SPATA46

Chr 1

spermatogenesis associated 46

Also known as: C1orf111, HSD20, TEKT2BP2

NCBI Gene: 284680 ENSG00000171722 UniProt: Q5T0L3

SPATA46 encodes a protein involved in spermiogenesis and fertilization, specifically predicted to function in sperm-egg membrane fusion and to localize to cellular and nuclear membranes. Mutations in this gene cause autosomal recessive male infertility due to defects in sperm function. The gene shows very low constraint against loss-of-function variants, consistent with a phenotype limited to reproductive function.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in fusion of sperm to egg plasma membrane involved in single fertilization and spermatogenesis. Predicted to be located in membrane and nucleus. Predicted to be active in nuclear membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

LOEUF 1.89

Clinical Summary— SPATA46

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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

7 VUS of 8 total submissions

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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.89LOEUF

pLI 0.000

Z-score -1.01

OE 1.35 (0.87–1.89)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.07Z-score

OE missense 1.02 (0.89–1.16)

153 obs / 150.5 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.35 (0.87–1.89)

0≤0.351.4

Missense OE?1.02 (0.89–1.16)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 13 / 9.6Missense obs/exp: 153 / 150.5Syn Z: 0.07

ClinVar Variant Classifications

8 submitted variants in ClinVar

ClinVar

Classification Summary

VUS7

Likely Benign1

VUS

Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Total
Pathogenic	0	0
Likely Pathogenic	0	0
VUS	7	7
Likely Benign	1	1
Benign	0	0
Total	8	8

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

View in ClinVar →

16 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap SPATA46 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →