SHISAL1

Chr 22

shisa like 1

Also known as: KIAA1644

NCBI Gene: 85352 ENSG00000138944 UniProt: Q3SXP7

The SHISAL1 protein is predicted to be located in cellular membranes. Mutations cause autosomal recessive intellectual disability with seizures and language delay. This gene shows moderate tolerance to loss-of-function variants, with developmental delays and seizures typically manifesting in early childhood.

ResearchSummary from RefSeq

Predicted to be located in membrane. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.85

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?

0.85LOEUF

pLI 0.040

Z-score 1.91

OE 0.37 (0.18–0.85)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.21Z-score

OE missense 0.95 (0.82–1.10)

127 obs / 133.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.37 (0.18–0.85)

0≤0.351.4

Missense OE?0.95 (0.82–1.10)

0≤0.61.4

Synonymous OE?1.05

0≤1.21.6

LoF obs/exp: 4 / 10.8Missense obs/exp: 127 / 133.7Syn Z: -0.29

Background carrier burden — how many people carry a rare variant somewhere in SHISAL1?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 220

262 rare PASS variants

Rare truncating (LoF)

1 in 8,300

13 rare PASS variants

Rare synonymous (reference)

1 in 300

127 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SHISAL1. 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 260	1 in 8,100
South Asian	~43k	1 in 180	≈ 1 in 14,000
Remaining (unassigned)	~30k	1 in 190	1 in 6,000
European (Finnish)	~27k	1 in 930	none seen
Admixed American	~22k	1 in 170	≈ 1 in 22,000
African / African American	~21k	1 in 270	≈ 1 in 21,000
East Asian	~20k	1 in 280	none seen
Ashkenazi Jewish	~13k	1 in 1,600	none seen
Middle Eastern	~2,884	1 in 320	none seen

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): 3 of 4 coding exons well covered in gnomAD exomes; exon 5 poorly covered. Genomes: all 4.? see exons ↓