LHX4 (LIM homeobox 4)

Gene

• Entrez ID: 89884
• Gene name: LIM homeobox 4
• Gene symbol: LHX4
• Synonyms (NCBI Gene): CPHD4
• Chromosome: 1
• Chromosome location: 1q25.2
• Summary: This gene encodes a member of a large protein family which contains the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor involved in the control of differentiation and development of the pituitary gland

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs587776662	->C	Pathogenic	Coding sequence variant, frameshift variant
rs886041420	A>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023725	hsa-miR-1-3p	Microarray	18668037
MIRT702277	hsa-miR-548as-3p	HITS-CLIP	23313552
MIRT702276	hsa-miR-3614-5p	HITS-CLIP	23313552
MIRT702275	hsa-miR-6500-3p	HITS-CLIP	23313552
MIRT702274	hsa-miR-4768-3p	HITS-CLIP	23313552
MIRT702273	hsa-miR-4459	HITS-CLIP	23313552
MIRT702272	hsa-miR-4433a-3p	HITS-CLIP	23313552
MIRT702271	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT702270	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT702269	hsa-miR-4786-5p	HITS-CLIP	23313552
MIRT702268	hsa-miR-4470	HITS-CLIP	23313552
MIRT702267	hsa-miR-3926	HITS-CLIP	23313552
MIRT702266	hsa-miR-3688-5p	HITS-CLIP	23313552
MIRT702265	hsa-miR-548s	HITS-CLIP	23313552
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT623389	hsa-miR-4313	HITS-CLIP	23824327
MIRT656745	hsa-miR-6894-5p	HITS-CLIP	23824327
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT656745	hsa-miR-6894-5p	HITS-CLIP	23824327
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT623389	hsa-miR-4313	HITS-CLIP	23824327
MIRT576487	hsa-miR-548as-3p	HITS-CLIP	23313552
MIRT702276	hsa-miR-3614-5p	HITS-CLIP	23313552
MIRT702275	hsa-miR-6500-3p	HITS-CLIP	23313552
MIRT576486	hsa-miR-4768-3p	HITS-CLIP	23313552
MIRT576485	hsa-miR-4459	HITS-CLIP	23313552
MIRT576484	hsa-miR-4433a-3p	HITS-CLIP	23313552
MIRT576483	hsa-miR-6849-3p	HITS-CLIP	23313552
MIRT576482	hsa-miR-3190-5p	HITS-CLIP	23313552
MIRT576481	hsa-miR-4786-5p	HITS-CLIP	23313552
MIRT576480	hsa-miR-4470	HITS-CLIP	23313552
MIRT576479	hsa-miR-3926	HITS-CLIP	23313552
MIRT576478	hsa-miR-3688-5p	HITS-CLIP	23313552
MIRT576477	hsa-miR-548s	HITS-CLIP	23313552
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT623389	hsa-miR-4313	HITS-CLIP	23824327
MIRT656745	hsa-miR-6894-5p	HITS-CLIP	23824327
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT656745	hsa-miR-6894-5p	HITS-CLIP	23824327
MIRT623391	hsa-miR-6832-3p	HITS-CLIP	23824327
MIRT623390	hsa-miR-3605-5p	HITS-CLIP	23824327
MIRT623389	hsa-miR-4313	HITS-CLIP	23824327
MIRT2453014	hsa-miR-1294	CLIP-seq
MIRT2453015	hsa-miR-4316	CLIP-seq
MIRT2453016	hsa-miR-4446-3p	CLIP-seq
MIRT2453017	hsa-miR-4675	CLIP-seq
MIRT2453018	hsa-miR-4677-3p	CLIP-seq
MIRT2453019	hsa-miR-4741	CLIP-seq
MIRT2453020	hsa-miR-4753-5p	CLIP-seq
MIRT2453021	hsa-miR-4757-5p	CLIP-seq
MIRT2453022	hsa-miR-888	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000977	Function	RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA
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:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IDA	15998782
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	20211142, 25416956, 25910212, 26871637, 27820671, 28514442, 31515488, 32296183, 33961781, 35140242
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	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:0008327	Function	Methyl-CpG binding	IDA	28473536
GO:0009887	Process	Animal organ morphogenesis	IEA
GO:0021526	Process	Medial motor column neuron differentiation	IEA
GO:0030182	Process	Neuron differentiation	IBA
GO:0043066	Process	Negative regulation of apoptotic process	IEA
GO:0043565	Function	Sequence-specific DNA binding	IDA	28473536
GO:0043565	Function	Sequence-specific DNA binding	IEA
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	15998782
GO:0046872	Function	Metal ion binding	IEA
GO:1990837	Function	Sequence-specific double-stranded DNA binding	IDA	28473536

Other IDs

• MIM: 602146
• HGNC: 21734
• e!Ensembl: ENSG00000121454

Protein

• UniProt ID: Q969G2
• Protein name: LIM/homeobox protein Lhx4 (LIM homeobox protein 4)
• Protein function: May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung. Binds preferentially to methylated DNA (PubMed:28473536).
• PDB: 5HOD
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00412	LIM	30 → 85	LIM domain	Domain
  PF00412	LIM	89 → 148	LIM domain	Domain
  PF00046	Homeodomain	158 → 214	Homeodomain	Domain

• Sequence:

  MMQSATVPAEGAVKGLPEMLGVPMQQIPQCAGCNQHILDKFILKVLDRHWHSSCLKCADC
  QMQLADRCFSRAGSVYCKEDFFKRFGTKCTACQQGIPPTQVVRKAQDFVYHLHCFACIIC
  NRQLATGDEFYLMEDGRLVCKEDYETAKQNDDSEAGAKRPRTTITAKQLETLKNAYKNSP
  KPARHVREQLSSETGLDMRVVQVWFQNRRAKEKRLKKDAGRHRWGQFYKSVKRSRGSSKQ
  EKESSAEDCGVSDSELSFREDQILSELGHTNRIYGNVGDVTGGQLMNGSFSMDGTGQSYQ
  DLRDGSPYGIPQSPSSISSLPSHAPLLNGLDYTVDSNLGIIAHAGQGVSQTLRAMAGGPT
  SDISTGSSVGYPDFPTSPGSWLDEMDHPPF

• Sequence length: 390

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
Short stature-pituitary and cerebellar defects-small sella turcica syndrome	Pathogenic	rs786204780, rs748268631, rs121912641, rs121912643, rs121912644, rs587776662	RCV000169664 RCV000007935 RCV000007936 RCV000007938 RCV000007939 RCV000007940	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Combined pituitary hormone deficiencies, genetic form	Benign; Likely benign	ClinVar GWAS catalog	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
COMBINED PITUITARY HORMONE DEFICIENCIES, GENETIC FORMS	—	Orphanet	★★☆☆☆ 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, Dominant	Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DESBUQUOIS SYNDROME	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPOTHYROIDISM DUE TO DEFICIENT TRANSCRIPTION FACTORS INVOLVED IN PITUITARY DEVELOPMENT OR FUNCTION	—	Disgenet, Orphanet Disgenet, 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
LHX4-related disorder	Benign; Likely benign; Uncertain significance; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PANHYPOPITUITARISM	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary hormone deficiency, combined, 1	Uncertain significance	ClinVar Disgenet	★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY STALK INTERRUPTION SYNDROME	—	ClinVar, Disgenet ClinVar, Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute lymphocytic leukemia	Lymphocytic Leukemia	BEFREE	14506703		★☆☆☆☆ Found in Text Mining only
Adrenocorticotropic hormone (ACTH) deficiency (disorder)	Adrenocorticotropic Hormone Deficiency	BEFREE	12914740, 17201807, 17527005, 25955177		★☆☆☆☆ Found in Text Mining only
Adult Acute Lymphocytic Leukemia	Lymphocytic Leukemia	BEFREE	14506703		★☆☆☆☆ Found in Text Mining only
Agenesis of corpus callosum	Agenesis Of Corpus Callosum	HPO_DG			★☆☆☆☆ Found in Text Mining only
Blast Phase	Blast phase chronic myelogenous leukemia	BEFREE	14506703		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	BEFREE	12914740		★☆☆☆☆ Found in Text Mining only
Central hypothyroidism	Central hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Diseases	Cerebellar diseases	Pubtator	11567216	Associate	★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	BEFREE	12914740		★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	BEFREE	14506703		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	25034524	Stimulate	★☆☆☆☆ Found in Text Mining only
Combined pituitary hormone deficiencies, genetic forms	Pituitary Hormone Deficiency	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Combined Pituitary Hormone Deficiency	Combined pituitary hormone deficiency	Pubtator	17527005, 25871839, 25955177, 32796691	Associate	★☆☆☆☆ Found in Text Mining only
Congenital exomphalos	Congenital Exomphalos	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital hypoplasia of penis	Congenital Hypoplasia Of Penis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital myopathy (disorder)	Congenital myopathy	BEFREE	27464418		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	Pubtator	25871839	Associate	★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cyclic neutropenia	Cyclic Neutropenia	BEFREE	23029363		★☆☆☆☆ Found in Text Mining only
Diabetes Insipidus	Diabetes Insipidus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dwarfism	Dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dyssomnias	Dyssomnia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ectopic anterior pituitary gland	Ectopic anterior pituitary gland	HPO_DG			★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Growth Disorders	Growth disorder	Pubtator	11567216	Associate	★☆☆☆☆ Found in Text Mining only
Hemochromatosis	Hemochromatosis	Pubtator	23761422, 25955177	Associate	★☆☆☆☆ Found in Text Mining only
Holoprosencephaly	Holoprosencephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	Pubtator	17527005	Associate	★☆☆☆☆ Found in Text Mining only
Hypoglycemia	Hypoglycemia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypogonadotropic hypogonadism	Hypogonadotropic Hypogonadism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	GENOMICS_ENGLAND_DG	11567216		★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	BEFREE	17201807, 18445675, 22466334, 23029363, 25871839, 25955177, 27820671		★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	LHGDN	18445675		★☆☆☆☆ Found in Text Mining only
Hypopituitarism	Hypopituitarism	Pubtator	25871839, 25955177, 34124982	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	BEFREE	12914740		★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	Pubtator	25955177	Associate	★☆☆☆☆ Found in Text Mining only
Hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ 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	15998782, 20389107, 25557026, 27820671		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	GWASCAT_DG	27903959		★☆☆☆☆ Found in Text Mining only
Myeloid Leukemia, Chronic	Myeloid Leukemia	BEFREE	14506703		★☆☆☆☆ Found in Text Mining only
Oral cleft	Oral cleft	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteopenia	Osteopenia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Osteoporosis of vertebrae	Osteoporosis of vertebrae	HPO_DG			★☆☆☆☆ Found in Text Mining only
Panhypopituitarism	Panhypopituitarism	BEFREE	12812307, 15567726, 17201807, 17527005, 18157385, 19337183, 19856252, 20534763, 25557026, 25955177, 27464418, 27820671		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Diseases	Pituitary Diseases	BEFREE	23029363, 27820671		★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	BEFREE	17201807, 25557026, 27820671		★☆☆☆☆ Found in Text Mining only
Pituitary dwarfism	Pituitary dwarfism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pituitary Hormone Deficiency Combined 2	Pituitary hormone deficiency	Pubtator	25871839	Associate	★☆☆☆☆ Found in Text Mining only
Pituitary Hormone Deficiency, Combined, 1	Pituitary Hormone Deficiency	ORPHANET_DG	25871839		★★★☆☆ Reported in Unknown/Other Associations (≥2 sources)
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	Pituitary Hormone Deficiency	ORPHANET_DG	11567216		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	Pituitary Hormone Deficiency	UNIPROT_DG	17527005, 18073311		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	Pituitary Hormone Deficiency	GENOMICS_ENGLAND_DG	18445675, 25955177		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	Pituitary Hormone Deficiency	CLINVAR_DG	23990694		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PITUITARY HORMONE DEFICIENCY, COMBINED, 4	Pituitary Hormone Deficiency	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary Neoplasms	Pituitary neoplasm	Pubtator	31745224	Associate	★☆☆☆☆ Found in Text Mining only
Pituitary stalk interruption syndrome	Pituitary Stalk Interruption Syndrome	ORPHANET_DG	21270112		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pituitary stalk interruption syndrome	Pituitary Stalk Interruption Syndrome	BEFREE	23199197		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Polydactyly	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Primary physiologic amenorrhea	Physiologic Amenorrhea	HPO_DG			★☆☆☆☆ Found in Text Mining only
Respiratory Tract Diseases	Respiratory system infectious disease	Pubtator	17527005	Associate	★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	BEFREE	12914740		★☆☆☆☆ Found in Text Mining only
Secondary hypothyroidism	Hypothyroidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
Septo-Optic Dysplasia	Septo-Optic Dysplasia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Short stature-pituitary and cerebellar defects-small sella turcica syndrome	Short Stature-Pituitary And Cerebellar Defects-Small Sella Turcica Syndrome	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Sleep Disorders	Sleep Disorders	HPO_DG			★☆☆☆☆ Found in Text Mining only
Somatotropin deficiency	Somatotropin Deficiency	BEFREE	23761422		★☆☆☆☆ Found in Text Mining only
Turner Syndrome	Turner syndrome	Pubtator	23761422	Associate	★☆☆☆☆ Found in Text Mining only