LHFPL5

LHFPL tetraspan subfamily member 5, the group of LHFPL tetraspan proteins

Basic information

Region (hg38): 6:35797206-35845397

Previous symbols: [ "DFNB67" ]

Links

ENSG00000197753 ∙ NCBI:222662 ∙ OMIM:609427 ∙ HGNC:21253 ∙ Uniprot:Q8TAF8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive nonsyndromic hearing loss 67 (Strong), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 67 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AR
• autosomal recessive nonsyndromic hearing loss 67 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 67	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	16752389; 16459341

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LHFPL5 gene.

• not_provided (58 variants)
• Autosomal_recessive_nonsyndromic_hearing_loss_67 (31 variants)
• Inborn_genetic_diseases (19 variants)
• not_specified (13 variants)
• LHFPL5-related_disorder (9 variants)
• Hearing_loss,_autosomal_recessive (3 variants)
• Hearing_impairment (2 variants)
• Nonsyndromic_genetic_hearing_loss (1 variants)
• Deafness (1 variants)
• Rare_genetic_deafness (1 variants)
• Autosomal_recessive_non-syndromic_intellectual_disability (1 variants)
• Ear_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LHFPL5 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000182548.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	14		18
missense	2	5	52	3		62
nonsense	1	2	1			4
start loss		1				1
frameshift	5	2				7
splice donor/acceptor (+/-2bp)	2	1				3
Total	10	11	57	17	0

Highest pathogenic variant AF is 0.0000830225

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LHFPL5	protein_coding	protein_coding	ENST00000360215	3	28582

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000402	0.652	125729	0	19	125748	0.0000756

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.300	124	134	0.927	0.00000913	1430
Missense in Polyphen		56	64.621	0.86659		702
Synonymous	1.29	46	58.5	0.786	0.00000458	450
Loss of Function	0.724	6	8.24	0.728	4.43e-7	86

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000202	0.000202
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000793	0.0000791
Middle Eastern	0.00	0.00
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: In the inner ear, may be a component of the hair cell's mechanotransduction machinery that functionally couples PCDH15 to the transduction channel. Regulates transducer channel conductance and is required for fast channel adaptation (By similarity). {ECO:0000250}.
• Disease: DISEASE: Deafness, autosomal recessive, 67 (DFNB67) [MIM:610265]: A form of non-syndromic sensorineural hearing loss. 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:16459341, ECO:0000269|PubMed:16752389, ECO:0000269|PubMed:26437881, ECO:0000269|PubMed:28281779}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.138

Intolerance Scores

• loftool: 0.285
• rvis_EVS: -0.34
• rvis_percentile_EVS: 30.07

Haploinsufficiency Scores

• pHI: 0.151
• hipred: N
• hipred_score: 0.492
• ghis: 0.485

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.306

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lhfpl5
• Phenotype: hearing/vestibular/ear phenotype; 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: lhfpl5a
• Affected structure: musculoskeletal movement
• Phenotype tag: abnormal
• Phenotype quality: quality

Gene ontology

• Biological process: ion transport
• Cellular component: plasma membrane;integral component of membrane
• Molecular function: protein binding