LHX4 LIM homeobox 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LHX4provided by HGNC
Official Full Name: LIM homeobox 4provided by HGNC
Primary source: HGNC:HGNC:21734
See related: Ensembl:ENSG00000121454 MIM:602146; AllianceGenome:HGNC:21734
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CPHD4
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. Mutations in this gene cause combined pituitary hormone deficiency 4. [provided by RefSeq, Dec 2010]
Expression: Ubiquitous expression in testis (RPKM 1.2), placenta (RPKM 0.8) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q25.2

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (180228375..180278984)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (179583799..179634371)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (180199399..180248119)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.
Title: Genetic diagnosis of congenital hypopituitarism in Turkish patients by a target gene panel: novel pathogenic variants in GHRHR, GLI2, LHX4 and POU1F1 genes.
LHX4 Mutation is associated with Pituitary Deficits.
Title: Contribution of LHX4 Mutations to Pituitary Deficits in a Cohort of 417 Unrelated Patients.
The study identified 4 new LHX4 heterozygous allelic variants in patients with congenital hypopituitarism: W204X, delK242, N271S and Q346R.
Title: Identifying the Deleterious Effect of Rare LHX4 Allelic Variants, a Challenging Issue.
A novel homozygous mutation in LHX4 associated with a lethal phenotype, implying that recessive mutations in LHX4 may be incompatible with life.
Title: Novel Lethal Form of Congenital Hypopituitarism Associated With the First Recessive LHX4 Mutation.
we found that LHX4 upregulated beta-catenin levels in human colorectal cancer cell lines
Title: Oncogenicity of LHX4 in colorectal cancer through Wnt/β-catenin/TCF4 cascade.
Data indicate that HESX1, LHX4 and SOX3 polymorphisms may be associated with pituitary stalk interruption syndrome (PSIS).
Title: Pituitary stalk interruption syndrome in 58 Chinese patients: clinical features and genetic analysis.
This study is the first to describe, a gradual loss of ACTH in a patient carrying an LHX4 mutation.
Title: Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism.
Variably penetrant pituitary insufficiency, including this severe and atypical presentation, can be correlated with LHX4 insufficiency and highlights the role of LHX4 for pituitary development.
Title: Panhypopituitarism presenting as life-threatening heart failure caused by an inherited microdeletion in 1q25 including LHX4.
data indicate that LHX4 may act as a potential tumor suppressor in hepatocarcinogenesis, suggesting that targeting LHX4 to downregulate AFP might have therapeutic implications
Title: Downregulation of alpha-fetoprotein expression by LHX4: a critical role in hepatocarcinogenesis.
A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial Pituitary stalk interruption syndrome.
Title: Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms.

Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Short stature-pituitary and cerebellar defects-small sella turcica syndrome MedGen: C2678408 OMIM: 262700 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2022-04-25) ClinGen Genome Curation Page Haploinsufficency Little evidence for dosage pathogenicity (Last evaluated 2022-04-25) ClinGen Genome Curation PagePubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AL009306 (e-PCR)
- UniSTS:64339

WI-15451 (e-PCR)
- UniSTS:80510

G20828 (e-PCR)
- UniSTS:35247

A006H48 (e-PCR)
- UniSTS:35248

SHGC-75972 (e-PCR)
- UniSTS:29939

LHX4_2030 (e-PCR)
- UniSTS:280822

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables methyl-CpG binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in animal organ morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in medial motor column neuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in motor neuron axon guidance	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in placenta development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in chromatin	ISA Inferred from Sequence Alignment more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: LIM/homeobox protein Lhx4

Names: LIM homeobox protein 4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008081.1 RefSeqGene

Range

4992..49747

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_033343.4 → NP_203129.1 LIM/homeobox protein Lhx4

See identical proteins and their annotated locations for NP_203129.1

Status: REVIEWED

Source sequence(s)

AF179849, AL139141, BC011759, BX954266

Consensus CDS

CCDS1338.1

UniProtKB/Swiss-Prot

Q8NHE0, Q8NHM1, Q8TCJ1, Q8WWX2, Q969G2, Q969W2

UniProtKB/TrEMBL

A0A0S2Z5S4

Related

ENSP00000263726.2, ENST00000263726.4

Conserved Domains (3) summary

cd09376
Location:89 → 144

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

cd09468
Location:30 → 81

LIM1_Lhx4; The first LIM domain of Lhx4

pfam00046
Location:160 → 214

Homeobox; Homeobox domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

180228375..180278984

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011510105.3 → XP_011508407.1 LIM/homeobox protein Lhx4 isoform X1

See identical proteins and their annotated locations for XP_011508407.1

Conserved Domains (3) summary

cd09376
Location:28 → 83

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

pfam00046
Location:99 → 152

Homeobox; Homeobox domain

cl02475
Location:1 → 20

LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
XM_011510106.4 → XP_011508408.1 LIM/homeobox protein Lhx4 isoform X1

See identical proteins and their annotated locations for XP_011508408.1

Conserved Domains (3) summary

cd09376
Location:28 → 83

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

pfam00046
Location:99 → 152

Homeobox; Homeobox domain

cl02475
Location:1 → 20

LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
XM_011510108.3 → XP_011508410.1 LIM/homeobox protein Lhx4 isoform X2

See identical proteins and their annotated locations for XP_011508410.1

Conserved Domains (2) summary

cd09376
Location:14 → 69

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

pfam00046
Location:85 → 138

Homeobox; Homeobox domain