TNP2

Summary

TNP2 (transition protein 2, HGNC:11952) is a protein-coding gene on chromosome 16p13.13, encoding Nuclear transition protein 2 (Q05952). Plays a key role in the replacement of histones to protamine in the elongating spermatids of mammals.

Predicted to enable zinc ion binding activity. Predicted to be involved in several processes, including penetration of zona pellucida; positive regulation of protein processing; and sperm DNA condensation. Predicted to act upstream of or within binding activity of sperm to zona pellucida and flagellated sperm motility. Predicted to be located in male germ cell nucleus. Predicted to be part of nucleosome. Predicted to be active in nucleus.

Source: NCBI Gene 7142 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 32 total
• MANE Select transcript: NM_005425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11952
Approved symbol	TNP2
Name	transition protein 2
Location	16p13.13
Locus type	gene with protein product
Status	Approved
Aliases	TP2
Ensembl gene	ENSG00000178279
Ensembl biotype	protein_coding
OMIM	190232
Entrez	7142

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000312693, ENST00000560751

RefSeq mRNA: 1 — MANE Select: NM_005425 NM_005425

CCDS: CCDS45410

Canonical transcript exons

ENST00000312693 — 2 exons

Exon	Start	End
ENSE00001231205	11268863	11269325
ENSE00001702190	11267857	11268012

Expression profiles

Bgee: expression breadth broad, 32 present calls, max score 93.79.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0605 / max 62.2497, expressed in 3 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156241	0.0605	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	93.79	gold quality
male germ cell	CL:0000015	90.86	gold quality
left testis	UBERON:0004533	88.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.93	gold quality
right testis	UBERON:0004534	85.46	gold quality
testis	UBERON:0000473	84.48	gold quality
olfactory bulb	UBERON:0002264	66.80	gold quality
buccal mucosa cell	CL:0002336	64.27	gold quality
adult organism	UBERON:0007023	61.50	gold quality
endometrium epithelium	UBERON:0004811	59.84	gold quality
gluteal muscle	UBERON:0002000	56.22	gold quality
triceps brachii	UBERON:0001509	56.13	gold quality
myocardium	UBERON:0002349	54.32	gold quality
lower lobe of lung	UBERON:0008949	52.76	silver quality
tendon of biceps brachii	UBERON:0008188	50.93	gold quality
quadriceps femoris	UBERON:0001377	50.55	gold quality
frontal pole	UBERON:0002795	50.41	gold quality
middle frontal gyrus	UBERON:0002702	50.30	gold quality
paraflocculus	UBERON:0005351	50.18	gold quality
Brodmann (1909) area 10	UBERON:0013541	50.18	gold quality
vastus lateralis	UBERON:0001379	49.84	gold quality
thymus	UBERON:0002370	49.61	gold quality
metanephric glomerulus	UBERON:0004736	49.61	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	49.32	silver quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
cerebellar vermis	UBERON:0004720	49.25	gold quality
cardiac muscle of right atrium	UBERON:0003379	49.23	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
hair follicle	UBERON:0002073	49.18	gold quality
oviduct epithelium	UBERON:0004804	49.16	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.81

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

7 targeting TNP2, 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-802	99.61	67.70	1254
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-3074-5P	98.82	66.56	1414
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760

Literature-anchored findings (GeneRIF, showing 8)

• We found significantly lower levels of HILS1, TNP1, and TNP2 transcripts in spermatozoa from asthenozoospermic men compared to normozoospermic men. (PMID:17852044)
• 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)
• Acetylation of transition protein 2 (TP2) by KAT3B (p300) alters its DNA condensation property and interaction with putative histone chaperone NPM3. (PMID:19710011)
• analysis of the TNP2 gene did not show any association with infertility. (PMID:20522125)
• MiR-122 may influence spermatozoa-like cells by suppressing TNP2 expression and inhibiting the expression of proteins associated with sperm development. (PMID:23327642)
• the quantity of PRM1, PRM2, and TNP2 transcripts and the PRM1/PRM2 mRNA ratio affect spermiogenesis, sperm morphology (PMID:25536093)
• Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. (PMID:33440036)
• Spermatozoa retrieval in azoospermia and expression profile of JMJD1A, TNP2, and PRM2 in a subset of the Karachi population. (PMID:34235877)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Tnp2	ENSMUSG00000043050
rattus_norvegicus	Tnp2	ENSRNOG00000002566

Protein

Protein identifiers

Nuclear transition protein 2 — Q05952 (reviewed: Q05952)

All UniProt accessions (3): Q05952, A0A2R8Y7P0, Q4VB56

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. Nucleolus. Chromosome.

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

Similarity. Belongs to the nuclear transition protein 2 family.

RefSeq proteins (1): NP_005416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000678	TP2	Family

Pfam: PF01254

UniProt features (12 total): binding site 4, compositionally biased region 3, chain 1, region of interest 1, modified residue 1, sequence variant 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q05952-F1	59.17	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.

Ligand- & substrate-binding residues (4): 12; 16; 26; 30

Post-translational modifications (1): 133

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 83 (showing top): GOBP_POSITIVE_REGULATION_OF_PROTEIN_MATURATION, GOBP_SINGLE_FERTILIZATION, YAGI_AML_WITH_INV_16_TRANSLOCATION, DARWICHE_SKIN_TUMOR_PROMOTER_UP, DARWICHE_PAPILLOMA_RISK_LOW_DN, DARWICHE_PAPILLOMA_RISK_HIGH_DN, DARWICHE_SQUAMOUS_CELL_CARCINOMA_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_PROTEIN_MATURATION, GOBP_NUCLEUS_ORGANIZATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_SPERMATID_NUCLEUS_DIFFERENTIATION, GOBP_REGULATION_OF_PROTEIN_MATURATION, GOBP_MULTI_MULTICELLULAR_ORGANISM_PROCESS, GOBP_ACROSOME_REACTION

GO Biological Process (6): spermatogenesis (GO:0007283), acrosome reaction (GO:0007340), penetration of zona pellucida (GO:0007341), positive regulation of protein processing (GO:0010954), sperm DNA condensation (GO:0035092), cell differentiation (GO:0030154)

GO Molecular Function (4): DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleosome (GO:0000786), nucleolus (GO:0005730), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
single fertilization	2
intracellular membraneless organelle	2
developmental process involved in reproduction	1
male gamete generation	1
membrane fusion involved in acrosome reaction	1
reproductive process	1
acrosomal vesicle exocytosis	1
multi-multicellular organism process	1
multicellular organismal reproductive process	1
protein processing	1
positive regulation of proteolysis	1
regulation of protein processing	1
positive regulation of protein maturation	1
chromatin organization	1
spermatid nucleus differentiation	1
cellular developmental process	1
nucleic acid binding	1
transition metal ion binding	1
binding	1
cation binding	1
chromatin	1
protein-DNA complex	1
nuclear lumen	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

957 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TNP2	PRM2	P04554	980
TNP2	TNP1	P09430	973
TNP2	PRM1	P04553	948
TNP2	PRM3	Q9NNZ6	808
TNP2	KPNA3	O00505	771
TNP2	KDM3A	Q9Y4C1	667
TNP2	NUPR2	A6NF83	633
TNP2	SPEM1	Q8N4L4	609
TNP2	SYCP3	Q8IZU3	592
TNP2	H1-7	Q75WM6	590
TNP2	SMCP	P49901	571
TNP2	DDX25	Q9UHL0	550
TNP2	ODF1	Q14990	548
TNP2	KPNA4	O00629	548
TNP2	H1-6	P22492	541

IntAct

28 interactions, top by confidence:

A	B	Type	Score
MDFI	TNP2	psi-mi:“MI:0915”(physical association)	0.670
TNP2	MDFI	psi-mi:“MI:0915”(physical association)	0.670
KRTAP10-8	TNP2	psi-mi:“MI:0915”(physical association)	0.560
TNP2	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.560
TNP2	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	TNP2	psi-mi:“MI:0915”(physical association)	0.560
TNP2	APPBP2	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-3	TNP2	psi-mi:“MI:0915”(physical association)	0.560
	TNP2	psi-mi:“MI:0915”(physical association)	0.560
TNP2	RBM6	psi-mi:“MI:0914”(association)	0.350
TNP2	C1QBP	psi-mi:“MI:0914”(association)	0.350
TNP2	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
TNP2	KRTAP2-4	psi-mi:“MI:0915”(physical association)	0.000
TNP2	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.000
TNP2	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.000
TNP2	APPBP2	psi-mi:“MI:0915”(physical association)	0.000
TNP2	MDFI	psi-mi:“MI:0915”(physical association)	0.000
TNP2	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.000
	TNP2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (35): TNP2 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-5 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), NOTCH2NL (Two-hybrid), TNP2 (Two-hybrid), TNP2 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), KRTAP12-3 (Two-hybrid), KRTAP2-3 (Two-hybrid), KRTAP2-4 (Two-hybrid), KRTAP10-1 (Two-hybrid)

ESM2 similar proteins: A0A023PXA5, A0A0B4J1W7, A6NHN6, E9PJ23, E9PJI5, E9PKD4, E9PQR5, F8W1W9, F8WFD2, O13761, O70561, O75200, P03849, P0DM63, P0DXC3, P14588, P15099, P16802, P21085, P26377, P32450, P35929, P40057, P41708, P89478, P92521, Q03831, Q05952, Q107X0, Q53SZ7, Q86SH4, Q89863, Q8CH20, Q8N2A0, Q8N976, Q8NA96, Q8NHX4, Q8ST90, Q8WNV1, Q96M85

Diamond homologs: O77645, P11101, P11378, P26377, P29258, Q05952, Q8WNV1, Q9N1A3, Q9N1A4, Q9N1A5, Q9N1A6, Q9N1A7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	27
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

93 predictions. Top by Δscore:

Variant	Effect	Δscore
16:11268008:CCATC:C	acceptor_gain	0.9900
16:11268009:CATC:C	acceptor_gain	0.9900
16:11268009:CATCC:C	acceptor_gain	0.9900
16:11268011:TC:T	acceptor_gain	0.9900
16:11268011:TCCT:T	acceptor_loss	0.9900
16:11268012:CC:C	acceptor_gain	0.9900
16:11268012:CCTAA:C	acceptor_loss	0.9900
16:11268013:C:CC	acceptor_gain	0.9800
16:11268014:T:C	acceptor_loss	0.9800
16:11268858:GGTA:G	donor_loss	0.9800
16:11268861:A:T	donor_loss	0.9800
16:11268849:T:TA	donor_gain	0.9700
16:11268930:G:A	donor_gain	0.9700
16:11268020:A:C	acceptor_gain	0.9600
16:11268884:TGTAC:T	donor_gain	0.9400
16:11268867:G:C	donor_gain	0.9300
16:11268010:ATC:A	acceptor_gain	0.9100
16:11268020:A:AC	acceptor_gain	0.9100
16:11268841:TCCCC:T	donor_gain	0.9100
16:11268886:TAC:T	donor_gain	0.8800
16:11268887:ACA:A	donor_gain	0.8800
16:11268888:CAC:C	donor_gain	0.8800
16:11268013:C:T	acceptor_gain	0.8600
16:11268875:T:TA	donor_gain	0.8000
16:11268689:T:A	donor_gain	0.7900
16:11268934:T:TA	donor_gain	0.7700
16:11268746:T:TA	donor_gain	0.7200
16:11268844:C:T	donor_gain	0.7100
16:11268707:A:C	donor_gain	0.6800
16:11268858:GGTAC:G	donor_gain	0.6800

AlphaMissense

934 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:11268882:T:A	K127N	0.725
16:11268882:T:G	K127N	0.725
16:11268900:C:A	R121S	0.656
16:11268900:C:G	R121S	0.656
16:11268876:C:A	K129N	0.632
16:11268876:C:G	K129N	0.632
16:11268883:T:A	K127I	0.625
16:11269164:G:C	F33L	0.624
16:11269164:G:T	F33L	0.624
16:11269166:A:G	F33L	0.624
16:11268945:T:A	R106S	0.592
16:11268945:T:G	R106S	0.592
16:11268903:C:A	K120N	0.584
16:11268903:C:G	K120N	0.584
16:11268942:C:A	K107N	0.570
16:11268942:C:G	K107N	0.570

dbSNP variants (sampled 300 via entrez): RS1000207233 (16:11269363 C>A,G), RS1001788282 (16:11271282 G>A), RS1001857062 (16:11271054 A>G), RS1001903285 (16:11270275 G>C), RS1002279559 (16:11268361 C>G), RS1002601288 (16:11270711 A>G), RS1002956894 (16:11270363 G>A), RS1003809646 (16:11270790 T>G), RS1005225596 (16:11267833 A>C,G), RS1005911066 (16:11269647 A>C,G), RS1006355124 (16:11268754 G>A,T), RS1006690937 (16:11269607 T>A,C), RS1006828239 (16:11269785 G>C), RS1007164479 (16:11268785 C>G), RS1008498398 (16:11270683 C>G)

Disease associations

OMIM: gene MIM:190232 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000258_5	Type 1 diabetes	3.000000e-06
GCST001341_12	Multiple sclerosis	6.000000e-07
GCST001958_14	Bulimia nervosa	2.000000e-06
GCST004131_115	Inflammatory bowel disease	1.000000e-06
GCST004132_39	Crohn’s disease	1.000000e-07
GCST005537_99	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	5.000000e-14
GCST009798_15	Asthma	2.000000e-33

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Arsenic	affects methylation	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Valproic Acid	increases methylation	1
Aflatoxin B1	increases expression	1
Sodium Selenite	decreases expression	1

Clinical trials (associated diseases)

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