SPATA33

Chr 16

spermatogenesis associated 33

Also known as: C16orf55

NCBI Gene: 124045 ENSG00000167523 UniProt: Q96N06 OMIM: 615409

The SPATA33 protein is required for sperm motility and male fertility, promoting mitophagy and linking damaged mitochondria to autophagosomes in male germline cells. Mutations cause autosomal recessive male infertility due to multiple morphological abnormalities of the flagella (MMAF), affecting sperm function and reproductive capability. This gene is not highly constrained against loss-of-function variants in the general population.

OMIM ResearchSummary from RefSeq, UniProt

Predicted to be involved in mitophagy. Predicted to act upstream of or within fertilization; flagellated sperm motility; and protein localization. Predicted to be located in male germ cell nucleus and sperm mitochondrial sheath. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.93

Clinical Summary— SPATA33

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

44 VUS of 52 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.93LOEUF

pLI 0.000

Z-score -0.78

OE 1.45 (0.69–1.93)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.13Z-score

OE missense 1.67 (1.45–1.90)

135 obs / 81.1 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.45 (0.69–1.93)

0≤0.351.4

Missense OE?1.67 (1.45–1.90)

0≤0.61.4

Synonymous OE?1.30

0≤1.21.6

LoF obs/exp: 5 / 3.4Missense obs/exp: 135 / 81.1Syn Z: -1.39

This gene — mechanism propensity

0.6358th %ile

GOF

0.6444th %ile

LOF

0.48top 25%

This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

GOFprediction above median

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

52 submitted variants in ClinVar

ClinVar

Classification Summary

VUS44

Likely Benign2

Benign2

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	44	0	44
Likely Benign	2	0	2
Benign	0	2	2
Total	46	2	48

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

View in ClinVar →

42 pathogenic / likely-pathogenic (of 79) ClinVar copy-number / structural variants overlap SPATA33 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →