TERB2

Summary

TERB2 (telomere repeat binding bouquet formation protein 2, HGNC:28520) is a protein-coding gene on chromosome 15q21.1, encoding Telomere repeats-binding bouquet formation protein 2 (Q8NHR7). Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis.

Predicted to be involved in homologous chromosome pairing at meiosis and meiotic attachment of telomere to nuclear envelope. Predicted to act upstream of or within meiosis I; oogenesis; and spermatogenesis. Predicted to be located in chromosome, telomeric region. Predicted to be active in nuclear inner membrane. Implicated in spermatogenic failure 59.

Source: NCBI Gene 145645 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spermatogenic failure 59 (Moderate, GenCC)
• Clinical variants (ClinVar): 13 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_152448

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28520
Approved symbol	TERB2
Name	telomere repeat binding bouquet formation protein 2
Location	15q21.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC33951
Ensembl gene	ENSG00000167014
Ensembl biotype	protein_coding
OMIM	617131
Entrez	145645

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 nonsense_mediated_decay, 1 protein_coding

ENST00000340827, ENST00000557864, ENST00000559137

RefSeq mRNA: 1 — MANE Select: NM_152448 NM_152448

CCDS: CCDS10115

Canonical transcript exons

ENST00000340827 — 7 exons

Exon	Start	End
ENSE00001140454	44956896	44956977
ENSE00001182995	44956687	44956782
ENSE00001380316	44978489	44979229
ENSE00003469541	44966158	44966243
ENSE00003549113	44961523	44961584
ENSE00003576450	44973867	44973955
ENSE00003646400	44958373	44958512

Expression profiles

Bgee: expression breadth broad, 29 present calls, max score 87.27.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1131 / max 108.7115, expressed in 5 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146417	0.1096	5
207494	0.0035	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.27	gold quality
right testis	UBERON:0004534	83.04	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	82.63	gold quality
left testis	UBERON:0004533	82.32	gold quality
testis	UBERON:0000473	80.99	gold quality
adult organism	UBERON:0007023	60.46	silver quality
sperm	CL:0000019	58.47	silver quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
epithelial cell of pancreas	CL:0000083	53.81	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
pancreatic ductal cell	CL:0002079	53.08	silver quality
right lobe of liver	UBERON:0001114	53.06	gold quality
myocardium	UBERON:0002349	50.25	gold quality
liver	UBERON:0002107	47.12	gold quality
ileal mucosa	UBERON:0000331	47.11	silver quality
nasal cavity epithelium	UBERON:0005384	47.03	gold quality
quadriceps femoris	UBERON:0001377	46.49	gold quality
tibialis anterior	UBERON:0001385	46.48	silver quality
deltoid	UBERON:0001476	46.29	gold quality
skin of hip	UBERON:0001554	45.87	silver quality
vastus lateralis	UBERON:0001379	45.40	gold quality
upper leg skin	UBERON:0004262	45.33	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	44.92	gold quality
nasal cavity mucosa	UBERON:0001826	43.99	gold quality
oviduct epithelium	UBERON:0004804	43.65	gold quality
layer of synovial tissue	UBERON:0007616	43.55	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	43.37	gold quality
sural nerve	UBERON:0015488	43.08	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.44

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

47 targeting TERB2, 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-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-8067	99.86	69.59	2260
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6715A-3P	99.83	68.05	1473
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-1179	99.71	68.70	1040
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-580-3P	99.67	69.23	1841
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-5584-5P	99.49	68.22	2814

Literature-anchored findings (GeneRIF, showing 3)

• complementary structured illumination microscopy studies and biochemical findings reveal a telomere attachment mechanism in which MAJIN-TERB2-TERB1 recruits telomere-bound TRF1, which is then displaced during pachytene, allowing MAJIN-TERB2-TERB1 to bind telomeric DNA and form a mature attachment plate. (PMID:30559341)
• The meiotic TERB1-TERB2-MAJIN complex tethers telomeres to the nuclear envelope (PMID:30718482)
• Disruption of human meiotic telomere complex genes TERB1, TERB2 and MAJIN in men with non-obstructive azoospermia. (PMID:33211200)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-1h4.5	ENSDARG00000039477
mus_musculus	Terb2	ENSMUSG00000027229
rattus_norvegicus	Terb2	ENSRNOG00000037178

Protein

Protein identifiers

Telomere repeats-binding bouquet formation protein 2 — Q8NHR7 (reviewed: Q8NHR7)

All UniProt accessions (3): Q8NHR7, H0YKV2, H0YNH3

UniProt curated annotations — full annotation on UniProt →

Function. Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA.

Subunit / interactions. Component of the MAJIN-TERB1-TERB2 complex, composed of MAJIN, TERB1 and TERB2.

Subcellular location. Chromosome. Telomere. Nucleus inner membrane.

Disease relevance. Spermatogenic failure 59 (SPGF59) [MIM:619645] An autosomal recessive male infertility disorder characterized by non-obstructive azoospermia, due to sperm maturation arrest. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TERB2 family.

RefSeq proteins (1): NP_689661* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR028065	TERB2	Family

Pfam: PF15101

UniProt features (21 total): strand 9, helix 7, sequence variant 3, chain 1, turn 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6GNY	X-RAY DIFFRACTION	1.85
6GNX	X-RAY DIFFRACTION	2.9
6J08	X-RAY DIFFRACTION	2.9
6J07	X-RAY DIFFRACTION	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NHR7-F1	70.93	0.45

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 107 (showing top): GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, GOBP_CHROMOSOME_LOCALIZATION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_SYNAPTONEMAL_COMPLEX_ORGANIZATION, GOBP_ORGANELLE_FISSION, GOBP_DNA_DAMAGE_RESPONSE, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_CHROMOSOME_ORGANIZATION_INVOLVED_IN_MEIOTIC_CELL_CYCLE, GOBP_FEMALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_HOMOLOGOUS_CHROMOSOME_SEGREGATION, GOBP_MEIOTIC_CELL_CYCLE_PROCESS, GOBP_ORGANELLE_LOCALIZATION

GO Biological Process (7): homologous chromosome pairing at meiosis (GO:0007129), synaptonemal complex assembly (GO:0007130), spermatogenesis (GO:0007283), meiotic telomere clustering (GO:0045141), oogenesis (GO:0048477), meiotic attachment of telomere to nuclear envelope (GO:0070197), double-strand break repair involved in meiotic recombination (GO:1990918)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): chromosome, telomeric region (GO:0000781), nuclear envelope (GO:0005635), nuclear inner membrane (GO:0005637), nuclear membrane (GO:0031965), nucleus (GO:0005634), chromosome (GO:0005694), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromosome organization involved in meiotic cell cycle	3
meiotic cell cycle process	2
nucleus	2
homologous chromosome segregation	1
homologous chromosome pairing at meiosis	1
cellular component assembly	1
synaptonemal complex organization	1
developmental process involved in reproduction	1
male gamete generation	1
telomere localization	1
chromosome localization to nuclear envelope involved in homologous chromosome segregation	1
germ cell development	1
female gamete generation	1
meiotic telomere tethering at nuclear periphery	1
chromosome attachment to the nuclear envelope	1
double-strand break repair	1
reciprocal meiotic recombination	1
binding	1
chromosomal region	1
endomembrane system	1
organelle envelope	1
organelle inner membrane	1
nuclear membrane	1
nuclear envelope	1
organelle membrane	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TERB2	TERB1	Q8NA31	995
TERB2	H0YEC1	H0YEC1	992
TERB2	TERF1	P54274	858
TERB2	KASH5	Q8N6L0	839
TERB2	SUN1	O94901	826
TERB2	SPDYA	Q5MJ70	750
TERB2	SUN2	Q9UH99	745
TERB2	HORMAD1	Q86X24	547
TERB2	TINF2	Q9BSI4	512
TERB2	HORMAD2	Q8N7B1	512
TERB2	STAG3	Q9UJ98	488
TERB2	SYCP3	Q8IZU3	481
TERB2	OR2T5	Q6IEZ7	480
TERB2	OR6T1	Q8NGN1	474
TERB2	C14orf39	Q8N1H7	452

IntAct

4 interactions, top by confidence:

A	B	Type	Score
MAJIN	TERB2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (2): C11orf85 (Two-hybrid), APP (Reconstituted Complex)

ESM2 similar proteins: A0A2R8VHF7, A0JM23, A2QRA0, A4IIA7, A4IIV4, A6NFN9, A6NHR9, A7MBF6, F4IG73, F4JSE7, O17482, O95876, P12540, P21784, P34089, P38899, P55895, P56696, Q08AW4, Q0D2D7, Q12789, Q13829, Q28DC9, Q2WGJ8, Q3E7Y5, Q3UUE9, Q4R907, Q4VXA5, Q5BK83, Q5EA90, Q5F476, Q5HZS2, Q5M9F0, Q5RAX4, Q5RBH4, Q5RD21, Q6AYL6, Q6DGA7, Q6PIY5, Q70XZ2

Diamond homologs: Q2M2T9, Q5BJD2, Q8NHR7, Q9D494

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
TERB2	“form complex”	“TTM complex”	binding
TERB2	“up-regulates activity”	“Cohesin complex”	relocalization

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
1326957	NM_152448.3(TERB2):c.457_458del (p.Thr153fs)	Pathogenic
1326958	NM_152448.3(TERB2):c.544dup (p.Met182fs)	Pathogenic
1244236	NM_152448.3(TERB2):c.434G>A (p.Ser145Asn)	Likely pathogenic

SpliceAI

1040 predictions. Top by Δscore:

Variant	Effect	Δscore
15:44966152:CCACA:C	acceptor_loss	1.0000
15:44966153:CACA:C	acceptor_loss	1.0000
15:44966154:ACAG:A	acceptor_loss	1.0000
15:44966155:CA:C	acceptor_loss	1.0000
15:44966156:A:AC	acceptor_loss	1.0000
15:44966156:A:AG	acceptor_gain	1.0000
15:44966156:AGCAT:A	acceptor_gain	1.0000
15:44966157:G:A	acceptor_loss	1.0000
15:44966157:G:GA	acceptor_gain	1.0000
15:44966157:GC:G	acceptor_gain	1.0000
15:44966157:GCAT:G	acceptor_gain	1.0000
15:44966157:GCATG:G	acceptor_gain	1.0000
15:44958372:GAAT:G	acceptor_gain	0.9900
15:44958441:T:TA	donor_gain	0.9900
15:44958442:A:AA	donor_gain	0.9900
15:44966157:GCA:G	acceptor_gain	0.9900
15:44966239:AAAAG:A	donor_loss	0.9900
15:44966240:AAAGG:A	donor_loss	0.9900
15:44966242:AG:A	donor_loss	0.9900
15:44966243:G:GA	donor_loss	0.9900
15:44966245:T:C	donor_loss	0.9900
15:44973952:ACAG:A	donor_gain	0.9900
15:44978483:TTGTA:T	acceptor_loss	0.9900
15:44978484:TGTA:T	acceptor_loss	0.9900
15:44978485:GTAG:G	acceptor_loss	0.9900
15:44978486:TAGG:T	acceptor_loss	0.9900
15:44956973:CTGAG:C	donor_loss	0.9800
15:44956974:TGAGG:T	donor_loss	0.9800
15:44956977:GG:G	donor_loss	0.9800
15:44956978:GT:G	donor_loss	0.9800

AlphaMissense

1479 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:44956946:A:C	S39R	0.991
15:44956948:C:A	S39R	0.991
15:44956948:C:G	S39R	0.991
15:44958414:T:A	V63D	0.978
15:44961552:T:A	W106R	0.978
15:44961552:T:C	W106R	0.978
15:44956944:T:C	F38S	0.977
15:44956743:T:C	F9L	0.974
15:44956745:T:A	F9L	0.974
15:44956745:T:G	F9L	0.974
15:44956740:T:A	W8R	0.973
15:44956740:T:C	W8R	0.973
15:44956779:T:A	W21R	0.973
15:44956779:T:C	W21R	0.973
15:44958417:T:C	F64S	0.964
15:44958482:T:C	F86L	0.964
15:44958484:C:A	F86L	0.964
15:44958484:C:G	F86L	0.964
15:44956943:T:C	F38L	0.963
15:44956945:C:A	F38L	0.963
15:44956945:C:G	F38L	0.963
15:44961554:G:C	W106C	0.961
15:44961554:G:T	W106C	0.961
15:44978539:T:C	F192L	0.961
15:44978541:C:A	F192L	0.961
15:44978541:C:G	F192L	0.961
15:44958489:T:C	L88P	0.957
15:44956722:T:C	F2L	0.953
15:44956724:T:A	F2L	0.953
15:44956724:T:G	F2L	0.953

dbSNP variants (sampled 300 via entrez): RS1000485417 (15:44960253 T>C), RS1000714197 (15:44955017 A>C,G), RS1000737318 (15:44966856 A>C,T), RS1000766533 (15:44959897 C>T), RS1000936232 (15:44956699 T>C,G), RS1000988581 (15:44956917 G>T), RS1001121697 (15:44977368 T>C,G), RS1001123698 (15:44970745 A>T), RS1001278648 (15:44970009 AATG>A), RS1001394531 (15:44965355 C>T), RS1001401551 (15:44975708 A>G), RS1001402133 (15:44976031 A>C,G), RS1001469538 (15:44977115 A>C), RS1001596889 (15:44973920 C>G,T), RS1001649149 (15:44974289 C>T)

Disease associations

OMIM: gene MIM:617131 | disease phenotypes: MIM:619645

GenCC curated gene-disease

Disease	Classification	Inheritance
spermatogenic failure 59	Moderate	Autosomal recessive

Mondo (1): spermatogenic failure 59 (MONDO:0030492)

Orphanet (0):

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000118	Phenotypic abnormality
HP:0000837	Increased circulating gonadotropin level
HP:0003251	Male infertility
HP:0008669	Abnormal spermatogenesis
HP:0008734	Decreased testicular size
HP:0011462	Young adult onset
HP:0011961	Non-obstructive azoospermia
HP:0011962	Obstructive azoospermia
HP:0031038	Spermatogenesis maturation arrest

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

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	increases methylation	1
Methotrexate	increases expression	1
Aflatoxin B1	increases methylation	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

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