TNP1

Summary

TNP1 (transition protein 1, HGNC:11951) is a protein-coding gene on chromosome 2q35, encoding Spermatid nuclear transition protein 1 (P09430). Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals.

Transition protein-1 is a spermatid-specific product of the haploid genome which replaces histone and is itself replaced in the mature sperm by the protamines (see PRM1, MIM 182880; PRM2, MIM 182890) (Luerssen et al., 1990 [PubMed 2249851]).

Source: NCBI Gene 7141 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_003284

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11951
Approved symbol	TNP1
Name	transition protein 1
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000118245
Ensembl biotype	protein_coding
OMIM	190231
Entrez	7141

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000236979

RefSeq mRNA: 1 — MANE Select: NM_003284 NM_003284

CCDS: CCDS2406

Canonical transcript exons

ENST00000236979 — 2 exons

Exon	Start	End
ENSE00000796863	216859458	216859695
ENSE00000796864	216859896	216860064

Expression profiles

Bgee: expression breadth ubiquitous, 150 present calls, max score 100.00.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 5.7500 / max 4864.5005, expressed in 22 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
33848	5.7500	22

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	100.00	gold quality
male germ cell	CL:0000015	99.92	gold quality
adult organism	UBERON:0007023	99.78	gold quality
right testis	UBERON:0004534	99.74	gold quality
left testis	UBERON:0004533	99.36	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	97.12	gold quality
testis	UBERON:0000473	96.93	gold quality
cartilage tissue	UBERON:0002418	85.70	gold quality
cauda epididymis	UBERON:0004360	79.59	gold quality
endometrium epithelium	UBERON:0004811	78.93	gold quality
cerebellar vermis	UBERON:0004720	76.29	silver quality
caput epididymis	UBERON:0004358	76.19	gold quality
paraflocculus	UBERON:0005351	74.60	silver quality
corpus epididymis	UBERON:0004359	73.49	silver quality
right coronary artery	UBERON:0001625	73.10	gold quality
frontal pole	UBERON:0002795	72.99	gold quality
metanephros cortex	UBERON:0010533	72.40	gold quality
middle frontal gyrus	UBERON:0002702	72.15	gold quality
olfactory bulb	UBERON:0002264	71.46	gold quality
left lobe of thyroid gland	UBERON:0001120	68.86	gold quality
type B pancreatic cell	CL:0000169	68.84	gold quality
right lobe of thyroid gland	UBERON:0001119	68.55	gold quality
Brodmann (1909) area 10	UBERON:0013541	68.13	gold quality
right uterine tube	UBERON:0001302	67.90	gold quality
thyroid gland	UBERON:0002046	66.99	gold quality
ectocervix	UBERON:0012249	66.91	gold quality
tongue squamous epithelium	UBERON:0006919	66.29	gold quality
diaphragm	UBERON:0001103	66.12	gold quality
endocervix	UBERON:0000458	64.79	gold quality
vastus lateralis	UBERON:0001379	64.79	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	31677.66
E-GEOD-124263	yes	14692.27
E-HCAD-38	yes	9078.94
E-ANND-3	no	1.32

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): MBD2, RBPJ

miRNA regulators (miRDB)

10 targeting TNP1, 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-4425	100.00	67.59	1049
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-3147	99.52	66.34	388
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
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

Literature-anchored findings (GeneRIF, showing 7)

• a deletion of 15 nucleotides encompassing the recognition site for the cAMP response element transcription factor was found in the 5’-promoter region of the TNP1 gene in infertile men; this deletion reduces TNP1 expression and may cause infertility (PMID:16291974)
• We found significantly lower levels of HILS1, TNP1, and TNP2 transcripts in spermatozoa from asthenozoospermic men compared to normozoospermic men. (PMID:17852044)
• The TNP1 contributes not only to successful fertilization, but may has an important impact in development of preimplantation embryos. (PMID:18292840)
• The presence of transition proteins (TP1 and/or TP2) in spermatids in semen indicates inhibition in the differentiation pathway from round spermatids to spermatozoa in infertile men. (PMID:18727729)
• frequency of the haplotype GCG (H3) was increased in azoospermic men compared with fertile men. expression analysis of the TNP1 gene in obstructive azoospermic men showed that haplotypes of the TNP1 gene do not affect its expression level. (PMID:20522125)
• Among Systemic lupus erythematosus patients, 63.6% and 45.5% of those with lupus nephritis were positive for anti-RRP8 and anti-TNP1 antibodies, compared with 12.5% and 9.4% of Systemic lupus erythematosus patients without nephritis, respectively. (PMID:26098692)
• Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. (PMID:33440036)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnp1	ENSMUSG00000026182
rattus_norvegicus	Tnp1	ENSRNOG00000017611

Protein

Protein identifiers

Spermatid nuclear transition protein 1 — P09430 (reviewed: P09430)

All UniProt accessions (2): P09430, Q4ZG82

UniProt curated annotations — full annotation on UniProt →

Function. Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals. In condensing spermatids, loaded onto the nucleosomes, where it promotes the recruitment and processing of protamines, which are responsible for histone eviction.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed by spermatids (at protein level).

Similarity. Belongs to the nuclear transition protein 1 family.

RefSeq proteins (1): NP_003275* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001319	Nuclear_transition_prot1	Family
IPR020062	Nuclear_transition_prot1_CS	Conserved_site

Pfam: PF02079

UniProt features (5 total): modified residue 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09430-F1	61.97	0.00

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 (2): 9, 40

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 125 (showing top): MORF_RAGE, GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_SINGLE_FERTILIZATION, CAR_TNFRSF25, WWTAAGGC_UNKNOWN, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_PROTEIN_MATURATION, GOBP_NUCLEUS_ORGANIZATION, GOBP_CILIUM_MOVEMENT, CAR_MYST2, GOBP_CILIUM_OR_FLAGELLUM_DEPENDENT_CELL_MOTILITY, GOBP_DNA_DAMAGE_RESPONSE, GOBP_ORGANELLE_ASSEMBLY, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM

GO Biological Process (15): single strand break repair (GO:0000012), nucleosome disassembly (GO:0006337), chromatin remodeling (GO:0006338), spermatid development (GO:0007286), spermatid nucleus differentiation (GO:0007289), spermatid nucleus elongation (GO:0007290), positive regulation of protein processing (GO:0010954), sexual reproduction (GO:0019953), flagellated sperm motility (GO:0030317), heterochromatin formation (GO:0031507), sperm DNA decondensation (GO:0035041), sperm DNA condensation (GO:0035092), negative regulation of DNA-templated transcription (GO:0045892), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (4): nucleosome (GO:0000786), male germ cell nucleus (GO:0001673), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	3
nucleus organization	2
spermatid nucleus differentiation	2
DNA repair	1
protein-DNA complex disassembly	1
nucleosome organization	1
germ cell development	1
spermatid differentiation	1
spermatid development	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
reproductive process	1
cilium-dependent cell motility	1
cilium movement involved in cell motility	1
sperm motility	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
male pronucleus assembly	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
developmental process involved in reproduction	1
male gamete generation	1
cellular developmental process	1
nucleic acid binding	1
binding	1
chromatin	1
protein-DNA complex	1
germ cell nucleus	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1140 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNP1	TNP2	Q05952	973
TNP1	PRM1	P04553	959
TNP1	PRM2	P04554	958
TNP1	KDM3A	Q9Y4C1	855
TNP1	NUPR1	O60356	838
TNP1	TSSK6	Q9BXA6	812
TNP1	VIL1	P09327	772
TNP1	SPEM1	Q8N4L4	743
TNP1	ACR	P10323	712
TNP1	PRM3	Q9NNZ6	681
TNP1	SYCP3	Q8IZU3	666
TNP1	KPNA3	O00505	645
TNP1	ODF1	Q14990	617
TNP1	DMRT1	Q9Y5R6	581
TNP1	STRA8	Q7Z7C7	576

IntAct

8 interactions, top by confidence:

A	B	Type	Score
TNP1	SDCBP2	psi-mi:“MI:0915”(physical association)	0.670
SDCBP2	TNP1	psi-mi:“MI:0915”(physical association)	0.670
TNP1	DVL3	psi-mi:“MI:0915”(physical association)	0.560
TNP1	DVL3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): SDCBP2 (Two-hybrid), DVL3 (Two-hybrid), RPL6 (Cross-Linking-MS (XL-MS)), TNP1 (Biochemical Activity), TNP1 (Biochemical Activity), TNP1 (Biochemical Activity), TNP1 (Biochemical Activity), TNP1 (Affinity Capture-Western), TNP1 (Reconstituted Complex), TNP1 (Two-hybrid), TNP1 (Two-hybrid), TNP1 (Two-hybrid), PPARG (Reconstituted Complex)

ESM2 similar proteins: A1RRN8, A2STI9, A4G029, A4WLS6, A6UVQ6, A6VIE9, A9A8D5, B1YAF1, B6YWY4, B8GEU4, O16130, O27650, O28212, O97965, P02317, P04650, P05733, P09430, P10856, P11340, P13275, P17305, P17306, P22613, P49166, P52814, P59289, P59473, P61927, P61928, P79244, P83266, P83267, P87558, Q09821, Q43292, Q54MG6, Q6L2L2, Q6M0V9, Q8JN70

Diamond homologs: P02317, P09430, P10856, P17305, P17306, P22613

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	14
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

155 predictions. Top by Δscore:

Variant	Effect	Δscore
2:216859967:C:CA	donor_gain	1.0000
2:216859915:A:AC	donor_gain	0.9900
2:216859916:C:CC	donor_gain	0.9900
2:216859933:A:AC	donor_gain	0.9900
2:216859934:C:CC	donor_gain	0.9900
2:216859950:TGC:T	donor_gain	0.9800
2:216859952:C:CT	donor_gain	0.9800
2:216859953:C:CT	donor_gain	0.9800
2:216859696:C:CC	acceptor_gain	0.9600
2:216859692:TTGG:T	acceptor_gain	0.9500
2:216859714:T:TC	acceptor_gain	0.9500
2:216859934:CGGTA:C	donor_gain	0.9500
2:216859714:T:C	acceptor_gain	0.9400
2:216859949:CTG:C	donor_gain	0.9400
2:216859693:TGG:T	acceptor_gain	0.9300
2:216859694:GG:G	acceptor_gain	0.9300
2:216859696:C:T	acceptor_loss	0.9300
2:216859697:T:A	acceptor_loss	0.9300
2:216859934:CGGT:C	donor_gain	0.9300
2:216859888:TCAC:T	donor_loss	0.9200
2:216859890:ACT:A	donor_loss	0.9200
2:216859891:CTCA:C	donor_loss	0.9200
2:216859892:T:TA	donor_loss	0.9200
2:216859698:G:C	acceptor_gain	0.9100
2:216859917:T:C	donor_gain	0.9100
2:216859710:A:T	acceptor_gain	0.8800
2:216859951:G:GC	donor_gain	0.8800
2:216859691:ATTGG:A	acceptor_gain	0.8600
2:216859911:T:A	donor_gain	0.8600
2:216859698:G:GC	acceptor_gain	0.8500

AlphaMissense

361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:216859969:C:A	K22N	0.961
2:216859969:C:G	K22N	0.961
2:216859968:C:G	G23R	0.956
2:216859968:C:T	G23R	0.956
2:216859967:C:T	G23E	0.926
2:216859960:C:A	K25N	0.915
2:216859960:C:G	K25N	0.915
2:216859971:T:C	K22E	0.915
2:216859964:A:T	V24D	0.909
2:216860023:G:C	S4R	0.902
2:216860023:G:T	S4R	0.902
2:216860025:T:G	S4R	0.902
2:216859970:T:A	K22M	0.898
2:216859957:T:A	R26S	0.895
2:216859957:T:G	R26S	0.895
2:216859970:T:G	K22T	0.880
2:216860022:G:T	R5S	0.877
2:216860011:C:A	K8N	0.857
2:216860011:C:G	K8N	0.857
2:216859974:G:C	H21D	0.851
2:216859962:T:C	K25E	0.849
2:216859945:T:A	K30N	0.847
2:216859945:T:G	K30N	0.847
2:216860013:T:C	K8E	0.843
2:216860008:A:C	S9R	0.830
2:216860008:A:T	S9R	0.830
2:216860010:T:G	S9R	0.830
2:216860021:C:G	R5P	0.826
2:216860030:G:C	S2W	0.817
2:216859946:T:A	K30I	0.813

dbSNP variants (sampled 300 via entrez): RS1000538377 (2:216861338 A>G), RS1000833661 (2:216861014 C>T), RS1000926993 (2:216861070 G>C), RS1001809463 (2:216860088 G>C), RS1003315001 (2:216859384 T>C), RS1004905445 (2:216859076 G>A,C), RS1007109873 (2:216861819 T>C), RS1008043943 (2:216860905 A>G), RS1008213844 (2:216860336 G>C), RS1009210192 (2:216861757 G>A), RS1009471859 (2:216861410 T>C), RS1010537148 (2:216860950 AG>A), RS1013014909 (2:216861290 T>C), RS1014052375 (2:216861417 AT>A), RS1014607101 (2:216860419 A>C)

Disease associations

OMIM: gene MIM:190231 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001221_3	Permanent tooth development	2.000000e-14
GCST002647_80	Height	4.000000e-09
GCST003094_2	Mitral valve prolapse	3.000000e-11
GCST003988_20	Hypothyroidism	6.000000e-09
GCST005351_1	Carboplatin disposition in epthelial ovarian cancer	5.000000e-06
GCST005984_27	Glomerular filtration rate	1.000000e-09
GCST005985_63	Creatinine levels	4.000000e-09
GCST007096_6	Pulse pressure	5.000000e-08
GCST008058_174	Estimated glomerular filtration rate	2.000000e-34
GCST008059_138	Estimated glomerular filtration rate	3.000000e-29
GCST008060_20	Estimated glomerular filtration rate	4.000000e-06
GCST008064_12	Chronic kidney disease	2.000000e-06
GCST008839_204	Height	5.000000e-07
GCST010653_62	Thyroid stimulating hormone levels	3.000000e-78

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005763	pulse pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

10 total (human), top 10 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
uranyl acetate	affects expression	1
hydroxyhydroquinone	decreases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
CGP 52608	affects binding, increases reaction	1
Air Pollutants	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Uranium	affects expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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