HSFX2

Summary

HSFX2 (heat shock transcription factor family, X-linked 2, HGNC:32701) 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 100130086 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• MANE Select transcript: NM_001164415

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32701
Approved symbol	HSFX2
Name	heat shock transcription factor family, X-linked 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000268738
Ensembl biotype	protein_coding
Entrez	100130086

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000598963

RefSeq mRNA: 1 — MANE Select: NM_001164415 NM_001164415

CCDS: CCDS48179

Canonical transcript exons

ENST00000598963 — 2 exons

Exon	Start	End
ENSE00003053324	149592512	149593299
ENSE00003215793	149594137	149595314

Expression profiles

Bgee: expression breadth ubiquitous, 124 present calls, max score 66.42.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	66.42	gold quality
right uterine tube	UBERON:0001302	64.14	gold quality
cerebellum	UBERON:0002037	63.44	gold quality
cerebellar hemisphere	UBERON:0002245	63.32	gold quality
cerebellar cortex	UBERON:0002129	63.31	gold quality
granulocyte	CL:0000094	62.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	61.90	gold quality
right lung	UBERON:0002167	60.97	gold quality
right coronary artery	UBERON:0001625	60.65	gold quality
endocervix	UBERON:0000458	60.32	gold quality
right testis	UBERON:0004534	60.28	gold quality
fallopian tube	UBERON:0003889	59.28	gold quality
testis	UBERON:0000473	59.03	gold quality
left testis	UBERON:0004533	58.25	gold quality
ventricular zone	UBERON:0003053	58.24	gold quality
left uterine tube	UBERON:0001303	57.65	gold quality
ganglionic eminence	UBERON:0004023	57.38	gold quality
right frontal lobe	UBERON:0002810	57.18	gold quality
cortical plate	UBERON:0005343	56.97	gold quality
right ovary	UBERON:0002118	56.51	gold quality
smooth muscle tissue	UBERON:0001135	56.33	gold quality
ovary	UBERON:0000992	55.89	gold quality
left ovary	UBERON:0002119	55.80	gold quality
popliteal artery	UBERON:0002250	55.71	gold quality
tibial artery	UBERON:0007610	55.52	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	55.50	silver quality
frontal cortex	UBERON:0001870	55.25	gold quality
uterine cervix	UBERON:0000002	54.51	gold quality
colonic epithelium	UBERON:0000397	54.51	gold quality
anterior cingulate cortex	UBERON:0009835	54.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.28

Regulation

Is transcription factor: no

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), HSFX1 (ENSG00000171116), HSFY1 (ENSG00000172468), HSF5 (ENSG00000176160), HSF1 (ENSG00000185122), 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_001157887* (*=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): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrXq28, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, GOMF_DNA_BINDING_TRANSCRIPTION_FACTOR_ACTIVITY, GOMF_CIS_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GOMF_RNA_POLYMERASE_II_TRANSCRIPTION_REGULATORY_REGION_SEQUENCE_SPECIFIC_DNA_BINDING, GSE6269_HEALTHY_VS_STAPH_AUREUS_INF_PBMC_DN, 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
HSFX2	VCX3B	Q9H321	452
HSFX2	EOLA2	Q96DE9	447
HSFX2	CXorf51A	A0A1B0GTR3	447
HSFX2	PDZD4	Q76G19	447
HSFX2	VCX2	Q9H322	418
HSFX2	ZNF41	P51814	399
HSFX2	TMEM185A	Q8NFB2	398
HSFX2	VCX3A	Q9NNX9	377
HSFX2	TSPYL2	Q9H2G4	374
HSFX2	SPANXN4	Q5MJ08	369
HSFX2	SPANXN3	Q5MJ09	355
HSFX2	ARSF	P54793	353
HSFX2	DNAL1	Q4LDG9	348
HSFX2	HRC	P23327	347
HSFX2	SPANXN2	Q5MJ10	324
HSFX2	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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

297 predictions. Top by Δscore:

Variant	Effect	Δscore
X:149593296:CTAA:C	acceptor_gain	0.9900
X:149594131:CATTA:C	donor_loss	0.9900
X:149594132:ATTAC:A	donor_loss	0.9900
X:149594133:TTACC:T	donor_loss	0.9900
X:149594134:TA:T	donor_loss	0.9900
X:149594135:ACCT:A	donor_loss	0.9900
X:149593300:C:CC	acceptor_gain	0.9800
X:149593270:T:C	acceptor_gain	0.9600
X:149593297:TAA:T	acceptor_gain	0.9600
X:149593245:T:TA	acceptor_gain	0.9500
X:149594480:T:TA	donor_gain	0.9400
X:149593246:C:A	acceptor_gain	0.9300
X:149594157:G:A	donor_gain	0.9300
X:149593270:T:TC	acceptor_gain	0.9200
X:149593266:CT:C	acceptor_gain	0.9000
X:149594108:AACC:A	donor_gain	0.9000
X:149593266:CTCTT:C	acceptor_gain	0.8800
X:149593267:TCTTT:T	acceptor_gain	0.8800
X:149593268:C:G	acceptor_gain	0.8800
X:149593308:C:CT	acceptor_gain	0.8700
X:149593268:C:CC	acceptor_gain	0.8400
X:149593309:A:T	acceptor_gain	0.8400
X:149593314:T:C	acceptor_gain	0.8300
X:149594135:A:AC	donor_gain	0.8300
X:149594136:C:CC	donor_gain	0.8300
X:149593264:GTCT:G	acceptor_gain	0.8100
X:149593300:CT:C	acceptor_loss	0.8100
X:149593248:C:CT	acceptor_gain	0.8000
X:149593314:T:TC	acceptor_gain	0.8000
X:149593299:ACTAT:A	acceptor_gain	0.7900

AlphaMissense

2777 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1157699406 (X:149596594 G>A), RS1157776314 (X:149592064 C>T), RS1159182780 (X:149597300 A>G), RS1159232756 (X:149596445 C>T), RS1159444761 (X:149592057 T>C), RS1160398581 (X:149594322 T>C), RS1161383318 (X:149597050 C>T), RS1161578401 (X:149596927 G>A), RS1163731267 (X:149594284 G>A), RS1164015388 (X:149592320 G>T), RS1165068942 (X:149594974 G>A), RS1167137785 (X:149594946 G>A), RS1168183243 (X:149596802 A>G), RS1169457360 (X:149596793 G>A), RS1169550655 (X:149592204 T>C)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
perfluorooctanoic acid	increases expression	1
Benzo(a)pyrene	decreases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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