HOMER2

homer scaffold protein 2, the group of Homer scaffold proteins

Basic information

Region (hg38): 15:82836946-82986153

Links

ENSG00000103942 ∙ NCBI:9455 ∙ OMIM:604799 ∙ HGNC:17513 ∙ Uniprot:Q9NSB8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal dominant nonsyndromic hearing loss 68 (Strong), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 68 (Moderate), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
• autosomal dominant nonsyndromic hearing loss 68 (Strong), mode of inheritance: AD
• nonsyndromic genetic hearing loss (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal dominant 68	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic	25816005

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the HOMER2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the HOMER2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				19	3	22
missense			39	10	1	50
nonsense			1			1
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)				1		1
splice region			4	3	3	10
non coding				22	22	44
Total	0	0	40	52	26

Variants in HOMER2

This is a list of pathogenic ClinVar variants found in the HOMER2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-82849543-G-A			Likely benign (Jan 13, 2019)
15-82849716-T-A			Uncertain significance (Jan 08, 2024)
15-82849716-T-C		Autosomal dominant nonsyndromic hearing loss 68	Likely pathogenic (-)
15-82849717-A-C			Uncertain significance (Oct 09, 2023)
15-82849722-T-C		HOMER2-related disorder	Benign (Jul 17, 2023)
15-82849724-G-A			Likely benign (Oct 23, 2022)
15-82849724-G-C		HOMER2-related disorder	Benign/Likely benign (Mar 03, 2023)
15-82849725-G-T		Autosomal dominant nonsyndromic hearing loss 68	Uncertain significance (Dec 17, 2023)
15-82849731-A-T		HOMER2-related disorder	Uncertain significance (May 30, 2024)
15-82849743-C-T		Inborn genetic diseases	Uncertain significance (Oct 22, 2023)
15-82849746-C-T		Inborn genetic diseases	Uncertain significance (Aug 11, 2024)
15-82849749-C-T			Uncertain significance (Jun 23, 2022)
15-82849766-G-A		not specified	Benign (Jan 31, 2024)
15-82849770-A-G			Uncertain significance (Aug 23, 2023)
15-82849773-T-C			Likely benign (Aug 17, 2023)
15-82849778-G-A			Likely benign (Jun 30, 2020)
15-82849780-C-T			Uncertain significance (Jan 29, 2024)
15-82849803-A-T		HOMER2-related disorder	Uncertain significance (Jan 03, 2023)
15-82849822-G-A			Uncertain significance (Oct 13, 2023)
15-82849827-C-T		Inborn genetic diseases	Uncertain significance (Sep 10, 2024)
15-82849832-T-C			Likely benign (Nov 16, 2023)
15-82849851-G-A			Uncertain significance (Dec 30, 2023)
15-82849946-G-T			Likely benign (Sep 11, 2021)
15-82849950-G-A			Benign (Jun 16, 2018)
15-82851142-C-T		HOMER2-related disorder	Likely benign (Mar 20, 2019)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
HOMER2	protein_coding	protein_coding	ENST00000304231	9	144824

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00939	0.989	124763	0	21	124784	0.0000841

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.314	195	208	0.939	0.0000120	2343
Missense in Polyphen		55	64.765	0.84923		703
Synonymous	0.492	77	82.7	0.931	0.00000524	644
Loss of Function	2.69	7	20.0	0.351	0.00000102	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000252	0.000251
Ashkenazi Jewish	0.0000998	0.0000994
East Asian	0.00	0.00
Finnish	0.0000467	0.0000464
European (Non-Finnish)	0.000116	0.000115
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000168	0.000165

dbNSFP

Source: dbNSFP

• Function: 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 (PubMed:9808459). Required for normal hearing (PubMed:25816005). Negatively regulates T cell activation through negative regulation of IL2 expression by inhibiting calcineurin-NFAT pathway activation through interaction with NFATC2 (PubMed:18218901). {ECO:0000269|PubMed:18218901, ECO:0000269|PubMed:25816005, ECO:0000269|PubMed:9808459}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:25816005}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Glutamatergic synapse - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);Neuronal System;Neurexins and neuroligins;Protein-protein interactions at synapses (Consensus)

Recessive Scores

• pRec: 0.213

Intolerance Scores

• loftool: 0.530
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.36

Haploinsufficiency Scores

• pHI: 0.450
• hipred: N
• hipred_score: 0.462
• ghis: 0.403

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.855

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Homer2
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: homer2
• Affected structure: olfactory bulb glomerulus
• Phenotype tag: abnormal
• Phenotype quality: aplastic/hypoplastic

Gene ontology

• Biological process: G protein-coupled glutamate receptor signaling pathway;sensory perception of sound;regulation of G protein-coupled receptor signaling pathway;negative regulation of interleukin-2 production;calcium-mediated signaling using intracellular calcium source;behavioral response to cocaine;chemical homeostasis within a tissue;negative regulation of calcineurin-NFAT signaling cascade;regulation of store-operated calcium entry
• Cellular component: cytoplasm;cytosol;plasma membrane;postsynaptic density;cell junction;dendrite;stereocilium tip;neuron projection;neuronal cell body;apical part of cell;postsynaptic membrane;glutamatergic synapse
• Molecular function: actin binding;protein binding;protein domain specific binding;GKAP/Homer scaffold activity;G protein-coupled glutamate receptor binding;protein homodimerization activity;protein heterodimerization activity