SHROOM2

Chr X

shroom family member 2

Also known as: APXL, HSAPXL

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.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.53
Clinical SummarySHROOM2
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.32) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.53LOEUF
pLI 0.003
Z-score 3.70
OE 0.32 (0.200.53)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
-0.33Z-score
OE missense 1.03 (0.971.10)
710 obs / 686.0 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.32 (0.200.53)
00.351.4
Missense OE1.03 (0.971.10)
00.61.4
Synonymous OE1.09
01.21.6
LoF obs/exp: 11 / 34.5Missense obs/exp: 710 / 686.0Syn Z: -1.26
DN
0.6355th %ile
GOF
0.5562th %ile
LOF
0.4332th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

SHROOM2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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