SPATA13

Chr 13

spermatogenesis associated 13

Also known as: ARHGEF29, ASEF2

NCBI Gene: 221178 ENSG00000182957 UniProt: Q96N96

SPATA13 encodes a guanine nucleotide exchange factor that activates RHO family GTPases (RHOA, RAC1, CDC42) to regulate cell migration, adhesion, and plasma membrane projection assembly. Mutations cause autosomal recessive intellectual disability with macrocephaly and seizures, typically presenting in early childhood. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.462), suggesting some intolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt

Enables guanyl-nucleotide exchange factor activity and identical protein binding activity. Involved in cell migration; plasma membrane bounded cell projection assembly; and regulation of cell migration. Located in several cellular components, including filopodium; lamellipodium; and ruffle membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Clinical highlights

Gene–disease validity (ClinGen)

Limited · primary angle-closure glaucoma · AD · ClinGen 2023

not for standalone diagnostic reporting

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.46

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.46LOEUF

pLI 0.003

Z-score 4.50

OE 0.30 (0.19–0.46)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.03Z-score

OE missense 0.80 (0.75–0.85)

636 obs / 796.9 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.30 (0.19–0.46)

0≤0.351.4

Missense OE?0.80 (0.75–0.85)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 14 / 47.4Missense obs/exp: 636 / 796.9Syn Z: 1.78

Background carrier burden — how many people carry a rare variant somewhere in SPATA13?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 30

1,707 rare PASS variants

Rare truncating (LoF)

1 in 1,300

149 rare PASS variants

Rare synonymous (reference)

1 in 59

681 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SPATA13. 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 46	1 in 1,300
South Asian	~43k	1 in 29	1 in 3,100
Remaining (unassigned)	~30k	1 in 24	1 in 1,200
European (Finnish)	~27k	1 in 89	1 in 1,100
Admixed American	~22k	1 in 27	1 in 1,700
African / African American	~21k	1 in 28	1 in 1,200
East Asian	~20k	1 in 37	1 in 800
Ashkenazi Jewish	~13k	1 in 150	1 in 1,100
Middle Eastern	~2,884	1 in 26	≈ 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): All 12 coding exons well covered in gnomAD exomes and genomes.? see exons ↓