FRMD5

protein-coding

FERM domain containing 5, the group of FERM domain containing

Gene summary

Enables integrin binding activity and protein kinase binding activity. Involved in negative regulation of cell motility; positive regulation of cell adhesion; and regulation of cell migration. Located in adherens junction. Implicated in neurodevelopmental disorder with eye movement abnormalities and ataxia. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_032892.5

Inheritance

ClinVar variants

P:8U:104B:14

Top phenotype

Neurodevelopmental disorder with eye movement abnormalities and ataxia

gnomAD constraint

pLI —, LoF o/e 0.1

Max pathogenic AF

—

Genomic locus

chr15:43,870,761-44,195,271

External References & Databases

Ensembl (ENSG00000171877)

Transcript & Mutation Effects

hg38 • Region Span ~324.5 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

neurodevelopmental disorder with eye movement abnormalities and ataxiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859305

Submitter: Labcorp Genetics (formerly Invitae)

neurodevelopmental disorder with eye movement abnormalities and ataxiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859305

Submitter: G2P

neurodevelopmental disorder with eye movement abnormalities and ataxiaMODERATE

Inheritance Pattern: AD

Disease ID:MONDO:0859305

Submitter: Ambry Genetics

neurodevelopmental disorder with eye movement abnormalities and ataxiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0859305

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with eye movement abnormalities and ataxiaAD

Manifestation: Neurologic

Intervention: General

Rationale: 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

Refs: 36206744

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to FRMD5 variants in ClinVar

7 Conditions Cataloged

Inborn genetic diseasesTotal: 58

not providedTotal: 45

Neurodevelopmental disorder with eye movement abnormalities and ataxiaTotal: 16

not specifiedTotal: 8

FRMD5-related conditionTotal: 8

See casesTotal: 3

Neurodevelopmental delayTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_032892.5. 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			1 clinvar	9 clinvar	1 clinvar	11
missense	2 clinvar	5 clinvar	91 clinvar	4 clinvar		102
nonsense			2 clinvar			2
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)	1 clinvar		4 clinvar			5
Total	3	5	104	13	1	126

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 22 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_032892.5	RefSeq	NP_116281.2	14	MANE Select
ENST00000417257.6	Ensembl	ENSP00000403067.1	14	MANE Select
NM_001286490.2	RefSeq	NP_001273419.1	12	Standard
NM_001286491.2	RefSeq	NP_001273420.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of cell migration
actomyosin structure organization
positive regulation of cell adhesion
negative regulation of cell motility

Molecular Function

integrin binding
protein binding
cytoskeletal protein binding
protein kinase binding

Cellular Component

cytoskeleton
adherens junction
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000417257
Coding exons: 14
Length: 324489
Individuals with no LoFs: 125739
Homozygous LoFs: 0
Heterozygous LoFs: 7
Defined: 125746
p: 0.0000278

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.98	221	321	0.689	0.0000180	3722
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.000054	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.000035	0.000035	rare
South Asian	0.000033	0.000033	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

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

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.665

Gene Damage Prediction

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