SPANXD

Chr X

SPANX family member D

Also known as: CT11.4, SPANX-D, SPANX-E, SPANXE, dJ171K16.1

NCBI Gene: 64648ENSG00000196406UniProt: Q9BXN6

Temporally regulated transcription and translation of several testis-specific genes is required to initiate the series of molecular and morphological changes in the male germ cell lineage necessary for the formation of mature spermatozoa. This gene is a member of the SPANX family of cancer/testis-associated genes, which are located in a cluster on chromosome X. The SPANX genes encode differentially expressed testis-specific proteins that localize to various subcellular compartments. This particular gene encodes a sperm protein that is associated with the nucleus but, although a role in spermatogenesis is suggested, the specific function of this family member has not yet been determined. Polymorphisms in this gene may be associated with prostate cancer susceptibility. [provided by RefSeq, Apr 2014]

133
ClinVar variants
86
Pathogenic / LP
0.08
pLI score
0
Active trials
Clinical Summary— SPANXD
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.08) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
86 Pathogenic / Likely Pathogenic· 43 VUS of 133 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.
1.92LOEUF
pLI 0.077
Z-score -0.35
OE 1.46 (0.31–1.92)
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.
-3.54Z-score
OE missense 2.63 (1.81–2.00)
98 obs / 37.2 exp
Tolerant

Tolerant to missense variation

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.1.46 (0.31–1.92)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.2.63 (1.81–2.00)
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.1.60
0≤1.21.6
LoF obs/exp: 1 / 0.7Missense obs/exp: 98 / 37.2Syn Z: -1.86

ClinVar Variant Classifications

133 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic3
VUS43
Likely Benign4
83
Pathogenic
3
Likely Pathogenic
43
VUS
4
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
83
0
83
Likely Pathogenic
0
0
3
0
3
VUS
0
35
8
0
43
Likely Benign
0
2
1
1
4
Benign
0
0
0
0
0
Total037951133

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

View in ClinVar →

Protein Context — Lollipop Plot

SPANXD · 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
Hypermethylation of genes in testicular embryonal carcinomas.
Cheung HH et al.·Br J Cancer
2016
Multiomic Selection of Cancer-Testis Antigens as Precision Immuno-oncologic Targets in Head and Neck Cancer.
Memon AA et al.·JAMA Otolaryngol Head Neck Surg
2025
Hominoid-specific SPANXA/D genes demonstrate differential expression in individuals and protein localization to a distinct nuclear envelope domain during spermatid morphogenesis.
Westbrook VA et al.·Mol Hum Reprod
2006
Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27.
Kouprina N et al.·Genome Res
2005
The cancer-testis antigens SPANX-A/C/D and CTAG2 promote breast cancer invasion.
Maine EA et al.·Oncotarget
2016
Mutational analysis of SPANX genes in families with X-linked prostate cancer.
Kouprina N et al.·Prostate
2007
Genomic organization, incidence, and localization of the SPAN-x family of cancer-testis antigens in melanoma tumors and cell lines.
Westbrook VA et al.·Clin Cancer Res
2004
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

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