LHX3

LIM homeobox 3, the group of LIM class homeoboxes

Basic information

Region (hg38): 9:136196250-136205128

Links

ENSG00000107187 ∙ NCBI:8022 ∙ OMIM:600577 ∙ HGNC:6595 ∙ Uniprot:Q9UBR4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• non-acquired combined pituitary hormone deficiency with spine abnormalities (Strong), mode of inheritance: AR
• non-acquired combined pituitary hormone deficiency with spine abnormalities (Definitive), mode of inheritance: AR
• non-acquired combined pituitary hormone deficiency with spine abnormalities (Strong), mode of inheritance: AR
• hypothyroidism due to deficient transcription factors involved in pituitary development or function (Supportive), mode of inheritance: AD
• non-acquired combined pituitary hormone deficiency with spine abnormalities (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pituitary hormone deficiency, combined, 3	AR	Audiologic/Otolaryngologic; Endocrine	Medical treatment of endocrine deficiencies, which can include congenital hypothyroidism and ACTH deficiency, can be beneficial; Awareness of hearing impairment can allow prompt interventions related to speech and language development	Audiologic/Otolaryngologic; Endocrine; Musculoskeletal; Neurologic	10835633; 16394081; 17327381; 18407919; 22238406; 22286346

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the LHX3 gene.

• not provided (13 variants)
• Non-acquired combined pituitary hormone deficiency with spine abnormalities (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the LHX3 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			1	232	2	235
missense			73	2		75
nonsense	7	1				8
start loss						0
frameshift	6	1	3			10
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	7				8
splice region			2	22		24
non coding		1	36	63	21	121
Total	14	10	115	297	23

Variants in LHX3

This is a list of pathogenic ClinVar variants found in the LHX3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-136196262-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 15, 2018)
9-136196294-T-C		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196369-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196468-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196500-G-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Benign (Jan 12, 2018)
9-136196534-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Likely benign (Jan 12, 2018)
9-136196535-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196545-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196552-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196578-G-C		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Likely benign (Jan 12, 2018)
9-136196606-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Apr 20, 2018)
9-136196610-G-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196633-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196687-C-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196688-A-G		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196743-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196755-G-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196771-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196807-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196808-G-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196824-T-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196869-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196888-C-T		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 12, 2018)
9-136196916-C-A		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Jan 13, 2018)
9-136196922-A-G		Non-acquired combined pituitary hormone deficiency with spine abnormalities	Uncertain significance (Apr 27, 2017)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
LHX3	protein_coding	protein_coding	ENST00000371746	6	8860

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0109	0.981	125490	0	10	125500	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.333	218	232	0.938	0.0000112	2532
Missense in Polyphen		68	77.233	0.88045		821
Synonymous	0.0936	104	105	0.988	0.00000534	831
Loss of Function	2.31	6	16.0	0.376	7.38e-7	176

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000933	0.0000932
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000522	0.0000462
European (Non-Finnish)	0.0000553	0.0000529
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with POU1F1/Pit-1 (By similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system. Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. {ECO:0000250, ECO:0000269|PubMed:21149718}.
• Disease: DISEASE: Pituitary hormone deficiency, combined, 3 (CPHD3) [MIM:221750]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD3 is characterized by a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation. {ECO:0000269|PubMed:10835633, ECO:0000269|PubMed:17327381, ECO:0000269|PubMed:28302169}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Developmental Biology;Regulation of expression of SLITs and ROBOs;Signaling by ROBO receptors;Axon guidance (Consensus)

Recessive Scores

• pRec: 0.257

Haploinsufficiency Scores

• pHI: 0.312
• hipred: Y
• hipred_score: 0.756
• ghis: 0.511

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.795

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Lhx3
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype; cellular phenotype; craniofacial 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); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: placenta development;motor neuron axon guidance;animal organ morphogenesis;spinal cord motor neuron cell fate specification;ventral spinal cord interneuron specification;medial motor column neuron differentiation;spinal cord association neuron differentiation;pituitary gland development;lung development;negative regulation of apoptotic process;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;inner ear development
• Cellular component: nucleus;transcription factor complex
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II transcription factor binding;DNA-binding transcription activator activity, RNA polymerase II-specific;sequence-specific DNA binding;metal ion binding