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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FRMD7
FERM domain containing 7
Chromosome X Β· Xq26.2
NCBI Gene: 90167Ensembl: ENSG00000165694.11HGNC: HGNC:8079UniProt: Q6ZUT3
63PubMed Papers
21Diseases
0Drugs
59Pathogenic Variants
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
GO:0005615protein bindinggrowth coneneuron projectionnystagmus 1, congenital, X-linkedgenetic disordercongenital nystagmusendometriosis
✦AI Summary

FRMD7 (FERM domain containing 7) is an X-linked gene essential for ocular motor control and neuronal development. The protein functions as a guanyl-nucleotide exchange factor that regulates the Rho family of GTPases, particularly affecting cytoskeletal dynamics through F-actin interactions 1. FRMD7 expression is predominantly localized to the brainstem, the region governing ocular motor control 1, and influences neurite elongation, complexity, and neuronal maturation during development 2. Two functionally relevant FRMD7 isoforms (FRMD7-FL and FRMD7-S) interact during neuronal differentiation 3. Mutations in FRMD7 cause X-linked idiopathic congenital nystagmus (ICN/infantile nystagmus), the most frequent genetic cause of this oculomotor disorder 4. Over 50 mutations have been identified, with loss-of-function as the common pathogenic mechanism, predominantly affecting the FERM-C domain 5. FRMD7 mutations reduce neuronal process complexity through dysregulation of Rho GTPase signaling 2, though affected individuals show similar nystagmus parameters regardless of mutation type 5. Unlike GPR143-related nystagmus, FRMD7 mutations typically do not cause foveal hypoplasia 6. Understanding FRMD7's role in oculomotor development may guide future gene therapy approaches 4.

Sources cited
1
FRMD7 mutations reduce neuronal process complexity and maturation; mutations increase Rho GTPase expression
PMID: 31743612
2
FRMD7 is the major genetic cause of hereditary X-linked nystagmus; gene therapy is a potential future treatment
PMID: 25086850
3
FRMD7 variants account for 3.5% of foveal hypoplasia cases; all FRMD7 cases showed photoreceptor specialization
PMID: 35157951
4
FRMD7 is expressed primarily in brainstem; C-terminus is critical for subcellular localization; interacts with F-actin cytoskeleton
PMID: 21386928
5
Two FRMD7 isoforms (FRMD7-FL and FRMD7-S) interact and co-localize; both upregulated during neuronal differentiation
PMID: 22128244
6
Over 50 FRMD7 mutations identified; FERM-C domain is mutation hotspot; loss-of-function is common mechanism
PMID: 35705619
7
FRMD7 mutations cause congenital nystagmus; mutations can occur in hemizygous, heterozygous, and homozygous states
PMID: 22490987
8
FRMD7 mutations do not cause foveal hypoplasia, distinguishing them from GPR143-related nystagmus
PMID: 38648460
Disease Associationsβ“˜21
nystagmus 1, congenital, X-linkedOpen Targets
0.83Strong
genetic disorderOpen Targets
0.42Moderate
congenital nystagmusOpen Targets
0.38Weak
endometriosisOpen Targets
0.35Weak
Retinal dystrophyOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.34Weak
uterine fibroidOpen Targets
0.31Weak
NystagmusOpen Targets
0.24Weak
Ovarian EndometriosisOpen Targets
0.21Weak
foveal hypoplasiaOpen Targets
0.19Weak
eye diseaseOpen Targets
0.17Weak
Abnormal conjugate eye movementOpen Targets
0.17Weak
appendicitisOpen Targets
0.16Weak
OligomenorrheaOpen Targets
0.03Suggestive
PolymenorrheaOpen Targets
0.03Suggestive
placental retentionOpen Targets
0.02Suggestive
MenorrhagiaOpen Targets
0.02Suggestive
cervical squamous intraepithelial neoplasiaOpen Targets
0.02Suggestive
congenital mesoblastic nephromaOpen Targets
0.02Suggestive
acute myeloid leukemiaOpen Targets
0.01Suggestive
Nystagmus 1, congenital, X-linkedUniProt
Pathogenic Variants59
NM_194277.3(FRMD7):c.580G>A (p.Ala194Thr)Pathogenic
not provided|Nystagmus 1, congenital, X-linked
β˜…β˜…β˜†β˜†2025β†’ Residue 194
NM_194277.3(FRMD7):c.425T>G (p.Leu142Arg)Pathogenic
Nystagmus 1, congenital, X-linked|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 142
NM_194277.3(FRMD7):c.47T>C (p.Phe16Ser)Pathogenic
not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 16
NM_194277.3(FRMD7):c.910C>T (p.Arg304Ter)Pathogenic
not provided|Nystagmus 1, congenital, X-linked
β˜…β˜…β˜†β˜†2025β†’ Residue 304
NM_194277.3(FRMD7):c.782G>A (p.Arg261Gln)Pathogenic
not provided|Nystagmus 1, congenital, X-linked
β˜…β˜…β˜†β˜†2025β†’ Residue 261
NM_194277.3(FRMD7):c.1003C>T (p.Arg335Ter)Pathogenic
Nystagmus 1, congenital, X-linked|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 335
NM_194277.3(FRMD7):c.1370dup (p.Met457fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 457
NM_194277.3(FRMD7):c.902A>G (p.Tyr301Cys)Likely pathogenic
not provided|Nystagmus 1, congenital, X-linked|Thyroid cancer, nonmedullary, 1
β˜…β˜…β˜†β˜†2024β†’ Residue 301
NM_194277.3(FRMD7):c.906-2A>GLikely pathogenic
not provided
β˜…β˜…β˜†β˜†2024
NM_194277.3(FRMD7):c.70G>A (p.Gly24Arg)Pathogenic
Nystagmus 1, congenital, X-linked|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 24
NM_194277.3(FRMD7):c.781C>T (p.Arg261Ter)Pathogenic
not provided|Nystagmus 1, congenital, X-linked
β˜…β˜…β˜†β˜†2022β†’ Residue 261
NM_194277.3(FRMD7):c.886G>C (p.Gly296Arg)Pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 296
NM_194277.3(FRMD7):c.134T>G (p.Leu45Ter)Pathogenic
not provided
β˜…β˜…β˜†β˜†2022β†’ Residue 45
NM_194277.3(FRMD7):c.646-2A>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2026
NM_194277.3(FRMD7):c.162+1G>ALikely pathogenic
Nystagmus 1, congenital, X-linked
β˜…β˜†β˜†β˜†2025
NM_194277.3(FRMD7):c.689_710del (p.Lys230fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 230
NM_194277.3(FRMD7):c.812G>T (p.Cys271Phe)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 271
NM_194277.3(FRMD7):c.79_80insA (p.Leu27fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 27
NM_194277.3(FRMD7):c.162+2T>GLikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_194277.3(FRMD7):c.799T>G (p.Phe267Val)Likely pathogenic
Nystagmus 1, congenital, X-linked
β˜…β˜†β˜†β˜†2025β†’ Residue 267
View on ClinVar β†—
Related Genes
CASKProtein interaction93%NYXProtein interaction80%OPN1MWProtein interaction79%OPN1LWProtein interaction77%GPR143Protein interaction72%NCS1Shared pathway33%
Tissue Expression6 tissues
Heart
100%
Liver
83%
Brain
28%
Bone Marrow
0%
Ovary
0%
Lung
0%
Gene Interaction Network
Click a node to explore
FRMD7CASKNYXOPN1MWOPN1LWGPR143NCS1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt Q6ZUT3
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.50Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.32 [0.21–0.50]
RankingsWhere FRMD7 stands among ~20K protein-coding genes
  • #7,362of 20,598
    Most Researched63
  • #1,188of 5,498
    Most Pathogenic Variants59 Β· top quartile
  • #2,943of 17,882
    Most Constrained (LOEUF)0.50 Β· top quartile
Genes detectedFRMD7
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Nystagmus-related FRMD7 gene influences the maturation and complexities of neuronal processes in human neurons.
PMID: 31743612
Brain Behav Β· 2019
1.00
2
Nystagmus in childhood.
PMID: 25086850
Pediatr Neonatol Β· 2014
0.90
3
Genotypic and Phenotypic Spectrum of Foveal Hypoplasia: A Multicenter Study.
PMID: 35157951
Ophthalmology Β· 2022
0.80
4
Expression and localization of FRMD7 in human fetal brain, and a role for F-actin.
PMID: 21386928
Mol Vis Β· 2011
0.70
5
Identification of a novel FRMD7 splice variant and functional analysis of two FRMD7 transcripts during human NT2 cell differentiation.
PMID: 22128244
Mol Vis Β· 2011
0.60