HSFY1

Summary

HSFY1 (heat shock transcription factor Y-linked 1, HGNC:18568) 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 centromeric copy. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 86614 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 3 total
• Phenotypes (HPO): 4
• MANE Select transcript: NM_033108

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18568
Approved symbol	HSFY1
Name	heat shock transcription factor Y-linked 1
Location	Yq11.222
Locus type	gene with protein product
Status	Approved
Aliases	HSF2L
Ensembl gene	ENSG00000172468
Ensembl biotype	protein_coding
OMIM	400029
Entrez	86614

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 nonsense_mediated_decay

ENST00000307393, ENST00000309834, ENST00000338876, ENST00000382856

RefSeq mRNA: 3 — MANE Select: NM_033108 NM_001425398, NM_033108, NM_152584

CCDS: CCDS14790, CCDS35475

Canonical transcript exons

ENST00000307393 — 2 exons

Exon	Start	End
ENSE00001603573	18546720	18547300
ENSE00001822279	18547779	18548592

Expression profiles

Bgee: expression breadth broad, 59 present calls, max score 87.58.

Top tissues by expression

108 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	87.58	gold quality
left testis	UBERON:0004533	82.14	gold quality
right testis	UBERON:0004534	82.02	gold quality
testis	UBERON:0000473	81.34	gold quality
ventricular zone	UBERON:0003053	40.43	silver quality
cortical plate	UBERON:0005343	40.34	silver quality
lower esophagus mucosa	UBERON:0035834	38.52	gold quality
apex of heart	UBERON:0002098	38.13	silver quality
skeletal muscle tissue	UBERON:0001134	37.75	gold quality
right coronary artery	UBERON:0001625	37.63	silver quality
colonic epithelium	UBERON:0000397	37.20	gold quality
superior frontal gyrus	UBERON:0002661	36.49	gold quality
Ammon’s horn	UBERON:0001954	36.21	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
right frontal lobe	UBERON:0002810	35.67	gold quality
amygdala	UBERON:0001876	35.65	gold quality
temporal lobe	UBERON:0001871	35.58	gold quality
gastrocnemius	UBERON:0001388	35.05	silver quality
muscle of leg	UBERON:0001383	34.92	silver quality
kidney	UBERON:0002113	34.92	gold quality
right lung	UBERON:0002167	34.40	gold quality
cortex of kidney	UBERON:0001225	34.31	gold quality
muscle tissue	UBERON:0002385	34.27	gold quality
tibial artery	UBERON:0007610	34.19	silver quality
bone marrow	UBERON:0002371	34.16	gold quality
popliteal artery	UBERON:0002250	34.13	silver quality
Brodmann (1909) area 9	UBERON:0013540	34.13	gold quality
urinary bladder	UBERON:0001255	33.95	silver quality
putamen	UBERON:0001874	33.89	gold quality
frontal cortex	UBERON:0001870	33.84	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6058	no	8.10
E-ANND-3	no	0.27

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

30 targeting HSFY1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-6134	99.63	65.68	1537
HSA-MIR-885-5P	99.59	68.59	879
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3609	99.52	69.89	2587
HSA-MIR-548AH-5P	99.52	69.73	2626
HSA-MIR-4761-5P	99.51	66.69	804
HSA-MIR-302B-5P	99.50	69.49	1857
HSA-MIR-302D-5P	99.50	69.34	1863
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-499A-3P	99.18	69.20	1392
HSA-MIR-499B-3P	99.18	69.27	1391
HSA-MIR-4777-3P	99.15	68.92	626
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4710	98.61	65.96	1048
HSA-MIR-6754-5P	98.60	65.54	1627
HSA-MIR-4289	98.26	66.90	810
HSA-MIR-561-5P	98.25	68.13	1365
HSA-MIR-526B-5P	97.41	67.99	1074
HSA-MIR-875-5P	96.74	66.48	579
HSA-MIR-4653-3P	96.26	67.03	725
HSA-MIR-24-1-5P	95.57	65.85	492
HSA-MIR-24-2-5P	95.57	66.16	484
HSA-MIR-4754	88.00	62.03	37

Literature-anchored findings (GeneRIF, showing 3)

• Could have an important role in human spermatogenesis. (PMID:14985478)
• genetic association studies: Data from 4 unrelated azoospermic patients in France with Y chromosome deletions exclude HSFY1/HSF2 genes as factors in AZFb/P4 palindrome haplogroup required for spermatogenesis. (PMID:22158087)
• data indicate that CDY2 and HSFY are located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with MA (PMID:22820855)

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), HSFY2 (ENSG00000169953), HSFX1 (ENSG00000171116), 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 (3): NP_001412327, NP_149099, NP_689797 (=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: 24 (showing top): GOMF_SEQUENCE_SPECIFIC_DNA_BINDING, chrYq11, GOMF_TRANSCRIPTION_REGULATOR_ACTIVITY, MIR548AZ_5P, MIR548T_5P, MIR4311, MIR6134, MIR885_5P, HP_ABNORMALITY_OF_REPRODUCTIVE_SYSTEM_PHYSIOLOGY, HP_DECREASED_FERTILITY, HP_INFERTILITY, HP_Y_LINKED_INHERITANCE, HP_ADULT_ONSET, HP_YOUNG_ADULT_ONSET, HP_DECREASED_FERTILITY_IN_MALES

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
HSFY1	TSPY1	P09002	772
HSFY1	RBMY1A1	P0DJD3	769
HSFY1	BPY2	O14599	762
HSFY1	CDY2A	Q9Y6F7	761
HSFY1	VCY	O14598	720
HSFY1	CDY1	Q9Y6F8	714
HSFY1	DAZ1	Q9NQZ3	707
HSFY1	USP9Y	O00507	692
HSFY1	PRY	O14603	691
HSFY1	RPS4Y2	Q8TD47	634
HSFY1	ZFY	P08048	624
HSFY1	DDX3Y	O15523	623
HSFY1	EIF1AY	O14602	606
HSFY1	KDM5D	Q9BY66	597
HSFY1	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

3 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	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

790 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:18547296:GCAAG:G	donor_gain	0.9900
Y:18547297:CAAGG:C	donor_loss	0.9900
Y:18547298:AAG:A	donor_loss	0.9900
Y:18547300:GGTAT:G	donor_loss	0.9900
Y:18547301:G:GC	donor_loss	0.9900
Y:18547302:T:A	donor_loss	0.9900
Y:18547904:G:GT	donor_gain	0.9800
Y:18547972:A:T	donor_gain	0.9800
Y:18578539:G:GT	donor_gain	0.9800
Y:18547921:GGGC:G	donor_gain	0.9700
Y:18550898:GC:G	donor_gain	0.9700
Y:18550979:G:GT	donor_gain	0.9700
Y:18561486:T:TA	donor_gain	0.9700
Y:18561487:A:AA	donor_gain	0.9700
Y:18550846:G:GT	donor_gain	0.9600
Y:18550993:G:GA	donor_gain	0.9500
Y:18551009:A:G	donor_gain	0.9500
Y:18561489:C:G	donor_gain	0.9500
Y:18550781:A:AG	acceptor_gain	0.9300
Y:18550782:G:GG	acceptor_gain	0.9300
Y:18578546:C:G	donor_gain	0.9300
Y:18547777:A:AG	acceptor_gain	0.9200
Y:18547778:G:GG	acceptor_gain	0.9200
Y:18578539:GAA:G	donor_gain	0.9000
Y:18547314:T:G	donor_gain	0.8900
Y:18550782:GTGGA:G	acceptor_gain	0.8800
Y:18550906:C:A	donor_gain	0.8800
Y:18547332:TA:T	donor_gain	0.8700
Y:18547333:AA:A	donor_gain	0.8700
Y:18547334:AA:A	donor_gain	0.8700

AlphaMissense

2620 scored. Top likely-pathogenic:

dbSNP variants (sampled 299 via entrez): RS111433822 (Y:18539474 A>G), RS112948836 (Y:18540493 T>C), RS113127496 (Y:18562483 C>A), RS113400567 (Y:18531739 T>C), RS113411234 (Y:18554971 A>C), RS113581231 (Y:18527944 T>C), RS1191116058 (Y:18550462 C>T), RS1213877345 (Y:18535206 G>A), RS1242664951 (Y:18550184 C>T), RS1251696807 (Y:18561391 CTTTT>C,CTT,CTTT,CTTTTT), RS1260255587 (Y:18538791 C>CCA), RS1314184148 (Y:18531640 G>T), RS1378360042 (Y:18574424 A>G), RS1454168539 (Y:18573315 G>A), RS1475066090 (Y:18550810 T>C)

Disease associations

OMIM: gene MIM:400029 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0001450	Y-linked inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset

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

1 total (human), top 1 by PubMed support.

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

Clinical trials (associated diseases)

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