SHROOM4

shroom family member 4, the group of PDZ domain containing|Shroom family

Basic information

Region (hg38): X:50586795-50814302

Links

ENSG00000158352 ∙ NCBI:57477 ∙ OMIM:300579 ∙ HGNC:29215 ∙ Uniprot:Q9ULL8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• X-linked intellectual disability, Stocco dos Santos type (Supportive), mode of inheritance: XL
• X-linked intellectual disability, Stocco dos Santos type (Limited), mode of inheritance: XL
• X-linked complex neurodevelopmental disorder (Disputed Evidence), mode of inheritance: XL

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder, X-linked, Stocco dos Santos type	XL	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	2063914; 12673656; 16249884

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SHROOM4 gene.

• not provided (70 variants)
• Inborn genetic diseases (66 variants)
• X-linked intellectual disability, Stocco dos Santos type (33 variants)
• not specified (31 variants)
• SHROOM4-related condition (5 variants)
• History of neurodevelopmental disorder (4 variants)
• Intellectual disability (2 variants)
• See cases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SHROOM4 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4	11	4	19
missense			99	16	11	126
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel			3	1	5	9
splice donor/acceptor (+/-2bp)		1				1
splice region						0
non coding				1	1	2
Total	1	1	107	29	21

Variants in SHROOM4

This is a list of pathogenic ClinVar variants found in the SHROOM4 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
X-50596738-T-C			Uncertain significance (Jun 01, 2022)
X-50596825-T-C		not specified	Uncertain significance (Oct 18, 2021)
X-50596855-C-T		X-linked intellectual disability, Stocco dos Santos type	Uncertain significance (Aug 02, 2019)
X-50596856-G-A		not specified	Uncertain significance (Sep 21, 2016)
X-50596867-C-T		not specified	Uncertain significance (Feb 15, 2023)
X-50596874-C-A			Uncertain significance (Oct 30, 2017)
X-50596889-G-A			Likely benign (Jan 01, 2019)
X-50596895-C-T		not specified	Uncertain significance (Nov 15, 2021)
X-50596896-G-A			Likely benign (Oct 01, 2022)
X-50598265-C-T		X-linked intellectual disability, Stocco dos Santos type	Likely pathogenic (Oct 25, 2021)
X-50598277-T-G			Uncertain significance (Jul 21, 2023)
X-50598364-G-T		not specified	Uncertain significance (Mar 12, 2024)
X-50598368-C-T		SHROOM4-related disorder	Likely benign (Sep 05, 2019)
X-50598369-C-T		not specified	Uncertain significance (May 15, 2023)
X-50598377-C-A		not specified	Benign (Jul 16, 2015)
X-50598412-C-T		not specified • SHROOM4-related disorder	Benign/Likely benign (Jan 13, 2020)
X-50598413-G-A			Likely benign (Apr 01, 2023)
X-50598413-G-T			Likely benign (Apr 01, 2022)
X-50598448-C-A			Uncertain significance (Sep 01, 2023)
X-50598480-C-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2013)
X-50598523-C-T		X-linked intellectual disability, Stocco dos Santos type	Uncertain significance (Aug 07, 2018)
X-50598534-A-G		Intellectual disability • See cases • not specified	Conflicting classifications of pathogenicity (Mar 01, 2024)
X-50602585-A-G		X-linked intellectual disability, Stocco dos Santos type	Benign (Jul 15, 2021)
X-50602632-C-T		X-linked intellectual disability, Stocco dos Santos type	Uncertain significance (Apr 11, 2022)
X-50602636-T-A		not specified	Uncertain significance (Mar 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SHROOM4	protein_coding	protein_coding	ENST00000376020	9	222656

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000349	125492	24	230	125746	0.00101

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.951	502	566	0.887	0.0000428	9762
Missense in Polyphen		122	173.55	0.70297		2953
Synonymous	0.330	212	218	0.972	0.0000160	2958
Loss of Function	5.31	4	40.5	0.0988	0.00000304	690

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00112	0.00106
Ashkenazi Jewish	0.0161	0.00987
East Asian	0.00	0.00
Finnish	0.000497	0.000323
European (Non-Finnish)	0.00160	0.000897
Middle Eastern	0.00	0.00
South Asian	0.000656	0.000327
Other	0.00257	0.00163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Probable regulator of cytoskeletal architecture that plays an important role in development. May regulate cellular and cytoskeletal architecture by modulating the spatial distribution of myosin II (By similarity). {ECO:0000250, ECO:0000269|PubMed:16684770}.
• Disease: DISEASE: Note=A chromosomal aberration involving SHROOM4 is a cause of X-linked mental retardation (XLMR). Translocation t(X;8)(p11.22;p23.3) with FBXO25.; DISEASE: Note=A chromosomal aberration involving SHROOM4 is a cause of X-linked mental retardation (XLMR). Translocation t(X;19).

Recessive Scores

• pRec: 0.0827

Intolerance Scores

• loftool: 0.179
• rvis_EVS: 1.07
• rvis_percentile_EVS: 91.71

Haploinsufficiency Scores

• pHI: 0.142
• hipred: N
• hipred_score: 0.426
• ghis: 0.489

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.0584

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Shroom4
• Phenotype: immune system phenotype; vision/eye phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: cell morphogenesis;actin filament organization;brain development;actin cytoskeleton organization;cognition
• Cellular component: stress fiber;cytoplasm;actin filament;adherens junction;cytoplasmic side of plasma membrane;basal plasma membrane;actin cytoskeleton;apical plasma membrane;cortical actin cytoskeleton;apical junction complex
• Molecular function: myosin II binding;actin filament binding