SHISA2

Chr 13

shisa family member 2

Also known as: C13orf13, PRO28631, TMEM46, WGAR9166, bA398O19.2, hShisa

NCBI Gene: 387914 ENSG00000180730 UniProt: Q6UWI4

The protein attenuates FGF and WNT signaling pathways and is essential for presomitic mesoderm cell maturation. Mutations cause neurodevelopmental disorders with intellectual disability, seizures, and developmental delays affecting the nervous system. The condition follows autosomal recessive inheritance.

ResearchSummary from RefSeq, UniProt

Predicted to be involved in negative regulation of Wnt signaling pathway and negative regulation of fibroblast growth factor receptor signaling pathway. Predicted to be located in endoplasmic reticulum membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.95

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

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.95LOEUF

pLI 0.073

Z-score 1.67

OE 0.37 (0.17–0.95)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.07Z-score

OE missense 0.98 (0.87–1.12)

163 obs / 165.5 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.17–0.95)

0≤0.351.4

Missense OE?0.98 (0.87–1.12)

0≤0.61.4

Synonymous OE?1.11

0≤1.21.6

LoF obs/exp: 3 / 8.1Missense obs/exp: 163 / 165.5Syn Z: -0.70

Background carrier burden — how many people carry a rare variant somewhere in SHISA2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 89

488 rare PASS variants

Rare truncating (LoF)

1 in 5,500

55 rare PASS variants

Rare synonymous (reference)

1 in 160

218 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SHISA2. 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 150	1 in 6,200
South Asian	~43k	1 in 93	1 in 5,200
Remaining (unassigned)	~30k	1 in 64	1 in 4,700
European (Finnish)	~27k	1 in 380	≈ 1 in 27,000
Admixed American	~22k	1 in 86	≈ 1 in 7,600
African / African American	~21k	1 in 120	1 in 3,600
East Asian	~20k	1 in 120	≈ 1 in 20,000
Ashkenazi Jewish	~13k	1 in 430	none seen
Middle Eastern	~2,884	1 in 100	≈ 1 in 2,800

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 2 coding exons well covered in gnomAD exomes and genomes.? see exons ↓