ERAL1

Summary

ERAL1 (Era like 12S mitochondrial rRNA chaperone 1, HGNC:3424) is a protein-coding gene on chromosome 17q11.2, encoding GTPase Era, mitochondrial (O75616). Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. It is a selective cancer dependency (DepMap: 38.2% of cell lines).

The protein encoded by this gene is a GTPase that localizes to the mitochondrion. The encoded protein binds to the 3’ terminal stem loop of 12S mitochondrial rRNA and is required for proper assembly of the 28S small mitochondrial ribosomal subunit. Deletion of this gene has been shown to cause mitochondrial dysfunction, growth retardation, and apoptosis. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 26284 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Perrault syndrome 6 (Moderate, GenCC) — +1 more curated relationship
• GWAS associations: 10
• Clinical variants (ClinVar): 73 total — 1 pathogenic
• Phenotypes (HPO): 8
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 38.2% of screened cell lines
• MANE Select transcript: NM_005702

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3424
Approved symbol	ERAL1
Name	Era like 12S mitochondrial rRNA chaperone 1
Location	17q11.2
Locus type	gene with protein product
Status	Approved
Aliases	HERA-B
Ensembl gene	ENSG00000132591
Ensembl biotype	protein_coding
OMIM	607435
Entrez	26284

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 2 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000254928, ENST00000412138, ENST00000461894, ENST00000471992, ENST00000577942, ENST00000578001, ENST00000580917, ENST00000583487, ENST00000878946, ENST00000878947, ENST00000878948, ENST00000878949, ENST00000919429, ENST00000919430, ENST00000919431, ENST00000919432, ENST00000969112, ENST00000969113, ENST00000969114, ENST00000969115

RefSeq mRNA: 3 — MANE Select: NM_005702 NM_001317985, NM_001317986, NM_005702

CCDS: CCDS11244

Canonical transcript exons

ENST00000254928 — 10 exons

Exon	Start	End
ENSE00001941036	28860431	28861061
ENSE00002718129	28855016	28855317
ENSE00003518098	28858146	28858207
ENSE00003585526	28856264	28856391
ENSE00003586822	28857939	28857985
ENSE00003622421	28859203	28859283
ENSE00003633048	28856505	28856582
ENSE00003652478	28858576	28858824
ENSE00003674418	28858374	28858486
ENSE00003784448	28858964	28859113

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 93.98.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 52.8606 / max 299.3541, expressed in 1821 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
160069	52.8606	1821

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	93.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.93	gold quality
cerebellar hemisphere	UBERON:0002245	93.85	gold quality
cerebellar cortex	UBERON:0002129	93.71	gold quality
apex of heart	UBERON:0002098	93.67	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.53	gold quality
gastrocnemius	UBERON:0001388	93.27	gold quality
right frontal lobe	UBERON:0002810	93.22	gold quality
right adrenal gland cortex	UBERON:0035827	93.14	gold quality
right adrenal gland	UBERON:0001233	93.03	gold quality
muscle of leg	UBERON:0001383	92.79	gold quality
right lobe of liver	UBERON:0001114	92.46	gold quality
ventricular zone	UBERON:0003053	92.41	gold quality
left adrenal gland	UBERON:0001234	92.29	gold quality
left adrenal gland cortex	UBERON:0035825	91.89	gold quality
rectum	UBERON:0001052	91.78	gold quality
heart left ventricle	UBERON:0002084	91.74	gold quality
ganglionic eminence	UBERON:0004023	91.53	gold quality
metanephros cortex	UBERON:0010533	91.44	gold quality
prefrontal cortex	UBERON:0000451	91.32	gold quality
body of stomach	UBERON:0001161	91.18	gold quality
right ovary	UBERON:0002118	91.13	gold quality
cardiac ventricle	UBERON:0002082	91.07	gold quality
cerebellum	UBERON:0002037	91.06	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	90.87	gold quality
stromal cell of endometrium	CL:0002255	90.86	gold quality
lower esophagus mucosa	UBERON:0035834	90.81	gold quality
right uterine tube	UBERON:0001302	90.74	gold quality
cingulate cortex	UBERON:0003027	90.74	gold quality
adrenal gland	UBERON:0002369	90.71	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

36 targeting ERAL1, 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-6825-5P	99.96	69.81	3431
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-6727-3P	99.49	65.92	1333
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-4722-3P	99.35	65.22	1099
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-6895-3P	98.79	65.69	996
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-6878-5P	98.49	67.91	2142
HSA-MIR-1233-5P	98.19	66.71	1201
HSA-MIR-6778-5P	98.19	66.59	1239
HSA-MIR-4768-3P	98.16	66.02	2330

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 38.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Data show that loss of ERAL1 leads to rapid decay of nascent 12S mt-rRNA, consistent with a role as a mitochondrial RNA chaperone. (PMID:20604745)
• Three women from three different families presented with signs of PS, including deafness and ovarian dysgenesis. We employed exome sequencing and identified a homozygous missense mutation in the ERAL1 gene, c.707A > T. The mutation leads to a damaging p.Asn236Ile substitution that is likely to interfere with the GTP binding capacity of the ERAL1 protein. (PMID:28449065)
• The mitochondrial protein ERAL1 suppresses RNA virus infection by facilitating RIG-I-like receptor signaling. (PMID:33472079)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	eral1	ENSDARG00000059887
mus_musculus	Eral1	ENSMUSG00000020832
rattus_norvegicus	Eral1	ENSRNOG00000010673
drosophila_melanogaster	CG7488	FBGN0038106
caenorhabditis_elegans		WBGENE00008456

Paralogs (1): GTPBP3 (ENSG00000130299)

Protein

Protein identifiers

GTPase Era, mitochondrial — O75616 (reviewed: O75616)

Alternative names: Conserved ERA-like GTPase, ERA-W, ERA-like protein 1

All UniProt accessions (5): O75616, J3QRV9, J3QSB2, J3QT61, K7EQJ8

UniProt curated annotations — full annotation on UniProt →

Function. Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3’ terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly.

Subcellular location. Mitochondrion matrix. Mitochondrion inner membrane.

Disease relevance. Perrault syndrome 6 (PRLTS6) [MIM:617565] A form of Perrault syndrome, a sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. PRLTS6 inheritance is autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Era GTPase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75616-1	HERA-A	yes
O75616-2	HERA-B

RefSeq proteins (3): NP_001304914, NP_001304915, NP_005693* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005225	Small_GTP-bd	Domain
IPR005662	GTPase_Era-like	Family
IPR006073	GTP-bd	Domain
IPR009019	KH_sf_prok-type	Homologous_superfamily
IPR015946	KH_dom-like_a/b	Homologous_superfamily
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR030388	G_ERA_dom	Domain

Pfam: PF01926

UniProt features (44 total): helix 11, strand 9, region of interest 6, sequence conflict 4, turn 4, binding site 3, domain 2, transit peptide 1, chain 1, modified residue 1, splice variant 1, sequence variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8CSQ	ELECTRON MICROSCOPY	2.54
8CSP	ELECTRON MICROSCOPY	2.66

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75616-F1	78.44	0.59

Functional residue map

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

Ligand- & substrate-binding residues (3): 120–127; 167–171; 236–239

Post-translational modifications (1): 173

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5368286	Mitochondrial translation initiation
R-HSA-5389840	Mitochondrial translation elongation
R-HSA-5419276	Mitochondrial translation termination
R-HSA-9937383	Mitochondrial ribosome-associated quality control

MSigDB gene sets: 0 (showing top):

GO Biological Process (3): ribosomal small subunit assembly (GO:0000028), mitochondrial small ribosomal subunit assembly (GO:0180026), ribosome biogenesis (GO:0042254)

GO Molecular Function (7): RNA binding (GO:0003723), GTP binding (GO:0005525), rRNA binding (GO:0019843), ribosomal small subunit binding (GO:0043024), RNA folding chaperone (GO:0140691), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (5): mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Mitochondrial translation	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	2
cellular anatomical structure	2
protein-RNA complex assembly	1
ribosome assembly	1
ribosomal small subunit biogenesis	1
ribosomal small subunit assembly	1
mitochondrial ribosome assembly	1
ribonucleoprotein complex biogenesis	1
nucleic acid binding	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
RNA binding	1
ribosome binding	1
molecular_function	1
RNA folding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1866 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ERAL1	NOA1	Q8NC60	776
ERAL1	DDX28	Q9NUL7	752
ERAL1	MRPS7	Q9Y2R9	741
ERAL1	MTG1	Q9BT17	734
ERAL1	MTG2	Q9H4K7	730
ERAL1	GTPBP10	A4D1E9	728
ERAL1	CLPP	Q16740	718
ERAL1	LARS2	Q15031	709
ERAL1	MRPS22	P82650	689
ERAL1	NSUN4	Q96CB9	672
ERAL1	TWNK	Q96RR1	667
ERAL1	MTERF3	Q96E29	655
ERAL1	MRPS18B	Q9Y676	655
ERAL1	TFB1M	Q8WVM0	644
ERAL1	RBFA	Q8N0V3	635

IntAct

145 interactions, top by confidence:

A	B	Type	Score
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
FAM120A	SYNCRIP	psi-mi:“MI:0914”(association)	0.640
MRPS27	MRPS14	psi-mi:“MI:0914”(association)	0.640
CEP44	ERAL1	psi-mi:“MI:0915”(physical association)	0.560
ERAL1	SSX2IP	psi-mi:“MI:0915”(physical association)	0.560
ERAL1	A2M	psi-mi:“MI:0915”(physical association)	0.560
TOR1A	ERAL1	psi-mi:“MI:0915”(physical association)	0.560
ERAL1	SMN1	psi-mi:“MI:0915”(physical association)	0.560
NP	KPNA6	psi-mi:“MI:0914”(association)	0.550
ERAL1	COL1A1	psi-mi:“MI:0914”(association)	0.530
ERAL1	DAP3	psi-mi:“MI:0403”(colocalization)	0.530
MRPS26	ERAL1	psi-mi:“MI:0914”(association)	0.530
MRPS18B	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS34	MRPS12	psi-mi:“MI:0914”(association)	0.530
MRPS11	MRPS14	psi-mi:“MI:0914”(association)	0.530
MRPS18C	MRPS14	psi-mi:“MI:0914”(association)	0.530
NDUFAB1	MIEF1	psi-mi:“MI:0915”(physical association)	0.490
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
HNRNPDL	ERAL1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (283): ERAL1 (Affinity Capture-MS), CEP44 (Two-hybrid), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), COL1A1 (Affinity Capture-MS), ATPAF1 (Affinity Capture-MS), COL1A2 (Affinity Capture-MS), MCAT (Affinity Capture-MS), COL3A1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS), ERAL1 (Affinity Capture-MS)

ESM2 similar proteins: A2VD13, A4D126, A5PK43, A6H751, A7E3N7, B0S6U7, B0S8I0, B5DFG1, D2GU20, E1BCH6, O75127, O75616, O95382, P36915, P36916, P48760, Q05932, Q2TBP8, Q2VPK5, Q3SZK4, Q3U269, Q3U5Q7, Q3V300, Q4R8D2, Q5E9Z1, Q5EBA0, Q5ND52, Q5QJC3, Q5R655, Q5RA07, Q5RJG7, Q5S6T3, Q5TM59, Q6MG06, Q7YR35, Q8C2E4, Q8CJ00, Q8JIF5, Q8K045, Q8NC60

Diamond homologs: A0LJ92, A0Q125, A1APR9, A1KCP8, A1U2V4, A1V7D3, A2S8D8, A3MS17, A3NPX5, A4GAN2, A4JJ44, A4T0N1, A4XSC5, A4YWC7, A5EKL6, A5GPA1, A5IIK3, A5PK43, A6LSI6, A6T4D6, A6U7A9, A6VQS6, A7IIE4, A7MN03, A8LLE0, A9IJ97, A9WHH9, B0JFL6, B0S6U7, B1K0Y2, B1ZWP5, B2A470, B2S3S8, B2V5W6, B2V968, B3E421, B4F0U0, B5X2B8, B8DQN1, B8GAY7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 154 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
Mitochondrial ribosome-associated quality control	24	29.5×	6e-27
Mitochondrial translation	21	28.9×	1e-23
Mitochondrial translation initiation	22	27.9×	2e-24
Mitochondrial translation elongation	22	27.9×	2e-24
Mitochondrial translation termination	22	24.2×	4e-23
Translation	22	13.7×	2e-17
mRNA 3’-end processing	5	9.8×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial translation	23	30.0×	3e-25
translation	12	9.3×	2e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	45
Likely benign	8
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
430638	NM_005702.4(ERAL1):c.707A>T (p.Asn236Ile)	Pathogenic

SpliceAI

1353 predictions. Top by Δscore:

Variant	Effect	Δscore
17:28855315:GAG:G	donor_gain	1.0000
17:28856252:A:AG	acceptor_gain	1.0000
17:28856255:T:A	acceptor_gain	1.0000
17:28856258:A:AG	acceptor_gain	1.0000
17:28856259:CATA:C	acceptor_loss	1.0000
17:28856260:A:AG	acceptor_gain	1.0000
17:28856261:T:G	acceptor_gain	1.0000
17:28856261:TA:T	acceptor_loss	1.0000
17:28856262:A:AG	acceptor_gain	1.0000
17:28856262:A:C	acceptor_loss	1.0000
17:28856263:G:GG	acceptor_gain	1.0000
17:28856263:GAT:G	acceptor_gain	1.0000
17:28856263:GATGA:G	acceptor_gain	1.0000
17:28856355:G:T	donor_gain	1.0000
17:28856389:AAGGT:A	donor_loss	1.0000
17:28856390:AGG:A	donor_loss	1.0000
17:28856391:GGT:G	donor_loss	1.0000
17:28856392:GTATG:G	donor_loss	1.0000
17:28856393:T:A	donor_loss	1.0000
17:28856599:G:GT	donor_gain	1.0000
17:28858209:T:G	donor_gain	1.0000
17:28858219:G:GT	donor_gain	1.0000
17:28858356:T:A	acceptor_gain	1.0000
17:28858361:T:TA	acceptor_gain	1.0000
17:28858366:T:G	acceptor_gain	1.0000
17:28858372:A:AG	acceptor_gain	1.0000
17:28858372:AGTT:A	acceptor_gain	1.0000
17:28858373:G:GA	acceptor_gain	1.0000
17:28858373:GT:G	acceptor_gain	1.0000
17:28858373:GTT:G	acceptor_gain	1.0000

AlphaMissense

2838 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:28859061:G:C	R353P	0.995
17:28859070:T:C	L356P	0.995
17:28857949:A:C	D167A	0.994
17:28858473:T:C	L233P	0.994
17:28858476:T:A	V234D	0.994
17:28858486:G:C	K237N	0.994
17:28858486:G:T	K237N	0.994
17:28858997:T:A	W332R	0.994
17:28858997:T:C	W332R	0.994
17:28858483:C:A	N236K	0.993
17:28858483:C:G	N236K	0.993
17:28858999:G:C	W332C	0.993
17:28858999:G:T	W332C	0.993
17:28856338:G:A	G120R	0.992
17:28856338:G:C	G120R	0.992
17:28856350:G:C	A124P	0.992
17:28856353:G:T	G125W	0.992
17:28856354:G:A	G125E	0.992
17:28856366:T:C	L129P	0.992
17:28856356:A:C	K126Q	0.991
17:28856378:T:C	L133P	0.991
17:28857949:A:T	D167V	0.991
17:28859215:T:A	W375R	0.991
17:28859215:T:C	W375R	0.991
17:28856366:T:A	L129H	0.990
17:28856387:G:C	R136P	0.990
17:28857948:G:C	D167H	0.990
17:28858473:T:A	L233Q	0.990
17:28856349:T:A	N123K	0.989
17:28856349:T:G	N123K	0.989

dbSNP variants (sampled 300 via entrez): RS1000274437 (17:28857803 A>G), RS1000857312 (17:28855351 C>A), RS1001285364 (17:28856418 C>T), RS1001695509 (17:28855988 T>C), RS1002295153 (17:28854243 C>A), RS1002691817 (17:28854573 A>G), RS1002743515 (17:28859626 G>A), RS1002995516 (17:28858131 A>G), RS1003588250 (17:28853157 C>T), RS1004118478 (17:28856954 G>A), RS1004261086 (17:28856708 C>G,T), RS1005255053 (17:28860881 G>A,C), RS1005928079 (17:28857005 C>T), RS1005978524 (17:28856481 C>A,G), RS1006198600 (17:28858404 G>A)

Disease associations

OMIM: gene MIM:607435 | disease phenotypes: MIM:617565, MIM:233400

GenCC curated gene-disease

Disease	Classification	Inheritance
Perrault syndrome 6	Moderate	Autosomal recessive
Perrault syndrome	Supportive	Autosomal recessive

Mondo (3): Perrault syndrome 6 (MONDO:0033047), hearing loss disorder (MONDO:0005365), Perrault syndrome (MONDO:0017312)

Orphanet (1): Perrault syndrome (Orphanet:2855)

HPO phenotypes

8 total (8 of 8 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000407	Sensorineural hearing impairment
HP:0000786	Primary amenorrhea
HP:0000858	Irregular menstruation
HP:0000869	Secondary amenorrhea
HP:0008209	Premature ovarian insufficiency
HP:0010464	Streak ovary

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST004006_14	Mean corpuscular hemoglobin	6.000000e-06
GCST004611_215	High light scatter reticulocyte count	2.000000e-29
GCST004612_205	High light scatter reticulocyte percentage of red cells	6.000000e-25
GCST004628_16	Immature fraction of reticulocytes	4.000000e-53
GCST006011_47	Mean corpuscular volume	4.000000e-09
GCST006629_7	Pulse pressure	8.000000e-15
GCST007954_4	Glycated hemoglobin levels	3.000000e-11
GCST008837_5	Estimated glomerular filtration rate reduction (30%)	9.000000e-06
GCST90002387_25	Immature fraction of reticulocytes	3.000000e-80
GCST90002404_152	Red cell distribution width	5.000000e-193

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0007986	reticulocyte count
EFO:0005763	pulse pressure measurement
EFO:0004541	HbA1c measurement
EFO:0009188	Red cell distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D034381	Hearing Loss	C09.218.458.341; C10.597.751.418.341; C23.888.592.763.393.341

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067005 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.16	Kd	69.7	nM	CHEMBL5653589
7.16	ED50	69.7	nM	CHEMBL5653589

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148328: Binding affinity to human ERAL1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0697	uM

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	increases reaction, affects binding	1
bisphenol S	affects expression	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation	1
Dexamethasone	increases expression, affects cotreatment	1
Indomethacin	increases expression, affects cotreatment	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651370	Binding	Binding affinity to human ERAL1 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00205881	PHASE4	COMPLETED	Bilateral Benefit in Adult Users of the HiRes 90K Bionic Ear System
NCT00331539	PHASE4	UNKNOWN	Relationship Between Auto NRT and Behavioural T & C Levels With the Nucleus Freedom Cochlear Implant
NCT00424307	PHASE4	UNKNOWN	Bilateral Cochlear Implant Benefit in Young Children
NCT00765635	PHASE4	COMPLETED	Chlorobutanol, Potassium Carbonate, and Irrigation in Cerumen Removal
NCT03321006	PHASE4	COMPLETED	Treating Hearing Loss to Improve Mood and Cognition in Older Adults
NCT01499901	PHASE3	WITHDRAWN	Comparison of the Bilateral Sequential and Simultaneous Cochlear Implantation in the Deaf Children
NCT02561091	PHASE3	COMPLETED	AM-111 in the Treatment of Acute Inner Ear Hearing Loss
NCT03331627	PHASE3	COMPLETED	Safety and Efficacy of STR001-IT and STR001-ER in Patients With SSHL
NCT05532657	PHASE3	ACTIVE_NOT_RECRUITING	ACHIEVE Brain Health Follow-Up Study
NCT00013455	PHASE2	COMPLETED	Quantifying Auditory Perceptual Learning Following Hearing Aid Fitting
NCT00323427	PHASE2	COMPLETED	Clinical Trial of the Living Well With Hearing Loss Workshop
NCT00552786	PHASE2	COMPLETED	Antioxidation Medication for Noise-induced Hearing Loss
NCT00802425	PHASE2	COMPLETED	Efficacy of AM-111 in Patients With Acute Sensorineural Hearing Loss
NCT01139281	PHASE2	COMPLETED	The Protective Effect of Ginkgo Biloba Extract on Cisplatin-induced Ototoxicity in Humans
NCT01451853	PHASE2	UNKNOWN	SPI-1005 for Prevention and Treatment of Chemotherapy Induced Hearing Loss
NCT01588925	PHASE2	COMPLETED	Hearing Preservation Using Dexamethasone and Hyaluronic Acid for Cochlear Implantation
NCT01773278	PHASE2	RECRUITING	Cholesterol and Antioxidant Treatment in Patients With Smith-Lemli-Opitz Syndrome (SLOS)
NCT02832128	PHASE2	COMPLETED	Evaluating Possible Improvement in Speech and Hearing Tests After 28 Days of Dosing of the Study Drug AUT00063 Compared to Placebo (QuicKfire)
NCT04915183	PHASE2	RECRUITING	Atorvastatin to Reduce Cisplatin-Induced Hearing Loss Among Individuals With Head and Neck Cancer
NCT05258773	PHASE2	COMPLETED	Evaluation of the Presence of SENS-401 in the Perilymph
NCT06340633	PHASE2	RECRUITING	SPI-1005 in Adults Receiving Cochlear Implant
NCT00582946	PHASE1	COMPLETED	Wide-Bandwidth Open Canal Hearing Aid For Better Multitalker Speech Understanding
NCT00584155	PHASE1	WITHDRAWN	Protection From Cisplatin Ototoxicity by Lactated Ringers
NCT01206829	PHASE1	UNKNOWN	Hearing Impairment, Cognitive Therapy and Coping
NCT01256229	PHASE1	COMPLETED	Outcomes In Children With Developmental Delay And Deafness
NCT01343394	PHASE1	WITHDRAWN	Safety of Autologous Human Umbilical Cord Blood Mononuclear Fraction to Treat Acquired Hearing Loss in Children
NCT01452607	PHASE1	COMPLETED	Study to Evaluate the Safety and Pharmacokinetics of SPI-1005
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT04041440	PHASE1	COMPLETED	Speech Recognition Training in Children With Hearing Loss
NCT07218913	PHASE1	RECRUITING	Testing the Addition of Pedmark to Cisplatin Chemotherapy for Reducing Drug-Induced Ear Damage in Men With Stage II-III Metastatic Testicular Germ Cell Tumors
NCT00486577	PHASE2/PHASE3	COMPLETED	Chronic Electrical Stimulation of the Auditory Cortex for Intractable Tinnitus
NCT00789061	PHASE2/PHASE3	UNKNOWN	Applying Proton Pump Inhibitor to Prevent and Treat Acute Fluctuating Hearing Loss in Patients With SLC26A4 Mutation
NCT01423409	PHASE2/PHASE3	COMPLETED	Multicenter Trial Assessing an Innovative VAS of Pain Among Deaf People
NCT05786378	PHASE2/PHASE3	UNKNOWN	Assessment of The Efficacy of Intratympanic Platelet Rich Plasma for Treatment of Sensorineural Hearing Loss.
NCT01108601	PHASE1/PHASE2	UNKNOWN	Transtympanic Ringer’s Lactate for the Prevention of Cisplatin Ototoxicity
NCT01621256	PHASE1/PHASE2	COMPLETED	Efficacy, Safety, and Tolerability of Ancrod in Patients With Sudden Hearing Loss
NCT06370351	PHASE1/PHASE2	RECRUITING	A Phase I/II Clinical Trial with SENS-501 in Children Suffering from Severe to Profound Hearing Loss Due to Otoferlin (OTOF) Mutations
NCT06545175	PHASE1/PHASE2	RECRUITING	Intracochlear Application of VSF1.01 for the Reduction of Cochlear Implant Surgery Related Trauma
NCT07304024	PHASE1/PHASE2	RECRUITING	A Treatment for a Form of Age-Related Central Auditory Processing Disorder Consisting of Clemastine Fumarate Plus Engineered Sound
NCT01109576	EARLY_PHASE1	COMPLETED	Workshops for Veterans With Vision and Hearing Loss