SPATA6L

Chr 9

spermatogenesis associated 6 like

Also known as: C9orf68, bA6J24.2

NCBI Gene: 55064 ENSG00000106686 UniProt: Q8N4H0

The protein is predicted to bind myosin light chains and function in spermatogenesis, localizing to the sperm head-tail coupling apparatus. Mutations cause autosomal recessive primary ciliary dyskinesia with severe asthenozoospermia, typically presenting in adulthood with respiratory symptoms and male infertility. The gene is not highly constrained against loss-of-function variants.

ResearchSummary from RefSeq

Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm head-tail coupling apparatus. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

MultiplemechanismLOEUF 1.74

Clinical Summary— SPATA6L

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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

122 VUS of 152 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?

1.74LOEUF

pLI 0.000

Z-score -0.93

OE 1.24 (0.88–1.74)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.46Z-score

OE missense 1.53 (1.38–1.69)

265 obs / 173.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.24 (0.88–1.74)

0≤0.351.4

Missense OE?1.53 (1.38–1.69)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 22 / 17.8Missense obs/exp: 265 / 173.7Syn Z: -0.70

This gene — mechanism propensity

0.6839th %ile

GOF

0.6639th %ile

LOF

0.4528th %ile

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

DNprediction above median

GOFprediction 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

152 submitted variants in ClinVar

ClinVar

Classification Summary

VUS122

Likely Benign9

Benign4

122

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0
Likely Pathogenic	0	0	0	0
VUS	122	0	0	122
Likely Benign	6	0	3	9
Benign	3	1	0	4
Total	131	1	3	135

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

View in ClinVar →

170 pathogenic / likely-pathogenic (of 192) ClinVar copy-number / structural variants overlap SPATA6L — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →