LHX3 (LIM homeobox 3)

Gene

• Entrez ID: 8022
• Gene name: LIM homeobox 3
• Gene symbol: LHX3
• Synonyms (NCBI Gene): CPHD3, LIM3, M2-LHX3
• Chromosome: 9
• Chromosome location: 9q34.3
• Summary: This gene encodes a member of a large family of proteins which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Mutat

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs104894117	T>C	Pathogenic	Coding sequence variant, missense variant
rs137854503	G>A	Pathogenic	Coding sequence variant, missense variant
rs137854504	GC>AGGA	Pathogenic	Coding sequence variant, frameshift variant
rs137854505	C>T	Pathogenic	Coding sequence variant, stop gained
rs137854506	T>A	Pathogenic	Coding sequence variant, stop gained
rs190916587	G>A,C	Conflicting-interpretations-of-pathogenicity	Coding sequence variant, synonymous variant
rs587776711	GTCGTCCCCTCGGCTGACCTCGC>-	Pathogenic	Splice donor variant, coding sequence variant, intron variant
rs587776712	A>-	Pathogenic	Coding sequence variant, frameshift variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1108993	hsa-miR-4761-5p	CLIP-seq
MIRT1108994	hsa-miR-545	CLIP-seq
MIRT1108995	hsa-miR-1207-5p	CLIP-seq
MIRT1108996	hsa-miR-125a-5p	CLIP-seq
MIRT1108997	hsa-miR-125b	CLIP-seq
MIRT1108998	hsa-miR-1271	CLIP-seq
MIRT1108999	hsa-miR-1321	CLIP-seq
MIRT1109000	hsa-miR-15a	CLIP-seq
MIRT1109001	hsa-miR-15b	CLIP-seq
MIRT1109002	hsa-miR-16	CLIP-seq
MIRT1109003	hsa-miR-182	CLIP-seq
MIRT1109004	hsa-miR-195	CLIP-seq
MIRT1109005	hsa-miR-302a	CLIP-seq
MIRT1109006	hsa-miR-302b	CLIP-seq
MIRT1109007	hsa-miR-302c	CLIP-seq
MIRT1109008	hsa-miR-302d	CLIP-seq
MIRT1109009	hsa-miR-302e	CLIP-seq
MIRT1109010	hsa-miR-3150b-3p	CLIP-seq
MIRT1109011	hsa-miR-342-5p	CLIP-seq
MIRT1109012	hsa-miR-3616-3p	CLIP-seq
MIRT1109013	hsa-miR-372	CLIP-seq
MIRT1109014	hsa-miR-373	CLIP-seq
MIRT1109015	hsa-miR-424	CLIP-seq
MIRT1109016	hsa-miR-4270	CLIP-seq
MIRT1109017	hsa-miR-4319	CLIP-seq
MIRT1109018	hsa-miR-4436b-3p	CLIP-seq
MIRT1109019	hsa-miR-4441	CLIP-seq
MIRT1109020	hsa-miR-4524	CLIP-seq
MIRT1109021	hsa-miR-4651	CLIP-seq
MIRT1109022	hsa-miR-4664-5p	CLIP-seq
MIRT1109023	hsa-miR-4687-3p	CLIP-seq
MIRT1109024	hsa-miR-4689	CLIP-seq
MIRT1109025	hsa-miR-4710	CLIP-seq
MIRT1109026	hsa-miR-4725-5p	CLIP-seq
MIRT1109027	hsa-miR-4728-5p	CLIP-seq
MIRT1109028	hsa-miR-4739	CLIP-seq
MIRT1109029	hsa-miR-4756-5p	CLIP-seq
MIRT1109030	hsa-miR-4763-3p	CLIP-seq
MIRT1109031	hsa-miR-4784	CLIP-seq
MIRT1109032	hsa-miR-497	CLIP-seq
MIRT1109033	hsa-miR-503	CLIP-seq
MIRT1109034	hsa-miR-504	CLIP-seq
MIRT1109035	hsa-miR-520a-3p	CLIP-seq
MIRT1109036	hsa-miR-520b	CLIP-seq
MIRT1109037	hsa-miR-520c-3p	CLIP-seq
MIRT1109038	hsa-miR-520d-3p	CLIP-seq
MIRT1109039	hsa-miR-520e	CLIP-seq
MIRT1109040	hsa-miR-544b	CLIP-seq
MIRT1109041	hsa-miR-608	CLIP-seq
MIRT1109042	hsa-miR-646	CLIP-seq
MIRT1109043	hsa-miR-765	CLIP-seq
MIRT1109044	hsa-miR-96	CLIP-seq
MIRT1108998	hsa-miR-1271	CLIP-seq
MIRT1109003	hsa-miR-182	CLIP-seq
MIRT1109023	hsa-miR-4687-3p	CLIP-seq
MIRT2030143	hsa-miR-543	CLIP-seq
MIRT1109044	hsa-miR-96	CLIP-seq
MIRT2261025	hsa-miR-4492	CLIP-seq
MIRT2261026	hsa-miR-4498	CLIP-seq
MIRT2261027	hsa-miR-762	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
SOX2	Activation	18407919

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	IEA
GO:0000785	Component	Chromatin	ISA
GO:0000976	Function	Transcription cis-regulatory region binding	IEA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001221	Function	Transcription coregulator binding	IEA
GO:0001223	Function	Transcription coactivator binding	IEA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	15271874
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IEA
GO:0001890	Process	Placenta development	IEA
GO:0003677	Function	DNA binding	IEA
GO:0005515	Function	Protein binding	IPI	32296183
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IEA
GO:0005634	Component	Nucleus	TAS	10598593
GO:0005667	Component	Transcription regulator complex	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006915	Process	Apoptotic process	IEA
GO:0008045	Process	Motor neuron axon guidance	IEA
GO:0008270	Function	Zinc ion binding	IEA
GO:0009887	Process	Animal organ morphogenesis	TAS	10598593
GO:0009953	Process	Dorsal/ventral pattern formation	IEA
GO:0021520	Process	Spinal cord motor neuron cell fate specification	IEA
GO:0021521	Process	Ventral spinal cord interneuron specification	IEA
GO:0021526	Process	Medial motor column neuron differentiation	IEA
GO:0021527	Process	Spinal cord association neuron differentiation	IEA
GO:0021983	Process	Pituitary gland development	IEA
GO:0030182	Process	Neuron differentiation	IBA
GO:0030324	Process	Lung development	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	15271874
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	IEA
GO:0045893	Process	Positive regulation of DNA-templated transcription	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	15271874
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IEA
GO:0046872	Function	Metal ion binding	IEA
GO:0048839	Process	Inner ear development	IEP	18407919
GO:0060126	Process	Somatotropin secreting cell differentiation	IEA
GO:0060127	Process	Prolactin secreting cell differentiation	IEA
GO:0060129	Process	Thyroid-stimulating hormone-secreting cell differentiation	IEA
GO:0061629	Function	RNA polymerase II-specific DNA-binding transcription factor binding	IPI	26612202

Other IDs

• MIM: 600577
• HGNC: 6595
• e!Ensembl: ENSG00000107187

Protein

• UniProt ID: Q9UBR4
• Protein name: LIM/homeobox protein Lhx3 (LIM homeobox protein 3)
• Protein function: Transcription factor. Recognizes and binds to the consensus sequence motif 5'-AATTAATTA-3' in the regulatory elements of target genes, such as glycoprotein hormones alpha chain CGA and visual system homeobox CHX10, positively modulating transcri
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00412	LIM	31 → 86	LIM domain	Domain
  PF00412	LIM	90 → 149	LIM domain	Domain
  PF00046	Homeodomain	158 → 214	Homeodomain	Domain

• Sequence:

  MLLETGLERDRARPGAAAVCTLGGTREIPLCAGCDQHILDRFILKALDRHWHSKCLKCSD
  CHTPLAERCFSRGESVYCKDDFFKRFGTKCAACQLGIPPTQVVRRAQDFVYHLHCFACVV
  CKRQLATGDEFYLMEDSRLVCKADYETAKQREAEATAKRPRTTITAKQLETLKSAYNTSP
  KPARHVREQLSSETGLDMRVVQVWFQNRRAKEKRLKKDAGRQRWGQYFRNMKRSRGGSKS
  DKDSVQEGQDSDAEVSFPDEPSLAEMGPANGLYGSLGEPTQALGRPSGALGNFSLEHGGL
  AGPEQYRELRPGSPYGVPPSPAAPQSLPGPQPLLSSLVYPDTSLGLVPSGAPGGPPPMRV
  LAGNGPSSDLSTGSSGGYPDFPASPASWLDEVDHAQF

• Sequence length: 397

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Combined pituitary hormone deficiencies, genetic form	Likely pathogenic	rs969810391, rs137854503	RCV005237768 RCV005237364	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Non-acquired combined pituitary hormone deficiency with spine abnormalities	Likely pathogenic; Pathogenic	rs969810391, rs774533927, rs2131036410, rs2131034777, rs2131032901, rs2490918969, rs104894117, rs587776711, rs587776712, rs137854503, rs137854504, rs137854505, rs137854506, rs2490915299	RCV001826139 RCV001831393 RCV001826161 RCV001782383 RCV001837058 RCV005050703 RCV000009587 RCV000009588 RCV000009589 RCV000009590 RCV000009591 RCV000009593 RCV000009595 RCV003152945	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Amenorrhea	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION	—	CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog CTD, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CHRONIC KIDNEY DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COMBINED PITUITARY HORMONE DEFICIENCY GENETIC FORM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Combined Pituitary Hormone Deficiency, Recessive	Benign; Likely benign; Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC NEPHROPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM DUE TO DEFICIENT TRANSCRIPTION FACTORS INVOLVED IN PITUITARY DEVELOPMENT OR FUNCTION	—	GWAS catalog, Orphanet GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM DUE TO MUTATION IN TRANSCRIPTION FACTOR OF PITUITARY DEVELOPMENT	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LHX3-related disorder	Likely benign; Uncertain significance; Conflicting classifications of pathogenicity; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LUNG ADENOCARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANHYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary hormone deficiency, combined, 1	Uncertain significance; Likely benign	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PITUITARY HORMONE DEFICIENCY, COMBINED, 3	—	Disgenet, HPO Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
WINKELMAN BETHGE PFEIFFER SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenocarcinoma of lung (disorder)	Lung adenocarcinoma	BEFREE	28731174		★☆☆☆☆ Found in Text Mining only
Adrenocorticotropic hormone (ACTH) deficiency (disorder)	Adrenocorticotropic Hormone Deficiency	BEFREE	12914740, 21249393		★☆☆☆☆ Found in Text Mining only
Adrenocorticotropic hormone (ACTH) deficiency (disorder)	Adrenocorticotropic Hormone Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Adult Oligodendroglioma	Oligodendroglioma	BEFREE	25399296		★☆☆☆☆ Found in Text Mining only
Arnold-Chiari Malformation, Type I	Arnold-Chiari malformation	BEFREE	15279086		★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	CTD_human_DG	29892015, 30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Atrial Fibrillation	Atrial Fibrillation	GWASCAT_DG	30061737		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Breast Neoplasms	Breast neoplasm	Pubtator	19153192	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	31306102	Associate	★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	BEFREE	12914740, 21249393		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	BEFREE	12914740		★☆☆☆☆ Found in Text Mining only
Childhood Oligodendroglioma	Oligodendroglioma	BEFREE	25399296		★☆☆☆☆ Found in Text Mining only
Combined Pituitary Hormone Deficiency	Combined pituitary hormone deficiency	Pubtator	22286346, 28302169, 29261175	Associate	★☆☆☆☆ Found in Text Mining only
Combined Pituitary Hormone Deficiency	Combined pituitary hormone deficiency	Pubtator	28302169	Inhibit	★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Development Disorder	BEFREE	22286346		★☆☆☆☆ Found in Text Mining only
Developmental Disabilities	Developmental disability	Pubtator	22286346	Associate	★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism Pituitary	Pituitary dwarfism	Pubtator	34589056	Associate	★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Endometrial Neoplasms	Endometrial neoplasm	Pubtator	35832124	Associate	★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	22983390	Associate	★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Gonadotropin deficiency	Gonadotropin Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Head and Neck Neoplasms	Head and neck neoplasm	Pubtator	22286346, 28302169	Associate	★☆☆☆☆ Found in Text Mining only
Hearing Loss Sensorineural	Hearing loss	Pubtator	28302169	Associate	★☆☆☆☆ Found in Text Mining only
Hypogonadism	Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	BEFREE	10946868, 18407919, 30262920		★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	Pubtator	34124982	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	12914740, 21249393		★☆☆☆☆ Found in Text Mining only
Hypothyroidism due to deficient transcription factors involved in pituitary development or function	Hypothyroidism	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Intellectual Disability	Mental retardation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Isolated somatotropin deficiency	Isolated Somatotropin Deficiency	BEFREE	25557026		★☆☆☆☆ Found in Text Mining only
Isolated somatotropin deficiency	Isolated Somatotropin Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	31306102		★☆☆☆☆ Found in Text Mining only
Lung Diseases	Lung disease	Pubtator	26635082	Associate	★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25399296		★☆☆☆☆ Found in Text Mining only
Non-acquired combined pituitary hormone deficiency-sensorineural hearing loss-spine abnormalities syndrome	Non-acquired combined pituitary hormone deficiency-sensorineural hearing loss-spine abnormalities syndrome	Orphanet			★☆☆☆☆ Found in Text Mining only
Non-Small Cell Lung Carcinoma	Lung carcinoma	BEFREE	28731174		★☆☆☆☆ Found in Text Mining only
Obesity	Obesity	BEFREE	12536356		★☆☆☆☆ Found in Text Mining only
oligodendroglioma	Oligodendroglioma	BEFREE	25399296		★☆☆☆☆ Found in Text Mining only
Oral cleft	Oral cleft	HPO_DG			★☆☆☆☆ Found in Text Mining only
Panhypopituitarism	Panhypopituitarism	BEFREE	10835633, 10946868, 12812307, 15567726, 17327381, 18157385, 19126629, 21149718, 21249393, 22238406, 22286346, 25557026, 28302169, 28734020, 29261175, 30262920		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Paroxysmal atrial fibrillation	Paroxysmal atrial fibrillation	CTD_human_DG	29892015, 30061737		★☆☆☆☆ Found in Text Mining only
Pituitary Diseases	Pituitary Diseases	BEFREE	19126629, 28302169		★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	BEFREE	17327381, 25557026		★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	ORPHANET_DG	10835633, 19762173		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	GENOMICS_ENGLAND_DG	10835633, 18407919		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	UNIPROT_DG	10835633, 17327381, 28302169		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	CLINVAR_DG	18407919		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	BEFREE	28302169		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Hormone Deficiency, Combined, 3	Pituitary Hormone Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Secondary hypothyroidism	Hypothyroidism	BEFREE	12914740, 21249393		★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	BEFREE	18407919, 21249393, 28302169		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	LHGDN	18407919		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	GENOMICS_ENGLAND_DG	18407919		★☆☆☆☆ Found in Text Mining only
Sensorineural Hearing Loss (disorder)	Hearing Loss	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sensorineural hearing loss, bilateral	Sensorineural hearing loss	BEFREE	18407919		★☆☆☆☆ Found in Text Mining only
Septo-Optic Dysplasia	Septo-Optic Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Somatotropin deficiency	Somatotropin Deficiency	HPO_DG			★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma	Carcinoma	BEFREE	28731174		★☆☆☆☆ Found in Text Mining only
Well Differentiated Oligodendroglioma	Oligodendroglioma	BEFREE	25399296		★☆☆☆☆ Found in Text Mining only