SHROOM2

Chr X

shroom family member 2

Also known as: APXL, HSAPXL

NCBI Gene: 357 ENSG00000146950 UniProt: Q13796

The SHROOM2 protein facilitates contractile network formation in endothelial cells and regulates melanosome biogenesis in retinal pigment epithelium. Mutations cause ocular albinism type 1, an X-linked recessive condition affecting retinal pigmentation and vision. The gene shows high constraint against loss-of-function variants (LOEUF 0.53), indicating intolerance to complete protein loss.

ResearchSummary from RefSeq, UniProt

This gene represents the human homolog of Xenopus laevis apical protein (APX) gene, which is implicated in amiloride-sensitive sodium channel activity. It is expressed in endothelial cells and facilitates the formation of a contractile network within endothelial cells. Depletion of this gene results in an increase in endothelial sprouting, migration, and angiogenesis. This gene is highly expressed in the retina, and is a strong candidate for ocular albinism type 1 syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2016]

ResearchGenerating clinical summary…

Clinical highlights

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

0.53

LOEUF

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?

0.53LOEUF

pLI 0.003

Z-score 3.70

OE 0.32 (0.20–0.53)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

-0.33Z-score

OE missense 1.03 (0.97–1.10)

710 obs / 686.0 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.32 (0.20–0.53)

0≤0.351.4

Missense OE?1.03 (0.97–1.10)

0≤0.61.4

Synonymous OE?1.09

0≤1.21.6

LoF obs/exp: 11 / 34.5Missense obs/exp: 710 / 686.0Syn Z: -1.26

Background carrier burden — how many people carry a rare variant somewhere in SHROOM2?

gnomAD v4 · ~732k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 28

1,539 rare PASS variants

Rare truncating (LoF)

1 in 2,400

88 rare PASS variants

Rare synonymous (reference)

1 in 60

699 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SHROOM2. 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)	~561k	1 in 48	1 in 2,500
South Asian	~36k	1 in 30	1 in 530
Remaining (unassigned)	~31k	1 in 23	1 in 2,700
European (Finnish)	~27k	1 in 120	1 in 4,900
Admixed American	~23k	1 in 28	1 in 760
African / African American	~21k	1 in 29	1 in 1,300
East Asian	~20k	1 in 31	≈ 1 in 5,400
Ashkenazi Jewish	~13k	1 in 150	none seen
Middle Eastern	~2,758	1 in 33	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): 9 of 10 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 10.? see exons ↓