FRMD4A

FERM domain containing 4A, the group of FERM domain containing

Basic information

Region (hg38): 10:13643705-14462142

Previous symbols: [ "FRMD4" ]

Links

ENSG00000151474 ∙ NCBI:55691 ∙ OMIM:616305 ∙ HGNC:25491 ∙ Uniprot:Q9P2Q2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome (Limited), mode of inheritance: AR
• severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome (Supportive), mode of inheritance: AR
• severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Corpus callosum, agenesis of, with facial anomalies and cerebellar ataxia (Fine-Flusser syndrome)	AR	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	Craniofacial; Neurologic	25388005

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FRMD4A gene.

• Inborn genetic diseases (42 variants)
• not provided (28 variants)
• Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome (4 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FRMD4A 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				15	4	19
missense			43	1	2	46
nonsense						0
start loss						0
frameshift				1		1
inframe indel				1	1	2
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding					2	2
Total	0	0	43	18	9

Variants in FRMD4A

This is a list of pathogenic ClinVar variants found in the FRMD4A region.

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

Position	Type	Phenotype	Significance	ClinVar
10-13651897-C-T		FRMD4A-related disorder	Likely benign (Apr 02, 2020)
10-13651898-G-A			Likely benign (-)
10-13651947-C-AGAATG		Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome	Likely pathogenic (Mar 14, 2024)
10-13651960-T-A		FRMD4A-related disorder	Benign (Dec 31, 2019)
10-13654453-G-A		not specified	Uncertain significance (Feb 28, 2023)
10-13654467-A-G		not specified	Uncertain significance (Dec 15, 2023)
10-13654482-G-A		not specified	Uncertain significance (Jun 02, 2023)
10-13654510-C-T		not specified	Uncertain significance (Sep 26, 2023)
10-13656641-G-A		not specified	Uncertain significance (Feb 16, 2023)
10-13656703-G-A			Likely benign (Aug 01, 2022)
10-13656707-G-A		not specified	Uncertain significance (Aug 15, 2023)
10-13656710-C-T		not specified	Uncertain significance (Aug 10, 2021)
10-13656714-A-C		not specified	Uncertain significance (Oct 04, 2022)
10-13656719-G-A		not specified	Uncertain significance (Jan 03, 2022)
10-13656727-G-T		not specified	Uncertain significance (Jan 03, 2024)
10-13656729-C-G		not specified	Uncertain significance (Jan 29, 2024)
10-13656752-G-A		Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome • not specified	Uncertain significance (May 03, 2023)
10-13656788-C-A		not specified	Uncertain significance (Mar 07, 2023)
10-13656839-T-A		not specified	Uncertain significance (Feb 01, 2023)
10-13656866-G-A			Uncertain significance (Mar 01, 2022)
10-13656890-C-T		not specified	Uncertain significance (Jan 16, 2024)
10-13656896-G-A		not specified	Uncertain significance (Mar 01, 2024)
10-13656905-C-T		not specified	Uncertain significance (Feb 28, 2024)
10-13656906-G-A		not specified	Uncertain significance (Jan 26, 2023)
10-13656908-C-A		not specified	Uncertain significance (May 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FRMD4A	protein_coding	protein_coding	ENST00000357447	23	818436

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	1.28e-7	125740	0	8	125748	0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.46	447	619	0.722	0.0000398	6702
Missense in Polyphen		167	257.14	0.64945		2735
Synonymous	-0.847	288	270	1.07	0.0000199	2022
Loss of Function	6.64	3	57.2	0.0524	0.00000299	657

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000116	0.000116
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000188	0.0000176
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Scaffolding protein that regulates epithelial cell polarity by connecting ARF6 activation with the PAR3 complex (By similarity). Plays a redundant role with FRMD4B in epithelial polarization (By similarity). May regulate MAPT secretion by activating ARF6-signaling (PubMed:27044754). {ECO:0000250|UniProtKB:Q8BIE6, ECO:0000269|PubMed:27044754}.
• Disease: DISEASE: Agenesis of the corpus callosum, with facial anomalies and cerebellar ataxia (CCAFCA) [MIM:616819]: An autosomal recessive intellectual disability syndrome characterized by congenital microcephaly, low anterior hairline, bitemporal narrowing, low-set protruding ears, strabismus and tented thick eyebrows with sparse hair in their medial segment. {ECO:0000269|PubMed:25388005}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Recessive Scores

• pRec: 0.110

Intolerance Scores

• loftool: 0.0714
• rvis_EVS: -1.57
• rvis_percentile_EVS: 3.17

Haploinsufficiency Scores

• pHI: 0.372
• hipred: Y
• hipred_score: 0.728
• ghis: 0.607

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.836

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Frmd4a

Gene ontology

• Biological process: establishment of epithelial cell polarity
• Cellular component: cytoplasm;cytoskeleton;adherens junction;bicellular tight junction
• Molecular function: protein binding, bridging