SHROOM3

protein-coding

shroom family member 3, the group of MicroRNA protein coding host genes|Shroom family|PDZ domain containing

Gene summary

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]

MANE transcript

NM_020859.4

Inheritance

AR, AD

ClinVar variants

U:316B:108

Top phenotype

neural tube defect

gnomAD constraint

pLI —, LoF o/e 0.23

Max pathogenic AF

—

Genomic locus

chr4:76,435,229-76,783,253

External References & Databases

Ensembl (ENSG00000138771)

Transcript & Mutation Effects

hg38 • Region Span ~348.0 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

syndromic diseaseMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0002254

Submitter: PanelApp Australia

neural tube defectSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0018075

Submitter: G2P

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to SHROOM3 variants in ClinVar

5 Conditions Cataloged

not specifiedTotal: 368

SHROOM3-related disorderTotal: 38

not providedTotal: 35

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

Neural tube defectTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_020859.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			2 clinvar	43 clinvar	7 clinvar	52
missense			309 clinvar	51 clinvar	7 clinvar	367
nonsense			2 clinvar			2
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	316	94	14	424

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_020859.4	RefSeq	NP_065910.3	11	MANE Select
ENST00000296043.7	Ensembl	ENSP00000296043.6	11	MANE Select
ENST00000644244.1	Ensembl	ENSP00000496523.1	2	Standard
ENST00000646790.1	Ensembl	ENSP00000494970.1	10	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
shroom3	Danio rerio	Structure: pronephric glomerular basement membrane Quality: increased permeability abnormal

Gene / Model

Organism

Observed Phenotype

shroom3

Danio rerio

Structure: pronephric glomerular basement membrane

Quality: increased permeability

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

cell morphogenesis
neural tube closure
epithelial cell development
actin filament organization
pattern specification process

Molecular Function

actin filament binding

Cellular Component

cytoskeleton
microtubule
adherens junction
apical plasma membrane
cortical actin cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000296043
Coding exons: 11
Length: 348154
Individuals with no LoFs: 123704
Homozygous LoFs: 0
Heterozygous LoFs: 2044
Defined: 125748
p: 0.00816

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.24	1037	1.16e+3	0.897	0.0000721	12833
Missense (PolyPhen)		269	323.63	0.83119		3763
Synonymous	1.39	455	494	0.920	0.0000330	4224
Loss of Function	5.79	15	65.6	0.229	0.00000387	739

Population LoF Frequency

Population	CAF	p-value	Status
African	0.032	0.031	notable
Latino/Admixed American	0.0019	0.0019	notable
Ashkenazi Jewish	0.0036	0.0036	notable
East Asian	0.011	0.011	notable
Finnish	0.011	0.011	notable
European (Non-Finnish)	0.0083	0.0083	notable
South Asian	0.00046	0.00046	rare
Other	0.010	0.010	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Controls cell shape changes in the neuroepithelium during neural tube closure. Induces apical constriction in epithelial cells by promoting the apical accumulation of F-actin and myosin II, and probably by bundling stress fibers. Induces apicobasal cell elongation by redistributing gamma-tubulin and directing the assembly of robust apicobasal microtubule arrays (By similarity). {ECO:0000250}.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.425
RVIS EVS: 1.4
RVIS percentile EVS: 94.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.381

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High