PLS1

Summary

PLS1 (plastin 1, HGNC:9090) is a protein-coding gene on chromosome 3q23, encoding Plastin-1 (Q14651). Actin-bundling protein.

Plastins are a family of actin-binding proteins that are conserved throughout eukaryote evolution and expressed in most tissues of higher eukaryotes. In humans, two ubiquitous plastin isoforms (L and T) have been identified. The protein encoded by this gene is a third distinct plastin isoform, which is specifically expressed at high levels in the small intestine. Alternatively spliced transcript variants varying in the 5’ UTR, but encoding the same protein, have been found for this gene. A pseudogene of this gene is found on chromosome 11.

Source: NCBI Gene 5357 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hearing loss, autosomal dominant 76 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 163 total — 3 likely-pathogenic
• Phenotypes (HPO): 6
• MANE Select transcript: NM_001145319

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9090
Approved symbol	PLS1
Name	plastin 1
Location	3q23
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000120756
Ensembl biotype	protein_coding
OMIM	602734
Entrez	5357

Gene structure

Transcript identifiers

Ensembl transcripts: 90 — 88 protein_coding, 2 retained_intron

ENST00000337777, ENST00000457734, ENST00000460104, ENST00000461644, ENST00000464320, ENST00000475296, ENST00000476044, ENST00000483373, ENST00000483507, ENST00000495744, ENST00000497002, ENST00000497199, ENST00000900957, ENST00000900958, ENST00000900959, ENST00000900960, ENST00000900961, ENST00000900962, ENST00000900963, ENST00000900964, ENST00000900965, ENST00000900966, ENST00000900967, ENST00000900968, ENST00000900969, ENST00000900970, ENST00000900971, ENST00000900972, ENST00000900973, ENST00000900974, ENST00000900975, ENST00000900976, ENST00000900977, ENST00000900978, ENST00000900979, ENST00000900980, ENST00000900981, ENST00000900982, ENST00000900983, ENST00000900984, ENST00000900985, ENST00000900986, ENST00000900987, ENST00000900988, ENST00000900989, ENST00000900990, ENST00000900991, ENST00000900992, ENST00000900993, ENST00000900994, ENST00000900995, ENST00000900996, ENST00000900997, ENST00000900998, ENST00000900999, ENST00000901000, ENST00000901001, ENST00000901002, ENST00000901003, ENST00000901004, ENST00000901005, ENST00000901006, ENST00000901007, ENST00000901008, ENST00000901009, ENST00000901010, ENST00000901011, ENST00000901012, ENST00000901013, ENST00000937733, ENST00000937734, ENST00000937735, ENST00000968171, ENST00000968172, ENST00000968173, ENST00000968174, ENST00000968175, ENST00000968176, ENST00000968177, ENST00000968178, ENST00000968179, ENST00000968180, ENST00000968181, ENST00000968182, ENST00000968183, ENST00000968184, ENST00000968185, ENST00000968186, ENST00000968187, ENST00000968188

RefSeq mRNA: 3 — MANE Select: NM_001145319 NM_001145319, NM_001172312, NM_002670

CCDS: CCDS3125

Canonical transcript exons

ENST00000457734 — 16 exons

Exon	Start	End
ENSE00000779238	142711501	142711625
ENSE00000779239	142704463	142704586
ENSE00000779240	142703868	142704001
ENSE00000968012	142684253	142684395
ENSE00001023400	142689618	142689813
ENSE00001077560	142684006	142684171
ENSE00001077562	142678032	142678113
ENSE00001077563	142664202	142664307
ENSE00001077564	142697953	142698067
ENSE00001077566	142686284	142686376
ENSE00001077567	142676157	142676289
ENSE00001660820	142596393	142596509
ENSE00001947768	142711872	142713664
ENSE00003547722	142670993	142671122
ENSE00003594282	142669390	142669553
ENSE00003693796	142694469	142694547

Expression profiles

Bgee: expression breadth ubiquitous, 236 present calls, max score 99.71.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 8.8977 / max 1101.3834, expressed in 1148 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
38950	7.8788	1146
38951	0.5625	202
38956	0.4383	9
38955	0.0154	4
38954	0.0026	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.71	gold quality
jejunal mucosa	UBERON:0000399	99.68	gold quality
ileal mucosa	UBERON:0000331	99.19	gold quality
colonic mucosa	UBERON:0000317	99.05	gold quality
mucosa of sigmoid colon	UBERON:0004993	99.02	gold quality
rectum	UBERON:0001052	98.45	gold quality
oocyte	CL:0000023	98.44	gold quality
duodenum	UBERON:0002114	97.81	gold quality
palpebral conjunctiva	UBERON:0001812	97.39	gold quality
bronchial epithelial cell	CL:0002328	96.39	gold quality
mucosa of transverse colon	UBERON:0004991	95.63	gold quality
epithelium of bronchus	UBERON:0002031	95.16	gold quality
islet of Langerhans	UBERON:0000006	94.76	gold quality
bronchus	UBERON:0002185	94.56	gold quality
choroid plexus epithelium	UBERON:0003911	94.31	gold quality
nasal cavity epithelium	UBERON:0005384	93.45	gold quality
esophagus squamous epithelium	UBERON:0006920	92.84	gold quality
gall bladder	UBERON:0002110	91.25	gold quality
epithelial cell of pancreas	CL:0000083	90.22	gold quality
pancreatic ductal cell	CL:0002079	90.17	gold quality
nasal cavity mucosa	UBERON:0001826	89.35	gold quality
epithelium of esophagus	UBERON:0001976	89.21	gold quality
small intestine	UBERON:0002108	89.06	gold quality
nephron tubule	UBERON:0001231	88.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	88.51	gold quality
colonic epithelium	UBERON:0000397	88.33	gold quality
transverse colon	UBERON:0001157	87.92	gold quality
endometrium epithelium	UBERON:0004811	87.82	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	87.78	gold quality
epithelium of nasopharynx	UBERON:0001951	87.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting PLS1, 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-5692A	100.00	74.40	6850
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-8082	99.95	67.27	1170
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-17-5P	99.89	73.83	2665

Literature-anchored findings (GeneRIF, showing 10)

• upregulated in eosinophils from atopic dermatitis patients (PMID:27304220)
• In this study, the authors found that the actin filament bundling abilities of PLS1 and PLS2 were similarly sensitive to Ca(2+) (pCa50 ~6.4), whereas PLS3 was less sensitive (pCa50 ~5.9). (PMID:28694070)
• Increased expression of L-plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD. (PMID:30479022)
• a diverse genetic hearing impairment (HI) etiology in the Hungarian Roma and identify a new gene PLS1, for autosomal dominant human non-syndromic HI. (PMID:30872814)
• Findings identified missense variants in PLS1 gene in three unrelated autosomal dominant nonsyndromic hearing loss (NSHL) families. In silico protein modeling suggests that all variants destabilize the structure of the actin-binding domain 1. These results clearly support that PLS1 is required for normal hearing and is a novel gene for autosomal dominant HL. (PMID:31397523)
• Novel variant p.E269K confirms causative role of PLS1 mutations in autosomal dominant hearing loss. (PMID:31432506)
• Plastin 1 promotes osteoblast differentiation by regulating intracellular Ca2. (PMID:32318696)
• Plastin 1 drives metastasis of colorectal cancer through the IQGAP1/Rac1/ERK pathway. (PMID:32350953)
• L-plastin Ser5 phosphorylation is modulated by the PI3K/SGK pathway and promotes breast cancer cell invasiveness. (PMID:33618712)
• L-Plastin Promotes Gastric Cancer Growth and Metastasis in a Helicobacter pylori cagA-ERK-SP1-Dependent Manner. (PMID:33771880)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pls1	ENSDARG00000039272
mus_musculus	Pls1	ENSMUSG00000049493
rattus_norvegicus	Pls1	ENSRNOG00000009945
drosophila_melanogaster	Fim	FBGN0024238
caenorhabditis_elegans		WBGENE00022223
caenorhabditis_elegans		WBGENE00022425

Paralogs (2): PLS3 (ENSG00000102024), LCP1 (ENSG00000136167)

Protein

Protein identifiers

Plastin-1 — Q14651 (reviewed: Q14651)

Alternative names: Intestine-specific plastin

All UniProt accessions (8): C9J0F3, C9J359, C9JAM3, C9JAM8, C9JU08, C9JVY2, C9JYI1, Q14651

UniProt curated annotations — full annotation on UniProt →

Function. Actin-bundling protein. In the inner ear, it is required for stereocilia formation. Mediates liquid packing of actin filaments that is necessary for stereocilia to grow to their proper dimensions.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cell projection. Stereocilium.

Tissue specificity. In small intestine, colon, and kidney; relatively lower levels of expression are detected in the lung and stomach.

Post-translational modifications. Phosphorylated.

Disease relevance. Deafness, autosomal dominant, 76 (DFNA76) [MIM:618787] A form of non-syndromic deafness characterized by mild to profound sensorineural hearing loss and variable age at onset. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (3): NP_001138791, NP_001165783, NP_002661 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001589	Actinin_actin-bd_CS	Conserved_site
IPR001715	CH_dom	Domain
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site
IPR036872	CH_dom_sf	Homologous_superfamily
IPR039959	Fimbrin/Plastin	Family

Pfam: PF00307, PF13499

UniProt features (29 total): binding site 10, domain 6, sequence variant 6, sequence conflict 3, region of interest 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q14651-F1	87.52	0.67

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 (10): 26; 28; 30; 35; 64; 66; 68; 70; 75; 24

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-9662360	Sensory processing of sound by inner hair cells of the cochlea
R-HSA-9662361	Sensory processing of sound by outer hair cells of the cochlea

MSigDB gene sets: 260 (showing top): GOBP_DIGESTION, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION_TO_CELL_PERIPHERY, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_ANATOMICAL_STRUCTURE_SIZE, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_REGULATION_OF_MULTICELLULAR_ORGANISM_GROWTH, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION

GO Biological Process (9): intestinal D-glucose absorption (GO:0001951), regulation of microvillus length (GO:0032532), positive regulation of multicellular organism growth (GO:0040018), actin filament bundle assembly (GO:0051017), actin filament network formation (GO:0051639), auditory receptor cell stereocilium organization (GO:0060088), vestibular receptor cell stereocilium organization (GO:0060121), terminal web assembly (GO:1902896), positive regulation of protein localization to plasma membrane (GO:1903078)

GO Molecular Function (6): structural constituent of cytoskeleton (GO:0005200), calcium ion binding (GO:0005509), actin filament binding (GO:0051015), actin binding (GO:0003779), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (10): cytoplasm (GO:0005737), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), brush border (GO:0005903), stereocilium (GO:0032420), actin filament bundle (GO:0032432), extracellular exosome (GO:0070062), terminal web (GO:1990357), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Sensory processing of sound	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
inner ear receptor cell stereocilium organization	2
actin cytoskeleton	2
intestinal hexose absorption	1
regulation of microvillus organization	1
regulation of cell projection size	1
multicellular organism growth	1
regulation of multicellular organism growth	1
positive regulation of developmental growth	1
positive regulation of multicellular organismal process	1
cellular component assembly	1
actin filament bundle organization	1
actin filament organization	1
auditory receptor cell morphogenesis	1
vestibular receptor cell morphogenesis	1
neuron projection organization	1
cortical actin cytoskeleton organization	1
membraneless organelle assembly	1
protein localization to plasma membrane	1
regulation of protein localization to plasma membrane	1
positive regulation of protein localization to cell periphery	1
positive regulation of protein localization to membrane	1
structural molecule activity	1
cytoskeleton	1
cytoskeleton organization	1
metal ion binding	1
actin binding	1
protein-containing complex binding	1
cytoskeletal protein binding	1
binding	1
cation binding	1
intracellular anatomical structure	1
cytoplasm	1
polymeric cytoskeletal fiber	1
membrane	1
cell periphery	1
microvillus	1
apical part of cell	1
cluster of actin-based cell projections	1
stereocilium bundle	1

Protein interactions and networks

STRING

1448 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLS1	PCOLCE2	Q9UKZ9	826
PLS1	FSCN1	Q16658	777
PLS1	ESPN	B1AK53	666
PLS1	TRPC1	P48995	548
PLS1	PCOLCE	Q15113	497
PLS1	ESPNL	Q6ZVH7	487
PLS1	LYSMD4	Q5XG99	481
PLS1	EPS8L2	Q9H6S3	463
PLS1	FSCN2	O14926	448
PLS1	VIL1	P09327	435
PLS1	ITGB2	P05107	425
PLS1	SYK	P43405	425
PLS1	KRT19	P08727	422
PLS1	EXOC1	Q9NV70	418
PLS1	AKT1	P31749	409

IntAct

121 interactions, top by confidence:

A	B	Type	Score
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
KRT31	HGS	psi-mi:“MI:0914”(association)	0.780
INO80C	YY1	psi-mi:“MI:0914”(association)	0.740
DDRGK1	UFL1	psi-mi:“MI:0914”(association)	0.710
NFKBIA	POLRMT	psi-mi:“MI:0914”(association)	0.670
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
CRHBP	CCNB2	psi-mi:“MI:0914”(association)	0.640
LCP1	PLS3	psi-mi:“MI:0914”(association)	0.640
PLS3	LCP1	psi-mi:“MI:0914”(association)	0.640
SNRNP27	UBA6	psi-mi:“MI:0914”(association)	0.530
FYTTD1	UBA6	psi-mi:“MI:0914”(association)	0.530
METTL6	TYW5	psi-mi:“MI:0914”(association)	0.530
GALK2	POTEF	psi-mi:“MI:0914”(association)	0.530
FSD1	UBFD1	psi-mi:“MI:0914”(association)	0.530
LIPG	NRP1	psi-mi:“MI:0914”(association)	0.530
CNPPD1	SLC27A2	psi-mi:“MI:0914”(association)	0.530
USP47	DENR	psi-mi:“MI:0914”(association)	0.530
LINC02908	SEMG1	psi-mi:“MI:0914”(association)	0.530
GSTM3	ECT2L	psi-mi:“MI:0914”(association)	0.530
OR10H3	HMGCS1	psi-mi:“MI:0914”(association)	0.530
PLS3	PLS1	psi-mi:“MI:0914”(association)	0.530
STAT3	CLIC1	psi-mi:“MI:0914”(association)	0.530

BioGRID (192): PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS), PLS1 (Affinity Capture-MS)

ESM2 similar proteins: A6H742, A7E3Q8, O13728, O14134, O14185, O59945, O88818, P05095, P13796, P13797, P19179, P19966, P32599, P37803, P37804, P37805, P41810, P53585, P53978, P54680, P78820, P87078, Q00955, Q01995, Q08873, Q14651, Q3V0K9, Q3ZBY2, Q4R5J4, Q54BC6, Q54HG2, Q550R2, Q55BP5, Q5R6R2, Q61233, Q63598, Q6DG81, Q6FIR8, Q6FM46, Q6P698

Diamond homologs: A0A2I0BVG8, A6H742, A7E3Q8, O23184, O50064, O59945, O88818, P13796, P13797, P19179, P28470, P32599, P48451, P54680, P62343, P62344, P87072, Q0DJ94, Q14651, Q24214, Q25088, Q338P8, Q3E9C0, Q3V0K9, Q61233, Q63598, Q63811, Q6DG81, Q6P698, Q6Z2M9, Q7F0J0, Q7G188, Q7XHW4, Q84UL5, Q8C5W0, Q96LZ3, Q99K51, Q9FI19, Q9FJ70, Q9FKI0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	97
Likely benign	6
Benign	29

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
4084990	NM_001145319.2(PLS1):c.981+1G>A	Likely pathogenic
590932	NM_001145319.2(PLS1):c.1087C>T (p.Leu363Phe)	Likely pathogenic
633603	NM_001145319.2(PLS1):c.383T>C (p.Phe128Ser)	Likely pathogenic

SpliceAI

3150 predictions. Top by Δscore:

Variant	Effect	Δscore
3:142669385:TACA:T	acceptor_loss	1.0000
3:142669386:ACAG:A	acceptor_loss	1.0000
3:142669387:CA:C	acceptor_loss	1.0000
3:142669388:A:AC	acceptor_loss	1.0000
3:142669388:A:AG	acceptor_gain	1.0000
3:142669389:G:GG	acceptor_gain	1.0000
3:142669389:G:GT	acceptor_loss	1.0000
3:142669389:GAT:G	acceptor_gain	1.0000
3:142669550:GTCA:G	donor_gain	1.0000
3:142669551:TCA:T	donor_gain	1.0000
3:142669554:G:GG	donor_gain	1.0000
3:142669554:G:T	donor_loss	1.0000
3:142669555:TAA:T	donor_loss	1.0000
3:142669556:AA:A	donor_loss	1.0000
3:142670980:T:G	acceptor_gain	1.0000
3:142670986:A:AG	acceptor_gain	1.0000
3:142670988:TCCA:T	acceptor_loss	1.0000
3:142670991:A:AG	acceptor_gain	1.0000
3:142670992:G:A	acceptor_loss	1.0000
3:142670992:G:GA	acceptor_gain	1.0000
3:142670992:GC:G	acceptor_gain	1.0000
3:142670992:GCT:G	acceptor_gain	1.0000
3:142670992:GCTA:G	acceptor_gain	1.0000
3:142670992:GCTAA:G	acceptor_gain	1.0000
3:142671120:CAG:C	donor_loss	1.0000
3:142671121:AG:A	donor_loss	1.0000
3:142671122:GGTAA:G	donor_loss	1.0000
3:142671123:G:A	donor_loss	1.0000
3:142671124:T:G	donor_loss	1.0000
3:142676155:A:AG	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000026003 (3:142621498 G>A), RS1000026927 (3:142629570 T>C), RS1000073259 (3:142638604 T>G), RS1000082631 (3:142629322 A>G), RS1000130607 (3:142674441 T>C,G), RS1000147819 (3:142647126 G>A), RS1000151890 (3:142692371 GA>G,GAA), RS1000219408 (3:142603680 G>T), RS1000258309 (3:142654588 A>G), RS1000289046 (3:142610262 T>C), RS1000294512 (3:142596191 G>A,C), RS1000295566 (3:142703767 G>A,T), RS1000328540 (3:142622694 C>A), RS1000387698 (3:142616754 C>T), RS1000419002 (3:142634203 A>G)

Disease associations

OMIM: gene MIM:602734 | disease phenotypes: MIM:618787, MIM:124900

GenCC curated gene-disease

Disease	Classification	Inheritance
hearing loss, autosomal dominant 76	Strong	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss	Moderate	AD

Mondo (3): hearing loss, autosomal dominant 76 (MONDO:0032917), autosomal dominant nonsyndromic hearing loss (MONDO:0019587), hearing loss disorder (MONDO:0005365)

Orphanet (1): Rare autosomal dominant non-syndromic sensorineural deafness type DFNA (Orphanet:90635)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment
HP:0001270	Motor delay
HP:0001751	Abnormal vestibular function
HP:0002403	Positive Romberg sign
HP:0003593	Infantile onset

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001033_17	Type 2 diabetes	9.000000e-06
GCST004611_54	High light scatter reticulocyte count	2.000000e-11
GCST004630_128	Mean corpuscular hemoglobin	3.000000e-60
GCST90002385_439	High light scatter reticulocyte count	2.000000e-28
GCST90002405_26	Reticulocyte count	2.000000e-34
GCST90002406_47	Reticulocyte fraction of red cells	9.000000e-21

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0007986	reticulocyte count
EFO:0004527	mean corpuscular hemoglobin

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: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	7
Acetaminophen	decreases expression	3
methylmercuric chloride	decreases expression	2
trichostatin A	affects expression, increases expression	2
potassium chromate(VI)	increases expression, affects cotreatment, decreases expression	2
epigallocatechin gallate	increases expression, affects cotreatment, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, decreases expression	2
Rotenone	decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Particulate Matter	increases abundance, affects expression, decreases expression	2
dicrotophos	decreases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	decreases expression	1
2,5,2’,5’-tetrachlorobiphenyl	decreases expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
afimoxifene	decreases expression, decreases reaction	1
sodium arsenite	decreases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chromium hexavalent ion	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	increases reaction, affects binding	1
perfluoro-n-nonanoic acid	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1

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