HOMER2

Summary

HOMER2 (homer scaffold protein 2, HGNC:17513) is a protein-coding gene on chromosome 15q25.2, encoding Homer protein homolog 2 (Q9NSB8). Postsynaptic density scaffolding protein.

This gene encodes a member of the homer family of dendritic proteins. Members of this family regulate group 1 metabotrophic glutamate receptor function. The encoded protein is a postsynaptic density scaffolding protein. Alternative splicing results in multiple transcript variants. Two related pseudogenes have been identified on chromosome 14.

Source: NCBI Gene 9455 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autosomal dominant nonsyndromic hearing loss 68 (Strong, GenCC) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 399 total — 3 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 2
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004839

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17513
Approved symbol	HOMER2
Name	homer scaffold protein 2
Location	15q25.2
Locus type	gene with protein product
Status	Approved
Aliases	CPD, Cupidin, Vesl-2, HOMER-2B, HOMER-2, HOMER-2A, DFNA68
Ensembl gene	ENSG00000103942
Ensembl biotype	protein_coding
OMIM	604799
Entrez	9455

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000304231, ENST00000450735, ENST00000500334, ENST00000558090, ENST00000558552, ENST00000558817, ENST00000560374, ENST00000561345, ENST00000619240, ENST00000619367, ENST00000855499, ENST00000855501, ENST00000855502, ENST00000855504, ENST00000855505, ENST00000960877, ENST00000960878, ENST00000960879, ENST00000960880

RefSeq mRNA: 2 — MANE Select: NM_004839 NM_004839, NM_199330

CCDS: CCDS45334, CCDS45336

Canonical transcript exons

ENST00000450735 — 9 exons

Exon	Start	End
ENSE00001159553	82852142	82852252
ENSE00001159560	82854644	82854800
ENSE00001533683	82952531	82952720
ENSE00002575475	82848983	82849903
ENSE00003532415	82859029	82859135
ENSE00003551318	82875273	82875404
ENSE00003559235	82892685	82892841
ENSE00003606019	82864167	82864259
ENSE00003687759	82851151	82851231

Expression profiles

Bgee: expression breadth ubiquitous, 237 present calls, max score 98.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.3215 / max 264.1528, expressed in 1407 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
151284	11.9638	1193
151285	2.3481	891
151282	0.0096	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
body of pancreas	UBERON:0001150	98.40	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.21	gold quality
pancreas	UBERON:0001264	96.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.90	gold quality
minor salivary gland	UBERON:0001830	94.36	gold quality
gastrocnemius	UBERON:0001388	94.33	gold quality
islet of Langerhans	UBERON:0000006	94.32	gold quality
saliva-secreting gland	UBERON:0001044	94.20	gold quality
muscle of leg	UBERON:0001383	93.77	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.54	gold quality
skin of leg	UBERON:0001511	93.08	gold quality
parotid gland	UBERON:0001831	92.56	gold quality
mouth mucosa	UBERON:0003729	92.44	gold quality
muscle organ	UBERON:0001630	92.26	gold quality
skin of abdomen	UBERON:0001416	91.25	gold quality
body of stomach	UBERON:0001161	90.97	gold quality
right lobe of liver	UBERON:0001114	90.76	gold quality
oocyte	CL:0000023	90.67	gold quality
sural nerve	UBERON:0015488	90.18	gold quality
skeletal muscle tissue	UBERON:0001134	89.80	gold quality
zone of skin	UBERON:0000014	89.67	gold quality
nasal cavity mucosa	UBERON:0001826	89.27	gold quality
stomach	UBERON:0000945	89.10	gold quality
lower esophagus mucosa	UBERON:0035834	88.90	gold quality
prostate gland	UBERON:0002367	88.85	gold quality
vastus lateralis	UBERON:0001379	88.79	gold quality
nasal cavity epithelium	UBERON:0005384	88.16	gold quality
quadriceps femoris	UBERON:0001377	87.48	gold quality
heart left ventricle	UBERON:0002084	87.01	gold quality
liver	UBERON:0002107	86.97	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-10553	yes	21.59
E-HCAD-9	yes	8.95
E-GEOD-110499	no	278.61
E-MTAB-6108	no	248.00
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

53 targeting HOMER2, 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-188-3P	100.00	68.76	1240
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-1200	99.71	70.42	1838
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-26A-1-3P	99.64	66.81	788
HSA-MIR-26A-2-3P	99.64	66.82	786
HSA-MIR-4261	99.59	70.30	3415
HSA-MIR-5004-3P	99.54	68.27	1371
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-147B-5P	99.45	70.62	2432
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-544B	99.18	67.41	1632
HSA-MIR-6807-3P	99.15	69.23	1275
HSA-MIR-328-5P	99.08	64.65	1000
HSA-MIR-4324	99.04	70.14	1569
HSA-MIR-129-1-3P	98.86	68.41	779
HSA-MIR-129-2-3P	98.86	68.41	779
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-3922-5P	98.77	66.53	1059
HSA-MIR-767-3P	98.61	67.69	1192

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• Polymorphism in the Homer2 gene is not a potential risk factor for the development of cocaine dependence in an African American population. (PMID:16314758)
• study found that Homer2 and Homer3 are negative regulators of T cell activation; this is achieved through binding of nuclear factor of activated T cells (NFAT) and by competing with calcineurin (PMID:18218901)
• This study supports a role for HOMER2 gene in schizophrenia susceptibility. (PMID:19914345)
• Haplotypes of the HOMER 1 and 2 genes are unlikely to play a major role in the pathophysiology of alcohol dependence. (PMID:20333726)
• monitored Homer1 and Homer2 expression and subcellular localization in skeletal muscle biopsies following 60 days of bedrest (PMID:21885651)
• This study showed that HOMER2 (rs1256429; intronic, p = 8.7 x 10(1)) associated with Alzheimer disease. (PMID:25649652)
• These data provide compelling evidence that HOMER2 is required for normal hearing and that its sequence alteration in humans leads to ADNSHL through a dominant-negative mode of action (PMID:25816005)
• Homer1 and Homer2 might be considered as novel diagnostic biomarkers for large-artery atherosclerosis stroke. (PMID:27832625)
• that HOMER2 may be involved in tumourigenesis of endometrioid uterine tumours (PMID:29891190)
• we have identified a distinct, novel insertion variant in HOMER2, which provides validating evidence that HOMER2 is indeed required for normal hearing. Its sequence alteration is responsible for late-onset, autosomal dominant, non-syndromic, SNHL in humans. (PMID:30047143)
• A Novel Truncating Mutation in HOMER2 Causes Nonsyndromic Progressive DFNA68 Hearing Loss in a Spanish Family. (PMID:33809266)
• Identification and in vivo functional investigation of a HOMER2 nonstop variant causing hearing loss. (PMID:37173411)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	homer2	ENSDARG00000059349
mus_musculus	Homer2	ENSMUSG00000025813
rattus_norvegicus	Homer2	ENSRNOG00000061450
drosophila_melanogaster	homer	FBGN0025777

Paralogs (2): HOMER3 (ENSG00000051128), HOMER1 (ENSG00000152413)

Protein

Protein identifiers

Homer protein homolog 2 — Q9NSB8 (reviewed: Q9NSB8)

Alternative names: Cupidin

All UniProt accessions (2): H0YNR9, Q9NSB8

UniProt curated annotations — full annotation on UniProt →

Function. Postsynaptic density scaffolding protein. Binds and cross-links cytoplasmic regions of GRM1, GRM5, ITPR1, DNM3, RYR1, RYR2, SHANK1 and SHANK3. By physically linking GRM1 and GRM5 with ER-associated ITPR1 receptors, it aids the coupling of surface receptors to intracellular calcium release. May also couple GRM1 to PI3 kinase through its interaction with AGAP2. Isoforms can be differently regulated and may play an important role in maintaining the plasticity at glutamatergic synapses. Required for normal hearing. Negatively regulates T cell activation by inhibiting the calcineurin-NFAT pathway. Acts by competing with calcineurin/PPP3CA for NFAT protein binding, hence preventing NFAT activation by PPP3CA.

Subunit / interactions. Forms coiled-coil structures that mediate homo- and heteromultimerization. Interacts with NFATC2; interaction is reduced by AKT activation. Interacts with NFATC1 and NFATC4. Interacts with DAGLA (via PPXXF motif); this interaction is required for the cell membrane localization of DAGLA.

Subcellular location. Cytoplasm. Cell membrane. Postsynaptic density. Synapse. Cell projection. Stereocilium.

Disease relevance. Deafness, autosomal dominant, 68 (DFNA68) [MIM:616707] A form of non-syndromic sensorineural hearing loss with postlingual onset. Sensorineural deafness 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.

Domain organisation. The WH1 domain interacts with the PPXXF motif in GRM1, GRM5, RYR1, RYR2, ITPR1, SHANK 1 and SHANK3.

Similarity. Belongs to the Homer family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NSB8-1	1, 2b	yes
Q9NSB8-2	2, 2a

RefSeq proteins (2): NP_004830, NP_955362 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000697	WH1/EVH1_dom	Domain
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR044100	Homer_EVH1	Domain
IPR045027	Homer	Family

Pfam: PF00568

UniProt features (13 total): sequence variant 3, sequence conflict 2, coiled-coil region 2, compositionally biased region 2, chain 1, domain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NSB8-F1	89.20	0.79

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-6794361	Neurexins and neuroligins

MSigDB gene sets: 607 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, KOBAYASHI_EGFR_SIGNALING_24HR_UP, ACTACCT_MIR196A_MIR196B, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CALCIUM_MEDIATED_SIGNALING, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_RESPONSE_TO_COCAINE, LU_IL4_SIGNALING, GOMF_METALLOPEPTIDASE_ACTIVITY, MODULE_255, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_SENSORY_PERCEPTION_OF_MECHANICAL_STIMULUS, GOBP_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_ADULT_BEHAVIOR, ATACCTC_MIR202

GO Biological Process (9): G protein-coupled glutamate receptor signaling pathway (GO:0007216), sensory perception of sound (GO:0007605), regulation of G protein-coupled receptor signaling pathway (GO:0008277), calcium-mediated signaling (GO:0019722), negative regulation of interleukin-2 production (GO:0032703), behavioral response to cocaine (GO:0048148), regulation of synaptic transmission, glutamatergic (GO:0051966), negative regulation of calcineurin-NFAT signaling cascade (GO:0070885), regulation of store-operated calcium entry (GO:2001256)

GO Molecular Function (4): actin binding (GO:0003779), synaptic receptor adaptor activity (GO:0030160), G protein-coupled glutamate receptor binding (GO:0035256), protein binding (GO:0005515)

GO Cellular Component (13): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), dendrite (GO:0030425), stereocilium tip (GO:0032426), intracellular organelle (GO:0043229), apical part of cell (GO:0045177), glutamatergic synapse (GO:0098978), membrane (GO:0016020), stereocilium (GO:0032420), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Protein-protein interactions at synapses	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
G protein-coupled receptor signaling pathway	2
intracellular anatomical structure	2
neuron projection	2
glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor activity	1
sensory perception of mechanical stimulus	1
regulation of signal transduction	1
intracellular signaling cassette	1
negative regulation of cytokine production	1
interleukin-2 production	1
regulation of interleukin-2 production	1
adult behavior	1
response to cocaine	1
synaptic transmission, glutamatergic	1
modulation of chemical synaptic transmission	1
calcineurin-NFAT signaling cascade	1
regulation of calcineurin-NFAT signaling cascade	1
negative regulation of calcineurin-mediated signaling	1
store-operated calcium entry	1
regulation of calcium ion transport	1
cytoskeletal protein binding	1
signaling receptor complex adaptor activity	1
G protein-coupled receptor binding	1
glutamate receptor binding	1
binding	1
cytoplasm	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
dendritic tree	1
stereocilium	1
organelle	1
synapse	1
stereocilium bundle	1
actin-based cell projection	1
cell junction	1

Protein interactions and networks

STRING

698 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HOMER2	GRM5	P41594	930
HOMER2	GRM1	Q13255	893
HOMER2	ITPR1	Q14643	846
HOMER2	SHANK1	Q9Y566	836
HOMER2	DLGAP1	P78335	707
HOMER2	AKT1	P31749	627
HOMER2	ITPR3	Q14573	621
HOMER2	HOMER3	Q9NSC5	587
HOMER2	DLG4	P78352	573
HOMER2	DAGLA	Q9Y4D2	563
HOMER2	SHANK2	Q9UPX8	545
HOMER2	LRRC7	Q96NW7	518
HOMER2	H1-1	Q02539	513
HOMER2	CALM1	P02593	513
HOMER2	SYP	P08247	511

IntAct

28 interactions, top by confidence:

A	B	Type	Score
HOMER1	TRAF5	psi-mi:“MI:0914”(association)	0.740
HOMER1	FRYL	psi-mi:“MI:0914”(association)	0.640
IFT57	IFT56	psi-mi:“MI:0914”(association)	0.640
SPOPL	SPOP	psi-mi:“MI:0914”(association)	0.590
LZTS2	HOMER2	psi-mi:“MI:0915”(physical association)	0.560
HOMER2	RNF41	psi-mi:“MI:0915”(physical association)	0.560
RNF41	HOMER2	psi-mi:“MI:0915”(physical association)	0.560
DBN1	GSN	psi-mi:“MI:0914”(association)	0.530
DBN1	SVIL	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530
HOMER2	APP	psi-mi:“MI:0915”(physical association)	0.400
HOMER2	FXR1	psi-mi:“MI:0915”(physical association)	0.370
KPNA2	HOMER2	psi-mi:“MI:0915”(physical association)	0.370
HOXB2	TNKS	psi-mi:“MI:0914”(association)	0.350
SHANK3	IGKV3D-15	psi-mi:“MI:0914”(association)	0.350
CD6	CIBAR1	psi-mi:“MI:0914”(association)	0.350
INSYN1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
SYCE1	RABGAP1L	psi-mi:“MI:0914”(association)	0.350
TPM3	SPAG9	psi-mi:“MI:0914”(association)	0.350
HOMER3	PEX14	psi-mi:“MI:0914”(association)	0.350
MYPN	ITPRID2	psi-mi:“MI:0914”(association)	0.350
PALLD	MYPN	psi-mi:“MI:0914”(association)	0.350
ABI3	TBKBP1	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350

BioGRID (50): RNF41 (Two-hybrid), LZTS2 (Two-hybrid), HOMER2 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER2 (Biochemical Activity), HOMER2 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER2 (Affinity Capture-MS), HOMER2 (Two-hybrid), HOMER2 (PCA), HOMER2 (Biochemical Activity), HOMER2 (Affinity Capture-MS), ABI3 (Two-hybrid)

ESM2 similar proteins: A8WUP2, A8WVU9, B3H6Z8, B4JAL5, B4KE73, B9F2Y7, F4JX00, F4K0J3, G5EGS3, O01583, O45935, O60282, O61493, O88801, P17210, P21613, P28738, P33175, P33176, P34537, P34540, P35978, P56536, P92199, Q01577, Q12840, Q22908, Q23529, Q2PQA9, Q498L9, Q5JKW1, Q5R9K7, Q60YN5, Q61768, Q619T5, Q6QLM7, Q7TT49, Q7XPJ0, Q7Z4S6, Q7ZXX2

Diamond homologs: O88801, Q2KJ56, Q86YM7, Q99JP6, Q9NSB8, Q9NSC5, Q9QWW1, Q9Z214, Q9Z2X5, Q9Z2Y3, Q5TJ65, P50551, P70460, Q2TA49

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SMURF1	unknown	HOMER2	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	2
Uncertain significance	237
Likely benign	76
Benign	36

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
1013607	NM_004839.4(HOMER2):c.799_803del (p.Pro267fs)	Pathogenic
218351	NM_004839.4(HOMER2):c.554G>C (p.Arg185Pro)	Pathogenic
922123	NM_004839.4(HOMER2):c.807dup (p.Met270fs)	Pathogenic
3572954	NM_004839.4(HOMER2):c.1031A>G (p.Ter344Trp)	Likely pathogenic
3601171	NM_004839.4(HOMER2):c.1023_1029del (p.Asp342fs)	Likely pathogenic

SpliceAI

4878 predictions. Top by Δscore:

Variant	Effect	Δscore
15:82849909:C:CT	acceptor_gain	1.0000
15:82851231:CCTA:C	acceptor_loss	1.0000
15:82851232:C:CA	acceptor_loss	1.0000
15:82851232:C:CC	acceptor_gain	1.0000
15:82851233:T:C	acceptor_loss	1.0000
15:82851236:A:C	acceptor_gain	1.0000
15:82852137:CTCA:C	donor_gain	1.0000
15:82852138:TCA:T	donor_loss	1.0000
15:82852139:CACTG:C	donor_loss	1.0000
15:82852140:A:AC	donor_gain	1.0000
15:82852140:ACTGT:A	donor_gain	1.0000
15:82852141:C:CA	donor_gain	1.0000
15:82852141:CT:C	donor_gain	1.0000
15:82852141:CTGT:C	donor_gain	1.0000
15:82852141:CTGTC:C	donor_gain	1.0000
15:82852258:A:AC	acceptor_gain	1.0000
15:82852261:C:CT	acceptor_gain	1.0000
15:82852263:C:CT	acceptor_gain	1.0000
15:82852266:C:CT	acceptor_gain	1.0000
15:82852266:C:T	acceptor_gain	1.0000
15:82852268:C:CT	acceptor_gain	1.0000
15:82852270:C:CT	acceptor_gain	1.0000
15:82852271:A:T	acceptor_gain	1.0000
15:82854640:CCAC:C	donor_loss	1.0000
15:82854643:CCT:C	donor_loss	1.0000
15:82854796:CTGCG:C	acceptor_gain	1.0000
15:82854797:TGCG:T	acceptor_gain	1.0000
15:82854798:GCG:G	acceptor_gain	1.0000
15:82854799:CG:C	acceptor_gain	1.0000
15:82854799:CGC:C	acceptor_gain	1.0000

AlphaMissense

2287 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:82875297:A:C	F90L	1.000
15:82875297:A:T	F90L	1.000
15:82875298:A:G	F90S	1.000
15:82875299:A:G	F90L	1.000
15:82875301:C:T	G89E	1.000
15:82875307:C:T	G87D	1.000
15:82875308:C:G	G87R	1.000
15:82875336:C:A	W77C	1.000
15:82875336:C:G	W77C	1.000
15:82875337:C:G	W77S	1.000
15:82875338:A:G	W77R	1.000
15:82875338:A:T	W77R	1.000
15:82875343:C:T	G75E	1.000
15:82875345:A:C	F74L	1.000
15:82875345:A:T	F74L	1.000
15:82875346:A:C	F74C	1.000
15:82875347:A:G	F74L	1.000
15:82875367:A:G	F67S	1.000
15:82875390:G:C	S59R	1.000
15:82875390:G:T	S59R	1.000
15:82875392:T:G	S59R	1.000
15:82892700:A:C	S49R	1.000
15:82892700:A:T	S49R	1.000
15:82892702:T:G	S49R	1.000
15:82892710:C:G	R46P	1.000
15:82892746:A:T	V34D	1.000
15:82892775:C:A	W24C	1.000
15:82892775:C:G	W24C	1.000
15:82892777:A:G	W24R	1.000
15:82892777:A:T	W24R	1.000

dbSNP variants (sampled 300 via entrez): RS1000016975 (15:82985575 TAAC>T), RS1000033747 (15:82898801 T>C), RS1000051941 (15:82857766 G>A,T), RS1000056914 (15:82977152 T>G), RS1000107679 (15:82963557 G>A,T), RS1000118384 (15:82910094 C>T), RS1000120758 (15:82840660 T>C,G), RS1000132685 (15:82973462 G>A,T), RS1000161094 (15:82875221 G>T), RS1000181796 (15:82946972 A>C), RS1000209982 (15:82973067 C>T), RS1000255421 (15:82947311 G>A), RS1000273617 (15:82870155 A>G), RS1000291693 (15:82910357 C>T), RS1000331586 (15:82843272 C>A)

Disease associations

OMIM: gene MIM:604799 | disease phenotypes: MIM:616707

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal dominant nonsyndromic hearing loss 68	Strong	Autosomal dominant
nonsyndromic genetic hearing loss	Moderate	Autosomal dominant
autosomal dominant nonsyndromic hearing loss	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
nonsyndromic genetic hearing loss	Moderate	AD

Mondo (3): autosomal dominant nonsyndromic hearing loss 68 (MONDO:0014740), nonsyndromic genetic hearing loss (MONDO:0019497), autosomal dominant nonsyndromic hearing loss (MONDO:0019587)

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

HPO phenotypes

2 total (2 of 2 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000407	Sensorineural hearing impairment

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST007277_21	Tourette syndrome	7.000000e-06
GCST010242_340	HDL cholesterol levels	4.000000e-13
GCST012227_330	Hip circumference adjusted for BMI	2.000000e-08
GCST012465_15	Bipolar disorder	1.000000e-08
GCST90020026_405	Hip index	2.000000e-11
GCST90020026_406	Hip index	5.000000e-09
GCST90020028_1760	Hip circumference adjusted for BMI	2.000000e-11
GCST90020028_1782	Hip circumference adjusted for BMI	5.000000e-12
GCST90020028_1783	Hip circumference adjusted for BMI	2.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C580334	Nonsyndromic Deafness (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	4
Valproic Acid	decreases expression, decreases methylation, increases expression	4
Aflatoxin B1	affects methylation, decreases expression, increases methylation, affects expression	4
Cyclosporine	decreases expression, increases expression	3
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
Diethylhexyl Phthalate	decreases expression, increases expression	2
Tamoxifen	affects expression, decreases expression	2
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
arsenite	increases methylation	1
butyraldehyde	increases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
aflatoxin B2	decreases methylation	1
pentanal	increases expression	1
di-n-butylphosphoric acid	affects expression	1
tebuconazole	decreases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
belinostat	decreases expression	1
licochalcone B	increases expression	1
picoxystrobin	decreases expression	1
(+)-JQ1 compound	increases expression	1
Resveratrol	decreases expression	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases expression	1
Allergens	increases expression	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Calcitriol	increases expression	1
Cisplatin	decreases expression	1
Doxorubicin	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01802190	Not specified	TERMINATED	Prevalence of POU4F3 and SLC17A8 Mutations