SHROOM3

Chr 4

shroom family member 3

Also known as: APXL3, MSTP013, SHRM, ShrmL

NCBI Gene: 57619 ENSG00000138771 UniProt: Q8TF72 OMIM: 604570

This protein controls neuroepithelial cell shape changes during neural tube closure by promoting apical accumulation of F-actin and myosin II, and directing assembly of apicobasal microtubule arrays. Mutations cause neural tube defects including spina bifida and anencephaly, following an autosomal recessive inheritance pattern. The gene shows significant constraint against loss-of-function variants (LOEUF 0.35), reflecting its critical role in early nervous system development.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a PDZ-domain-containing protein that belongs to a family of Shroom-related proteins. This protein may be involved in regulating cell shape in certain tissues. A similar protein in mice is required for proper neurulation. [provided by RefSeq, Jan 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.35

Clinical Summary— SHROOM3

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

📋

ClinVar Variants

304 VUS of 438 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.35LOEUF

pLI 0.317

Z-score 5.79

OE 0.23 (0.15–0.35)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

1.24Z-score

OE missense 0.90 (0.85–0.94)

1037 obs / 1155.6 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.23 (0.15–0.35)

0≤0.351.4

Missense OE?0.90 (0.85–0.94)

0≤0.61.4

Synonymous OE?0.92

0≤1.21.6

LoF obs/exp: 15 / 65.6Missense obs/exp: 1037 / 1155.6Syn Z: 1.39

ClinVar Variant Classifications

438 submitted variants in ClinVar

ClinVar

Classification Summary

VUS304

Likely Benign67

Benign42

Conflicting2

304

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	0	0	0
Likely Pathogenic	0	0	0	0	0
VUS	2	302	0	0	304
Likely Benign	0	45	0	22	67
Benign	0	14	17	11	42
Conflicting	—				2
Total	2	361	17	33	415

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

23 pathogenic / likely-pathogenic (of 29) ClinVar copy-number / structural variants overlap SHROOM3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →