ERFE

Summary

ERFE (erythroferrone, HGNC:26727) is a protein-coding gene on chromosome 2q37.3, encoding Erythroferrone (Q4G0M1). Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores.

Enables molecular sequestering activity. Involved in negative regulation of BMP signaling pathway. Predicted to be located in extracellular region. Predicted to be active in extracellular space.

Source: NCBI Gene 151176 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001291832

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26727
Approved symbol	ERFE
Name	erythroferrone
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ37034, CTRP15, C1QTNF15
Ensembl gene	ENSG00000178752
Ensembl biotype	protein_coding
OMIM	615099
Entrez	151176

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 4 retained_intron, 3 protein_coding

ENST00000344233, ENST00000357303, ENST00000473274, ENST00000479091, ENST00000481917, ENST00000486834, ENST00000546354

RefSeq mRNA: 1 — MANE Select: NM_001291832 NM_001291832

CCDS: CCDS77548

Canonical transcript exons

ENST00000546354 — 8 exons

Exon	Start	End
ENSE00002218772	238166956	238168890
ENSE00002310406	238158970	238159205
ENSE00003461159	238164270	238164360
ENSE00003490355	238162736	238162838
ENSE00003502323	238163737	238163999
ENSE00003537464	238164075	238164183
ENSE00003566152	238165606	238165684
ENSE00003611650	238161594	238161716

Expression profiles

Bgee: expression breadth ubiquitous, 165 present calls, max score 84.40.

FANTOM5 (CAGE): breadth broad, TPM avg 2.0867 / max 251.2798, expressed in 656 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26332	1.4116	486
26331	0.6605	309
26335	0.0097	4
26334	0.0050	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tibialis anterior	UBERON:0001385	84.40	silver quality
right testis	UBERON:0004534	82.99	gold quality
left testis	UBERON:0004533	82.84	gold quality
oocyte	CL:0000023	82.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.31	gold quality
cerebellar hemisphere	UBERON:0002245	81.22	gold quality
cerebellar cortex	UBERON:0002129	81.18	gold quality
pancreatic ductal cell	CL:0002079	81.12	silver quality
testis	UBERON:0000473	80.54	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.43	silver quality
gastrocnemius	UBERON:0001388	80.03	gold quality
cerebellum	UBERON:0002037	80.02	gold quality
cartilage tissue	UBERON:0002418	77.53	gold quality
muscle of leg	UBERON:0001383	77.16	gold quality
sperm	CL:0000019	77.06	gold quality
secondary oocyte	CL:0000655	76.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	75.60	gold quality
hindlimb stylopod muscle	UBERON:0004252	75.01	gold quality
cardiac muscle of right atrium	UBERON:0003379	74.01	gold quality
left ventricle myocardium	UBERON:0006566	73.90	gold quality
right lobe of thyroid gland	UBERON:0001119	73.68	gold quality
metanephros cortex	UBERON:0010533	73.61	gold quality
ventricular zone	UBERON:0003053	73.53	gold quality
stromal cell of endometrium	CL:0002255	72.70	gold quality
anterior cingulate cortex	UBERON:0009835	72.49	gold quality
left lobe of thyroid gland	UBERON:0001120	72.34	gold quality
thyroid gland	UBERON:0002046	71.96	gold quality
prefrontal cortex	UBERON:0000451	70.85	gold quality
ganglionic eminence	UBERON:0004023	70.78	gold quality
right frontal lobe	UBERON:0002810	70.33	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.35

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

61 targeting ERFE, 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-3646	100.00	73.56	5283
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-1915-3P	99.58	66.79	1988
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-148A-5P	99.30	68.27	1141
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-7157-3P	98.95	68.70	1582
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914

Literature-anchored findings (GeneRIF, showing 27)

• Myonectin links skeletal muscle to lipid homeostasis in liver and adipose tissue in response to alterations in energy state, revealing a novel myonectin-mediated metabolic circuit. (PMID:22351773)
• In hemodialysis patients DA and CERA increased levels of ERFE that regulated hepcidin 25 and led to iron mobilization from body stores during erythropoiesis. (PMID:26978524)
• Data suggest hepcidin is the master regulator of systemic iron homeostasis; hepcidin levels are suppressed when erythropoiesis is stimulated; the erythroid-derived hormone erythroferrone appears to be a convincing candidate for link between increased erythropoiesis and hepcidin suppression. [REVIEW] (PMID:27146013)
• FAM132b expression is upregulated in Congenital Dyserythropoietic Anemia type II. (PMID:27540014)
• From a clinical point of view, erythroferrone could become a useful biological marker of iron metabolism and a therapeutic target. [review] (PMID:28666715)
• serum ERFE levels acutely increase in response to EPO in the setting of normal or impaired kidney function (PMID:29419424)
• Serum CTRP15 concentrations were associated with the key components of MetS and insulin resistance. (PMID:30303269)
• The expression of the variant ERFE transcript that was restricted to SF3B1-mutated erythroblasts decreased in lenalidomide-responsive anemic patients, identifying variant ERFE as a specific biomarker of clonal erythropoiesis. (PMID:31292266)
• A recurrent low-frequency variant, A260S, in the ERFE gene was found in 12.5% of congenital dyserythropoietic anemia type II patients with a severe phenotype. This variant leads to increased levels of ERFE, with subsequently marked impairment of iron regulation pathways at the hepatic level. It modified iron overload by impairing the BMP/SMAD pathway. (PMID:31400017)
• Higher serum level of CTRP15 in patients with coronary artery disease is associated with disease severity, body mass index and insulin resistance. (PMID:31608708)
• using the ERFE gene expression, combined with serum hepcidin estimation, can substantiate the role of estimated TS% as a promising tool in screening for iron overload in beta-TM patients. (PMID:31834456)
• Implications of C1q/TNF-related protein superfamily in patients with coronary artery disease. (PMID:31965030)
• Association of decreased myonectin levels with metabolic and hormonal disturbance in polycystic ovary syndrome. (PMID:32314610)
• Interplay of erythropoietin, fibroblast growth factor 23, and erythroferrone in patients with hereditary hemolytic anemia. (PMID:32324886)
• Disordered serum erythroferrone and hepcidin levels as indicators of the spontaneous abortion occurrence during early pregnancy in humans. (PMID:32866306)
• Erythroferrone structure, function, and physiology: Iron homeostasis and beyond. (PMID:33372284)
• High erythroferrone expression in CD71(+) erythroid progenitors predicts superior survival in myelodysplastic syndromes. (PMID:33486765)
• The impacts of C1q/TNF-related protein-15 and adiponectin on Interleukin-6 and tumor necrosis factor-alpha in primary macrophages of patients with coronary artery diseases. (PMID:33676229)
• Umbilical Cord Erythroferrone Is Inversely Associated with Hepcidin, but Does Not Capture the Most Variability in Iron Status of Neonates Born to Teens Carrying Singletons and Women Carrying Multiples. (PMID:34236433)
• Differentiating iron-loading anemias using a newly developed and analytically validated ELISA for human serum erythroferrone. (PMID:34283879)
• Erythroferrone and hepcidin as mediators between erythropoiesis and iron metabolism during allogeneic hematopoietic stem cell transplant. (PMID:34310730)
• Serum erythroferrone levels during the first month of life in premature infants. (PMID:34376791)
• Plasma Complement C1q/tumor necrosis factor-related protein 15 concentration is associated with polycystic ovary syndrome. (PMID:35700181)
• In Silico Pan-Cancer Analysis Reveals Prognostic Role of the Erythroferrone (ERFE) Gene in Human Malignancies. (PMID:36675239)
• Placental Erythroferrone and Erythropoietin mRNA Expression is not Associated with Maternal or Neonatal Iron Status in Adolescents Carrying Singletons and Adult Women Carrying Multiples. (PMID:37253412)
• Characterization of erythroferrone structural domains relevant to its iron-regulatory function. (PMID:37866631)
• Characterization of erythroferrone oligomerization and its impact on BMP antagonism. (PMID:37949218)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Erfe	ENSMUSG00000047443
rattus_norvegicus	Erfe	ENSRNOG00000024688

Paralogs (1): C1QTNF12 (ENSG00000184163)

Protein

Protein identifiers

Erythroferrone — Q4G0M1 (reviewed: Q4G0M1)

Alternative names: Complement C1q tumor necrosis factor-related protein 15, Myonectin

All UniProt accessions (3): Q4G0M1, H0Y2X4, H7BY19

UniProt curated annotations — full annotation on UniProt →

Function. Iron-regulatory hormone that acts as an erythroid regulator after hemorrhage: produced by erythroblasts following blood loss and mediates suppression of hepcidin (HAMP) expression in the liver, thereby promoting increased iron absorption and mobilization from stores. Promotes lipid uptake into adipocytes and hepatocytes via transcriptional up-regulation of genes involved in fatty acid uptake. Inhibits apoptosis and inflammatory response in cardiomyocytes via promotion of sphingosine-1-phosphate (S1P) and cAMP-dependent activation of AKT signaling. Inhibits autophagy induced by nutrient deficiency in hepatocytes via promoting the phosphorylation of IRS1, AKT, and MTOR, and thereby subsequent activation of the AKT-MTOR signaling pathway. Negatively regulates the differentiation of osteoblasts, potentially via sequestering BMP2, and thereby inhibits the activation of SMAD signaling. The reduction in BMP2 signaling in osteoblasts also results in an increase in expression of the osteoclastogenesis-promoting factors TNFSF11/RANKL and SOST, thereby indirectly promotes bone resorption.

Subunit / interactions. Homodimer; disulfide-linked. Forms trimer, hexamers and higher molecular weight oligomers. May form heteromeric complexes with C1QTNF2 and C1QTNF12 and, to a lesser extent, with C1QTNF5 and C1QTNF10. Interacts with BMP5 and BMP7; the interaction inhibits BMP-induced transcription of HAMP. Interacts with BMP6; the interaction inhibits BMP-induced transcription of HAMP. Interacts with BMP2. Interacts with heterodimers composed of BMP2 and BMP6 in vitro, the interaction inhibits the heterodimer binding to its receptor BMPR1A /ALK3 and thereby suppresses expression of HAMP.

Subcellular location. Secreted.

Post-translational modifications. N-glycosylated; required for secretion of the mature protein.

Similarity. Belongs to the adipolin/erythroferrone family.

RefSeq proteins (1): NP_001278761* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001073	C1q_dom	Domain
IPR008983	Tumour_necrosis_fac-like_dom	Homologous_superfamily
IPR052136	Adipolin/Erythroferrone-rel	Family

UniProt features (20 total): modified residue 6, compositionally biased region 5, glycosylation site 3, signal peptide 1, chain 1, sequence conflict 1, domain 1, region of interest 1, site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q4G0M1-F1	71.15	0.33

Functional residue map

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

Catalytic / active sites (1): 333 (required for correct protein folding in the endoplasmic reticulum)

Post-translational modifications (6): 111, 113, 114, 116, 117, 119

Glycosylation sites (3): 243, 295, 333

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CARBOHYDRATE_TRANSPORT, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_NEGATIVE_REGULATION_OF_CELL_DEVELOPMENT, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_REGULATION_OF_ORGANIC_ACID_TRANSPORT, PEREZ_TP63_TARGETS, GOBP_INTRACELLULAR_IRON_ION_HOMEOSTASIS, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_KETONE_METABOLIC_PROCESS

GO Biological Process (16): intracellular iron ion homeostasis (GO:0006879), negative regulation of autophagy (GO:0010507), fatty acid transport (GO:0015908), regulation of fatty acid metabolic process (GO:0019217), negative regulation of BMP signaling pathway (GO:0030514), negative regulation of apoptotic process (GO:0043066), negative regulation of osteoblast differentiation (GO:0045668), negative regulation of osteoclast differentiation (GO:0045671), negative regulation of gluconeogenesis (GO:0045721), positive regulation of D-glucose import across plasma membrane (GO:0046326), positive regulation of insulin receptor signaling pathway (GO:0046628), establishment of localization in cell (GO:0051649), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), positive regulation of fatty acid transport (GO:2000193), regulation of signal transduction (GO:0009966), BMP signaling pathway (GO:0030509)

GO Molecular Function (4): hormone activity (GO:0005179), identical protein binding (GO:0042802), molecular sequestering activity (GO:0140313), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular monoatomic cation homeostasis	1
inorganic ion homeostasis	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
lipid transport	1
monocarboxylic acid transport	1
fatty acid metabolic process	1
regulation of ketone metabolic process	1
regulation of lipid metabolic process	1
regulation of small molecule metabolic process	1
BMP signaling pathway	1
regulation of BMP signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
negative regulation of cellular response to growth factor stimulus	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
osteoblast differentiation	1
negative regulation of cell differentiation	1
regulation of osteoblast differentiation	1
negative regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1
regulation of osteoclast differentiation	1
gluconeogenesis	1
regulation of gluconeogenesis	1
negative regulation of biosynthetic process	1
negative regulation of carbohydrate metabolic process	1
negative regulation of small molecule metabolic process	1
positive regulation of D-glucose transmembrane transport	1
regulation of D-glucose import across plasma membrane	1
D-glucose import across plasma membrane	1
insulin receptor signaling pathway	1
positive regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
positive regulation of cellular response to insulin stimulus	1
establishment of localization	1
cellular localization	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1

Protein interactions and networks

STRING

282 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERFE	HAMP	P81172	840
ERFE	EPO	P01588	659
ERFE	C1QTNF1	Q9BXJ1	624
ERFE	TMPRSS6	Q8IU80	581
ERFE	TFR2	Q9UP52	560
ERFE	GDF15	P78360	545
ERFE	HJV	Q6ZVN8	534
ERFE	TFRC	P02786	529
ERFE	C1QTNF9	P0C862	527
ERFE	SLC11A2	P49281	506
ERFE	TWSG1	Q9GZX9	497
ERFE	CYBRD1	Q53TN4	479
ERFE	C1QTNF3	Q9BXJ4	478
ERFE	HFE	Q30201	471
ERFE	BMP6	P22004	446

IntAct

31 interactions, top by confidence:

A	B	Type	Score
P4HA2	P4HB	psi-mi:“MI:0914”(association)	0.740
LRP1	NME4	psi-mi:“MI:0914”(association)	0.530
TMEM25	FUZ	psi-mi:“MI:0914”(association)	0.350
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
PSCA	METTL15	psi-mi:“MI:0914”(association)	0.350
TMEM25	NME4	psi-mi:“MI:0914”(association)	0.350
SFTPA2	POTEF	psi-mi:“MI:0914”(association)	0.350
IL5RA	POTEF	psi-mi:“MI:0914”(association)	0.350
PI15		psi-mi:“MI:0914”(association)	0.350
DPEP2	QSOX1	psi-mi:“MI:0914”(association)	0.350
CA6	QSOX1	psi-mi:“MI:0914”(association)	0.350
PDGFRA	QSOX1	psi-mi:“MI:0914”(association)	0.350
PRG2	QSOX1	psi-mi:“MI:0914”(association)	0.350
HHIPL1	POLRMT	psi-mi:“MI:0914”(association)	0.350
C1QTNF9B	RTCA	psi-mi:“MI:0914”(association)	0.350
SDF2L1	MANBA	psi-mi:“MI:0914”(association)	0.350
TRGV3	MANBA	psi-mi:“MI:0914”(association)	0.350
ECEL1	ADAM10	psi-mi:“MI:0914”(association)	0.350
KLK15	APAF1	psi-mi:“MI:0914”(association)	0.350
FCN3	MAP2K7	psi-mi:“MI:0914”(association)	0.350
LILRA5	HGS	psi-mi:“MI:0914”(association)	0.350
ITLN1	RAB29	psi-mi:“MI:0914”(association)	0.350
ARSA	CLGN	psi-mi:“MI:0914”(association)	0.350
TSHR	PLXNB2	psi-mi:“MI:0914”(association)	0.350
TMEM25	CRLF1	psi-mi:“MI:0914”(association)	0.350
DHFR2	FGFR1	psi-mi:“MI:0914”(association)	0.350
TCTN1	GUSB	psi-mi:“MI:0914”(association)	0.350

BioGRID (30): FAM132B (Affinity Capture-MS), FAM132B (Biochemical Activity), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Proximity Label-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS), FAM132B (Affinity Capture-MS)

ESM2 similar proteins: A4FV93, A4IIA2, A5A8Y8, B2LW77, D3Z7H8, D3ZUK3, D4AB34, O75074, O88204, P07204, P15306, P24592, P35572, P47880, P51693, P60882, Q03157, Q2KJ51, Q32L50, Q3SWY4, Q3TYX2, Q4G0M1, Q501P1, Q53RD9, Q5RKR3, Q5W7P8, Q5XHC5, Q61810, Q6AZ60, Q6GUQ1, Q6MG84, Q6PGN1, Q6UY11, Q71U07, Q7Z7M0, Q86VZ4, Q8CB67, Q8IVN8, Q8K099, Q8K1E3

Diamond homologs: A1A5X5, A4IH36, D4AB34, Q4G0M1, Q5T7M4, Q6PGN1, Q8R2Z0

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 45 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Innate Immune System	8	6.6×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

1598 predictions. Top by Δscore:

Variant	Effect	Δscore
2:238159202:GCCG:G	donor_gain	1.0000
2:238159203:CCGG:C	donor_loss	1.0000
2:238159204:CGGT:C	donor_loss	1.0000
2:238159205:GGT:G	donor_loss	1.0000
2:238159206:G:GG	donor_gain	1.0000
2:238159206:GT:G	donor_loss	1.0000
2:238159207:TAAGA:T	donor_loss	1.0000
2:238161714:AAG:A	donor_loss	1.0000
2:238161715:AGG:A	donor_loss	1.0000
2:238161716:GGTG:G	donor_loss	1.0000
2:238161717:G:GA	donor_loss	1.0000
2:238163998:TGGTG:T	donor_loss	1.0000
2:238164000:G:GG	donor_gain	1.0000
2:238164001:T:G	donor_loss	1.0000
2:238164359:GC:G	donor_gain	1.0000
2:238164361:G:GG	donor_gain	1.0000
2:238165597:T:TA	acceptor_gain	1.0000
2:238165602:ACAGC:A	acceptor_loss	1.0000
2:238165603:C:G	acceptor_gain	1.0000
2:238165603:CAG:C	acceptor_loss	1.0000
2:238165604:A:AG	acceptor_gain	1.0000
2:238165604:AG:A	acceptor_loss	1.0000
2:238165605:G:GT	acceptor_gain	1.0000
2:238165605:GCTCC:G	acceptor_gain	1.0000
2:238165682:CAGG:C	donor_loss	1.0000
2:238165683:AGGT:A	donor_loss	1.0000
2:238165684:GGT:G	donor_loss	1.0000
2:238165685:G:C	donor_loss	1.0000
2:238165686:T:G	donor_loss	1.0000
2:238163792:C:A	acceptor_gain	0.9900

AlphaMissense

2237 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:238163928:T:C	F206L	0.993
2:238163930:C:A	F206L	0.993
2:238163930:C:G	F206L	0.993
2:238164132:T:G	Y249D	0.993
2:238161639:T:A	W82R	0.992
2:238161639:T:C	W82R	0.992
2:238161641:G:C	W82C	0.992
2:238161641:G:T	W82C	0.992
2:238164334:C:G	C287W	0.992
2:238164333:G:A	C287Y	0.991
2:238167029:T:C	F347S	0.991
2:238164133:A:C	Y249S	0.990
2:238166988:C:A	N333K	0.990
2:238166988:C:G	N333K	0.990
2:238163929:T:C	F206S	0.988
2:238164132:T:A	Y249N	0.987
2:238164169:C:A	A261D	0.987
2:238164332:T:C	C287R	0.986
2:238166975:T:A	V329E	0.985
2:238164127:G:A	G247D	0.983
2:238164132:T:C	Y249H	0.983
2:238165680:T:C	L321P	0.983
2:238164330:T:A	I286N	0.982
2:238164332:T:A	C287S	0.982
2:238164333:G:C	C287S	0.982
2:238167023:C:T	S345F	0.982
2:238167035:C:A	A349D	0.982
2:238164324:T:C	L284P	0.981
2:238166977:T:C	F330L	0.981
2:238166979:C:A	F330L	0.981

dbSNP variants (sampled 300 via entrez): RS1000219574 (2:238159857 G>GA), RS1000943062 (2:238160066 T>A,C), RS1001015721 (2:238165050 C>T), RS1001164802 (2:238164453 C>G,T), RS1001201740 (2:238158582 G>C), RS1001366815 (2:238167236 C>T), RS1001452680 (2:238162670 G>T), RS1001737953 (2:238164226 C>T), RS1001854890 (2:238167841 G>A), RS1001857054 (2:238158474 G>A), RS1001974449 (2:238158922 G>C), RS1002250251 (2:238168201 GAC>G), RS1002459995 (2:238163853 G>A), RS1002656680 (2:238158930 A>G), RS1003001765 (2:238162968 G>A,T)

Disease associations

OMIM: gene MIM:615099 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST004605_62	Mean corpuscular hemoglobin concentration	3.000000e-10
GCST011366_1	Iron status biomarkers (transferrin saturation)	1.000000e-12
GCST011367_7	Iron status biomarkers (iron levels)	2.000000e-12
GCST90002384_195	Hemoglobin	6.000000e-13
GCST90002390_470	Mean corpuscular hemoglobin	6.000000e-26
GCST90002392_178	Mean corpuscular volume	3.000000e-21
GCST90002404_37	Red cell distribution width	3.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0006333	transferrin saturation measurement
EFO:0004509	hemoglobin measurement
EFO:0004527	mean corpuscular hemoglobin
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects cotreatment, decreases expression, increases abundance	2
entinostat	increases expression, affects cotreatment	2
Valproic Acid	affects expression, increases methylation	2
aristolochic acid I	decreases expression	1
bisphenol A	affects expression	1
ethyl-p-hydroxybenzoate	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
manganese chloride	decreases expression, increases abundance, affects cotreatment	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MT19c compound	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Benzo(a)pyrene	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ethinyl Estradiol	affects expression	1
Manganese	decreases expression, increases abundance, affects cotreatment	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	decreases expression	1
Aflatoxin B1	increases expression	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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