HSFX1

Summary

HSFX1 (heat shock transcription factor family, X-linked 1, HGNC:29603) is a protein-coding gene on chromosome Xq28, encoding Heat shock transcription factor, X-linked (Q9UBD0).

Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 100506164 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_016153

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29603
Approved symbol	HSFX1
Name	heat shock transcription factor family, X-linked 1
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	LW-1
Ensembl gene	ENSG00000171116
Ensembl biotype	protein_coding
Entrez	100506164

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000370416

RefSeq mRNA: 1 — MANE Select: NM_016153 NM_016153

CCDS: CCDS44011

Canonical transcript exons

ENST00000370416 — 2 exons

Exon	Start	End
ENSE00001452651	149774068	149775245
ENSE00001452704	149776083	149776867

Expression profiles

Bgee: expression breadth ubiquitous, 128 present calls, max score 85.51.

Top tissues by expression

132 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	75.59	gold quality
cortical plate	UBERON:0005343	72.20	gold quality
lower esophagus mucosa	UBERON:0035834	71.53	gold quality
apex of heart	UBERON:0002098	69.73	gold quality
stromal cell of endometrium	CL:0002255	67.19	gold quality
right coronary artery	UBERON:0001625	66.83	gold quality
hindlimb stylopod muscle	UBERON:0004252	65.99	gold quality
mucosa of transverse colon	UBERON:0004991	65.36	gold quality
descending thoracic aorta	UBERON:0002345	64.40	gold quality
mucosa of stomach	UBERON:0001199	63.82	gold quality
right uterine tube	UBERON:0001302	63.29	gold quality
right ovary	UBERON:0002118	62.75	gold quality
left ovary	UBERON:0002119	62.75	gold quality
ovary	UBERON:0000992	61.95	gold quality
ventricular zone	UBERON:0003053	61.62	gold quality
right testis	UBERON:0004534	61.61	gold quality
primary visual cortex	UBERON:0002436	61.40	gold quality
ganglionic eminence	UBERON:0004023	60.96	gold quality
left coronary artery	UBERON:0001626	60.14	gold quality
sural nerve	UBERON:0015488	59.45	silver quality
prefrontal cortex	UBERON:0000451	59.05	gold quality
Brodmann (1909) area 9	UBERON:0013540	58.32	gold quality
right hemisphere of cerebellum	UBERON:0014890	58.23	gold quality
granulocyte	CL:0000094	57.96	gold quality
gall bladder	UBERON:0002110	57.94	gold quality
myometrium	UBERON:0001296	57.46	gold quality
cerebellar hemisphere	UBERON:0002245	57.39	gold quality
left testis	UBERON:0004533	56.94	gold quality
cerebellum	UBERON:0002037	56.84	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.57

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• LW-1 is a novel risk marker that is robustly and independently associated with the future progression of microvascular disease, intima-media thickness and left ventricular mass in type 1 diabetes. (PMID:26864236)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
drosophila_melanogaster	Hsf	FBGN0001222
caenorhabditis_elegans	hsf-1	WBGENE00002004

Paralogs (9): HSF2 (ENSG00000025156), HSF4 (ENSG00000102878), HSFY2 (ENSG00000169953), HSFY1 (ENSG00000172468), HSF5 (ENSG00000176160), HSF1 (ENSG00000185122), HSFX2 (ENSG00000268738), HSFX4 (ENSG00000283463), HSFX3 (ENSG00000283697)

Protein

Protein identifiers

Heat shock transcription factor, X-linked — Q9UBD0 (reviewed: Q9UBD0)

All UniProt accessions (2): A0A140VK21, Q9UBD0

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Testis-specific.

Similarity. Belongs to the HSF family.

RefSeq proteins (1): NP_057237* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000232	HSF_DNA-bd	Domain
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily

Pfam: PF00447

UniProt features (8 total): region of interest 3, compositionally biased region 2, chain 1, DNA-binding region 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBD0-F1	56.38	0.15

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 215

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 9 (showing top): ACEVEDO_LIVER_CANCER_WITH_H3K27ME3_UP, GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXq28, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, PULVER_FOREY_PERTURB_ACCUMULATION_G2_M, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOCC_CHROMATIN

GO Biological Process (2): regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (5): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific DNA binding (GO:0043565), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of DNA-templated transcription	2
cellular anatomical structure	2
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription by RNA polymerase II	1
chromatin	1
RNA polymerase II transcription regulatory region sequence-specific DNA binding	1
DNA-binding transcription factor activity	1
regulation of transcription by RNA polymerase II	1
DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

512 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSFX1	VCX3B	Q9H321	452
HSFX1	EOLA2	Q96DE9	447
HSFX1	CXorf51A	A0A1B0GTR3	447
HSFX1	PDZD4	Q76G19	447
HSFX1	VCX2	Q9H322	418
HSFX1	ZNF41	P51814	399
HSFX1	TMEM185A	Q8NFB2	398
HSFX1	VCX3A	Q9NNX9	377
HSFX1	TSPYL2	Q9H2G4	374
HSFX1	SPANXN4	Q5MJ08	369
HSFX1	SPANXN3	Q5MJ09	355
HSFX1	ARSF	P54793	353
HSFX1	DNAL1	Q4LDG9	348
HSFX1	HRC	P23327	347
HSFX1	SPANXN2	Q5MJ10	324
HSFX1	EOLA1	Q8TE69	324

IntAct

34 interactions, top by confidence:

A	B	Type	Score
ATXN1	HSFX1	psi-mi:“MI:0915”(physical association)	0.670
MAL2	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-2	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
SDR16C5	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
MTIF3	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
MICOS13	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
SYP	HSFX1	psi-mi:“MI:0915”(physical association)	0.560
HSFX1	CACFD1	psi-mi:“MI:0915”(physical association)	0.560
HSFX1	NCS1	psi-mi:“MI:0914”(association)	0.350
HSFX1	VCAN	psi-mi:“MI:0914”(association)	0.350
HSFX1	MAL2	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	KRTAP12-2	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	MTIF3	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	MICOS13	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	SYP	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	SDR16C5	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	CACFD1	psi-mi:“MI:0915”(physical association)	0.000
HSFX1	RBFOX1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (33): HSFX1 (Two-hybrid), HSFX2 (Two-hybrid), HSFX1 (Two-hybrid), HSFX2 (Two-hybrid), HSFX1 (Two-hybrid), HSFX2 (Two-hybrid), HSFX1 (Two-hybrid), HSFX2 (Two-hybrid), HSFX1 (Two-hybrid), HSFX2 (Two-hybrid), C19orf70 (Two-hybrid), AGTRAP (Two-hybrid), KRTAP12-2 (Two-hybrid), HSFX2 (Two-hybrid), HSFX2 (Two-hybrid)

ESM2 similar proteins: A0A5F9ZHS7, B1ASB6, C9JSJ3, I7HJS4, O08686, O35426, O60393, O88286, P17861, P20428, P31357, Q05AH6, Q15583, Q1WG82, Q2M1V0, Q2MHN3, Q2YDG1, Q32LE6, Q3SZZ2, Q3TQ03, Q495C1, Q497K7, Q4R2Z8, Q5HZG9, Q5IS58, Q6ZN32, Q7Z572, Q80W88, Q8BHP2, Q8CGW9, Q8IX15, Q8IXT2, Q8IY92, Q8IZ20, Q8K3E9, Q8N1L9, Q8N365, Q8N7G0, Q8R1H8, Q96MN9

Diamond homologs: A0A1B0GTS1, A0A1B0GWH4, B7XIV9, C4V6H6, D0VYS2, G0SB31, G5EFT5, J9VHZ9, O14283, O49403, P10961, P22121, P22335, P22813, P38529, P38530, P38531, P38532, P38533, P41151, P41153, P41154, Q00613, Q02953, Q03933, Q08DJ8, Q10PR4, Q1HGE8, Q1PDN3, Q338B0, Q40152, Q4G112, Q5A4X5, Q5AQ33, Q5CZP2, Q5KMX8, Q5ND04, Q652B0, Q67TP9, Q6F388

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

2 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

414 predictions. Top by Δscore:

Variant	Effect	Δscore
X:149774123:C:G	donor_gain	0.9900
X:149775241:ATAAG:A	donor_loss	0.9900
X:149775242:TAAGG:T	donor_loss	0.9900
X:149775243:AAGGT:A	donor_loss	0.9900
X:149775244:AGGT:A	donor_loss	0.9900
X:149775247:T:A	donor_loss	0.9900
X:149776082:GTTA:G	acceptor_gain	0.9900
X:149776081:A:AG	acceptor_gain	0.9800
X:149776082:G:GG	acceptor_gain	0.9800
X:149776082:GTT:G	acceptor_gain	0.9700
X:149776112:A:G	acceptor_gain	0.9700
X:149774175:GT:G	donor_gain	0.9400
X:149776114:GA:G	acceptor_gain	0.9400
X:149774112:GGGGC:G	donor_gain	0.9300
X:149776111:A:AG	acceptor_gain	0.9300
X:149775225:C:T	donor_gain	0.9200
X:149776135:TG:T	acceptor_gain	0.9200
X:149776136:G:GT	acceptor_gain	0.9200
X:149776132:TCGTG:T	acceptor_gain	0.9100
X:149776133:CGTG:C	acceptor_gain	0.9100
X:149775270:GGGT:G	donor_gain	0.9000
X:149776069:ACTTT:A	acceptor_gain	0.8900
X:149776073:T:TA	acceptor_gain	0.8900
X:149774184:T:A	donor_gain	0.8800
X:149776068:A:G	acceptor_gain	0.8800
X:149776113:A:AG	acceptor_gain	0.8800
X:149776114:G:GG	acceptor_gain	0.8800
X:149776114:GAGA:G	acceptor_gain	0.8800
X:149774117:A:AG	donor_gain	0.8700
X:149774118:G:GG	donor_gain	0.8700

AlphaMissense

2776 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:149775165:T:C	F162L	0.968
X:149775167:C:A	F162L	0.968
X:149775167:C:G	F162L	0.968
X:149775114:T:C	F145L	0.967
X:149775116:T:A	F145L	0.967
X:149775116:T:G	F145L	0.967
X:149775015:T:C	F112L	0.958
X:149775017:T:A	F112L	0.958
X:149775017:T:G	F112L	0.958
X:149774976:T:C	F99L	0.957
X:149774978:T:A	F99L	0.957
X:149774978:T:G	F99L	0.957
X:149776107:T:C	F197L	0.945
X:149776109:T:A	F197L	0.945
X:149776109:T:G	F197L	0.945
X:149775072:T:C	F131L	0.908
X:149775074:T:A	F131L	0.908
X:149775074:T:G	F131L	0.908
X:149776089:T:C	F191L	0.907
X:149776091:C:A	F191L	0.907
X:149776091:C:G	F191L	0.907
X:149775138:T:C	F153L	0.892
X:149775140:C:A	F153L	0.892
X:149775140:C:G	F153L	0.892
X:149775166:T:C	F162S	0.885
X:149775173:A:C	K164N	0.876
X:149775173:A:T	K164N	0.876
X:149775032:G:C	W117C	0.866
X:149775032:G:T	W117C	0.866
X:149774977:T:G	F99C	0.860

dbSNP variants (sampled 300 via entrez): RS1156257418 (X:149777266 G>A), RS1156318247 (X:149772586 C>T), RS1158464816 (X:149774936 C>T), RS1159286167 (X:149774842 C>T), RS1162824478 (X:149772337 A>G), RS1163545870 (X:149777144 G>A), RS1164096873 (X:149777064 G>A), RS1165996188 (X:149774706 A>G), RS1167050365 (X:149774544 C>T), RS1168110073 (X:149774510 A>G), RS1169371433 (X:149775160 A>G), RS1172775988 (X:149772163 T>G), RS1174192762 (X:149775144 C>T), RS1177909046 (X:149774339 A>G), RS1179532648 (X:149777174 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (1): male infertility (MONDO:0005372)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D007248	Infertility, Male	C12.100.500.430; C12.100.750.700; C12.200.294.430

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
Smoke	decreases expression	1
Okadaic Acid	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A3C3	SEES3-1V human HSFX1, clone1	Embryonic stem cell	Male
CVCL_A3C4	SEES3-1V human HSFX1, clone2	Embryonic stem cell	Male
CVCL_A3C5	SEES3-1V human HSFX1, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

125 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT02202382	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Male Infertility
NCT02204826	PHASE4	COMPLETED	Effects of Korean Red Ginseng on Semen Parameters in Male Infertility Patients: a Randomized, Placebo-controlled, Double-blind Clinical Study
NCT03802864	PHASE4	COMPLETED	Post-operative Pain Control of Testicular Sperm Extraction Using Liposomal Bupivacaine
NCT06100432	PHASE4	ACTIVE_NOT_RECRUITING	Effect of Eurycoma Longifolia (DLBS5055) and Multivitamins (Vitamin C+Vitamin E+ β-carotene) for Infertile Males
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00975117	PHASE3	COMPLETED	Spermotrend in the Treatment of Male Infertility
NCT01407432	PHASE3	COMPLETED	Impact of Folates in the Care of the Male Infertility
NCT01895816	PHASE3	COMPLETED	Herbal Tonic Fertile Supplement(ZO2C5)
NCT02605070	PHASE3	TERMINATED	Pilot Study on the Effects of FSH Treatment on the Epigenetic Characteristics of Spermatozoa in Infertile Patients With Severe Oligozoospermia
NCT07402759	PHASE3	ACTIVE_NOT_RECRUITING	Impact of tdrd9 Gene Mutations in the Therapeutic Response to L-carnitine in Oligoasthenozoospermic Men
NCT01880086	PHASE2	COMPLETED	Clomiphene Citrate for the Treatment of Low Testosterone Associated With Chronic Opioid Pain Medication Administration
NCT02061384	PHASE2	COMPLETED	RA-2 13-cis Retinoic Acid (Isotretinoin)
NCT02421887	PHASE2	COMPLETED	Males, Antioxidants, and Infertility Trial
NCT05200663	PHASE2	UNKNOWN	Efficacy Comparison of Tamoxifen and Tamoxifen With Antioxidants on Semen Quality of Male With Idiopathic Infertility
NCT05290558	PHASE2	ACTIVE_NOT_RECRUITING	The Therapeutic Effects of Bu Shen Yi Jing Pill on Semen Quality in Sub Fertile Males: a Randomized Controlled Trial
NCT06091969	PHASE2	NOT_YET_RECRUITING	Supplementation for Male Subfertility
NCT01595308	PHASE1	COMPLETED	A Pilot Study to Evaluate the Effect of Pomegranate Juice on Semen Parameters in Healthy Male Volunteers
NCT02122211	PHASE1	COMPLETED	Choline Dehydrogenase and Sperm Function: Effects of Betaine
NCT02575924	PHASE1	UNKNOWN	Influence of Culture Media on Clinical Outcomes in Poor Responders or Severe Male Infertility
NCT01304927	PHASE2/PHASE3	COMPLETED	Vitamin D Supplementation and Male Infertility: The CBG-study a Randomized Clinical Trial
NCT02349945	PHASE2/PHASE3	COMPLETED	FSH Receptor Polymorphism p.N680S and Efficacy of FSH Therapy
NCT05222841	PHASE2/PHASE3	COMPLETED	The Effectiveness of Spermotrend Food Supplement in the Treatment of Male Infertility
NCT05616598	PHASE2/PHASE3	COMPLETED	Effect of New Oral Treatment for Hepatitis C Virus on Seminal Parameters
NCT02025270	PHASE1/PHASE2	COMPLETED	MSCs For Treatment of Azoospermic Patients
NCT04541459	EARLY_PHASE1	UNKNOWN	Validation of New Devices Against Ambient Electromagnetic Radiation
NCT05792813	EARLY_PHASE1	UNKNOWN	Efficacy and Safety of Linggui Yangyuan Paste in Patients With Male Infertility
NCT06188936	EARLY_PHASE1	COMPLETED	Home Semen Analysis Tests As a Screening Tool for Fertility Patients
NCT00012480	Not specified	COMPLETED	Effect of Environmental Exposures on the Egg Fertilizing Ability of Human Sperm
NCT00044369	Not specified	COMPLETED	Role of the Toxic Metal Cadmium in the Mechanism Producing Infertility With a Varicocele
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists
NCT00178516	Not specified	COMPLETED	Vitamin E and Male Infertility
NCT00315029	Not specified	COMPLETED	Patient-Centered Implementation Trial for Single Embryo Transfer
NCT00341120	Not specified	COMPLETED	Genetic Causes of Male Infertility
NCT00481403	Not specified	COMPLETED	Study of Sperm Molecular Factors Implicated in Male Fertility
NCT00548977	Not specified	COMPLETED	Genetic Studies Spermatogenic Failure
NCT00596739	Not specified	COMPLETED	A Study of the Pre- and Post-operative Semen Analyses and Reproductive Hormone Levels of Men Undergoing Weight-reduction Surgery
NCT00756561	Not specified	COMPLETED	HOP-2A - Intratesticular Hormone Levels
NCT00961558	Not specified	TERMINATED	Canadian Varicocelectomy Initiative (CVI): Effects on Male Fertility and Testicular Function of Varicocelectomy
NCT01075334	Not specified	UNKNOWN	Is a Carnitine Based Food Supplement (PorimoreTM) for Infertile Men Superior to Folate and Zinc With Regard to Pregnancy Rates in Intrauterine Insemination Cycles?
NCT01178463	Not specified	UNKNOWN	Spermatogonial Stem Cells in Azoospermic Patients: a Comparison Between Obstructive and Non-obstructive Azoospermia