HESX1 HESX homeobox 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: HESX1provided by HGNC
Official Full Name: HESX homeobox 1provided by HGNC
Primary source: HGNC:HGNC:4877
See related: Ensembl:ENSG00000163666 MIM:601802; AllianceGenome:HGNC:4877
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: ANF; RPX; CPHD5
Summary: This gene encodes a conserved homeobox protein that is a transcriptional repressor in the developing forebrain and pituitary gland. Mutations in this gene are associated with septooptic dysplasia, HESX1-related growth hormone deficiency, and combined pituitary hormone deficiency. [provided by RefSeq, Jul 2008]
Expression: Broad expression in testis (RPKM 1.6), skin (RPKM 0.6) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 3p14.3

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2025_08	current	GRCh38.p14 (GCF_000001405.40)	3	NC_000003.12 (57197838..57227615, complement)
RS_2025_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	3	NC_060927.1 (57238106..57267938, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	3	NC_000003.11 (57231866..57261643, complement)

Chromosome 3 - NC_000003.12 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Homozygous HESX1 and COL1A1 Gene Variants in a Boy with Growth Hormone Deficiency and Early Onset Osteoporosis.
Title: Homozygous HESX1 and COL1A1 Gene Variants in a Boy with Growth Hormone Deficiency and Early Onset Osteoporosis.
Study did not identify HESX1 and LHX3 mutations by Sanger in brazilian patients with combined pituitary hormone deficiency
Title: Molecular analysis of brazilian patients with combined pituitary hormone deficiency and orthotopic posterior pituitary lobe reveals eight different PROP1 alterations with three novel mutations.
HESX1 mutations cause variable clinical features in congenital hypopituitarism patients, which suggests an influence of modifier genes or environmental factors on the phenotype
Title: HESX1 mutations in patients with congenital hypopituitarism: variable phenotypes with the same genotype.
A novel heterozygous mutation in the HESX1 gene and a novel homozygous mutation in the PROP1 gene were detected in 2 pedigrees with combined pituitary hormone deficiency
Title: Novel Mutations in HESX1 and PROP1 Genes in Combined Pituitary Hormone Deficiency.
investigated the specific mutations in PROP1, POU1F1, LHX3, and HESX1 genes in patients with combined pituitary hormone deficiency (CPHD) in Turkey
Title: Molecular analysis of PROP1, POU1F1, LHX3, and HESX1 in Turkish patients with combined pituitary hormone deficiency: a multicenter study.
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.
expand the phenotypic spectrum of HESX1 mutations in Kallman syndrome.
Title: Identification of HESX1 mutations in Kallmann syndrome.
Data show no mutations in HESX1, PROP1, and POU1F1 genes, seven different mutations in CTNNB1 in 8/16 patients, and hyperexpression of miR-150.
Title: CTNNB1 gene mutations, pituitary transcription factors, and MicroRNA expression involvement in the pathogenesis of adamantinomatous craniopharyngiomas.
A c.357+3G>A mutation prevents the generation of one of the alternative isoforms normally produced by the wild-type allele, predicting a truncated HESX1 protein.
Title: A novel HESX1 splice mutation causes isolated GH deficiency by interfering with mRNA processing.
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 (27)

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
Anophthalmia-microphthalmia syndrome MedGen: C5680330 GeneReviews: Not available	Compare labs
Desbuquois dysplasia 2 MedGen: C4014294 OMIM: 615777 GeneReviews: Not available	Compare labs
Septo-optic dysplasia sequence MedGen: C0338503 OMIM: 182230 GeneReviews: Not available	Compare labs

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

NoName (e-PCR)
- UniSTS:480628

NoName (e-PCR)
- UniSTS:483477

RH48343 (e-PCR)
- UniSTS:58053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA binding	TAS Traceable Author Statement more info	PubMed
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription repressor activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables chromatin binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
enables sequence-specific double-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific double-stranded DNA binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within brain development	IEA Inferred from Electronic Annotation more info
involved_in brain development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within camera-type eye development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within_negative_effect canonical Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to cadmium ion	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain development	IEA Inferred from Electronic Annotation more info
involved_in forebrain development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within forebrain morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within gonad development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within leukemia inhibitory factor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism growth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within nose development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within otic vesicle formation	IEA Inferred from Electronic Annotation more info
involved_in pituitary gland development	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within pituitary gland development	IEA Inferred from Electronic Annotation more info
involved_in pituitary gland development	IEA Inferred from Electronic Annotation more info
involved_in pituitary gland development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of embryonic development	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within stem cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within stem cell population maintenance	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within thyroid gland development	IEA Inferred from Electronic Annotation 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
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: homeobox expressed in ES cells 1

Names: Rathke pouch homeobox; Rathke's pouch homeobox; homeobox protein ANF

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_008242.2 RefSeqGene

Range

32637..34777

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001376058.1 → NP_001362987.1 homeobox expressed in ES cells 1

Status: REVIEWED

Source sequence(s)

AC093928

Consensus CDS

CCDS2881.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Related

ENSP00000498190.1, ENST00000647958.1

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain
NM_001376059.1 → NP_001362988.1 homeobox expressed in ES cells 1

Status: REVIEWED

Source sequence(s)

AC093928

Consensus CDS

CCDS2881.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain
NM_001376060.1 → NP_001362989.1 homeobox expressed in ES cells 1

Status: REVIEWED

Source sequence(s)

AC093928

Consensus CDS

CCDS2881.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain
NM_001376061.1 → NP_001362990.1 homeobox expressed in ES cells 1

Status: REVIEWED

Source sequence(s)

AC093928

Consensus CDS

CCDS2881.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain
NM_003865.3 → NP_003856.1 homeobox expressed in ES cells 1

See identical proteins and their annotated locations for NP_003856.1

Status: REVIEWED

Source sequence(s)

AC093928, AI652412, BC112089

Consensus CDS

CCDS2881.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Related

ENSP00000295934.3, ENST00000295934.8

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain

RNA

NR_164757.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC093928

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000003.12 Reference GRCh38.p14 Primary Assembly

Range

57197838..57227615 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047449143.1 → XP_047305099.1 homeobox expressed in ES cells 1 isoform X1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9
XM_005265526.5 → XP_005265583.1 homeobox expressed in ES cells 1 isoform X1

See identical proteins and their annotated locations for XP_005265583.1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Conserved Domains (1) summary

pfam00046
Location:111 → 165

Homeobox; Homeobox domain
XM_047449142.1 → XP_047305098.1 homeobox expressed in ES cells 1 isoform X1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9

Alternate T2T-CHM13v2.0

Genomic

NC_060927.1 Alternate T2T-CHM13v2.0

Range

57238106..57267938 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054348269.1 → XP_054204244.1 homeobox expressed in ES cells 1 isoform X1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9
XM_054348270.1 → XP_054204245.1 homeobox expressed in ES cells 1 isoform X1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9
XM_054348271.1 → XP_054204246.1 homeobox expressed in ES cells 1 isoform X1

UniProtKB/Swiss-Prot

Q52LC5, Q99667, Q9UBX0

UniProtKB/TrEMBL

C9J0A9