Monogenic hearing loss

Gene: LHX3

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 12 Dec 2025, 10:28 a.m. | Last Modified: 12 Dec 2025, 10:28 a.m.

Panel Version: 5.49

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS update.

Created: 3 Feb 2025, 10:13 p.m. | Last Modified: 3 Feb 2025, 10:13 p.m.

Panel Version: 4.70

Comment on publications: PMID:39548529 paper was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 3 Feb 2025, 10:11 p.m. | Last Modified: 3 Feb 2025, 10:11 p.m.

Panel Version: 4.67

PMID:10835633 reported two unrelated families with combined pituitary hormone deficiency and with biallelic LHX3 variants. The three patients from a family identified with p.Tyr116Cys variant had mild-moderate bilateral sensorineural hearing loss, while the patient with 23bp deletion had profound sensorineural deafness, when re-investigated in PMID:18407919.

PMID:18407919 reported two families with novel recessive variants in LHX3 gene. They all exhibited varying degrees of bilateral sensorineural hearing loss.

PMID:39548529 reported a group of eight patients with combined pituitary hormone deficiency-3 and all of them were identified with the same homozygous variant, c.455-2A > G. They presented with progressive sensorineural hearing deficiency ranging from moderately severe to complete loss. This variant is present as a founder variant in the population in Northern Sweden and was also associated with vestibular impairment.

Created: 3 Feb 2025, 10:09 p.m. | Last Modified: 3 Feb 2025, 10:11 p.m.

Panel Version: 4.66

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Pituitary hormone deficiency, combined, 3, OMIM:221750; sensorineural hearing loss disorder, MONDO:0020678

Publications

• 10835633
• 18407919
• 39548529

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
#221750:Pituitary hormone deficiency, combined, 3[Short stature (if untreated); Deafness, sensorineural, variable; Short neck with limited rotation; Mental retardation (if untreated); Anterior pituitary hypoplasiaAnterior pituitary enlargement; Low or absent growth hormone (GH)Low or absent thyroid-stimulating hormone (TSH)Low or absent follicle-stimulating hormone (FSH)Low or absent luteinizing hormone (LH)Low or absent prolactin (PL)Low or absent adrenocorticotropic hormone (ACTH) in some patients; Caused by mutations in the LIM/homeodomain protein LHX3 gene (LHX3,)]

Publications

• PMID:10598593
• 10717474
• 10835633
• 10946868
• 10952312
• 12150931
• 12797958
• 16394081
• 17327381
• 18407919
• 1970421
• 2898300
• 7528105
• 7626792
• 7665181
• 8597642
• 8638120
• 9865699