STRA8

Chr 7

stimulated by retinoic acid 8

NCBI Gene: 346673ENSG00000146857UniProt: Q7Z7C7

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. [provided by RefSeq, Nov 2010]

73
ClinVar variants
32
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— STRA8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
32 Pathogenic / Likely Pathogenic· 37 VUS of 73 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.84LOEUF
pLI 0.001
Z-score 2.04
OE 0.47 (0.27–0.84)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.28Z-score
OE missense 0.74 (0.65–0.85)
144 obs / 194.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.47 (0.27–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.74 (0.65–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.75
0≤1.21.6
LoF obs/exp: 8 / 17.1Missense obs/exp: 144 / 194.3Syn Z: 1.73

ClinVar Variant Classifications

73 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic31
Likely Pathogenic1
VUS37
Likely Benign4
31
Pathogenic
1
Likely Pathogenic
37
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
31
0
31
Likely Pathogenic
0
0
1
0
1
VUS
0
30
7
0
37
Likely Benign
0
1
2
1
4
Benign
0
0
0
0
0
Total03141173

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

STRA8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Landscape of pathogenic mutations in premature ovarian insufficiency.
Ke H et al.·Nat Med
2023
How does retinoic acid (RA) signaling pathway regulate spermatogenesis?
Zhang HZ et al.·Histol Histopathol
2022Review
Homozygous missense variant in MEIOSIN causes premature ovarian insufficiency.
Zhang Q et al.·Hum Reprod
2023
Functional assessment of DMRT1 variants and their pathogenicity for isolated male infertility.
Emich J et al.·Fertil Steril
2023Functional
The Beginning of Meiosis in Mammalian Female Germ Cells: A Never-Ending Story of Intrinsic and Extrinsic Factors.
Farini D et al.·Int J Mol Sci
2022Review
Induction of Human Adipose-Derived Mesenchymal Stem Cells into Germ Lineage Using Retinoic Acid.
Liu H et al.·Cell Reprogram
2018
Carob extract induces spermatogenesis in an infertile mouse model via upregulation of Prm1, Plzf, Bcl-6b, Dazl, Ngn3, Stra8, and Smc1b.
Ghorbaninejad Z et al.·J Ethnopharmacol
2023Functional
A novel SNP in HUWE1 promoter confers increased risk of NOA by affecting the RA/RARα pathway in Chinese individuals.
Shan X et al.·Andrology
2024
Genetic variants in meiotic program initiation pathway genes are associated with spermatogenic impairment in a Han Chinese population.
Lu C et al.·PLoS One
2013
Sertoli-cell-specific knockout of connexin 43 leads to multiple alterations in testicular gene expression in prepubertal mice.
Giese S et al.·Dis Model Mech
2012
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools