GTSF1

Summary

GTSF1 (gametocyte specific factor 1, HGNC:26565) is a protein-coding gene on chromosome 12q13.13, encoding Gametocyte-specific factor 1 (Q8WW33). Required for spermatogenesis and is involved in the suppression of retrotransposon transcription in male germ cells.

Enables tRNA binding activity. Predicted to be involved in piRNA-mediated gene silencing by mRNA destabilization and secondary piRNA processing. Predicted to be located in cytoplasm. Predicted to be active in piP-body.

Source: NCBI Gene 121355 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_144594

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26565
Approved symbol	GTSF1
Name	gametocyte specific factor 1
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	FLJ32942, Cue110
Ensembl gene	ENSG00000170627
Ensembl biotype	protein_coding
OMIM	617484
Entrez	121355

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding_CDS_not_defined, 3 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000305879, ENST00000546575, ENST00000546739, ENST00000546931, ENST00000548538, ENST00000549083, ENST00000552336, ENST00000552395, ENST00000552397, ENST00000931625

RefSeq mRNA: 1 — MANE Select: NM_144594 NM_144594

CCDS: CCDS8881

Canonical transcript exons

ENST00000305879 — 9 exons

Exon	Start	End
ENSE00001147644	54465067	54465167
ENSE00001251872	54473546	54473602
ENSE00002381273	54455957	54456153
ENSE00003528206	54462642	54462725
ENSE00003549436	54459089	54459125
ENSE00003620439	54462109	54462172
ENSE00003625785	54471233	54471277
ENSE00003647524	54460377	54460471
ENSE00003661301	54463171	54463297

Expression profiles

Bgee: expression breadth ubiquitous, 166 present calls, max score 98.88.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8325 / max 204.1166, expressed in 311 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131359	5.8325	311

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.88	gold quality
right testis	UBERON:0004534	98.82	gold quality
left testis	UBERON:0004533	98.65	gold quality
adult organism	UBERON:0007023	97.15	gold quality
testis	UBERON:0000473	96.98	gold quality
oocyte	CL:0000023	95.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.86	gold quality
secondary oocyte	CL:0000655	91.10	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.95	gold quality
ileal mucosa	UBERON:0000331	80.07	silver quality
placenta	UBERON:0001987	80.05	gold quality
left ventricle myocardium	UBERON:0006566	79.47	gold quality
tibialis anterior	UBERON:0001385	79.35	silver quality
cardiac muscle of right atrium	UBERON:0003379	79.19	gold quality
monocyte	CL:0000576	76.50	gold quality
granulocyte	CL:0000094	76.45	gold quality
leukocyte	CL:0000738	76.45	gold quality
kidney epithelium	UBERON:0004819	74.28	gold quality
lymph node	UBERON:0000029	74.22	gold quality
vermiform appendix	UBERON:0001154	73.08	gold quality
blood	UBERON:0000178	71.87	gold quality
spleen	UBERON:0002106	71.69	gold quality
bone marrow	UBERON:0002371	71.69	gold quality
epithelial cell of pancreas	CL:0000083	70.72	gold quality
bone marrow cell	CL:0002092	70.31	gold quality
caecum	UBERON:0001153	70.09	gold quality
lower esophagus mucosa	UBERON:0035834	69.30	gold quality
muscle layer of sigmoid colon	UBERON:0035805	68.91	gold quality
rectum	UBERON:0001052	67.96	gold quality
deltoid	UBERON:0001476	66.80	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	30.47
E-ANND-3	no	3.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

24 targeting GTSF1, 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-3185	99.99	68.12	1959
HSA-MIR-223-3P	99.99	70.14	1140
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-6079	99.84	68.54	1170
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-6868-5P	99.06	65.69	1284
HSA-MIR-4695-5P	99.06	64.87	1151
HSA-MIR-4650-3P	99.01	68.39	1062
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-4266	98.53	67.29	1035
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4799-3P	97.78	65.97	893
HSA-MIR-4720-5P	97.46	65.67	893
HSA-MIR-5588-5P	97.46	65.70	913
HSA-MIR-1256	95.44	66.33	784

Literature-anchored findings (GeneRIF, showing 2)

• SYCP1, cTAGE1, and GTSF1 are expressed in cutaneous T-cell lymphoma, but not in normal skin or benign inflammatory dermatoses. (PMID:24850846)
• To our knowledge, this report is the first to describe the expression of the human GTSF1 gene in human gametes and preimplantation embryos. (PMID:27646122)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Gtsf1	ENSMUSG00000022487
rattus_norvegicus	Gtsf1	ENSRNOG00000036831

Paralogs (2): GTSF1L (ENSG00000124196), SNRNP48 (ENSG00000168566)

Protein

Protein identifiers

Gametocyte-specific factor 1 — Q8WW33 (reviewed: Q8WW33)

Alternative names: Protein FAM112B

All UniProt accessions (2): Q8WW33, G3V1V4

UniProt curated annotations — full annotation on UniProt →

Function. Required for spermatogenesis and is involved in the suppression of retrotransposon transcription in male germ cells.

Subcellular location. Cytoplasm.

Similarity. Belongs to the UPF0224 (FAM112) family.

RefSeq proteins (1): NP_653195* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR022776	TRM13/UPF0224_CHHC_Znf_dom	Domain
IPR036236	Znf_C2H2_sf	Homologous_superfamily
IPR051591	UPF0224_FAM112_RNA_Proc	Family

Pfam: PF05253

UniProt features (13 total): binding site 8, zinc finger region 2, chain 1, modified residue 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WW33-F1	76.69	0.37

Functional residue map

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

Ligand- & substrate-binding residues (8): 71; 17; 23; 33; 37; 51; 57; 67

Post-translational modifications (1): 8

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_MALE_GAMETE_GENERATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CATABOLIC_PROCESS, GOBP_PIRNA_PROCESSING, RYTTCCTG_ETS2_B, ELK1_01, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, NRF2_01, GTGACTT_MIR224, IZADPANAH_STEM_CELL_ADIPOSE_VS_BONE_UP

GO Biological Process (4): spermatogenesis (GO:0007283), cell differentiation (GO:0030154), secondary piRNA processing (GO:0140965), piRNA-mediated gene silencing by mRNA destabilization (GO:0140991)

GO Molecular Function (3): tRNA binding (GO:0000049), zinc ion binding (GO:0008270), metal ion binding (GO:0046872)

GO Cellular Component (2): piP-body (GO:0071547), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
piRNA processing	1
regulatory ncRNA-mediated post-transcriptional gene silencing	1
mRNA destabilization	1
RNA binding	1
transition metal ion binding	1
cation binding	1
P granule	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

816 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GTSF1	PIWIL1	Q96J94	878
GTSF1	PIWIL4	Q7Z3Z4	836
GTSF1	PIWIL2	Q8TC59	698
GTSF1	MOV10L1	Q9BXT6	667
GTSF1	TDRD9	Q8NDG6	662
GTSF1	TDRD1	Q9BXT4	626
GTSF1	ERI1	Q8IV48	615
GTSF1	HENMT1	Q5T8I9	602
GTSF1	TDRD12	Q587J7	600
GTSF1	TDRKH	Q9Y2W6	591
GTSF1	MAEL	Q96JY0	584
GTSF1	EXD1	Q8NHP7	546
GTSF1	FKBP6	O75344	545
GTSF1	NXF2B	Q9GZY0	529
GTSF1	SNRNP48	Q6IEG0	515

IntAct

15 interactions, top by confidence:

A	B	Type	Score
GTSF1	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
GTSF1	MFHAS1	psi-mi:“MI:0407”(direct interaction)	0.440
GTSF1	UBR3	psi-mi:“MI:0915”(physical association)	0.400
HSPB1	GTSF1	psi-mi:“MI:0915”(physical association)	0.370
GTSF1	HSPB1	psi-mi:“MI:0915”(physical association)	0.370
GTSF1	MAPK14	psi-mi:“MI:0914”(association)	0.350
PAAT	HIP1	psi-mi:“MI:0914”(association)	0.350
DGCR8	VWA8	psi-mi:“MI:2364”(proximity)	0.270
LIN28B	MEX3A	psi-mi:“MI:2364”(proximity)	0.270
QKI	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
RPS3	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
ZC3H11A	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (13): GTSF1 (Two-hybrid), RGP1 (Affinity Capture-MS), MAPK14 (Affinity Capture-MS), GTSF1 (Reconstituted Complex), GTSF1 (Reconstituted Complex), GTSF1 (Proximity Label-MS), GTSF1 (Proximity Label-MS), GTSF1 (Proximity Label-MS), MAPK14 (Affinity Capture-MS), RGP1 (Affinity Capture-MS), UBR3 (Affinity Capture-MS), GTSF1 (Affinity Capture-MS), GTSF1 (Protein-peptide)

ESM2 similar proteins: A0JMR6, A4IIA7, A5WW08, O60934, P14629, P55265, P79457, Q13434, Q149N8, Q2YDS5, Q3B7T1, Q3KQ71, Q3SZU0, Q3T026, Q3UDK1, Q4R8M9, Q4VBT5, Q561R3, Q5FWP4, Q5R4U2, Q5RCV3, Q5RGA4, Q5RL73, Q5VVJ2, Q66J91, Q69Z66, Q6A098, Q6IEG0, Q6P256, Q6PFK1, Q7TN31, Q7ZZ00, Q8JFF3, Q8K2X2, Q8N302, Q8S4P6, Q8WW33, Q93073, Q96T68, Q99MM4

Diamond homologs: P13007, Q3SZU0, Q4R8M9, Q8WW33, Q9DAN6

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

973 predictions. Top by Δscore:

Variant	Effect	Δscore
12:54459087:A:AC	donor_gain	1.0000
12:54459088:C:CC	donor_gain	1.0000
12:54460375:A:AC	donor_gain	1.0000
12:54460376:C:CC	donor_gain	1.0000
12:54460376:CT:C	donor_gain	1.0000
12:54460472:C:CC	acceptor_gain	1.0000
12:54462636:GCTCA:G	donor_loss	1.0000
12:54462637:CTCAC:C	donor_loss	1.0000
12:54462638:TCA:T	donor_loss	1.0000
12:54462639:CA:C	donor_loss	1.0000
12:54462640:A:AT	donor_loss	1.0000
12:54462641:C:CA	donor_loss	1.0000
12:54462721:GTTGA:G	acceptor_gain	1.0000
12:54462722:TTGA:T	acceptor_gain	1.0000
12:54462723:TGA:T	acceptor_gain	1.0000
12:54462724:GA:G	acceptor_gain	1.0000
12:54462725:AC:A	acceptor_loss	1.0000
12:54462726:C:CA	acceptor_loss	1.0000
12:54462726:C:CC	acceptor_gain	1.0000
12:54462727:T:G	acceptor_loss	1.0000
12:54463166:CTTA:C	donor_loss	1.0000
12:54463167:TTAC:T	donor_loss	1.0000
12:54463168:TACC:T	donor_loss	1.0000
12:54463169:A:AC	donor_gain	1.0000
12:54463169:ACC:A	donor_loss	1.0000
12:54463170:C:CC	donor_gain	1.0000
12:54463170:C:CT	donor_loss	1.0000
12:54463170:CCAA:C	donor_gain	1.0000
12:54463174:CAT:C	donor_gain	1.0000
12:54463193:T:TA	donor_gain	1.0000

AlphaMissense

1122 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:54463264:A:G	C51R	1.000
12:54465074:C:G	C37S	1.000
12:54465075:A:G	C37R	1.000
12:54465075:A:T	C37S	1.000
12:54465083:A:G	L34P	1.000
12:54465085:A:C	H33Q	1.000
12:54465085:A:T	H33Q	1.000
12:54465087:G:C	H33D	1.000
12:54465087:G:T	H33N	1.000
12:54465098:C:A	R29M	1.000
12:54465115:A:C	H23Q	1.000
12:54465115:A:T	H23Q	1.000
12:54465117:G:C	H23D	1.000
12:54465134:C:G	C17S	1.000
12:54465135:A:G	C17R	1.000
12:54465135:A:T	C17S	1.000
12:54462649:C:A	W107C	0.999
12:54462649:C:G	W107C	0.999
12:54462651:A:G	W107R	0.999
12:54462651:A:T	W107R	0.999
12:54463203:C:G	C71S	0.999
12:54463203:C:T	C71Y	0.999
12:54463204:A:G	C71R	0.999
12:54463204:A:T	C71S	0.999
12:54463214:A:C	H67Q	0.999
12:54463214:A:T	H67Q	0.999
12:54463244:G:C	H57Q	0.999
12:54463244:G:T	H57Q	0.999
12:54463251:G:T	A55D	0.999
12:54463253:A:C	N54K	0.999

dbSNP variants (sampled 300 via entrez): RS1000090565 (12:54473639 A>G), RS1000283501 (12:54459880 C>T), RS1000325094 (12:54464399 G>T), RS1000382262 (12:54468060 C>T), RS1000397881 (12:54460021 C>T), RS1000798618 (12:54469723 C>A,G), RS1000930467 (12:54462674 T>C), RS1001091115 (12:54472233 G>A,C), RS1001200658 (12:54456486 C>G), RS1001251951 (12:54471027 T>C,G), RS1001316676 (12:54456300 A>G), RS1001362379 (12:54456259 G>T), RS1001870758 (12:54475319 G>A), RS1001944825 (12:54469179 A>G), RS1002068067 (12:54461619 G>T)

Disease associations

OMIM: gene MIM:617484 | 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

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
beta-methylcholine	affects expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, increases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Antirheumatic Agents	decreases expression	1

Clinical trials (associated diseases)

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