PLSCR4

Summary

PLSCR4 (phospholipid scramblase 4, HGNC:16497) is a protein-coding gene on chromosome 3q24, encoding Phospholipid scramblase 4 (Q9NRQ2). Catalyzes metal ion-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane and participates in the redistribution of phospholipids between membrane le….

Enables CD4 receptor binding activity; enzyme binding activity; and phospholipid scramblase activity. Involved in calcium activated phosphatidylcholine scrambling and calcium activated phosphatidylserine scrambling. Located in nucleus and plasma membrane.

Source: NCBI Gene 57088 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 62 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_020353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16497
Approved symbol	PLSCR4
Name	phospholipid scramblase 4
Location	3q24
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000114698
Ensembl biotype	protein_coding
OMIM	607612
Entrez	57088

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 21 protein_coding, 1 retained_intron

ENST00000354952, ENST00000383083, ENST00000433593, ENST00000446574, ENST00000460350, ENST00000460885, ENST00000475019, ENST00000476202, ENST00000481701, ENST00000493382, ENST00000498625, ENST00000906243, ENST00000906244, ENST00000906245, ENST00000906246, ENST00000906247, ENST00000906248, ENST00000951288, ENST00000951289, ENST00000951290, ENST00000951291, ENST00000951292

RefSeq mRNA: 5 — MANE Select: NM_020353 NM_001128304, NM_001128305, NM_001128306, NM_001177304, NM_020353

CCDS: CCDS3133, CCDS54651

Canonical transcript exons

ENST00000354952 — 9 exons

Exon	Start	End
ENSE00000779326	146195124	146195282
ENSE00001823024	146250960	146251105
ENSE00003483070	146206526	146206761
ENSE00003556526	146220815	146220925
ENSE00003563946	146222065	146222092
ENSE00003685958	146201035	146201077
ENSE00003784091	146199813	146200039
ENSE00003785539	146196632	146196793
ENSE00003842153	146192335	146194455

Expression profiles

Bgee: expression breadth ubiquitous, 281 present calls, max score 98.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 21.2246 / max 569.0286, expressed in 1279 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
44922	7.9640	1121
44920	7.9444	783
44923	3.4911	1007
44924	0.9849	551
44911	0.2495	98
44918	0.1688	104
44921	0.1429	43
44914	0.0666	34
44916	0.0531	17
44919	0.0464	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
germinal epithelium of ovary	UBERON:0001304	98.62	gold quality
parietal pleura	UBERON:0002400	98.15	gold quality
calcaneal tendon	UBERON:0003701	97.87	gold quality
pleura	UBERON:0000977	97.41	gold quality
tibial nerve	UBERON:0001323	96.62	gold quality
pericardium	UBERON:0002407	96.45	gold quality
visceral pleura	UBERON:0002401	96.32	gold quality
ascending aorta	UBERON:0001496	96.18	gold quality
thoracic aorta	UBERON:0001515	96.14	gold quality
descending thoracic aorta	UBERON:0002345	96.04	gold quality
synovial joint	UBERON:0002217	95.79	gold quality
cranial nerve II	UBERON:0000941	95.66	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.53	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.52	gold quality
right coronary artery	UBERON:0001625	95.44	gold quality
skin of hip	UBERON:0001554	95.42	gold quality
gall bladder	UBERON:0002110	95.42	gold quality
adipose tissue	UBERON:0001013	95.26	gold quality
cauda epididymis	UBERON:0004360	95.26	gold quality
left coronary artery	UBERON:0001626	95.18	gold quality
peritoneum	UBERON:0002358	95.15	gold quality
omental fat pad	UBERON:0010414	95.15	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.13	gold quality
lower lobe of lung	UBERON:0008949	95.11	gold quality
aorta	UBERON:0000947	95.00	gold quality
coronary artery	UBERON:0001621	94.97	gold quality
mammary duct	UBERON:0001765	94.94	gold quality
connective tissue	UBERON:0002384	94.91	gold quality
dorsal root ganglion	UBERON:0000044	94.51	gold quality
thoracic mammary gland	UBERON:0005200	94.41	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.27
E-CURD-119	yes	11.10
E-GEOD-130148	yes	5.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

111 targeting PLSCR4, 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-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-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798

Literature-anchored findings (GeneRIF, showing 10)

• SLPI is a ligand for PLSCR1 and PLSCR4, which also interact directly with the CD4 receptor at the cell surface of T lymphocytes (PMID:19333378)
• Results show that binding affinities of the peptides are in the order hPLSCR1>hPLSCR3>hPLSCR2>hPLSCR4 for Ca2+ and in the order hPLSCR1>hPLSCR2>hPLSCR3>hPLSCR4 for Mg2+. (PMID:19540310)
• Crystallographic analysis of mammalian importin alpha1 in complex with the hPLSCR4-NLS reveals this minimal NLS binds specifically and exclusively to the minor binding site of importin alpha (PMID:21690087)
• biochemical and functional characterization of human phospholipid scramblase 4 (PMID:23089641)
• the first report on the transcriptional regulation of hPLSCR4, where Snail was shown to downregulate the expression of Human phospholipid scramblase 4 (PMID:27363667)
• LINC00641 suppressed cell proliferation and induced cell apoptosis in NSCLC, indicating that LINC00641 exerted tumor-suppressive role in NSCLC. Through mechanism investigation, we determined that LINC00641 acted as a competing endogenous RNA (ceRNA) in NSCLC by sponging miR-424-5p to upregulate phospholipid scramblase (PLSCR4) expression. (PMID:31322545)
• Specific DNA methylation signatures for aggressive choroid plexus carcinoma (CPC) revealed AK1, PER2, and PLSCR4 as potential biomarkers for CPC that can be used to improve molecular stratification for diagnosis and treatment. (PMID:31409384)
• LINC00641 induces the malignant progression of colorectal carcinoma through the miRNA-424-5p/PLSCR4 feedback loop. (PMID:33577029)
• Whole blood transcriptomic analysis reveals PLSCR4 as a potential marker for vaso-occlusive crises in sickle cell disease. (PMID:34772994)
• Phospholipid Scramblase 4 (PLSCR4) Regulates Adipocyte Differentiation via PIP3-Mediated AKT Activation. (PMID:36077184)

Cross-species orthologs

19 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:ch211-71m22.1	ENSDARG00000058638
danio_rerio	plscr3b	ENSDARG00000069432
danio_rerio	si:ch73-206p6.1	ENSDARG00000077468
danio_rerio	si:ch211-71m22.3	ENSDARG00000079075
danio_rerio	si:ch211-71m22.5	ENSDARG00000091266
danio_rerio	si:dkey-62k3.6	ENSDARG00000091614
danio_rerio	plscr3a	ENSDARG00000093078
danio_rerio		ENSDARG00000100828
danio_rerio	si:ch73-170d6.4	ENSDARG00000102460
mus_musculus	Plscr4	ENSMUSG00000032377
rattus_norvegicus	Plscr4	ENSRNOG00000008151
caenorhabditis_elegans	scrm-4	WBGENE00008681
caenorhabditis_elegans	scrm-6	WBGENE00009753
caenorhabditis_elegans	scrm-1	WBGENE00011935
caenorhabditis_elegans		WBGENE00013052
caenorhabditis_elegans	scrm-2	WBGENE00014200
caenorhabditis_elegans		WBGENE00015437
caenorhabditis_elegans		WBGENE00019530
caenorhabditis_elegans		WBGENE00019531

Paralogs (4): PLSCR2 (ENSG00000163746), PLSCR3 (ENSG00000187838), PLSCR1 (ENSG00000188313), PLSCR5 (ENSG00000231213)

Protein

Protein identifiers

Phospholipid scramblase 4 — Q9NRQ2 (reviewed: Q9NRQ2)

Alternative names: Ca(2+)-dependent phospholipid scramblase 4, Cell growth-inhibiting gene 43 protein, TRA1

All UniProt accessions (7): Q9NRQ2, C9J3P9, C9J664, C9J6E1, C9J916, C9JNW2, E9PHR9

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes metal ion-induced ATP-independent rapid bidirectional and non-specific movement of phospholipids (lipid scrambling or lipid flip-flop) between the inner and outer leaflet of the plasma membrane and participates in the redistribution of phospholipids between membrane leaflets. Metal ions bind to the calcium-binding site and induce conformation change in the protein. Has a greater affi nity for Ca(2+) than Mg(2+) and Zn(2+).

Subunit / interactions. Interacts with PDCD6. Interacts with KPNA2; this interaction mediates the nucleus import of PLSCR4.

Subcellular location. Cell membrane. Nucleus.

Tissue specificity. Expressed in heart, brain, placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, uterus, small intestine and colon. Not detected in peripheral blood lymphocytes.

Domain organisation. The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity.

Similarity. Belongs to the phospholipid scramblase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NRQ2-1	1	yes
Q9NRQ2-2	2

RefSeq proteins (5): NP_001121776, NP_001121777, NP_001121778, NP_001170775, NP_065086* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005552	Scramblase	Family

Pfam: PF03803

Enzyme classification (BRENDA):

• EC 7.6.2.1 — P-type phospholipid transporter (BRENDA: 22 organisms, 260 substrates, 62 inhibitors, 53 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.016–2.215	41
P-NITROPHENYL PHOSPHATE	1.17–1.46	3
ACETYL PHOSPHATE	1.03–1.31	2
1-PALMITOYL-2-OLEOYL-SN-GLYCERO-3-PHOSPHO-L-SERI	0.111	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-sn-glycero-3-phosphocholine(out) (RHEA:38571)
• a 1,2-diacyl-sn-glycero-3-phospho-L-serine(in) = a 1,2-diacyl-sn-glycero-3-phospho-L-serine(out) (RHEA:38663)

UniProt features (32 total): short sequence motif 5, lipid moiety-binding region 5, sequence conflict 5, mutagenesis site 4, topological domain 2, modified residue 2, splice variant 2, sequence variant 2, region of interest 2, chain 1, compositionally biased region 1, transmembrane region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
3Q5U	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NRQ2-F1	70.17	0.38

Functional residue map

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

Post-translational modifications (7): 83, 88, 197, 198, 199, 201, 202

Mutagenesis-validated functional residues (4):

Position	Phenotype
197–204	affects plasma membrane localization.
277–279	reduces nuclear localization.
277	markedly reduces nuclear localization.
290	50% decrease in scramblase activity in presence of ca2+, and 40% decrease in scramblase activity in presence of mg2+.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 163 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, WAMUNYOKOLI_OVARIAN_CANCER_LMP_DN, BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, chr3q24, GOBP_CELLULAR_RESPONSE_TO_LIPID, FISCHER_G1_S_CELL_CYCLE, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_PLASMA_MEMBRANE_ORGANIZATION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_REGULATION_OF_MEMBRANE_LIPID_DISTRIBUTION, GOBP_ORGANOPHOSPHATE_ESTER_TRANSPORT, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, PYEON_CANCER_HEAD_AND_NECK_VS_CERVICAL_UP, GOBP_ENDOMEMBRANE_SYSTEM_ORGANIZATION, GOBP_RESPONSE_TO_LIPID

GO Biological Process (4): plasma membrane phospholipid scrambling (GO:0017121), calcium activated phosphatidylserine scrambling (GO:0061589), calcium activated phosphatidylcholine scrambling (GO:0061590), cellular response to lipopolysaccharide (GO:0071222)

GO Molecular Function (6): calcium ion binding (GO:0005509), SH3 domain binding (GO:0017124), phospholipid scramblase activity (GO:0017128), enzyme binding (GO:0019899), CD4 receptor binding (GO:0042609), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), plasma membrane (GO:0005886), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
calcium activated phospholipid scrambling	2
plasma membrane organization	1
phospholipid translocation	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
metal ion binding	1
protein domain specific binding	1
plasma membrane phospholipid scrambling	1
intramembrane lipid carrier activity	1
protein binding	1
signaling receptor binding	1
binding	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

604 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLSCR4	CD4	P01730	567
PLSCR4	XKR8	Q9H6D3	361
PLSCR4	ANXA8L1	Q5VT79	357
PLSCR4	NREP	Q16612	352
PLSCR4	OR6C2	Q9NZP2	349
PLSCR4	CRLS1	Q9UJA2	332
PLSCR4	MFN2	O95140	328
PLSCR4	ANO6	Q4KMQ2	325
PLSCR4	MUC20	Q8N307	296
PLSCR4	VEPH1	Q14D04	283
PLSCR4	OLFM1	Q99784	279
PLSCR4	RPL22L1	Q6P5R6	276
PLSCR4	VCPIP1	Q96JH7	271
PLSCR4	LRRC57	Q8N9N7	271
PLSCR4	GOLGA8K	D6RF30	269

IntAct

210 interactions, top by confidence:

A	B	Type	Score
MTUS2	PLSCR4	psi-mi:“MI:0915”(physical association)	0.740
PLSCR4	MTUS2	psi-mi:“MI:0915”(physical association)	0.740
TRIP13	PLSCR4	psi-mi:“MI:0915”(physical association)	0.700
PLSCR4	NOTCH2NLA	psi-mi:“MI:0915”(physical association)	0.670
NOTCH2NLA	PLSCR4	psi-mi:“MI:0915”(physical association)	0.670
KRTAP6-1	PLSCR4	psi-mi:“MI:0915”(physical association)	0.600
Hoxa1	PLSCR4	psi-mi:“MI:0915”(physical association)	0.570
PLSCR4	Hoxa1	psi-mi:“MI:0915”(physical association)	0.570
SMP1	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	SMP1	psi-mi:“MI:0915”(physical association)	0.560
YOD1	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	KRTAP19-5	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	KRTAP19-7	psi-mi:“MI:0915”(physical association)	0.560
PLSCR4	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP6-3	PLSCR4	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (88): PLSCR4 (Two-hybrid), NOTCH2NL (Two-hybrid), IGHG2 (Affinity Capture-MS), ZDHHC17 (Affinity Capture-MS), TLE1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), DPH1 (Affinity Capture-MS), PLSCR4 (Two-hybrid), PLSCR4 (Two-hybrid), PLSCR4 (Two-hybrid), KRTAP4-12 (Two-hybrid), PLSCR4 (PCA), Hoxa1 (Affinity Capture-Western), PLSCR4 (Two-hybrid), ABHD17A (Two-hybrid)

ESM2 similar proteins: A0A178WF56, A3A4E0, A5PLE2, B4FF80, B4FUS3, B6TYV8, B6TZ45, D9HP19, D9HP23, D9HP25, D9HP27, I2HB52, O04023, O04133, O22802, O23035, O43125, O60154, O94425, P38216, P40388, P43582, P58196, Q00166, Q12489, Q1PEX8, Q28H62, Q32LK2, Q54YM7, Q55GT2, Q6NN03, Q6Q5X2, Q8K353, Q8L9S1, Q8LCL8, Q8LG30, Q8S8T8, Q8W472, Q94C26, Q94CD4

Diamond homologs: A0PG75, O15162, P58195, P58196, Q3ZBG9, Q6QBQ4, Q9DCW2, Q9JIZ9, Q9JJ00, Q9NRQ2, Q9NRY6, Q9NRY7

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 64 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
NOTCH2 Activation and Transmission of Signal to the Nucleus	5	54.9×	9e-07
Oncogene Induced Senescence	5	42.0×	2e-06
Ovarian tumor domain proteases	5	34.8×	3e-06
Cyclin D associated events in G1	5	29.1×	6e-06
Keratinization	19	26.5×	1e-20
Cargo recognition for clathrin-mediated endocytosis	5	13.1×	1e-04
RUNX1 regulates transcription of genes involved in differentiation of HSCs	5	11.9×	2e-04
Oxidative Stress Induced Senescence	5	11.3×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
keratinization	8	41.6×	4e-09

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2030 predictions. Top by Δscore:

Variant	Effect	Δscore
3:146195122:A:AC	donor_gain	1.0000
3:146195123:C:CC	donor_gain	1.0000
3:146196625:G:C	donor_gain	1.0000
3:146196651:C:CT	donor_gain	1.0000
3:146196678:CGAA:C	donor_gain	1.0000
3:146196681:A:AC	donor_gain	1.0000
3:146196682:C:CC	donor_gain	1.0000
3:146196685:T:A	donor_gain	1.0000
3:146196700:T:A	donor_gain	1.0000
3:146196790:CCAG:C	acceptor_gain	1.0000
3:146196791:CAG:C	acceptor_gain	1.0000
3:146196791:CAGC:C	acceptor_gain	1.0000
3:146199800:T:TA	donor_gain	1.0000
3:146220952:T:C	acceptor_gain	1.0000
3:146222062:TA:T	donor_loss	1.0000
3:146222063:A:AG	donor_loss	1.0000
3:146222093:C:CC	acceptor_gain	1.0000
3:146194326:G:A	donor_gain	0.9900
3:146195280:GACCT:G	acceptor_loss	0.9900
3:146195281:ACC:A	acceptor_loss	0.9900
3:146195282:CCTGG:C	acceptor_loss	0.9900
3:146195284:T:A	acceptor_loss	0.9900
3:146196624:A:AC	donor_gain	0.9900
3:146196628:TCA:T	donor_loss	0.9900
3:146196631:C:CA	donor_loss	0.9900
3:146196682:CT:C	donor_gain	0.9900
3:146196688:T:C	donor_gain	0.9900
3:146196703:T:TA	donor_gain	0.9900
3:146196789:TCCAG:T	acceptor_gain	0.9900
3:146196790:CCAGC:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000068707 (3:146245294 A>T), RS1000088790 (3:146244981 T>C), RS1000157552 (3:146198777 TA>T,TAA), RS1000210565 (3:146223259 A>T), RS1000266883 (3:146239090 TAAAG>T), RS1000286752 (3:146233011 A>T), RS1000291503 (3:146199076 G>A), RS1000420123 (3:146245108 A>C), RS1000431884 (3:146227830 T>C), RS1000450404 (3:146192928 T>A), RS1000452524 (3:146233321 A>G), RS1000465795 (3:146227365 A>C), RS1000497074 (3:146250260 A>G), RS1000530247 (3:146211095 T>C), RS1000685599 (3:146223406 T>A,C)

Disease associations

OMIM: gene MIM:607612 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): sensorineural hearing loss disorder (MONDO:0020678)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000407	Sensorineural hearing impairment

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST012490_466	Femur bone mineral density x serum urate levels interaction	6.000000e-10
GCST90002388_472	Lymphocyte count	3.000000e-13

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement
EFO:0004587	lymphocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	5
Cyclosporine	affects expression, decreases expression, increases expression	3
Particulate Matter	decreases expression, increases abundance	3
bisphenol A	increases methylation, affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Air Pollutants	decreases expression, increases abundance	2
Copper	affects binding, increases expression	2
Tetrachlorodibenzodioxin	decreases expression	2
afuresertib	increases expression	1
apocarotenal	increases expression	1
titanium dioxide	increases methylation	1
trichostatin A	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
nickel sulfate	increases expression	1
ciglitazone	affects binding, increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
monomethylarsonous acid	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
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
incobotulinumtoxinA	increases expression	1
NSC 689534	affects binding, increases expression	1
Dasatinib	increases expression	1
Sunitinib	increases expression	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01655212	PHASE3	TERMINATED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment in a Randomized Controlled Trial
NCT02005822	PHASE3	COMPLETED	Congenital Cytomegalovirus: Efficacy of Antiviral Treatment
NCT03374514	PHASE3	UNKNOWN	Cochlear Electrical Impedance and the Effect of Topical Dexamethasone on Cochlear Implant Surgery
NCT02497690	PHASE2	COMPLETED	Effectiveness of Therapy Via Telemedicine Following Cochlear Implants
NCT03107871	PHASE2	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Valganciclovir for Cytomegalovirus Infected Hearing Impaired Infants
NCT04120116	PHASE2	COMPLETED	FX-322 in Adults With Stable Sensorineural Hearing Loss
NCT05061758	PHASE2	WITHDRAWN	A Trial of LY3056480 in Patients With SNLH
NCT07364747	PHASE2	RECRUITING	Protective Effect of Acetylcysteine Against Cisplatinum-Induced Ototoxicity: A Randomized Controlled Trial
NCT02259595	PHASE1	COMPLETED	Study to Determine the Safety, Tolerability, and Pharmacokinetic Profile of HPN-07 and HPN-07 Plus NAC
NCT02693704	PHASE2/PHASE3	COMPLETED	Evaluation of a Binaural Spatialization Method for Hearing Aids
NCT02882477	PHASE2/PHASE3	UNKNOWN	Treatment of Wolfram Syndrome Type 2 With the Chelator Deferiprone and Incretin Based Therapy
NCT01267994	PHASE1/PHASE2	COMPLETED	A Clinical Trial of Anakinra for Steroid-Resistant Autoimmune Inner Ear Disease
NCT01902914	PHASE1/PHASE2	UNKNOWN	Effectiveness of P02 Digital Hearing Aids
NCT02038972	PHASE1/PHASE2	COMPLETED	Safety of Autologous Stem Cell Infusion for Children With Acquired Hearing Loss
NCT02616172	PHASE1/PHASE2	SUSPENDED	Autologous Bone Marrow Harvest and Transplant for Sensorineural Hearing Loss
NCT03616223	PHASE1/PHASE2	COMPLETED	FX-322 in Sensorineural Hearing Loss
NCT04129775	PHASE1/PHASE2	COMPLETED	OTO-413 in Subjects With Speech-in-Noise Hearing Impairment
NCT04462198	PHASE1/PHASE2	COMPLETED	Phase I/IIa Study Evaluating Safety and Efficacy of an Intratympanic Dose of PIPE-505 in Subjects With Hearing Loss
NCT07032038	PHASE1/PHASE2	NOT_YET_RECRUITING	First In Human Randomised Trial of Rincell-1 in Adults With a Cochlear Implant
NCT06025097	EARLY_PHASE1	COMPLETED	Intra-Tympanic Steroid With PRP Combination in Sensorineural Hearing Loss and Tinnitus.
NCT06707389	EARLY_PHASE1	NOT_YET_RECRUITING	Autologous Blood Monocyte Vesicles for the Treatment of Sudden Deafness
NCT07472023	EARLY_PHASE1	ENROLLING_BY_INVITATION	Regenerative Medicine and Stem Cell-Based Interventions for Inner Ear Trauma, Tinnitus, and Sensorineural Hearing Loss
NCT00023036	Not specified	COMPLETED	Clinical and Genetic Analysis of Enlarged Vestibular Aqueducts
NCT00023049	Not specified	COMPLETED	Genetic Analysis of Hereditary Disorders of Hearing and Balance
NCT00261768	Not specified	COMPLETED	Efficacy of Digital Noise Reduction Strategies: A Hearing Aid Trial
NCT00589511	Not specified	COMPLETED	Nucleus Freedom Cochlear Implant System Pediatric Post-approval Study
NCT00678899	Not specified	COMPLETED	Evaluation of the Nucleus Hybrid™ L24 Cochlear Implant System
NCT00787189	Not specified	COMPLETED	Study of Low Level Laser Therapy and Word Recognition in Hearing Impaired Individuals
NCT01184248	Not specified	COMPLETED	The Effect of Sound Stimulation on Pure-tone Hearing Threshold
NCT01434446	Not specified	COMPLETED	The Effect of Sound Stimulation on Hearing Ability
NCT01749592	Not specified	COMPLETED	Single-sided Deafness and Cochlear Implants
NCT01781039	Not specified	COMPLETED	Investigation of Anatomical Correlates of Speech Discrimination
NCT02082431	Not specified	COMPLETED	Determine the Incidence of Long QT Amongst a Large Cohort of Subjects Diagnosed With Unilateral or Bilateral Sensorineural Hearing Loss.
NCT02093806	Not specified	UNKNOWN	Clinical Applications of Round Window Imaging Anatomy in Cochlear Implant Surgery
NCT02252601	Not specified	UNKNOWN	Evaluation of the High Frequency Digit Triplet Test in Cystic Fibrosis
NCT02584361	Not specified	UNKNOWN	Cochlear Implant and Vestibular Function.
NCT02638883	Not specified	COMPLETED	Implantation of the Cochlear™ Nucleus® Hybrid S Round Window (S-RW) in Adults
NCT02689349	Not specified	COMPLETED	Esteem New Subject Enrollment Post Approval Study
NCT02698787	Not specified	COMPLETED	Fundamental Asynchronous Stimulus Timing Sound Coding Study
NCT02798783	Not specified	COMPLETED	Enlarged Vestibular Aqueduct Registry