TOPAZ1

Summary

TOPAZ1 (testis and ovary specific TOPAZ 1, HGNC:24746) is a protein-coding gene on chromosome 3p21.31, encoding Protein TOPAZ1 (Q8N9V7). Important for normal spermatogenesis and male fertility.

Predicted to be involved in spermatocyte division. Predicted to act upstream of or within apoptotic process; ectopic germ cell programmed cell death; and lncRNA transcription. Predicted to be located in cytosol.

Source: NCBI Gene 375337 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 247 total
• MANE Select transcript: NM_001145030

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24746
Approved symbol	TOPAZ1
Name	testis and ovary specific TOPAZ 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	FLJ36157
Ensembl gene	ENSG00000173769
Ensembl biotype	protein_coding
OMIM	614412
Entrez	375337

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000309765

RefSeq mRNA: 1 — MANE Select: NM_001145030 NM_001145030

CCDS: CCDS46809

Canonical transcript exons

ENST00000309765 — 20 exons

Exon	Start	End
ENSE00001179558	44242853	44245271
ENSE00001179564	44241886	44242399
ENSE00001596136	44304015	44304081
ENSE00001613594	44256151	44256278
ENSE00001645775	44309825	44309990
ENSE00001646400	44323092	44323295
ENSE00001663554	44266997	44267136
ENSE00001695963	44290771	44290886
ENSE00001696512	44328250	44328433
ENSE00001702117	44306326	44306426
ENSE00001713637	44270685	44270810
ENSE00001726568	44281968	44282031
ENSE00001736723	44321027	44321191
ENSE00001742740	44331792	44332098
ENSE00001744108	44287389	44287540
ENSE00001760686	44305147	44305321
ENSE00001763620	44262419	44262483
ENSE00001772451	44287747	44287839
ENSE00001783687	44254968	44255029
ENSE00001793949	44269216	44269301

Expression profiles

Bgee: expression breadth tissue_specific, 7 present calls, max score 85.23.

Top tissues by expression

136 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	85.23	gold quality
quadriceps femoris	UBERON:0001377	69.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	68.53	gold quality
cerebellar vermis	UBERON:0004720	67.75	gold quality
thymus	UBERON:0002370	66.63	silver quality
testis	UBERON:0000473	62.11	gold quality
right testis	UBERON:0004534	61.17	gold quality
left testis	UBERON:0004533	59.16	gold quality
sural nerve	UBERON:0015488	39.90	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
vermiform appendix	UBERON:0001154	34.69	gold quality
skeletal muscle tissue	UBERON:0001134	33.64	gold quality
prefrontal cortex	UBERON:0000451	32.96	gold quality
monocyte	CL:0000576	32.72	gold quality
nucleus accumbens	UBERON:0001882	32.30	gold quality
muscle tissue	UBERON:0002385	32.27	gold quality
leukocyte	CL:0000738	32.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.95	gold quality
putamen	UBERON:0001874	30.25	gold quality
primary visual cortex	UBERON:0002436	29.94	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
caudate nucleus	UBERON:0001873	29.58	gold quality
frontal cortex	UBERON:0001870	29.30	gold quality
Brodmann (1909) area 9	UBERON:0013540	29.01	gold quality
liver	UBERON:0002107	28.93	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.39

Regulation

Is transcription factor: no

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	topaz1	ENSDARG00000099801
mus_musculus	Topaz1	ENSMUSG00000094985
rattus_norvegicus	Topaz1	ENSRNOG00000025601

Protein

Protein identifiers

Protein TOPAZ1 — Q8N9V7 (reviewed: Q8N9V7)

Alternative names: Testis- and ovary-specific PAZ domain-containing protein 1

All UniProt accessions (1): Q8N9V7

UniProt curated annotations — full annotation on UniProt →

Function. Important for normal spermatogenesis and male fertility. Specifically required for progression to the post-meiotic stages of spermatocyte development. Seems to be necessary for normal expression levels of a number of testis-expressed gene transcripts, although its role in this process is unclear.

Subcellular location. Cytoplasm. Cytosol.

RefSeq proteins (1): NP_001138502* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029435	TOPAZ1_dom	Domain
IPR038952	TOPAZ1	Family

Pfam: PF14669

UniProt features (19 total): sequence variant 7, sequence conflict 4, compositionally biased region 4, region of interest 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N9V7-F1	51.36	0.18

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 11 (showing top): GOBP_MALE_GAMETE_GENERATION, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, ACEVEDO_METHYLATED_IN_LIVER_CANCER_DN, GOBP_CELL_DIVISION, chr3p21, NFKBIA_TARGET_GENES, ZNF618_TARGET_GENES, GOBP_SEXUAL_REPRODUCTION, GOBP_REPRODUCTIVE_PROCESS, GOBP_MULTICELLULAR_ORGANISMAL_REPRODUCTIVE_PROCESS, GOBP_LNCRNA_TRANSCRIPTION

GO Biological Process (6): apoptotic process (GO:0006915), ectopic germ cell programmed cell death (GO:0035234), spermatocyte division (GO:0048137), lncRNA transcription (GO:0140742), spermatogenesis (GO:0007283), cell differentiation (GO:0030154)

GO Molecular Function (0):

GO Cellular Component (2): cytosol (GO:0005829), cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
developmental process involved in reproduction	2
cellular anatomical structure	2
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
programmed cell death involved in cell development	1
spermatogenesis	1
cell division	1
DNA-templated transcription	1
male gamete generation	1
cellular developmental process	1
cytoplasm	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

1460 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TOPAZ1	CEP126	Q9P2H0	499
TOPAZ1	DYNLT2	Q8IZS6	481
TOPAZ1	LRRC3B	Q96PB8	479
TOPAZ1	LRRC58	Q96CX6	473
TOPAZ1	MTURN	Q8N3F0	472
TOPAZ1	TTC21A	Q8NDW8	457
TOPAZ1	CNBD2	Q96M20	449
TOPAZ1	APBA1	Q02410	413
TOPAZ1	BABAM1	Q9NWV8	413
TOPAZ1	SPATA45	Q537H7	405
TOPAZ1	QSER1	Q2KHR3	394
TOPAZ1	FZR1	Q9UM11	386
TOPAZ1	C14orf39	Q8N1H7	385
TOPAZ1	GREB1L	Q9C091	385
TOPAZ1	CGGBP1	Q9UFW8	384

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CBX6	IGF2BP3	psi-mi:“MI:0914”(association)	0.530

BioGRID (12): TOPAZ1 (Affinity Capture-MS), TOPAZ1 (Affinity Capture-MS), TOPAZ1 (Affinity Capture-MS), TOPAZ1 (Affinity Capture-MS), TOPAZ1 (Cross-Linking-MS (XL-MS)), LAD1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Cross-Linking-MS (XL-MS)), TOPAZ1 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LI88, A4D1E1, D3Z987, D3ZUC6, E5FYH0, E5FYH1, E9Q3S4, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, O35923, O54952, O88491, O95405, P38398, P48754, P51587, P97929, Q0VBV7, Q0VGT4, Q2M3C7, Q3V089, Q56UN5, Q5DTT3, Q5F2C3, Q5VWN6, Q61493, Q68DQ2, Q6J6I8, Q6J6I9, Q6J6J0, Q6NSW3, Q6ZP01, Q7TSY8, Q7Z570, Q80U44, Q864S8, Q864U1

Diamond homologs: D3ZUC6, E5FYH0, E5FYH1, F6ULY3, F7DF15, G3S077, G7H7V7, G7NY55, Q8N9V7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	217
Likely benign	20
Benign	7

Top pathogenic / likely-pathogenic (0)

SpliceAI

3925 predictions. Top by Δscore:

Variant	Effect	Δscore
3:44254966:A:AG	acceptor_gain	1.0000
3:44254967:G:GG	acceptor_gain	1.0000
3:44256145:TTTCA:T	acceptor_loss	1.0000
3:44256148:CAGA:C	acceptor_loss	1.0000
3:44256149:A:AC	acceptor_loss	1.0000
3:44256149:A:AG	acceptor_gain	1.0000
3:44256150:G:GC	acceptor_gain	1.0000
3:44256150:GA:G	acceptor_gain	1.0000
3:44256150:GAA:G	acceptor_gain	1.0000
3:44256150:GAAA:G	acceptor_gain	1.0000
3:44256277:AGGTA:A	donor_loss	1.0000
3:44256278:GG:G	donor_loss	1.0000
3:44256279:G:GC	donor_loss	1.0000
3:44266994:C:G	acceptor_gain	1.0000
3:44269298:GGGG:G	donor_gain	1.0000
3:44269299:GGGG:G	donor_gain	1.0000
3:44270806:AAAAG:A	donor_loss	1.0000
3:44270807:AAAG:A	donor_loss	1.0000
3:44270808:AAG:A	donor_loss	1.0000
3:44270809:AG:A	donor_loss	1.0000
3:44270810:G:GT	donor_loss	1.0000
3:44270811:GTA:G	donor_loss	1.0000
3:44270812:T:A	donor_loss	1.0000
3:44290766:TACA:T	acceptor_loss	1.0000
3:44290767:A:AG	acceptor_gain	1.0000
3:44290767:ACAG:A	acceptor_loss	1.0000
3:44290768:C:G	acceptor_gain	1.0000
3:44290768:CA:C	acceptor_loss	1.0000
3:44290769:A:AG	acceptor_gain	1.0000
3:44290769:A:C	acceptor_loss	1.0000

AlphaMissense

11209 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:44331955:T:A	W1675R	0.997
3:44331955:T:C	W1675R	0.997
3:44321087:G:C	R1456P	0.995
3:44270727:T:C	C1097R	0.994
3:44270729:C:G	C1097W	0.994
3:44270757:T:C	C1107R	0.994
3:44321035:T:A	W1439R	0.994
3:44321035:T:C	W1439R	0.994
3:44270772:T:C	C1112R	0.993
3:44331976:T:A	W1682R	0.993
3:44331976:T:C	W1682R	0.993
3:44331991:T:A	W1687R	0.993
3:44331991:T:C	W1687R	0.993
3:44270728:G:A	C1097Y	0.992
3:44321168:T:C	L1483P	0.992
3:44328337:A:T	E1588V	0.992
3:44331856:G:C	A1642P	0.992
3:44331957:G:C	W1675C	0.992
3:44331957:G:T	W1675C	0.992
3:44270727:T:A	C1097S	0.991
3:44270728:G:C	C1097S	0.991
3:44270772:T:A	C1112S	0.991
3:44270773:G:C	C1112S	0.991
3:44270728:G:T	C1097F	0.990
3:44270757:T:A	C1107S	0.990
3:44270758:G:C	C1107S	0.990
3:44328355:A:T	E1594V	0.990
3:44331857:C:A	A1642D	0.990
3:44305310:T:C	F1343S	0.989
3:44331959:T:C	L1676S	0.989

dbSNP variants (sampled 300 via entrez): RS1000001693 (3:44308472 G>C,T), RS1000007878 (3:44247567 C>T), RS1000033099 (3:44334847 G>A), RS1000083171 (3:44277802 C>A), RS1000105647 (3:44285677 C>A,G), RS1000125651 (3:44260177 C>T), RS1000126368 (3:44241441 C>T), RS1000169348 (3:44311737 A>G), RS1000176793 (3:44265182 T>A,C), RS1000271792 (3:44276624 C>A,T), RS1000337954 (3:44271147 C>T), RS1000361163 (3:44327812 T>G), RS1000401505 (3:44332424 G>A), RS1000406135 (3:44274562 T>A), RS1000415645 (3:44323893 T>C)

Disease associations

OMIM: gene MIM:614412 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST005839_8	Depression	5.000000e-08
GCST007324_129	Adventurousness	3.000000e-11
GCST007325_111	General risk tolerance (MTAG)	3.000000e-10
GCST009600_32	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	4.000000e-08
GCST010988_138	Adult body size	1.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

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
Benzo(a)pyrene	affects methylation, decreases methylation	2
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	decreases methylation	1
Arsenic	affects methylation	1
Methapyrilene	decreases methylation	1
Aflatoxin B1	decreases methylation	1

Clinical trials (associated diseases)

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