SPACA7

Chr 13

sperm acrosome associated 7

Also known as: C13orf28

NCBI Gene: 122258 ENSG00000153498 UniProt: Q96KW9

SPACA7 encodes a protein involved in fertilization that localizes to the acrosomal vesicle and regulates cell adhesion during the fertilization process. Loss-of-function mutations in SPACA7 cause autosomal recessive male infertility due to defects in sperm function. This gene is not highly constrained against loss-of-function variation in the general population.

ResearchSummary from RefSeq, UniProt

Predicted to act upstream of or within negative regulation of cell adhesion and single fertilization. Located in acrosomal vesicle. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.41

LOEUF

Multiple*

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.41LOEUF

pLI 0.000

Z-score 0.53

OE 0.83 (0.51–1.41)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.12Z-score

OE missense 0.97 (0.82–1.14)

100 obs / 103.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.83 (0.51–1.41)

0≤0.351.4

Missense OE?0.97 (0.82–1.14)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 10 / 12.0Missense obs/exp: 100 / 103.5Syn Z: -0.82

Background carrier burden — how many people carry a rare variant somewhere in SPACA7?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 120

273 rare PASS variants

Rare truncating (LoF)

1 in 1,600

53 rare PASS variants

Rare synonymous (reference)

1 in 170

99 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPACA7. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 130	1 in 2,100
South Asian	~43k	1 in 280	1 in 3,700
Remaining (unassigned)	~30k	1 in 93	1 in 1,100
European (Finnish)	~27k	1 in 790	1 in 610
Admixed American	~22k	1 in 180	1 in 2,000
African / African American	~21k	1 in 180	1 in 960
East Asian	~20k	1 in 120	1 in 1,000
Ashkenazi Jewish	~13k	1 in 690	≈ 1 in 13,000
Middle Eastern	~2,884	1 in 160	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 5 of 7 coding exons well covered in gnomAD exomes; exons 4, 6 marginal. Genomes: all 7.? see exons ↓