SPATA22

Chr 17AR

spermatogenesis associated 22

Also known as: NYD-SP20, NYDSP20, POF25, SPGF96

NCBI Gene: 84690 ENSG00000141255 UniProt: Q8NHS9 OMIM: 617673

This meiosis-specific protein is required for homologous recombination during meiosis I. Mutations cause autosomal recessive spermatogenic failure in males and premature ovarian failure in females, affecting reproductive function. The gene shows low constraint against loss-of-function variants in the general population, consistent with its reproductive-specific phenotype that would not affect survival to reproductive age.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Premature ovarian failure 25MIM #621002

Spermatogenic failure 96MIM #621001

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Premature ovarian failure 25; Spermatogenic failure 96; no ClinGen or GenCC tier

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.77

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.77LOEUF

pLI 0.000

Z-score 2.35

OE 0.44 (0.26–0.77)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.29Z-score

OE missense 0.94 (0.83–1.07)

171 obs / 182.1 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.44 (0.26–0.77)

0≤0.351.4

Missense OE?0.94 (0.83–1.07)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 9 / 20.5Missense obs/exp: 171 / 182.1Syn Z: -0.33

Background carrier burden — how many people carry a rare variant somewhere in SPATA22?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 160

450 rare PASS variants

Rare truncating (LoF)

1 in 1,200

74 rare PASS variants

Rare synonymous (reference)

1 in 420

140 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPATA22. 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 240	1 in 1,000
South Asian	~43k	1 in 95	1 in 1,200
Remaining (unassigned)	~30k	1 in 150	1 in 1,500
European (Finnish)	~27k	1 in 3,700	≈ 1 in 12,000
Admixed American	~22k	1 in 150	1 in 1,400
African / African American	~21k	1 in 140	1 in 1,100
East Asian	~20k	1 in 82	1 in 1,000
Ashkenazi Jewish	~13k	1 in 760	≈ 1 in 4,300
Middle Eastern	~2,884	1 in 160	1 in 580

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): 7 of 8 coding exons well covered in gnomAD exomes; exon 2 marginal. Genomes: all 8.? see exons ↓