FRMD5

FERM domain containing 5, the group of FERM domain containing

Basic information

Region (hg38): 15:43870760-44195271

Links

ENSG00000171877 ∙ NCBI:84978 ∙ OMIM:616309 ∙ HGNC:28214 ∙ Uniprot:Q7Z6J6 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• neurodevelopmental disorder with eye movement abnormalities and ataxia (Moderate), mode of inheritance: AD
• neurodevelopmental disorder with eye movement abnormalities and ataxia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with eye movement abnormalities and ataxia	AD	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	Neurologic	36206744

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRMD5 gene.

• Inborn genetic diseases (18 variants)
• Neurodevelopmental disorder with eye movement abnormalities and ataxia (7 variants)
• not provided (4 variants)
• See cases (3 variants)
• not specified (2 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRMD5 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					2	2
missense		1	24		1	26
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding				1		1
Total	0	1	25	1	3

Variants in FRMD5

This is a list of pathogenic ClinVar variants found in the FRMD5 region.

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

Position	Type	Phenotype	Significance	ClinVar
15-43873902-G-T		Inborn genetic diseases	Uncertain significance (Oct 17, 2023)
15-43873911-C-G		Inborn genetic diseases	Uncertain significance (Mar 01, 2023)
15-43873937-C-T		Inborn genetic diseases	Uncertain significance (Jul 06, 2021)
15-43873961-T-C		Neurodevelopmental delay • Neurodevelopmental disorder with eye movement abnormalities and ataxia	Uncertain significance (Aug 19, 2022)
15-43873985-G-T		Inborn genetic diseases	Uncertain significance (Mar 29, 2022)
15-43874076-T-A		Inborn genetic diseases	Uncertain significance (Mar 05, 2024)
15-43874090-C-T		Inborn genetic diseases	Uncertain significance (Jul 12, 2023)
15-43874207-G-A		Inborn genetic diseases	Uncertain significance (Jul 14, 2022)
15-43874219-T-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
15-43874289-C-T		Inborn genetic diseases	Uncertain significance (Jan 29, 2024)
15-43874294-A-G		Inborn genetic diseases	Uncertain significance (Mar 29, 2023)
15-43874304-G-A		Inborn genetic diseases	Uncertain significance (Sep 16, 2021)
15-43874310-C-T		Inborn genetic diseases	Uncertain significance (Oct 05, 2022)
15-43874319-C-T		Inborn genetic diseases	Uncertain significance (Feb 28, 2024)
15-43874320-A-G			Benign (May 16, 2018)
15-43874432-G-A		Inborn genetic diseases	Uncertain significance (Oct 04, 2022)
15-43874457-C-G		Inborn genetic diseases	Uncertain significance (Jan 06, 2023)
15-43883748-C-T		Inborn genetic diseases	Uncertain significance (Jun 18, 2021)
15-43883758-C-G		Inborn genetic diseases	Uncertain significance (Jun 09, 2022)
15-43883765-C-T		Neurodevelopmental disorder with eye movement abnormalities and ataxia	Uncertain significance (-)
15-43883778-A-G		Neurodevelopmental disorder with eye movement abnormalities and ataxia	Pathogenic (Oct 27, 2022)
15-43883784-A-G		See cases • Neurodevelopmental disorder with eye movement abnormalities and ataxia	Uncertain significance (Aug 19, 2022)
15-43883785-G-C		See cases • Neurodevelopmental disorder with eye movement abnormalities and ataxia	Uncertain significance (Aug 19, 2022)
15-43883786-C-T		Neurodevelopmental disorder with eye movement abnormalities and ataxia	Likely pathogenic (May 09, 2023)
15-43883787-T-C		Neurodevelopmental disorder with eye movement abnormalities and ataxia	Pathogenic (Oct 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRMD5	protein_coding	protein_coding	ENST00000417257	14	324489

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00276	125739	0	7	125746	0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.98	221	321	0.689	0.0000180	3722
Missense in Polyphen		83	134.02	0.61931		1553
Synonymous	-0.313	123	119	1.04	0.00000635	1100
Loss of Function	4.62	3	30.5	0.0983	0.00000163	361

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000353	0.0000352
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000327	0.0000327
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May be involved in regulation of cell migration (PubMed:22846708, PubMed:25448675). May regulate cell-matrix interactions via its interaction with ITGB5 and modifying ITGB5 cytoplasmic tail interactions such as with FERMT2 and TLN1. May regulate ROCK1 kinase activity possibly involved in regulation of actin stress fiber formation (PubMed:25448675).

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.242
• rvis_EVS: 0.13
• rvis_percentile_EVS: 63.36

Haploinsufficiency Scores

• pHI: 0.497
• hipred: Y
• hipred_score: 0.754
• ghis: 0.527

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.665

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Frmd5
• Phenotype: skeleton phenotype; vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); reproductive system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: regulation of cell migration;actomyosin structure organization;positive regulation of cell adhesion;negative regulation of cell motility
• Cellular component: cytoskeleton;adherens junction;integral component of membrane
• Molecular function: integrin binding;protein binding;cytoskeletal protein binding;protein kinase binding