0.992
3:52510485:G:C	C922S	0.992
3:52511664:C:G	C934W	0.992
3:52517893:T:A	C1551S	0.992
3:52517894:G:C	C1551S	0.992
3:52501737:G:C	W105C	0.991
3:52501737:G:T	W105C	0.991
3:52508318:T:A	C732S	0.991
3:52508319:G:C	C732S	0.991
3:52511662:T:C	C934R	0.991
3:52517983:T:A	C1581S	0.991
3:52517984:G:C	C1581S	0.991
3:52509210:T:A	C746S	0.990
3:52509211:G:C	C746S	0.990
3:52509273:T:A	C767S	0.990

dbSNP variants (sampled 300 via entrez): RS1000035091 (3:52498629 C>G,T), RS1000610084 (3:52500547 C>A,T), RS1000698102 (3:52514910 G>A,T), RS1000973912 (3:52496347 C>T), RS1001008385 (3:52496663 C>T), RS1001224490 (3:52495258 G>A), RS1001327170 (3:52500148 C>T), RS1001382671 (3:52494183 C>G), RS1001517840 (3:52515683 T>C), RS1001592273 (3:52495133 T>C), RS1001599947 (3:52509354 G>A), RS1001620420 (3:52511199 G>A), RS1001731903 (3:52520869 G>A), RS1001782684 (3:52521166 G>A), RS1001796634 (3:52516854 GC>G)

Disease associations

OMIM: gene MIM:608560 | disease phenotypes: MIM:620729

GenCC curated gene-disease

Disease	Classification	Inheritance
isolated hyperferritinemia	Strong	Autosomal recessive

Mondo (1): isolated hyperferritinemia (MONDO:0958237)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0031877	Elevated circulating hepcidin concentration
HP:0040130	Abnormal circulating iron concentration
HP:0040133	Abnormal circulating ferritin concentration

GWAS associations

49 associations (top):

Study	Trait	p-value
GCST000829_9	Waist-hip ratio	4.000000e-10
GCST001241_15	Bipolar disorder	2.000000e-06
GCST002149_14	Schizophrenia	1.000000e-08
GCST002223_55	HDL cholesterol	9.000000e-11
GCST002539_48	Schizophrenia	4.000000e-11
GCST002774_8	Cognitive function	5.000000e-06
GCST004232_63	HDL cholesterol levels	1.000000e-10
GCST004521_123	Autism spectrum disorder or schizophrenia	3.000000e-12
GCST004521_201	Autism spectrum disorder or schizophrenia	4.000000e-08
GCST004521_259	Autism spectrum disorder or schizophrenia	6.000000e-09
GCST004604_85	Hematocrit	1.000000e-09
GCST004902_20	Parkinson’s disease	3.000000e-08
GCST005316_132	Intelligence (MTAG)	4.000000e-10
GCST006479_58	Diverticular disease	3.000000e-07
GCST006803_55	Schizophrenia	1.000000e-11
GCST007483_42	Waist-to-hip ratio adjusted for BMI (additive genetic model)	5.000000e-18
GCST007487_24	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-19
GCST007492_2	Waist-to-hip ratio adjusted for BMI (additive genetic model)	7.000000e-07
GCST007494_4	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-07
GCST007500_9	Waist-to-hip ratio adjusted for BMI (additive genetic model)	5.000000e-14
GCST007502_25	Waist-to-hip ratio adjusted for BMI (additive genetic model)	2.000000e-14
GCST008103_3	Bipolar disorder	7.000000e-11
GCST008790_16	Urinary albumin-to-creatinine ratio	4.000000e-09
GCST008794_29	Urinary albumin-to-creatinine ratio	2.000000e-08
GCST008839_414	Height	9.000000e-13
GCST010050_11	Adiponectin levels	3.000000e-21
GCST010241_39	Apolipoprotein A1 levels	1.000000e-15
GCST010698_14	Subcortical volume (min-P)	8.000000e-09
GCST010699_73	Brain morphology (min-P)	1.000000e-18
GCST010701_137	Cortical surface area (MOSTest)	8.000000e-10

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0004343	waist-hip ratio
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004337	intelligence
EFO:0004348	hematocrit
EFO:0009959	diverticular disease
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004502	adiponectin measurement
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004346	neuroimaging measurement
EFO:0004459	ferritin measurement
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Scavenger receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
bexmarilimab	Binding	9.12	pKd

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation	2
Tretinoin	decreases expression	2
aristolochic acid I	increases expression	1
dimethylselenide	increases expression, increases oxidation	1
sodium bichromate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	decreases methylation	1
N-acetyl-4-benzoquinoneimine	affects response to substance	1
aflatoxin B2	decreases methylation	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Arsenic Trioxide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Cadmium	increases expression	1
Calcitriol	decreases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	decreases expression	1
Methapyrilene	decreases methylation	1
Methotrexate	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Tamoxifen	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin E	affects cotreatment, increases expression	1
Aflatoxin B1	decreases methylation	1
Reactive Oxygen Species	increases expression, increases oxidation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02526121	Not specified	COMPLETED	Effect of Therapeutic Phlebotomies on the Triglycerides Concentration in Patients With Hypertriglyceridemia and Hyperferritinemia
NCT03066401	Not specified	TERMINATED	Respiratory Variations for Assessing Blood Withdrawal 2
NCT05659017	Not specified	UNKNOWN	Candidate Gene for Hyperferritinemia
NCT05742035	Not specified	UNKNOWN	Quality and Biologic Characteristics of Red Blood Concentrates Obtained From Individuals With Elevated Ferritin.
NCT06820905	Not specified	NOT_YET_RECRUITING	Hyperinflammation and Hyperferritinemia in Critically Ill Patients