STRA8

Summary

STRA8 (stimulated by retinoic acid 8, HGNC:30653) is a protein-coding gene on chromosome 7q33, encoding Stimulated by retinoic acid gene 8 protein homolog (Q7Z7C7). Meiosis-inducer required for the transition into meiosis for both female and male germ cells.

This gene encodes a retinoic acid-responsive protein. A homologous protein in mouse has been shown to be involved in the regulation of meiotic initiation in both spermatogenesis and oogenesis, though feature differences between the mouse and human proteins suggest that these homologs are not entirely functionally equivalent. It is thought that this gene may play a role in spermatogenesis in humans.

Source: NCBI Gene 346673 — RefSeq curated summary.

At a glance

• Gene–disease (curated): male infertility with azoospermia or oligozoospermia due to single gene mutation (Moderate, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 45 total
• MANE Select transcript: NM_001394401

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30653
Approved symbol	STRA8
Name	stimulated by retinoic acid 8
Location	7q33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000146857
Ensembl biotype	protein_coding
OMIM	609987
Entrez	346673

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000275764, ENST00000662584, ENST00000667288

RefSeq mRNA: 2 — MANE Select: NM_001394401 NM_001394401, NM_182489

CCDS: CCDS5839, CCDS94209

Canonical transcript exons

ENST00000662584 — 9 exons

Exon	Start	End
ENSE00001021457	135246417	135246702
ENSE00001021487	135251796	135251869
ENSE00001222401	135243326	135243410
ENSE00001302319	135242781	135242856
ENSE00001326700	135255114	135255225
ENSE00003853356	135245288	135245527
ENSE00003859200	135233838	135233903
ENSE00003863981	135240519	135240716
ENSE00003934917	135258418	135258663

Expression profiles

Bgee: expression breadth broad, 54 present calls, max score 80.00.

Top tissues by expression

90 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	80.00	gold quality
sural nerve	UBERON:0015488	62.44	gold quality
adult mammalian kidney	UBERON:0000082	57.31	gold quality
placenta	UBERON:0001987	56.15	gold quality
kidney	UBERON:0002113	52.77	gold quality
right testis	UBERON:0004534	52.72	gold quality
cortex of kidney	UBERON:0001225	51.79	gold quality
testis	UBERON:0000473	50.31	gold quality
metanephros cortex	UBERON:0010533	50.21	gold quality
left testis	UBERON:0004533	49.97	gold quality
skin of abdomen	UBERON:0001416	47.96	gold quality
left uterine tube	UBERON:0001303	45.62	gold quality
putamen	UBERON:0001874	45.59	gold quality
granulocyte	CL:0000094	45.47	silver quality
fallopian tube	UBERON:0003889	44.95	gold quality
caudate nucleus	UBERON:0001873	43.35	gold quality
bone marrow cell	CL:0002092	42.75	gold quality
zone of skin	UBERON:0000014	42.47	gold quality
cortical plate	UBERON:0005343	41.59	gold quality
endometrium	UBERON:0001295	41.56	silver quality
tibial nerve	UBERON:0001323	40.30	gold quality
substantia nigra	UBERON:0002038	39.90	gold quality
nucleus accumbens	UBERON:0001882	39.39	silver quality
prefrontal cortex	UBERON:0000451	39.27	gold quality
skin of leg	UBERON:0001511	38.58	gold quality
duodenum	UBERON:0002114	38.17	silver quality
amygdala	UBERON:0001876	37.64	gold quality
Ammon’s horn	UBERON:0001954	37.57	silver quality
temporal lobe	UBERON:0001871	37.54	gold quality
gastrocnemius	UBERON:0001388	37.51	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.64

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DMRT1, FOXC1, NR0B2, RARG, RNF2

Literature-anchored findings (GeneRIF, showing 4)

• Expression restricted to testis (STRA8) (PMID:12489526)
• Functional characterization of an homologous mouse gene. (PMID:18799751)
• The genetic variant rs10269148 of STRA8 gene shows higher risk of spermatogenic impairment in the groups of abnormospermia than the controls (PMID:23320086)
• Stimulated by retinoic acid gene 8 (STRA8) interacts with the germ cell specific bHLH factor SOHLH1 and represses c-KIT expression in vitro. (PMID:33236849)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Stra8	ENSMUSG00000029848
rattus_norvegicus	Stra8	ENSRNOG00000010573

Protein

Protein identifiers

Stimulated by retinoic acid gene 8 protein homolog — Q7Z7C7 (reviewed: Q7Z7C7)

All UniProt accessions (3): Q7Z7C7, A0A590UJF1, A0A590UK75

UniProt curated annotations — full annotation on UniProt →

Function. Meiosis-inducer required for the transition into meiosis for both female and male germ cells. In female germ cells, acts downstream of ZGLP1 as a key effector of the meiotic program: required for premeiotic DNA replication and subsequent events in meiotic prophase. During spermatogenesis, next to its role in meiotic initiation, promotes (but is not required for) spermatogonial differentiation. In complex with MEIOSIN, directly activates the transcription of a subset of critical meiotic genes playing a central role in cell-cycle switching from mitosis to meiosis.

Subunit / interactions. Interacts with XPO1. Interacts with MEIOSIN.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed specifically in testis and fetal ovaries.

Post-translational modifications. Phosphorylated.

RefSeq proteins (2): NP_001381330, NP_872295 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR033537	Stra8	Family
IPR036638	HLH_DNA-bd_sf	Homologous_superfamily
IPR057021	bHLH_STRA8	Domain

Pfam: PF23175

UniProt features (4 total): chain 1, coiled-coil region 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z7C7-F1	64.14	0.02

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 80 (showing top): GOBP_POSITIVE_REGULATION_OF_REPRODUCTIVE_PROCESS, GOBP_REGULATION_OF_NUCLEAR_DIVISION, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_MEIOTIC_NUCLEAR_DIVISION, GOBP_OOGENESIS, GOBP_MALE_GAMETE_GENERATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_POSITIVE_REGULATION_OF_MEIOTIC_CELL_CYCLE, GOBP_CELLULAR_RESPONSE_TO_RETINOIC_ACID, GOBP_ORGANELLE_FISSION, GOBP_REGULATION_OF_CELL_CYCLE, GOBP_POSITIVE_REGULATION_OF_CELL_CYCLE_PROCESS, GOBP_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND

GO Biological Process (10): DNA replication (GO:0006260), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), oogenesis (GO:0048477), meiotic cell cycle (GO:0051321), cellular response to retinoic acid (GO:0071300), activation of meiosis (GO:0090427), cell differentiation (GO:0030154), positive regulation of transcription by RNA polymerase II (GO:0045944), male germ-line stem cell asymmetric division (GO:0048133)

GO Molecular Function (2): protein dimerization activity (GO:0046983), protein binding (GO:0005515)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), male germ cell nucleus (GO:0001673)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	2
DNA metabolic process	1
DNA biosynthetic process	1
regulation of DNA-templated transcription	1
developmental process involved in reproduction	1
male gamete generation	1
germ cell development	1
female gamete generation	1
cell cycle	1
sexual reproduction	1
reproductive process	1
meiotic nuclear division	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
positive regulation of meiotic nuclear division	1
cellular developmental process	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
spermatogenesis	1
germline stem cell asymmetric division	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
germ cell nucleus	1

Protein interactions and networks

STRING

996 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
STRA8	NANOS2	P60321	959
STRA8	CYP26B1	Q9NR63	935
STRA8	SYCP3	Q8IZU3	848
STRA8	DAZL	Q92904	847
STRA8	TAF4B	Q92750	830
STRA8	CYP26C1	Q6V0L0	823
STRA8	ZBTB16	Q05516	814
STRA8	CYP26A1	O43174	797
STRA8	REC8	O95072	792
STRA8	MEIOSIN	C9JSJ3	786
STRA8	SPO11	Q9Y5K1	760
STRA8	SOHLH1	Q5JUK2	736
STRA8	SYCP1	Q15431	730
STRA8	DDX4	Q9NQI0	711
STRA8	FOXL2	P58012	691

IntAct

26 interactions, top by confidence:

A	B	Type	Score
POU6F2	STRA8	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	STRA8	psi-mi:“MI:0915”(physical association)	0.560
SERTAD2	STRA8	psi-mi:“MI:0915”(physical association)	0.560
CTAG1A	STRA8	psi-mi:“MI:0915”(physical association)	0.560
STRA8	ZMYND12	psi-mi:“MI:0915”(physical association)	0.560
STRA8	CTDSP1	psi-mi:“MI:0915”(physical association)	0.560
STRA8	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
STRA8	TFIP11	psi-mi:“MI:0915”(physical association)	0.560
STRA8	NME2P1	psi-mi:“MI:0915”(physical association)	0.400
STRA8	POU6F2	psi-mi:“MI:0915”(physical association)	0.000
STRA8	MEOX2	psi-mi:“MI:0915”(physical association)	0.000
STRA8	TFIP11	psi-mi:“MI:0915”(physical association)	0.000
STRA8	SERTAD2	psi-mi:“MI:0915”(physical association)	0.000
STRA8	CTAG1A	psi-mi:“MI:0915”(physical association)	0.000
STRA8	ZMYND12	psi-mi:“MI:0915”(physical association)	0.000
STRA8	CTDSP1	psi-mi:“MI:0915”(physical association)	0.000
ANKRD11	STRA8	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (10): STRA8 (Two-hybrid), STRA8 (Two-hybrid), STRA8 (Two-hybrid), STRA8 (Two-hybrid), STRA8 (Two-hybrid), ANKRD11 (Two-hybrid), SERTAD2 (Two-hybrid), CTAG1B (Two-hybrid), CTAG1A (Two-hybrid), NME2P1 (Affinity Capture-MS)

ESM2 similar proteins: A1A4L6, F1QDF8, O35914, O75113, O95238, P01105, P10157, P13474, P14921, P15036, P15037, P15062, P15375, P18755, P18756, P19102, P19335, P27577, P40649, P41156, P78545, Q28EW4, Q28F43, Q32NH9, Q3MHT3, Q3UM89, Q3UPW2, Q3YFL6, Q4G112, Q4V7E1, Q5M7N6, Q5SW75, Q66IG8, Q6IE24, Q6NRK3, Q6PUR7, Q708W1, Q708W2, Q76I76, Q7M6U3

Diamond homologs: P70278, Q7Z7C7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	33
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1737 predictions. Top by Δscore:

Variant	Effect	Δscore
7:135232038:GGTA:G	donor_loss	1.0000
7:135232039:G:A	donor_loss	1.0000
7:135232040:T:G	donor_loss	1.0000
7:135240677:G:GT	donor_gain	1.0000
7:135243299:T:TA	acceptor_gain	1.0000
7:135243305:T:A	acceptor_gain	1.0000
7:135243306:G:A	acceptor_gain	1.0000
7:135243313:A:AG	acceptor_gain	1.0000
7:135243314:A:G	acceptor_gain	1.0000
7:135243315:C:G	acceptor_gain	1.0000
7:135243324:A:AG	acceptor_gain	1.0000
7:135243325:G:GG	acceptor_gain	1.0000
7:135243325:GC:G	acceptor_gain	1.0000
7:135243325:GCATC:G	acceptor_gain	1.0000
7:135243407:ACAGG:A	donor_loss	1.0000
7:135243409:AGG:A	donor_loss	1.0000
7:135243410:GGTAA:G	donor_loss	1.0000
7:135243411:GTA:G	donor_loss	1.0000
7:135243412:T:G	donor_loss	1.0000
7:135245286:A:AG	acceptor_gain	1.0000
7:135245287:G:GG	acceptor_gain	1.0000
7:135245287:GCC:G	acceptor_gain	1.0000
7:135245445:G:GT	donor_gain	1.0000
7:135245451:G:GT	donor_gain	1.0000
7:135245454:G:GT	donor_gain	1.0000
7:135245457:G:GT	donor_gain	1.0000
7:135245460:G:GT	donor_gain	1.0000
7:135246699:GGAG:G	donor_gain	1.0000
7:135246700:GAGG:G	donor_gain	1.0000
7:135246704:T:A	donor_loss	1.0000

AlphaMissense

2525 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:135246508:G:C	A180P	0.989
7:135246509:C:A	A180D	0.987
7:135246500:T:A	V177D	0.985
7:135246452:T:C	L161P	0.984
7:135246523:T:A	W185R	0.984
7:135246523:T:C	W185R	0.984
7:135258472:T:C	F325L	0.979
7:135258474:T:A	F325L	0.979
7:135258474:T:G	F325L	0.979
7:135246452:T:A	L161Q	0.976
7:135246512:T:A	I181N	0.975
7:135246521:T:C	L184P	0.974
7:135240673:T:C	L72P	0.973
7:135246430:T:G	Y154D	0.973
7:135246452:T:G	L161R	0.972
7:135246525:G:C	W185C	0.972
7:135246525:G:T	W185C	0.972
7:135246661:A:C	S231R	0.971
7:135246663:C:A	S231R	0.971
7:135246663:C:G	S231R	0.971
7:135242833:T:C	L104P	0.968
7:135258455:T:C	L319S	0.967
7:135240643:G:C	R62P	0.966
7:135246512:T:G	I181S	0.965
7:135242845:T:C	L108P	0.963
7:135246427:T:C	F153L	0.963
7:135246429:T:A	F153L	0.963
7:135246429:T:G	F153L	0.963
7:135242791:T:C	L90P	0.961
7:135251808:G:C	D249H	0.961

dbSNP variants (sampled 300 via entrez): RS1000167235 (7:135245589 G>A), RS1000193538 (7:135239518 G>A), RS1000218208 (7:135239814 T>C), RS1000331297 (7:135233023 C>G), RS1000479062 (7:135258324 G>A,C,T), RS1000569375 (7:135241144 C>T), RS1000680270 (7:135238397 T>C), RS1000784821 (7:135234823 G>A), RS1001096340 (7:135251987 G>GAC), RS1001367997 (7:135252991 G>C), RS1001706995 (7:135231506 A>G), RS1001725070 (7:135259017 A>G), RS1001740139 (7:135239199 A>G), RS1001773364 (7:135237751 T>C,G), RS1001905818 (7:135247396 T>A)

Disease associations

OMIM: gene MIM:609987 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
male infertility with azoospermia or oligozoospermia due to single gene mutation	Moderate	Autosomal recessive

Mondo (1): (MONDO:0018393)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST90013406_58	Liver enzyme levels (alkaline phosphatase)	7.000000e-23

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004533	alkaline phosphatase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases methylation, increases mutagenesis	2
benzo(e)pyrene	increases methylation	1
Methapyrilene	increases methylation	1
Tretinoin	increases expression	1
Aflatoxin B1	increases methylation	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A6V4	SEES3-1V human STRA8, clone1	Embryonic stem cell	Male
CVCL_A6V5	SEES3-1V human STRA8, clone2	Embryonic stem cell	Male
CVCL_A6V6	SEES3-1V human STRA8, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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