HSFY2

Summary

HSFY2 (heat shock transcription factor Y-linked 2, HGNC:23950) is a protein-coding gene on chromosome Yq11.222, encoding Heat shock transcription factor, Y-linked (Q96LI6).

This gene encodes a member of the heat shock factor (HSF) family of transcriptional activators for heat shock proteins. This gene is a candidate gene for azoospermia, since it localizes to a region of chromosome Y that is sometimes deleted in infertile males. The genome has two identical copies of this gene within a palindromic region; this record represents the more telomeric copy. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 159119 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 5 total
• MANE Select transcript: NM_153716

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23950
Approved symbol	HSFY2
Name	heat shock transcription factor Y-linked 2
Location	Yq11.222
Locus type	gene with protein product
Status	Approved
Aliases	FLJ25453
Ensembl gene	ENSG00000169953
Ensembl biotype	protein_coding
Entrez	159119

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000304790, ENST00000344884, ENST00000382852, ENST00000491902

RefSeq mRNA: 2 — MANE Select: NM_153716 NM_001001877, NM_153716

CCDS: CCDS14791, CCDS35476

Canonical transcript exons

ENST00000304790 — 2 exons

Exon	Start	End
ENSE00001674814	18773106	18773735
ENSE00001858694	18771814	18772627

Expression profiles

Bgee: expression breadth broad, 61 present calls, max score 71.22.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	71.22	gold quality
testis	UBERON:0000473	70.06	gold quality
left testis	UBERON:0004533	69.61	gold quality
right testis	UBERON:0004534	64.65	gold quality
Brodmann (1909) area 9	UBERON:0013540	56.53	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	48.30	gold quality
hypothalamus	UBERON:0001898	46.70	gold quality
right hemisphere of cerebellum	UBERON:0014890	43.77	gold quality
anterior cingulate cortex	UBERON:0009835	43.71	gold quality
cerebellar hemisphere	UBERON:0002245	43.56	gold quality
cerebellar cortex	UBERON:0002129	43.24	gold quality
cerebellum	UBERON:0002037	42.92	gold quality
right adrenal gland cortex	UBERON:0035827	41.76	gold quality
primary visual cortex	UBERON:0002436	40.68	gold quality
nucleus accumbens	UBERON:0001882	40.46	gold quality
cerebral cortex	UBERON:0000956	39.62	gold quality
metanephros cortex	UBERON:0010533	39.44	gold quality
right frontal lobe	UBERON:0002810	39.27	gold quality
putamen	UBERON:0001874	39.09	gold quality
cortex of kidney	UBERON:0001225	39.05	gold quality
brain	UBERON:0000955	38.76	gold quality
caudate nucleus	UBERON:0001873	38.52	gold quality
ganglionic eminence	UBERON:0004023	37.33	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.61	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
Ammon’s horn	UBERON:0001954	35.79	gold quality
substantia nigra	UBERON:0002038	35.39	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

miRNA regulators (miRDB)

9 targeting HSFY2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3678-3P	99.31	67.10	1432
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6755-3P	98.61	66.90	834
HSA-MIR-6852-3P	98.54	67.60	1468
HSA-MIR-3909	97.55	66.78	887
HSA-MIR-4474-5P	94.23	67.95	568

Literature-anchored findings (GeneRIF, showing 1)

• Could have an important role in human spermatogenesis. (PMID:14985478)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hsfy2	ENSMUSG00000045336
rattus_norvegicus	Hsfy2	ENSRNOG00000038569
drosophila_melanogaster	Hsf	FBGN0001222
caenorhabditis_elegans	hsf-1	WBGENE00002004

Paralogs (9): HSF2 (ENSG00000025156), HSF4 (ENSG00000102878), HSFX1 (ENSG00000171116), HSFY1 (ENSG00000172468), HSF5 (ENSG00000176160), HSF1 (ENSG00000185122), HSFX2 (ENSG00000268738), HSFX4 (ENSG00000283463), HSFX3 (ENSG00000283697)

Protein

Protein identifiers

Heat shock transcription factor, Y-linked — Q96LI6 (reviewed: Q96LI6)

Alternative names: Heat shock transcription factor 2-like protein

All UniProt accessions (1): Q96LI6

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Cytoplasm.

Tissue specificity. Testis-specific. Present in Sertoli cells and spermatogenic cells (at protein level).

Similarity. Belongs to the HSF family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q96LI6-1	1	yes
Q96LI6-2	2
Q96LI6-3	3

RefSeq proteins (2): NP_001001877, NP_714927* (*=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 (10 total): splice variant 4, sequence conflict 2, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96LI6-F1	58.77	0.23

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 20 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrYq11, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR548AZ_5P, MIR548T_5P, MIR4311, MIR6134, MIR885_5P, GSE15324_ELF4_KO_VS_WT_NAIVE_CD8_TCELL_DN, 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, GSE30962_PRIMARY_VS_SECONDARY_ACUTE_LCMV_INF_CD8_TCELL_DN, GOCC_CHROMATIN, GSE2770_UNTREATED_VS_IL12_TREATED_ACT_CD4_TCELL_6H_UP

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

GO Molecular Function (6): DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), sequence-specific double-stranded DNA binding (GO:1990837), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (5): chromatin (GO:0000785), nucleoplasm (GO:0005654), cytosol (GO:0005829), nucleus (GO:0005634), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulation of DNA-templated transcription	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
double-stranded DNA binding	1
sequence-specific DNA binding	1
nucleic acid binding	1
transcription cis-regulatory region binding	1
transcription regulator activity	1
binding	1
DNA binding	1
chromosome	1
nuclear lumen	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

670 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HSFY2	TSPY1	P09002	772
HSFY2	RBMY1A1	P0DJD3	769
HSFY2	BPY2	O14599	762
HSFY2	CDY2A	Q9Y6F7	761
HSFY2	VCY	O14598	720
HSFY2	CDY1	Q9Y6F8	714
HSFY2	DAZ1	Q9NQZ3	707
HSFY2	USP9Y	O00507	692
HSFY2	PRY	O14603	691
HSFY2	RPS4Y2	Q8TD47	634
HSFY2	ZFY	P08048	624
HSFY2	DDX3Y	O15523	623
HSFY2	EIF1AY	O14602	606
HSFY2	KDM5D	Q9BY66	597
HSFY2	RPS4Y1	P22090	585

IntAct

96 interactions, top by confidence:

A	B	Type	Score
GCM2	HSFY1	psi-mi:“MI:0915”(physical association)	0.890
HSFY1	GCM2	psi-mi:“MI:0915”(physical association)	0.890
TBX6	HSFY1	psi-mi:“MI:0915”(physical association)	0.780
HSFY1	TBX6	psi-mi:“MI:0915”(physical association)	0.780
HSFY1	RBM47	psi-mi:“MI:0915”(physical association)	0.560
HSFY1	SOX15	psi-mi:“MI:0915”(physical association)	0.560
HSFY1	HNRNPF	psi-mi:“MI:0915”(physical association)	0.560
QRICH1	HSFY1	psi-mi:“MI:0915”(physical association)	0.560
SV2B	HSFY1	psi-mi:“MI:0915”(physical association)	0.560
RBM47	HSFY1	psi-mi:“MI:0915”(physical association)	0.560
HNRNPF	HSFY1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (62): HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (Two-hybrid), HSFY1 (PCA), HSFY1 (Two-hybrid), TUBA3C (Affinity Capture-MS), SATB2 (Affinity Capture-MS), POTEF (Affinity Capture-MS), CHD4 (Affinity Capture-MS), CHD3 (Affinity Capture-MS), MIS12 (Affinity Capture-MS)

ESM2 similar proteins: B0FZN7, B0FZN8, B0FZN9, B0FZP0, B0FZP1, B0FZP2, B0FZP3, F4JYG0, O57437, P11308, P26323, P41157, P81270, Q01543, Q0DKP4, Q14B70, Q21263, Q24207, Q29RS8, Q4R361, Q4V7Y4, Q503H1, Q5ZKW8, Q64368, Q69V10, Q6F2E2, Q6R0H0, Q71RC2, Q75M35, Q76CY5, Q7Z353, Q804A9, Q80YT9, Q8K402, Q8N9W6, Q8W4I9, Q8WP23, Q90837, Q924M5, Q92904

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

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	1
Likely benign	3
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

96 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:18772628:C:CC	acceptor_gain	0.9900
Y:18773101:AATAC:A	donor_loss	0.9900
Y:18773102:ATAC:A	donor_loss	0.9900
Y:18773103:TA:T	donor_loss	0.9900
Y:18773104:A:AT	donor_loss	0.9900
Y:18773105:C:A	donor_loss	0.9900
Y:18773105:CCTTG:C	donor_gain	0.9800
Y:18772623:TTTAA:T	acceptor_gain	0.9600
Y:18773106:C:G	donor_loss	0.9500
Y:18772624:TTAA:T	acceptor_gain	0.9400
Y:18772625:TAA:T	acceptor_gain	0.8900
Y:18772625:TAAC:T	acceptor_loss	0.8600
Y:18772627:ACTAA:A	acceptor_loss	0.8600
Y:18772630:A:C	acceptor_loss	0.8300
Y:18773070:CT:C	donor_gain	0.8300
Y:18773071:TT:T	donor_gain	0.8300
Y:18773072:TT:T	donor_gain	0.8300
Y:18773109:G:A	donor_gain	0.8300
Y:18773467:A:AC	donor_gain	0.8200
Y:18773469:A:T	donor_gain	0.8200
Y:18772626:AA:A	acceptor_gain	0.8100
Y:18773092:A:C	donor_gain	0.8100
Y:18773466:CA:C	donor_gain	0.7900
Y:18773468:AA:A	donor_gain	0.7900
Y:18772631:AAA:A	acceptor_loss	0.7000
Y:18772141:CATTT:C	acceptor_gain	0.6900
Y:18772632:A:C	acceptor_loss	0.6600
Y:18773100:AAAT:A	donor_loss	0.6600
Y:18772635:C:CT	acceptor_gain	0.6400
Y:18773191:AAT:A	donor_gain	0.6400

AlphaMissense

2620 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:18773190:A:C	F143L	0.993
Y:18773190:A:T	F143L	0.993
Y:18773192:A:G	F143L	0.993
Y:18773327:A:G	W98R	0.990
Y:18773327:A:T	W98R	0.990
Y:18773325:C:A	W98C	0.989
Y:18773325:C:G	W98C	0.989
Y:18773191:A:G	F143S	0.981
Y:18772601:G:C	F180L	0.980
Y:18772601:G:T	F180L	0.980
Y:18772603:A:G	F180L	0.980
Y:18772602:A:G	F180S	0.978
Y:18773326:C:G	W98S	0.973
Y:18773379:A:C	F80L	0.971
Y:18773379:A:T	F80L	0.971
Y:18773381:A:G	F80L	0.971
Y:18773241:A:C	F126L	0.967
Y:18773241:A:T	F126L	0.967
Y:18773243:A:G	F126L	0.967
Y:18773206:A:G	L138P	0.966
Y:18773284:A:G	F112S	0.958
Y:18773242:A:G	F126S	0.956
Y:18773206:A:T	L138H	0.952
Y:18773368:A:T	L84H	0.952
Y:18772618:A:C	Y175D	0.950
Y:18773340:G:C	F93L	0.950
Y:18773340:G:T	F93L	0.950
Y:18773342:A:G	F93L	0.950
Y:18773212:C:G	R136P	0.949
Y:18773299:A:C	I107S	0.949

dbSNP variants (sampled 300 via entrez): RS111359694 (Y:18788648 G>C), RS113200071 (Y:18785109 A>C), RS113420648 (Y:18780608 T>A), RS113534513 (Y:18783474 A>G), RS113957233 (Y:18791384 G>C), RS1166542042 (Y:18785102 C>T), RS1173265774 (Y:18770299 G>A), RS1183125141 (Y:18733720 C>T), RS1184683725 (Y:18770182 C>T), RS1249496725 (Y:18733561 C>A), RS1309474642 (Y:18788730 C>A), RS1353113901 (Y:18788882 T>A), RS1366821706 (Y:18786307 T>A), RS1396199958 (Y:18785445 A>G), RS1397029336 (Y:18770218 T>A)

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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A3C6	SEES3-1V human HSFY2, clone1	Embryonic stem cell	Male
CVCL_A3C7	SEES3-1V human HSFY2, clone2	Embryonic stem cell	Male
CVCL_A3C8	SEES3-1V human HSFY2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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