TSPYL1

Chr 6AR

TSPY like 1

Also known as: TSPYL

NCBI Gene: 7259ENSG00000189241UniProt: Q9H0U9

The protein encoded by this gene is found in the nucleolus and is similar to that of a family of genes on the Y-chromosome. This gene is intronless. Defects in this gene are a cause of sudden infant death with dysgenesis of the testes syndrome (SIDDT). [provided by RefSeq, Dec 2009]

Primary Disease Associations & Inheritance

Sudden infant death with dysgenesis of the testes syndromeMIM #608800
AR
126
ClinVar variants
29
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TSPYL1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 69 VUS of 126 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.
1.32LOEUF
pLI 0.000
Z-score 0.69
OE 0.80 (0.50–1.32)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.42Z-score
OE missense 0.92 (0.83–1.03)
230 obs / 248.9 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.0.80 (0.50–1.32)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.03)
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.1.43
0≤1.21.6
LoF obs/exp: 11 / 13.8Missense obs/exp: 230 / 248.9Syn Z: -3.34

ClinVar Variant Classifications

126 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic5
VUS69
Likely Benign20
Benign7
Conflicting1
24
Pathogenic
5
Likely Pathogenic
69
VUS
20
Likely Benign
7
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
23
0
24
Likely Pathogenic
1
0
4
0
5
VUS
1
62
5
1
69
Likely Benign
0
6
1
13
20
Benign
0
5
1
1
7
Conflicting
—1
Total3733415126

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

View in ClinVar →

Protein Context — Lollipop Plot

TSPYL1 · 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
TSPY-LIKE 1; TSPYL1
MIM #604714 · *

Sudden infant death with dysgenesis of the testes syndrome

MIM #608800

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — TSPYL1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
TSPYL1 as a Critical Regulator of TGFβ Signaling through Repression of TGFBR1 and TSPYL2.
Tan H et al.·Adv Sci (Weinh)
2024
TSPYL Family Regulates CYP17A1 and CYP3A4 Expression: Potential Mechanism Contributing to Abiraterone Response in Metastatic Castration-Resistant Prostate Cancer.
Qin S et al.·Clin Pharmacol Ther
2018Functional
Unravelling the disease mechanism for TSPYL1 deficiency.
Buyse G et al.·Hum Mol Genet
2020Functional
Spermatogenic phenotype of testis-specific protein, Y-encoded, 1 (TSPY1) dosage deficiency is independent of variations in TSPY-like 1 (TSPYL1) and TSPY-like 5 (TSPYL5): a case-control study in a Han Chinese population.
Yang X et al.·Reprod Fertil Dev
2018
Should TSPYL1 mutation screening be included in routine diagnostics of male idiopathic infertility?
Javaher P et al.·Fertil Steril
2012
Genetic investigation of the TSPYL1 gene in sudden infant death syndrome.
Hering R et al.·Genet Med
2006
Variants in TSPYL1 are not associated with sudden infant death syndrome in a cohort of deceased infants from Switzerland.
Schubert S et al.·Mol Cell Probes
2015Cohort
Epileptic encephalopathy as a new feature of the sudden infant death with dysgenesis of the testes syndrome caused by TSPYL1 variants.
Mazel B et al.·Am J Med Genet A
2022Case report
Dual Roles for the TSPYL Family in Mediating Serotonin Transport and the Metabolism of Selective Serotonin Reuptake Inhibitors in Patients with Major Depressive Disorder.
Qin S et al.·Clin Pharmacol Ther
2020Cohort
Sudden infant death with dysgenesis of the testes syndrome in a non-Amish infant: A case report.
Slater B et al.·Am J Med Genet A
2020Case report
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